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1. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

Halliday, Alison, Bulbulia, Richard, Bonati, Leo H, Peto, Richard, Pan, Hongchao, Potter, John, Henning Eckstein, Hans, Farrell, Barbara, Flather, Marcus, Mansfield, Averil, Mihaylova, Boby, Rahimi, Kazim, Simpson, David, Thomas, Dafydd, Sandercock, Peter, Gray, Richard, Molyneux, Andrew, Shearman, Cliff P, Rothwell, Peter, Belli, Anna, Herrington, Will, Judge, Parminder, Leopold, Peter, Mafham, Marion, Gough, Michael, Cao, Piergiorgio, MacDonald, Sumaira, Bari, Vasha, Berry, Clive, Bradshaw, S, Brudlo, Wojciech, Clarke, Alison, Chester, Johanna, Cox, Robin, Cradduck-Bamford, Andrea, Fathers, Susan, Gaba, Kamran, Gray, Mo, Hayter, Elizabeth, Holliday, Constance, Kurien, Rijo, Lay, Michael, le Conte, Steffi, McManus, Jessica, Madgwick, Zahra, Morris, Dylan, Munday, Andrew, Pickworth, Sandra, Ostasz, Wiktor, Poorthuis, Michiel, Richards, Sue, Teixeira, Louisa, Tochlin, Sergey, Tully, Lynda, Wallis, Carol, Willet, Monique, Young, Alan, Casana, Renato, Malloggi, Chiara, Odero Jr, Andrea, Silani, Vincenzo, Parati, Gianfranco, Malchiodi, Giuseppe, Malferrari, Giovanni, Strozzi, Francesco, Tusini, Nicola, Vecchiati, Enrico, Coppi, Gioacchino, Lauricella, Antonio, Moratto, Roberto, Silingardi, Roberto, Veronesi, Jessica, Zini, Andrea, Ferrero, Emanuele, Ferri, Michelangelo, Gaggiano, Andrea, Labate, Carmelo, Nessi, Franco, Psacharopulo, Daniele, Viazzo, Andrea, Malacrida, Giovanni, Mazzaccaro, Daniela, Meola, Giovanni, Modafferi, Alfredo, Nano, Giovanni, Occhiuto, Maria Teresa, Righini, Paolo, Stegher, Silvia, Chiarandini, Stefano, Griselli, Filippo, Lepidi, Sandro, Pozzi Mucelli, Fabio, Naccarato, Marcello, D'Oria, Mario, Ziani, Barbara, Stella, Andrea, Dieng, Mortalla, Faggioli, Gianluca, Gargiulo, Mauro, Palermo, Sergio, Pini, Rodolfo, Puddu, Giovanni Maria, Vacirca, Andrea, Angiletta, Domenico, Desantis, Claudio, Marinazzo, Davide, Mastrangelo, Giovanni, Regina, Guido, Pulli, Raffaele, Bianchi, Paolo, Cireni, Lea, Coppi, Elisabetta, Pizzirusso, Rocco, Scalise, Filippo, Sorropago, Giovanni, Tolva, Valerio, Caso, Valeria, Cieri, Enrico, DeRango, Paola, Farchioni, Luca, Isernia, Giacomo, Lenti, Massimo, Parlani, Gian Battista, Pupo, Guglielmo, Pula, Grazia, Simonte, Gioele, Verzini, Fabio, Carimati, Federico, Delodovici, Maria Luisa, Fontana, Federico, Piffaretti, Gabriele, Tozzi, Matteo, Civilini, Efrem, Poletto, Giorgio, Reimers, Bernhard, Praquin, Barbara, Ronchey, Sonia, Capoccia, Laura, Mansour, Wassim, Sbarigia, Enrico, Speziale, Francesco, Sirignano, Pasqualino, Toni, Danilo, Galeotti, Roberto, Gasbarro, Vincenzo, Mascoli, Francesco, Rocca, Tiberio, Tsolaki, Elpiniki, Bernardini, Giulia, DeMarco, Ester, Giaquinta, Alessia, Patti, Francesco, Veroux, Massimiliano, Veroux, Pierfrancesco, Virgilio, Carla, Mangialardi, Nicola, Orrico, Matteo, Di Lazzaro, Vincenzo, Montelione, Nunzio, Spinelli, Francesco, Stilo, Francesco, Cernetti, Carlo, Irsara, Sandro, Maccarrone, Giuseppe, Tonello, Diego, Visonà, Adriana, Zalunardo, Beniamino, Chisci, Emiliano, Michelagnoli, Stefano, Troisi, Nicola, Masato, Maela, Dei Negri, Massimo, Pacchioni, Andrea, Saccà, Salvatore, Amatucci, Giovanni, Cannizzaro, Alfredo, Accrocca, Federico, Ambrogi, Cesare, Barbazza, Renzo, Marcucci, Giustino, Siani, Andrea, Bajardi, Guido, Savettieri, Giovanni, Argentieri, Angelo, Corbetta, Riccardo, Odero, Attilio, Quaretti, Pietro, Thyrion, Federico Z, Cappelli, Alessandro, Benevento, Domenico, De Donato, Gianmarco, Mele, Maria Agnese, Palasciano, Giancarlo, Pieragalli, Daniela, Rossi, Alessandro, Setacci, Carlo, Setacci, Francesco, Palombo, Domenico, Perfumo, Maria Cecilia, Martelli, Edoardo, Paolucci, Aldo, Trimarchi, Santi, Grassi, Viviana, Grimaldi, Luigi, La Rosa, Giuliana, Mirabella, Domenico, Scialabba, Matteo, Sichel, Leonildo, D'Angelo, Costantino L, Fadda, Gian Franco, Kasemi, Holta, Marino, Mario, Burzotta, Francesco, Codispoti, Francesco Alberto, Ferrante, Angela, Tinelli, Giovanni, Tshomba, Yamume, Vincenzoni, Claudio, Amis, Deborah, Anderson, Dawn, Catterson, Martin, Clarke, Mike, Davis, Michelle, Dixit, Anand, Dyker, Alexander, Ford, Gary, Jackson, Ralph, Kappadath, Sreevalsan, Lambert, David, Lees, Tim, Louw, Stephen, McCaslin, James, Parr, Noala, Robson, Rebecca, Stansby, Gerard, Wales, Lucy, Wealleans, Vera, Wilson, Lesley, Wyatt, Michael, Baht, Hardeep, Balogun, Ibrahim, Burger, Ilse, Cosier, Tracy, Cowie, Linda, Gunathilagan, Gunaratnam, Hargroves, David, Insall, Robert, Jones, Sally, Rudenko, Hannah, Schumacher, Natasha, Senaratne, Jawaharlal, Thomas, George, Thomson, Audrey, Webb, Tom, Brown, Ellen, Esisi, Bernard, Mehrzad, Ali, MacSweeney, Shane, McConachie, Norman, Southam, Alison, Sunman, Wayne, Abdul-Hamiq, Ahmed, Bryce, Jenny, Chetter, Ian, Ettles, Duncan, Lakshminarayan, Raghuram, Mitchelson, Kim, Rhymes, Christopher, Robinson, Graham, Scott, Paul, Vickers, Alison, Ashleigh, Ray, Butterfield, Stephen, Gamble, Ed, Ghosh, Jonathan, McCollum, Charles N, Welch, Mark, Welsh, Sarah, Wolowczyk, Leszek, Donnelly, Mary, D'Souza, Stephen, Egun, Anselm A, Gregary, Bindu, Joseph, Thomas, Kelly, Christine, Punekar, Shuja, Rahi, M Asad, Raj, Sonia, Seriki, Dare, Thomson, George, Brown, James, Durairajan, Ragunath, Grunwald, Iris, Guyler, Paul, Harman, Paula, Jakeways, Matthew, Khuoge, Christopher, Kundu, Ashish, Loganathan, Thayalini, Menon, Nisha, Prabakaran, Raji O, Sinha, Devesh, Thompson, Vicky, Tysoe, Sharon, Briley, Dennis, Darby, Chris, Hands, Linda, Howard, Dominic, Kuker, Wilhelm, Schulz, Ursula, Teal, Rachel, Barer, David, Brown, Andrew, Crawford, Susan, Dunlop, Paul, Krishnamurthy, Ramesh, Majmudar, Nikhil, Mitchell, Duncan, Myint, Min P, O'Brien, Richard, O'Connell, Janice, Sattar, Naweed, Vetrivel, Shanmugam, Beard, Jonathan, Cleveland, Trevor, Gaines, Peter, Humphreys, John, Jenkins, Alison, King, Craig, Kusuma, Daniel, Lindert, Ralph, Lonsdale, Robbie, Nair, Raj, Nawaz, Shah, Okhuoya, Faith, Turner, Douglas, Venables, Graham, Dorman, Paul, Hughes, Andrea, Jones, Deborah, Mendelow, David, Rodgers, Helen, Raudoniitis, Aidas, Enevoldson, Peter, Nahser, Hans, O'Brien, Imelda, Torella, Francesco, Watling, Dave, White, Richard, Brown, Pauline, Dutta, Dipankar, Emerson, Lorraine, Hilltout, Paula, Kulkarni, Sachin, Morrison, Jackie, Poskitt, Keith, Slim, Fiona, Smith, Sarah, Tyler, Amanda, Waldron, Joanne, Whyman, Mark, Bajoriene, Milda, Baker, Lucy, Colston, Amanda, Eliot-Jones, Bekky, Gramizadeh, Gita, Lewis-Clarke, Catherine, McCafferty, Laura, Oliver, Deborah, Palmer, Debbie, Patil, Abhijeet, Pegler, Suzannah, Ramadurai, Gopi, Roberts, Aisling, Sargent, Tracey, Siddegowda, Shivaprasad, Singh-Ranger, Ravi, Williams, Akintunde, Williams, Lucy, Windebank, Steve, Zuromskis, Tadas, Alwis, Lanka, Angus, Jane, Asokanathan, Asaipillai, Fornolles, Caroline, Hardy, Diana, Hunte, Sophy, Justin, Frances, Phiri, Duke, Mitabouana-Kibou, Marie, Sekaran, Lakshmanan, Sethuraman, Sakthivel, Tate, Margaret L, Akyea-Mensah, Joyce, Ball, Stephen, Chrisopoulou, Angela, Keene, Elizabeth, Phair, Alison, Rogers, Steven, Smyth, John V, Bicknell, Colin, Chataway, Jeremy, Cheshire, Nicholas, Clifton, Andrew, Eley, Caroline, Gibbs, Richard, Hamady, Mohammad, Hazel, Beth, James, Alex, Jenkins, Michael, Khanom, Nyma, Lacey, Austin, Mireskandari, Maz, O'Reilly, Joanna, Pereira, Antony, Sachs, Tina, Wolfe, John, Davey, Philip, Rogers, Gill, Smith, Gemma, Tervit, Gareth, Nichol, Ian, Parry, Andrew, Young, Gavin, Ashley, Simon, Barwell, James, Dix, Francis, Nor, Azlisham M, Parry, Chris, Birt, Angela, Davies, Paul, George, Jim, Graham, Anne, Jonker, Leon, Kelsall, Nicci, Potts, Caroline, Wilson, Toni, Crinnion, Jamie, Cuenoud, Larissa, Aleksic, Nikola, Babic, Srdan, Ilijevski, Nenad, Radak, Đorde, Sagic, Dragan, Tanaskovic, Slobodan, Colic, Momcilo, Cvetic, Vladimir, Davidovic, Lazar, Jovanovic, Dejana R, Koncar, Igor, Mutavdžic, Perica, Sladojevic, Miloš, Tomic, Ivan, Debus, Eike S, Grzyska, Ulrich, Otto, Dagmar, Thomalla, Götz, Barlinn, Jessica, Gerber, Johannes, Haase, Kathrin, Hartmann, Christian, Ludwig, Stefan, Pütz, Volker, Reeps, Christian, Schmidt, Christine, Weiss, Norbert, Werth, Sebastian, Winzer, Simon, Gemper, Janine, Günther, Albrecht, Heiling, Bianka, Jochmann, Elisabeth, Karvouniari, Panagiota, Klingner, Carsten, Mayer, Thomas, Schubert, Julia, Schulze-Hartung, Friederike, Zanow, Jürgen, Bausback, Yvonne, Borger, Franka, Botsios, Spiridon, Branzan, Daniela, Bräunlich, Sven, Hölzer, Henryk, Lenzer, Janin, Piorkowski, Christopher, Richter, Nadine, Schuster, Johannes, Scheinert, Dierk, Schmidt, Andrej, Staab, Holger, Ulrich, Matthias, Werner, Martin, Berger, Hermann, Biró, Gábor, Eckstein, Hans-Henning, Kallmayer, Michael, Kreiser, Kornelia, Zimmermann, Alexander, Berekoven, Bärbel, Frerker, Klaus, Gordon, Vera, Torsello, Giovanni, Arnold, Sebastian, Dienel, Cora, Storck, Martin, Biermaier, Bernhard, Gissler, Hans Martin, Klötzsch, Christof, Pfeiffer, Tomas, Schneider, Ralph, Söhl, Leander, Wennrich, Michael, Alonso, Angelika, Keese, Michael, Groden, Christoph, Cöster, Andreas, Engelhardt, Andreas, Ratusinski, Christoph-Maria, Berg, Bengt, Delle, Martin, Formgren, Johan, Gillgren, Peter, Jarl, Lotta, Kall, Torbjörn B, Konrad, Peter, Nyman, Niklas, Skiöldebrand, Claes, Steuer, Johnny, Takolander, Rabbe, Malmstedt, Jonas, Acosta, Stefan, Björses, Katarina, Brandt, Kerstin, Dias, Nuno, Gottsäter, Anders, Holst, Jan, Kristmundsson, Thorarinn, Kühme, Tobias, Kölbel, Tilo, Lindblad, Bengt, Lindh, Mats, Malina, Martin, Ohrlander, Tomas, Resch, Tim, Rönnle, Viola, Sonesson, Björn, Warvsten, Margareta, Zdanowski, Zbigniew, Campbell, Erik, Kjellin, Per, Lindgren, Hans, Nyberg, Johan, Petersen, Björn, Plate, Gunnar, Pärsson, Håkan, Qvarfordt, Peter, Ignatenko, Pavel, Karpenko, Andrey, Starodubtsev, Vladimir, Chernyavsky, Mikhail A, Golovkova, Maria S, Komakha, Boris B, Zherdev, Nikolay N, Belyasnik, Andrey, Chechulov, Pavel, Kandyba, Dmitry, Stepanishchev, Igor, Csobay-Novák, Csaba, Dósa, Edit, Entz, László, Nemes, Balázs, Szeberin, Zoltán, Barzó, Pál, Bodosi, Mihaly, Fákó, Eniko, Fülöp, Béla, Németh, Tamás, Pazdernyik, Szilárd, Skoba, Krisztina, Vörös, Erika, Chatzinikou, Eleni, Giannoukas, Athanasios, Karathanos, Christos, Koutsias, Stylianos, Kouvelos, Georgios, Matsagkas, Miltiadis, Ralli, Styliani, Rountas, Christos, Rousas, Nikolaos, Spanos, Konstantinos, Brountzos, Elias, Kakisis, John D, Lazaris, Andreas, Moulakakis, Konstantinos G, Stefanis, Leonidas, Tsivgoulis, Georgios, Vasdekis, Spyros, Antonopoulos, Constantine N, Bellenis, Ion, Maras, Dimitrios, Polydorou, Antonios, Polydorou, Victoria, Tavernarakis, Antonios, Ioannou, Nikolaos, Terzoudi, Maria, Lazarides, Miltos, Mantatzis, Michalis, Vadikolias, Kostas, Dzieciuchowicz, Lukasz, Gabriel, Marcin, Krasinski, Zbigniew, Oszkinis, Grzegorz, Pukacki, Fryderyk, Slowinski, Maciej, Stanišic, Michal-Goran, Staniszewski, Ryszard, Tomczak, Jolanta, Zielinski, Maciej, Myrcha, Piotr, Rózanski, Dorota, Drelichowski, Stanislaw, Iwanowski, Wojciech, Koncewicz, Katarzyna, Bialek, Pawel, Biejat, Zbigniew, Czepel, Wojciech, Czlonkowska, Anna, Dowzenko, Anatol, Jedrzejewska, Julia, Kobayashi, Adam, Leszczynski, Jerzy, Malek, Andrzej, Polanski, Jerzy, Proczka, Robert, Skorski, Maciej, Szostek, Mieczyslaw, Andziak, Piotr, Dratwicki, Maciej, Gil, Robert, Nowicki, Miroslaw, Pniewski, Jaroslaw, Rzezak, Jaroslaw, Seweryniak, Piotr, Dabek, Pawel, Juszynski, Michal, Madycki, Grzegorz, Pacewski, Bartosz, Raciborski, Witold, Slowinski, Piotr, Staszkiewicz, Walerian, Bombic, Martin, Chlouba, Vladimír, Fiedler, Jirí, Hes, Karel, Koštál, Petr, Sova, Jindrich, Kríž, Zdenek, Prívara, Mojmír, Reif, Michal, Staffa, Robert, Vlachovský, Robert, Vojtíšek, Bohuslav, Hrbác, Tomáš, Kuliha, Martin, Procházka, Václav, Roubec, Martin, Školoudík, David, Netuka, David, Šteklácová, Anna, Beneš III, Vladimír, Buchvald, Pavel, Endrych, Ladislav, Šercl, Miroslav, Campos Jr, Walter, Casella, Ivan B, de Luccia, Nelson, Estenssoro, André E V, Presti, Calógero, Puech-Leão, Pedro, Neves, Celso R B, da Silva, Erasmo S, Sitrângulo Jr, Cid J, Monteiro, José A T, Tinone, Gisela, Bellini Dalio, Marcelo, Joviliano, Edwaldo E, Pontes Neto, Octávio M, Serra Ribeiro, Mauricio, Cras, Patrick, Hendriks, Jeroen M H, Hoppenbrouwers, Mieke, Lauwers, Patrick, Loos, Caroline, Yperzeele, Laetitia, Geenens, Mia, Hemelsoet, Dimitri, van Herzeele, Isabelle, Vermassen, Frank, Astarci, Parla, Hammer, Frank, Lacroix, Valérie, Peeters, André, Verhelst, Robert, Cirelli, Silvana, Dormal, Pol, Grimonprez, Annelies, Lambrecht, Bart, Lerut, Philipe, Thues, Eddy, De Koster, Guy, Desiron, Quentin, Maertens de Noordhout, Alain, Malmendier, Danielle, Massoz, Mireille, Saad, Georges, Bosiers, Marc, Callaert, Joren, Deloose, Koen, Blanco Cañibano, Estrella, García Fresnillo, Beatriz, Guerra Requena, Mercedes, Morata Barrado, Pilar C, Muela Méndez, Miguel, Yusta Izquierdo, Antonio, Aparici Robles, Fernando, Blanes Orti, Paula, García Dominguez, Luis, Martínez López, Rafael, Miralles Hernández, Manuel, Tembl Ferrairo, José I, Chamorro, Ángel, Macho, Juan, Obach, Víctor, Riambau, Vincent, San Román, Luis, Ahlhelm, Frank J, Blackham, Kristine, Engelter, Stefan, Eugster, Thomas, Gensicke, Henrik, Gürke, Lorenz, Lyrer, Philippe, Mariani, Luigi, Maurer, Marina, Mujagic, Edin, Müller, Mandy, Psychogios, Marios, Stierli, Peter, Stippich, Christoph, Traenka, Christopher, Wolff, Thomas, Wagner, Benjamin, Wiegert, Martina M, Clarke, Sandra, Diepers, Michael, Gröchenig, Ernst, Gruber, Philipp, Isaak, Andrej, Kahles, Timo, Marti, Regula, Nedeltchev, Krassen, Remonda, Luca, Tissira, Nadir, Valença Falcão, Martina, de Borst, Gert J, Lo, Rob H, Moll, Frans L, Toorop, Raechel, van der Worp, Bart H, Vonken, Evert J, Kappelle, Jaap L, Jahrome, Ommid, Vos, Floris, Schuiling, Wouter, van Overhagen, Hendrik, Keunen, Rudolf W M, Knippenberg, Bob, Wever, Jan J, Lardenoije, Jan W, Reijnen, Michel, Smeets, Luuk, van Sterkenburg, Steven, Fraedrich, Gustav, Gizewski, Elke, Gruber, Ingrid, Knoflach, Michael, Kiechl, Stefan, Rantner, Barbara, Abdulamit, Timur, Bergeron, Patrice, Padovani, Raymond, Trastour, Jean-Christophe, Cardon, Jean-Marie, Le Gallou-Wittenberg, Anne, Allaire, Eric, Becquemin, Jean-Pierre, Cochennec-Paliwoda, Frédéric, Desgranges, Pascal, Hosseini, Hassan, Kobeiter, Hicham, Marzelle, Jean, Almekhlafi, Mohammed A, Bal, Simerpreet, Barber, Phillip A, Coutts, Shelagh B, Demchuk, Andrew M, Eesa, Muneer, Gillies, Michelle, Goyal, Mayank, Hill, Michael D, Hudon, Mark E, Jambula, Anitha, Kenney, Carol, Klein, Gary, McClelland, Marie, Mitha, Alim, Menon, Bijoy K, Morrish, William F, Peters, Steven, Ryckborst, Karla J, Samis, Greg, Save, Supriya, Smith, Eric E, Stys, Peter, Subramaniam, Suresh, Sutherland, Garnette R, Watson, Tim, Wong, John H, Zimmel, L, Flis, Vojko, Matela, Jože, Miksic, Kazimir, Milotic, Franko, Mrdja, Božidar, Stirn, Barbara, Tetickovic, Erih, Gasparini, Mladen, Grad, Anton, Kompara, Ingrid, Miloševic, Zoren, Palmiste, Veronika, Toomsoo, Toomas, Aidashova, Balzhan, Kospanov, Nursultan, Lyssenko, Roman, Mussagaliev, Daulet, Beyar, Rafi, Hoffman, Aaron, Karram, Tony, Kerner, Arthur, Nikolsky, Eugenia, Nitecki, Samy, Andonova, Silva, Bachvarov, Chavdar, Petrov, Vesko, Cvjetko, Ivan, Vidjak, Vinko, Halužan, Damir, Petrunic, Mladen, Liu, Bao, Liu, Chang-Wei, Bartko, Daniel, Beno, Peter, Rusnák, František, Zelenák, Kamil, Ezura, Masayuki, Inoue, Takashi, Kimura, Naoto, Kondo, Ryushi, Matsumoto, Yasushi, Shimizu, Hiroaki, Endo, Hidenori, Furui, Eisuke, Bakke, Søren, Krohg-Sørensen, Kristen, Nome, Terje, Skjelland, Mona, Tennøe, Bjørn, Albuquerque e Castro, João, Alves, Gonçalo, Bastos Gonçalves, Frederico, de Aragão Morais, José, Garcia, Ana C, Valentim, Hugo, Vasconcelos, Leonor, Belcastro, Fernando, Cura, Fernando, Zaefferer, Patricio, Abd-Allah, Foad, Eldessoki, Mohamed H, Heshmat Kassem, Hussein, Soliman Gharieb, Haytham, Colgan, Mary P, Haider, Syed N, Harbison, Joe, Madhavan, Prakash, Moore, Dermot, Shanik, Gregor, Kazan, Viviane, Nazzal, Munier, and Ramsey-Williams, Vicki

Published
2021
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3. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies

Author

Reuben Benjamin, Charlotte Graham, Deborah Yallop, Agnieszka Jozwik, Oana C Mirci-Danicar, Giovanna Lucchini, Danielle Pinner, Nitin Jain, Hagop Kantarjian, Nicolas Boissel, Marcela V Maus, Matthew J Frigault, André Baruchel, Mohamad Mohty, Athos Gianella-Borradori, Florence Binlich, Svetlana Balandraud, Fabien Vitry, Elisabeth Thomas, Anne Philippe, Sylvain Fouliard, Sandra Dupouy, Ibtissam Marchiq, Maria Almena-Carrasco, Nicolas Ferry, Sylvain Arnould, Cyril Konto, Paul Veys, Waseem Qasim, Antonio Pagliuca, Ghulam Mufti, Piers Patten, Shireen Kassam, Stephen Devereux, Majid Kazmi, Kirsty Cuthill, Victoria Potter, Andrea Kuhnl, Victoria Metaxa, Laarni Bonganay, Orla Stewart, Rose Ellard, Lorraine Catt, Jen Lewis, Farzin Farzaneh, Jackie Chappell, Alice Mason, Vicky Chu, Alan Dunlop, Adeel Saleem, Gary Cheung, Helena Munro, Elka Giemza, Oana Ciocarlie, Jan Chu, Persis Amrolia, Kanchan Rao, Robert Chiesa, Juliana Silva, Annette Hill, Maria Finch, Lindsey Young, Harvinder Hara, Sujith Samarasinghe, Anupama Rao, Ajay Vora, Kimberley Gilmour, Christine Rivat, Clare Murphy, Gulrukh Ahsan, Rasha Said Shamsah, Jesmina James, Sarah Inglott, Gary Wright, Stuart Adams, Natalia Izotova, Marina Konopleva, William Wierda, Elias Jabbour, Partow Kebrieai, Emily Jones, Kara McGee, Marcela Maus, Matthew Frigault, Jami Brown, Vesselina Toncheva, Keagan Casey, Hanno Hock, Meaghan A McKeown, Richard Mathews, Thomas Spitzer, Emmanuel Raffoux, Etienne Lengliné, Raphael Itzykson, Florence Rabian, Jérôme Larghero, Isabelle Madelaine, Elie Azoulay, Emmanuelle Clappier, Sophie Caillat-Zucman, Martine Meunier, Karine Celli-Lebras, Marie-Thérèse Tremorin, Karima Yakouben, Françoise Mechinaud-Heloury, Audrey Grain, Aurélia Alimi, Julie Roupret, Delphine Chaillou, Hélène Cavé, Aurelie Caye-Eude, Odile Fenneteau, Elodie Lainey, Jerome Naudin, Eolia Brissot, Remy Dulery, Florent Malard, Clémence Mediavilla, Agnès Bonnin, Anne Vekhoff, Tounes Ledraa, and Anne Daguenel-Nguyen

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Antigens, CD19, 030204 cardiovascular system & hematology, Immunotherapy, Adoptive, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Adverse effect, Gene Editing, Cytopenia, Receptors, Chimeric Antigen, business.industry, General Medicine, Immunotherapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Fludarabine, Cytokine release syndrome, Child, Preschool, Feasibility Studies, Alemtuzumab, Female, Cytokine Release Syndrome, business, Progressive disease, medicine.drug
Abstract

Summary Background Genome-edited donor-derived allogeneic anti-CD19 chimeric antigen receptor (CAR) T cells offer a novel form of CAR-T-cell product that is available for immediate clinical use, thereby broadening access and applicability. UCART19 is one such product investigated in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Two multicentre phase 1 studies aimed to investigate the feasibility, safety, and antileukaemic activity of UCART19 in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Methods We enrolled paediatric or adult patients in two ongoing, multicentre, phase 1 clinical trials to evaluate the safety and antileukaemic activity of UCART19. All patients underwent lymphodepletion with fludarabine and cyclophosphamide with or without alemtuzumab, then children received UCART19 at 1·1–2·3 × 106 cells per kg and adults received UCART19 doses of 6 × 106 cells, 6–8 × 107 cells, or 1·8–2·4 × 108 cells in a dose-escalation study. The primary outcome measure was adverse events in the period between first infusion and data cutoff. These studies were registered at ClinicalTrials.gov, NCT02808442 and NCT02746952. Findings Between June 3, 2016, and Oct 23, 2018, seven children and 14 adults were enrolled in the two studies and received UCART19. Cytokine release syndrome was the most common adverse event and was observed in 19 patients (91%); three (14%) had grade 3–4 cytokine release syndrome. Other adverse events were grade 1 or 2 neurotoxicity in eight patients (38%), grade 1 acute skin graft-versus-host disease in two patients (10%), and grade 4 prolonged cytopenia in six patients (32%). Two treatment-related deaths occurred; one caused by neutropenic sepsis in a patient with concurrent cytokine release syndrome and one from pulmonary haemorrhage in a patient with persistent cytopenia. 14 (67%) of 21 patients had a complete response or complete response with incomplete haematological recovery 28 days after infusion. Patients not receiving alemtuzumab (n=4) showed no UCART19 expansion or antileukaemic activity. The median duration of response was 4·1 months with ten (71%) of 14 responders proceeding to a subsequent allogeneic stem-cell transplant. Progression-free survival at 6 months was 27%, and overall survival was 55%. Interpretation These two studies show, for the first time, the feasibility of using allogeneic, genome-edited CAR T cells to treat patients with aggressive leukaemia. UCART19 exhibited in-vivo expansion and antileukaemic activity with a manageable safety profile in heavily pretreated paediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. The results this study are an encouraging step forward for the field of allogeneic CAR T cells, and UCART19 offers the opportunity to treat patients with rapidly progressive disease and where autologous CAR-T-cell therapy is unavailable. Funding Servier.

Published
2020

4. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial

Author

Burn, John, Gerdes, Anne-Marie, Macrae, Finlay, Mecklin, Jukka-Pekka, Moeslein, Gabriela, Olschwang, Sylviane, Eccles, Diane, Evans, D Gareth, Maher, Eamonn R, Bertario, Lucio, Bisgaard, Marie-Luise, Dunlop, Malcolm G, Ho, Judy WC, Hodgson, Shirley V, Lindblom, Annika, Lubinski, Jan, Morrison, Patrick J, Murday, Victoria, Ramesar, Raj, Side, Lucy, Scott, Rodney J, Thomas, Huw JW, Vasen, Hans F, Barker, Gail, Crawford, Gillian, Elliott, Faye, Movahedi, Mohammad, Pylvanainen, Kirsi, Wijnen, Juul T, Fodde, Riccardo, Lynch, Henry T, Mathers, John C, and Bishop, D Timothy

Published
2011
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5. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies

Author

Benjamin, Reuben, primary, Graham, Charlotte, additional, Yallop, Deborah, additional, Jozwik, Agnieszka, additional, Mirci-Danicar, Oana C, additional, Lucchini, Giovanna, additional, Pinner, Danielle, additional, Jain, Nitin, additional, Kantarjian, Hagop, additional, Boissel, Nicolas, additional, Maus, Marcela V, additional, Frigault, Matthew J, additional, Baruchel, André, additional, Mohty, Mohamad, additional, Gianella-Borradori, Athos, additional, Binlich, Florence, additional, Balandraud, Svetlana, additional, Vitry, Fabien, additional, Thomas, Elisabeth, additional, Philippe, Anne, additional, Fouliard, Sylvain, additional, Dupouy, Sandra, additional, Marchiq, Ibtissam, additional, Almena-Carrasco, Maria, additional, Ferry, Nicolas, additional, Arnould, Sylvain, additional, Konto, Cyril, additional, Veys, Paul, additional, Qasim, Waseem, additional, Benjamin, Reuben, additional, Pagliuca, Antonio, additional, Mufti, Ghulam, additional, Patten, Piers, additional, Kassam, Shireen, additional, Devereux, Stephen, additional, Kazmi, Majid, additional, Cuthill, Kirsty, additional, Potter, Victoria, additional, Kuhnl, Andrea, additional, Metaxa, Victoria, additional, Bonganay, Laarni, additional, Stewart, Orla, additional, Ellard, Rose, additional, Catt, Lorraine, additional, Lewis, Jen, additional, Farzaneh, Farzin, additional, Chappell, Jackie, additional, Mason, Alice, additional, Chu, Vicky, additional, Dunlop, Alan, additional, Saleem, Adeel, additional, Cheung, Gary, additional, Munro, Helena, additional, Giemza, Elka, additional, Ciocarlie, Oana, additional, Chu, Jan, additional, Amrolia, Persis, additional, Rao, Kanchan, additional, Chiesa, Robert, additional, Silva, Juliana, additional, Hill, Annette, additional, Finch, Maria, additional, Young, Lindsey, additional, Hara, Harvinder, additional, Samarasinghe, Sujith, additional, Rao, Anupama, additional, Vora, Ajay, additional, Gilmour, Kimberley, additional, Rivat, Christine, additional, Murphy, Clare, additional, Ahsan, Gulrukh, additional, Said Shamsah, Rasha, additional, James, Jesmina, additional, Inglott, Sarah, additional, Wright, Gary, additional, Adams, Stuart, additional, Izotova, Natalia, additional, Konopleva, Marina, additional, Wierda, William, additional, Jabbour, Elias, additional, Kebrieai, Partow, additional, Jones, Emily, additional, McGee, Kara, additional, Maus, Marcela, additional, Frigault, Matthew, additional, Brown, Jami, additional, Toncheva, Vesselina, additional, Casey, Keagan, additional, Hock, Hanno, additional, McKeown, Meaghan A, additional, Mathews, Richard, additional, Spitzer, Thomas, additional, Raffoux, Emmanuel, additional, Lengliné, Etienne, additional, Itzykson, Raphael, additional, Rabian, Florence, additional, Larghero, Jérôme, additional, Madelaine, Isabelle, additional, Azoulay, Elie, additional, Clappier, Emmanuelle, additional, Caillat-Zucman, Sophie, additional, Meunier, Martine, additional, Celli-Lebras, Karine, additional, Tremorin, Marie-Thérèse, additional, Yakouben, Karima, additional, Mechinaud-Heloury, Françoise, additional, Grain, Audrey, additional, Alimi, Aurélia, additional, Roupret, Julie, additional, Chaillou, Delphine, additional, Cavé, Hélène, additional, Caye-Eude, Aurelie, additional, Fenneteau, Odile, additional, Lainey, Elodie, additional, Naudin, Jerome, additional, Brissot, Eolia, additional, Dulery, Remy, additional, Malard, Florent, additional, Mediavilla, Clémence, additional, Bonnin, Agnès, additional, Vekhoff, Anne, additional, Ledraa, Tounes, additional, and Daguenel-Nguyen, Anne, additional

Published
2020
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6. Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

Author

Mullen, Michael, primary, Jin, Xu Yu, additional, Child, Anne, additional, Stuart, A Graham, additional, Dodd, Matthew, additional, Aragon-Martin, José Antonio, additional, Gaze, David, additional, Kiotsekoglou, Anatoli, additional, Yuan, Li, additional, Hu, Jiangting, additional, Foley, Claire, additional, Van Dyck, Laura, additional, Knight, Rosemary, additional, Clayton, Tim, additional, Swan, Lorna, additional, Thomson, John D R, additional, Erdem, Guliz, additional, Crossman, David, additional, Flather, Marcus, additional, Dean, John, additional, Was, Bartosz, additional, Gow, Heather, additional, Murray, Jane, additional, D'Allessandro, Mariella, additional, Christie, Michael, additional, Cooper, Patricia, additional, Booth, Philip, additional, Burns, Sharon, additional, Paterson, Yvonne, additional, Chikermane, Ashish, additional, Assing, Anthony, additional, Cotter, Catherine, additional, Atkins, Gillian, additional, Williamson, Helen, additional, Barclay, Justin, additional, Jennison, Alan, additional, Henderson, Alex, additional, McSkeane, Anna, additional, Fairlamb, Helen, additional, Kelly, Julie, additional, Kelsall, Nicola, additional, Prentice, Scott, additional, O'Sullivan, John, additional, Head-Baister, Alison, additional, Phillipson, Angela, additional, Johnson, Anna, additional, Crossland, D, additional, Oliver, Jack, additional, Davison, Jade, additional, Wake, Jill, additional, Quinn, Louise, additional, Foreman, Maureen, additional, Wealleans, Vera, additional, Walker, Niki, additional, Duncan, Alexis, additional, Tibbs, Evelyn, additional, Kelly, Ruth, additional, Khambadkone, Sachin, additional, Zotti, Bridget, additional, Brady, Cassie, additional, Cervi, Elena, additional, Field, Ella, additional, Szepezvary, Eszter, additional, Mantey, Florence, additional, Riley, Gillian, additional, Titmus, Heather, additional, Bo, Ilaria, additional, Kaski, Juan Pablo, additional, Green, Loren, additional, Jones, Nigel, additional, Banks, Rebecca, additional, Kiesewetter, Christopher, additional, Mathur, Sujeev, additional, Frigiola, Alessandra, additional, Savis, Alex, additional, Belfield, Holly, additional, Guzman, Josephine, additional, Harris, Julia, additional, Wilson, Karen, additional, Peacock, Kelly, additional, Gibson, Kirsty, additional, Wellman, Paul, additional, Simpson, John, additional, Kabir, Saleha, additional, Mushemi, Sitali, additional, Stewart, Michael, additional, Atkinson, Bev, additional, Richardson, Cath, additional, Leng, Elaine, additional, Brennan, Paul, additional, Nixon, Annabel, additional, Spencer, Collette, additional, Oliver, James, additional, Forster, Jan, additional, Turner, Louise, additional, Bainbridge, Samantha, additional, Choy, Anna Maria, additional, Dawson, Adelle, additional, Kiddie, Gwen, additional, Kerr, Heather, additional, Mordi, Ify, additional, Duff, Jackie, additional, Dunlop, Jacqueline, additional, Berg, Jonathan, additional, Armory, Pauline, additional, Freeman, Leisa, additional, Anwar, Amir, additional, Graham, Charles, additional, London, Clare, additional, Healey, Gail, additional, Gallagher, Ian, additional, Ilsley, Mary, additional, Ahmed, Rizwan, additional, Wood, Sheila, additional, Wheeldon, Nigel, additional, Mason, Cecilia, additional, Nassim, Farook, additional, Middle, Janet, additional, Adams, Justin, additional, Angelini, Karen, additional, Housley, Kay, additional, Ryalls, Kim, additional, Agyemang, Michael, additional, Walker, Rachel, additional, Batigan, Robina, additional, Bennett, Tina, additional, Clift, Paul, additional, Alvior, Amor Mia, additional, Nilsson, Annette, additional, Green, Carole, additional, Crook, Charlotte, additional, Palmer, Connie Becani, additional, Dwenger, Elizabeth, additional, Doherty, Phillipa, additional, Igbokwe, Rebecca, additional, Sharif, Saba, additional, MacDonald, Sonia, additional, West, Cathy, additional, Kirby, Kevin, additional, Naqvi, Nitha, additional, Welch, Sophie, additional, Warsama, Suad, additional, Li, Wei, additional, Farzad, Zohreh, additional, Smith, Ben, additional, Murday, Victoria, additional, Murtagh, Eamonn, additional, Adams, Emma, additional, Armour, Lesley, additional, Lilley, Stuart, additional, Pandya, Bejal, additional, Richards, Amy, additional, Andiapen, Mervyn, additional, Macrae, Rebecca, additional, Tome, Maite, additional, Hutchinson, Carmel, additional, Angulo, Kameka, additional, Kauppayamootoo, Rooba, additional, Gati, Sabiha, additional, Cruddas, Elizabeth, additional, Newman, William G, additional, Breen, Catherine, additional, Kumar, Dhavendra, additional, Wilson, Dirk G, additional, Farrugia, Adele, additional, Fraser, Alan, additional, Sumers, Jayne, additional, Powell, Jessie, additional, Edwards, Julie, additional, Hale, Terese, additional, Boult, Zoe, additional, Carroll, Aisling, additional, Veldtman, Gruschen, additional, Ho, Andrew, additional, Black, David, additional, Fletcher, Lisa, additional, Mapstone, Sue, additional, Bharucha, Tara, additional, Marsh, Gary, additional, Jones, Joanne, additional, Sheehan, Karen, additional, Selway, Kathleen, additional, Stevenson, Kirsty, additional, Nelson, Martin, additional, Fairweather, Rebecca, additional, Curtis, Stephanie, additional, Simpson, Sue, additional, Denvir, Martin, additional, White, Audrey, additional, Steven, Jill, additional, Munro, Joanna, additional, Lam, Wayne, additional, Toff, William, additional, Petrou, Mario, additional, Silcocks, Paul, additional, and MacAllister, Raymond, additional

Published
2019
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9. Physical activity and colorectal cancer risk: a two-sample Mendelian randomisation study

Author

Victoria Svinti, Xiaomeng Zhang, Evropi Theodoratou, Harry Campbell, Maria Timofeeva, Xue Li, Malcolm G. Dunlop, and Susan M. Farrington

Subjects
Inverse Association, Colorectal cancer, business.industry, Instrumental variable, General Medicine, Odds ratio, 030204 cardiovascular system & hematology, medicine.disease, Biobank, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Mendelian inheritance, symbols, medicine, Biomarker (medicine), Observational study, 030212 general & internal medicine, business, Demography
Abstract

Background Evidence from observational studies suggests a protective role for physical activity against colorectal cancer risk. However, whether the observed association is causal or not is not clear. We did a two sample Mendelian randomisation study to examine the causal relationship between physical activity and colorectal cancer risk. Methods This Mendelian randomisation study used common genetic variants associated with self-reported physical activity and accelerometer-based physical activity as instrumental variables. These variables were derived from the largest available genome-wide association study of physical activity, namely, UK Biobank. The effect of the instrumental variables for physical activity was analysed in a large colorectal cancer risk genome-wide association study using summary level data that included 31 197 cases and 61 770 controls. We applied inverse variance-weighted method as the main analysis method, with Mendelian randomisation-Egger, Mendelian randomisation–pleiotropy residual sum and outlier, Mendelian randomisation-robust, leave-one-out method, mode-based estimate, and the median-based method as sensitivity analyses. Findings Our results show a significant protective effect between accelerometer-based physical activity and colorectal cancer risk (the outlier-adjusted odds ratios [OR] of inverse variance-weighted Mendelian randomisation was 0·92 per one standard deviation increase of accelerometer-base physical activity (95% CI 0·87–0·98, p=0·0137). The effect between self-reported physical activity and colorectal cancer risk was not statistically significant but was supportive of an inverse association (the outlier-adjusted OR of inverse variance-weighted Mendelian randomisation was 0·61 per 1 SD increase of moderate-to-vigorous physical activity [95% CI 0·36–1·06, p=0·0783]). Interpretation The findings of this large Mendelian randomisation study show, for the first time to our knowledge, that objectively measured physical activity is causally implicated in reducing colorectal cancer risk. It suggests that physical activity is not merely a biomarker of good health. The limitations of the study are that it is based on only two genetic instruments and that it has limited power, despite the study size. Nonetheless, at a population level, these findings provide strong reinforcing evidence to support public health policy measures that encourage exercise, even in obese individuals. Funding This work was supported by cancer research UK programme grant C348/A18927 (MD). ET is supported by a cancer research UK Career Development Fellowship (C31250/A22804). XZ has a PhD studentship from The Darwin Trust of Edinburgh.

Published
2019

12. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis

Author

John Connolly, John C. Whittaker, Helen Ireland, Hynek Pikhart, Olaf H. Klungel, Claudia Langenberg, Juan P. Casas, Y. van der Graaf, Anne Peasey, Emelia J. Benjamin, Meena Kumari, Nicholas J. Timpson, Růžena Kubínová, P.J. Talmud, Nita G. Forouhi, Verschuren Wmm., KaWah Li, Engmann Jel., C Chung, Tina Shah, Damiano Baldassarre, Mika Kivimäki, Eric J. Brunner, John Hardy, Karoline Kuchenbaecker, Charles B. Eaton, Y. T. van der Schouw, Michael V. Holmes, S. J. Bielinski, Jaroslav A. Hubacek, P. A. Doevendans, Susan Redline, Berta Almoguera Castillo, Westendorp Rgj., Reecha Sofat, Yiran Guo, Leslie A. Lange, Debbie A Lawlor, James G. Wilson, John Gallacher, Richard S. Houlston, Martin Bobak, Maarten Leusink, Andrzej Pajak, George Davey Smith, James F. Meschia, Peter H. Whincup, Rebecca Hardy, Michael Marmot, Jeffrey W. Stephens, Brendan J. Keating, Diana Kuh, Delaney Jac., Mikhail I. Voevoda, N. C. Onland-Moret, Timothy M. Frayling, Hakon Hakonarson, S Bandenelli, Frank Dudbridge, G Jan de Borst, F G Fowkes, Migle Baceviciene, Gordon D.O. Lowe, Gerjan Navis, Alexander P. Reiner, Simon P. Mooijaart, Phil Howard, Boer Jma., Stephen E. Epstein, A. de Boer, Ian Ford, U de Faire, Abdonas Tamosiunas, Malcolm G. Dunlop, AB Singleton, Nicholas J. Wareham, Renate B. Schnabel, Johan Wouter Jukema, Naveed Sattar, Folkert W. Asselbergs, Fotios Drenos, Jutta Palmen, Christina L. Wassel, Sofia Malyutina, Daniel I. Swerdlow, Tetsu Tanaka, Ron T. Gansevoort, Julian Peto, Jenna Price, Bakker Sjl., Ian Tomlinson, Yun Li, Bengt Sennblad, Jackie A. Cooper, Jian'an Luan, Aroon D. Hingorani, JoAnn E. Manson, Roman Pfister, Mailand-van der Zee A-H., I. Mateo Leach, Anders Hamsten, Mike A. Nalls, Yoav Ben-Shlomo, Richard W Morris, Joe Devaney, Marlene C. W. Stewart, P A de Jong, Steve E. Humphries, Roman Topor-Madry, P. van der Harst, Jennifer G. Robinson, Andrew Wong, Luigi Ferrucci, Elena Tremoli, Ioanna Tzoulaki, Mary-Susan Burnett, Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT), Cardiovascular Centre (CVC), Pulmonology, Paediatric Pulmonology, APH - Personalized Medicine, and AII - Inflammatory diseases

Subjects
Coronary Disease, Genome-wide association study, 030204 cardiovascular system & hematology, PLACEBO-CONTROLLED TRIAL, Gastroenterology, chemistry.chemical_compound, DOUBLE-BLIND, 0302 clinical medicine, Gene Frequency, Randomized Controlled Trials as Topic, 0303 health sciences, biology, General Medicine, IL-6 RECEPTOR, C-REACTIVE PROTEIN, 3. Good health, SOLUBLE IL-6, Phenotype, Treatment Outcome, INDIVIDUAL PARTICIPANTS DATA, Rheumatoid arthritis, Inflammation Mediators, Signal Transduction, musculoskeletal diseases, medicine.medical_specialty, Genotype, Antibodies, Monoclonal, Humanized, Polymorphism, Single Nucleotide, 03 medical and health sciences, Tocilizumab, Internal medicine, medicine, Humans, Allele, GENOME-WIDE ASSOCIATION, Interleukin 6, Allele frequency, TOCILIZUMAB, Genetic Association Studies, 030304 developmental biology, business.industry, C-reactive protein, Genetic Variation, Odds ratio, JOINT ANALYSIS, Mendelian Randomization Analysis, medicine.disease, Receptors, Interleukin-6, RHEUMATOID-ARTHRITIS, chemistry, Immunology, biology.protein, business
Abstract

SummaryBackgroundA high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown.MethodsApplying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis.FindingsIn 40 studies including up to 133 449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34–10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31–9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60–1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4–8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25 458 coronary heart disease cases and 100 740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93–0·97, p=1·53×10−5).InterpretationOn the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses.FundingUK Medical Research Council; British Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute; Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL Comprehensive Medical Research Centre; US National Institute on Aging; Academy of Finland; Netherlands Organisation for Health Research and Development; SANCO; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish Research Council; Strategic Cardiovascular Programme of the Karolinska Institutet; Stockholm County Council; US National Institute of Neurological Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh Framework Programme; National Institute for Healthy Ageing; Cancer Research UK; MacArthur Foundation.

Published
2012
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13. Crisis in the National Health Service: a call to action

Author

David Mabey, Tehmina Bharucha, Aliki Traianou, Aaminah Verity, Catherine Dunlop, and Daniela E. Kirwan

Subjects
03 medical and health sciences, 0302 clinical medicine, business.industry, Environmental resource management, 030212 general & internal medicine, General Medicine, 030204 cardiovascular system & hematology, Public administration, National health service, business, Call to action
Published
2017

16. Investigation of gene–environment interactions between vitamin D and colorectal cancer susceptibility genetic variants in large bowel epithelium

Author

Karen Dunbar, Susan M. Farrington, Malcolm G. Dunlop, Maria Timofeeva, P G Vaughan-Shaw, Fahrat V N Din, Anna Maria Ochocka, and Graeme R. Grimes

Subjects
0301 basic medicine, medicine.medical_specialty, Calcitriol, Colorectal cancer, Single-nucleotide polymorphism, General Medicine, Biology, medicine.disease, Calcitriol receptor, vitamin D deficiency, CDH1, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Endocrinology, 030220 oncology & carcinogenesis, Internal medicine, Genotype, Immunology, medicine, Vitamin D and neurology, biology.protein, medicine.drug
Abstract

Background Observational data implicate vitamin D deficiency in the aetiology of colorectal cancer, yet causality is not established. In-house epidemiological data suggest that the colorectal cancer susceptibility locus rs9929218 might interact with vitamin D concentration to impact risk. This single nucleotide polymorphism is also intronic within CDH1 , a tumour suppressor gene. This study aimed to determine whether vitamin D impacts on expression of CDH1 and interacts with common genetic variance linked to colorectal cancer susceptibility. Methods Ten cell lines were treated with calcitriol (50 nM) for 16 h and induction of CDH1 assessed with real-time PCR. Colorectal epithelial organoids (three mouse, three human) were cultured and the effect of calcitriol (0·5–100 nM, 16–24 h) investigated. Samples from normal colorectal mucosa were taken from 110 study participants, and the association between vitamin D concentration and rs9929218 genotype with gene expression assessed (HT12 microarray). A subgroup underwent vitamin D supplementation (3200 IU orally) and repeat sampling at 6 and 12 weeks. Findings Calcitriol treatment increased CDH1 expression in five cell lines (1·3–2·8-fold, p CDH1 with calcitriol was not. Colorectal organoids were cultured for up to 6 weeks. Calcitriol increased CDH1 expression in human (1·9-fold [SD 0·28], p=0·02) but not murine organoids. Strong correlation between VDR and CDH1 expression ( r =0·74 p −5 ) was seen in human colorectal mucosa with a weaker correlation between vitamin D concentration and VDR expression ( r =0·22, p=0·009). GG genotype was associated with increased CDH1 (p=0·046) and VDR expression (p=0·015). Vitamin D supplements increased vitamin D concentration (2·2-fold [SD 1·1], p=0·006) and VDR expression (1·06 [0·09], p=0·02) but not CDH1 expression. Interpretation Our findings suggest that CDH1 expression in colorectal cancer cell lines is associated with rs9929218 genotype and is induced by calcitriol treatment, and that organoids offer potential as a biological model of normal colorectal mucosa. The correlation between CDH1 and VDR in normal human colorectal mucosa and the association with genotype further supports an interaction between vitamin D status, genotype at the rs9929218 locus, and CDH1 expression. The supplementation study is continuing and aims to demonstrate and further define this interaction. Funding Medical Research Council, Royal College of Surgeons of England, Tenovus, Melville Trust for Care and Cure of Cancer, Mason Medical Research Trust.

Published
2016

17. Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate

Author

G Todd, K Dunlop, J McNaboe, MF Ryan, D Carson, and MD Shields

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Administration, Topical, medicine.medical_treatment, Urinary system, Anti-Inflammatory Agents, Fluticasone propionate, chemistry.chemical_compound, Internal medicine, medicine, Humans, Anti-Asthmatic Agents, Child, Glucocorticoids, Growth Disorders, Fluticasone, Asthma, Chemotherapy, Creatinine, business.industry, General Medicine, medicine.disease, Androstadienes, Endocrinology, chemistry, Child, Preschool, Depression, Chemical, Adrenal Cortex, Corticosteroid, Female, Complication, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract

Background: Fluticasone propionate was introduced in 1993 in the UK as a potentially safer inhaled corticosteroid than those already in use. The efficacy and safety of fluticasone has been established at recommended doses of 200 µg/day, but not at the higher doses that are often used. Methods: Growth retardation was observed in six severely asthmatic children after introduction of high-dose fluticasone propionate treatment (dry powder). Assessment of cortisol response was by insulin-induced hypoglycaemia in three cases, by short tetracosactrin test in two, and by low-dose tetracosactrin and 24-hour urinary cortisol/creatinine ratio in one. Findings: Six children with growth retardation noted after treatment with high-dose fluticasone propionate were found to have adrenal suppression. In one case the growth rate and cortisol response returned to normal 9 months after the fluticasone dose was reduced to 500 µg/day. Interpretation: When high doses of fluticasone propionate are used, growth may be retarded and adrenal suppression may occur.

Published
1996

19. Isolation, purification, and culture of oogonial stem cells from adult human and bovine ovarian cortex

Author

Richard A. Anderson, Evelyn E. Telfer, Marie McLaughlin, Cheryl E. Dunlop, and Rosemary A. L. Bayne

Subjects
education.field_of_study, Pathology, medicine.medical_specialty, Ovarian Cortex, Population, Ovary, General Medicine, Cell sorting, Biology, Germline, Oogonial Stem Cells, Cell biology, medicine.anatomical_structure, medicine, Stem cell, Ovarian reserve, education
Abstract

Background The longstanding belief that women are born with a finite ovarian reserve has been debated for almost a decade, ever since the discovery, and subsequent isolation, of purported oogonial stem cells (OSCs). These cells, described in both mice and man, seemingly have the ability to generate oocytes when cultured in vitro under specific conditions, resulting in live offspring in the case of mice. The aims of this study were to verify independently the existence of OSCs in human ovarian tissue and to determine whether they could be isolated from bovine tissue. Methods We isolated OSCs from disaggregated bovine and human ovarian cortex using a fluorescence-activated cell sorting (FACS)-based technique, with cells being sorted for the presence of VASA, a germ-cell-specific protein. The cells were subsequently cultured in vitro without the need for a feeder layer, and mRNA expression of germline-specific markers was analysed with RT-PCR. The cells were transduced to express green fluorescent protein (GFP) by use of a lentivirus for the purposes of tracking. Findings A rare population of mitotically active VASA-positive cells was isolated from both bovine and human tissue and they have been grown in vitro for several months. Up to November, 2013, cells were retrieved from three human samples, but isolation has been replicated on five separate occasions in bovine ovary samples. RT-PCR demonstrated consistent expression of several germline markers, including IFITM3, DPPA3, PRDM1, POU5F1 , and KIT . It has been possible to cryopreserve the cells with successful re-initiation of growth on thawing, and stable expression of GFP was achieved after lentivirus transduction. Interpretation The expression of germline markers indicates that these cells have characteristics of germline (oogonial) stem cells. To our knowledge, this is the first report of such cells being isolated from bovine ovarian cortex and corroborates a previous report showing the isolation of OSCs from human ovary. These cells provide a novel model for investigating germ-cell development; future experiments will involve injection of OSCs into ovarian cortex to assess whether they have the capability to undergo follicle formation and oocyte development in an in-vitro environment. If their potential can be harnessed, OSCs might have a future role in clinical applications—eg, in fertility preservation. Funding UK Medical Research Council.

Published
2014

21. Reliability of presymptomatic test for adenomatous polyposis coli

Author

Waltraut Friedl, Sylviane Olschwang, Barbara Piechaczek, Malcolm G. Dunlop, Reiner Caspari, Gilles Thomas, Pierre Laurent-Puig, and Peter Propping

Subjects
medicine.medical_specialty, Adenomatous polyposis coli, Internal medicine, medicine, biology.protein, General Medicine, Biology, Gastroenterology, Reliability (statistics), Test (assessment)
Published
1991

23. Flecainide in cancer nerve pain

Author

Sinnott, Claire, primary, Edmonds, Polly, additional, Cropley, Ian, additional, Hanks, Geoffrey, additional, Dunlop, RobertJ., additional, Hockley, JosephineM., additional, Tate, Teresa, additional, and Turner, Paul, additional

Published
1991
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26. Flecainide in cancer nerve pain

Author

Ian Cropley, Polly Edmonds, RobertJ. Dunlop, JosephineM. Hockley, Geoffrey Hanks, Teresa Tate, Claire Sinnott, and Paul Turner

Subjects
business.industry, Anesthesia, medicine, Cancer, General Medicine, medicine.disease, business, Flecainide, medicine.drug
Published
1991

27. CHARCOAL HÆMOPERFUSION IN THE TREATMENT OF FULMINANT HEPATIC FAILURE

Author

I. M. Murray-Lyon, P. J. Mellon, C.O Record, E. H. Dunlop, Peter G. Langley, H. Flax, B. G. Gazzard, M.B Ward, M. J. Weston, Roger Williams, and Bernard Portmann

Subjects
Adult, Blood Platelets, Male, medicine.medical_specialty, Adolescent, Phenylalanine, Encephalopathy, Gastroenterology, Brain herniation, Methionine, Fulminant hepatic failure, Liver Function Tests, Internal medicine, Methods, medicine, Humans, Platelet, Amino Acids, Blood Coagulation, Coma, Blood Specimen Collection, business.industry, Liver Diseases, Biopsy, Needle, General Medicine, Middle Aged, medicine.disease, Blood Cell Count, Surgery, Perfusion, Blood, Liver, Activated charcoal, Supportive psychotherapy, Charcoal, Hepatic Encephalopathy, Tyrosine, Female, Autopsy, medicine.symptom, Halothane, business
Abstract

Twenty-two patients with fulminant hepatic failure who deteriorated to grade-IV coma despite full supportive therapy were treated by repeated periods of haemoperfusion through columns containing activated charcoal. The procedure was well tolerated clinically. Eleven of the patients regained consciousness and ten left hospital. Follow-up liver biopsies in the first three patients at around six months after discharge from hospital showed restitution of the normal lobular architecture. Of the eleven treatment failures, haemorrhage was responsible for death in three, and in six brain herniation secondary to cerebral œdema was an important contributory factor. The column extracted most aminoacids from plasma, and during perfusion arterial concentrations of phenylalanine, tyrosine, and methionine-aminoacids known to be involved in the pathogenesis of the encephalopathy—fell significantly. The charcoal was coated with a biocompatible polymer, and there was no evidence for removal of coagulation factors. The extraction of platelets was below 30% in most instances, and in only two patients was there evidence that bleeding may have been precipitated by the haemoperfusion. These survival figures are to be compared with a previous survival figure of 10% in a series of ninety-two cases with fulminant hepatic failure and grade III or IV encephalopathy treated by full supportive measures.

Published
1974

28. THE NATIONAL INSURANCE BILL

Author

FredJ. Smith, AlfredPearce Gould, H.B. Luard, John Dunlop, Stanley Hodgson, M.S. Harford, HubertH.B. Wilkinson, J.P. Walker, ArthurE. Larking, S.W. Carruthers, R.B. Fletcher, Robt. Saunderson, T.Cuming Askin, and E.W. Falconer

Subjects
General Medicine
Published
1911

29. CHARCOAL HÆMOPERFUSION IN THE TREATMENT OF FULMINANT HEPATIC FAILURE

Author

Gazzard, B.G, Weston, M.J, Murray-Lyon, I.M, Flax, H, Record, C.O, Portmann, B, Langley, P.G, Dunlop, E.H, Mellon, P.J, Ward, M.B, and Williams, Roger

Abstract

Twenty-two patients with fulminant hepatic failure who deteriorated to grade-IV coma despite full supportive therapy were treated by repeated periods of hæmoperfusion through columns containing activated charcoal. The procedure was well tolerated clinically. Eleven of the patients regained consciousness and ten left hospital. Follow-up liver biopsies in the first three patients at around six months after discharge from hospital showed restitution of the normal lobular architecture. Of the eleven treatment failures, haemorrhage was responsible for death in three, and in six brain herniation secondary to cerebral œdema was an important contributory factor. The column extracted most aminoacids from plasma, and during perfusion arterial concentrations of phenylalanine, tyrosine, and methionine-aminoacids known to be involved in the pathogenesis of the encephalopathy—fell significantly. The charcoal was coated with a biocompatible polymer, and there was no evidence for removal of coagulation factors. The extraction of platelets was below 30% in most instances, and in only two patients was there evidence that bleeding may have been precipitated by the hæmoperfusion. These survival figures are to be compared with a previous survival figure of 10% in a series of ninety-two cases with fulminant hepatic failure and grade III or IV encephalopathy treated by full supportive measures.

Published
1974
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30. EFFECT OF SUCCINIC ACID ON DIABETIC KETOSIS

Author

W.M. Arnott and Derrick Dunlop

Subjects
medicine.medical_specialty, business.industry, General Medicine, medicine.disease, chemistry.chemical_compound, Endocrinology, chemistry, Biochemistry, Succinic acid, Oral administration, Internal medicine, Diabetes mellitus, medicine, Ketosis, business, Diabetic ketosis
Published
1937

31. ON YELLOW FEVER

Author

Andrew Dunlop

Subjects
Veterinary medicine, Yellow fever, medicine, General Medicine, Biology, medicine.disease
Abstract

n/a

Published
1878

32. ON A CASE OF EMPYEMA

Author

Andrew Dunlop

Subjects
medicine.medical_specialty, business.industry, medicine, General Medicine, medicine.disease, business, Empyema, Surgery
Abstract

n/a

Published
1887

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