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2. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy
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Halliday, A., Bulbulia, R., Bonati, L. H., Chester, J., Cradduck-Bamford, A., Peto, R., Pan, H., Potter, J., Henning Eckstein, H., Farrell, B., Flather, M., Mansfield, A., Mihaylova, B., Rahimi, K., Simpson, D., Thomas, D., Sandercock, P., Gray, R., Molyneux, A., Shearman, C. P., Rothwell, P., Belli, A., Herrington, W., Judge, P., Leopold, P., Mafham, M., Gough, M., Cao, P., Macdonald, S., Bari, V., Berry, C., Bradshaw, S., Brudlo, W., Clarke, A., Cox, R., Fathers, S., Gaba, K., Gray, M., Hayter, E., Holliday, C., Kurien, R., Lay, M., le Conte, S., Mcmanus, J., Madgwick, Z., Morris, D., Munday, A., Pickworth, S., Ostasz, W., Poorthuis, M., Richards, S., Teixeira, L., Tochlin, S., Tully, L., Wallis, C., Willet, M., Young, A., Casana, R., Malloggi, C., Odero, A., Silani, V., Parati, G., Malchiodi, G., Malferrari, G., Strozzi, F., Tusini, N., Vecchiati, E., Coppi, G., Lauricella, A., Moratto, R., Silingardi, R., Veronesi, J., Zini, A., Ferrero, E., Ferri, M., Gaggiano, A., Labate, C., Nessi, F., Psacharopulo, D., Viazzo, A., Malacrida, G., Mazzaccaro, D., Meola, G., Modafferi, A., Nano, G., Occhiuto, M. T., Righini, P., Stegher, S., Chiarandini, S., Griselli, F., Lepidi, S., Pozzi Mucelli, F., Naccarato, M., D'Oria, M., Ziani, B., Stella, A., Dieng, M., Faggioli, G., Gargiulo, M., Palermo, S., Pini, R., Puddu, G. M., Vacirca, A., Angiletta, D., Desantis, C., Marinazzo, D., Mastrangelo, G., Regina, G., Pulli, R., Bianchi, P., Cireni, L., Coppi, E., Pizzirusso, R., Scalise, F., Sorropago, G., Tolva, V., Caso, V., Cieri, E., Derango, P., Farchioni, L., Isernia, G., Lenti, M., Parlani, G. B., Pupo, G., Pula, G., Simonte, G., Verzini, F., Carimati, F., Delodovici, M. L., Fontana, F., Piffaretti, G., Tozzi, M., Civilini, E., Poletto, G., Reimers, B., Praquin, B., Ronchey, S., Capoccia, L., Mansour, W., Sbarigia, E., Speziale, F., Sirignano, P., Toni, D., Galeotti, R., Gasbarro, V., Mascoli, F., Rocca, T., Tsolaki, E., Bernardini, G., Demarco, E., Giaquinta, A., Patti, F., Veroux, M., Veroux, P., Virgilio, C., Mangialardi, N., Orrico, M., Di Lazzaro, V., Montelione, N., Spinelli, F., Stilo, F., Cernetti, C., Irsara, S., Maccarrone, G., Tonello, D., Visona, A., Zalunardo, B., Chisci, E., Michelagnoli, S., Troisi, N., Masato, M., Dei Negri, M., Pacchioni, A., Sacca, S., Amatucci, G., Cannizzaro, A., Accrocca, F., Ambrogi, C., Barbazza, R., Marcucci, G., Siani, A., Bajardi, G., Savettieri, G., Argentieri, A., Corbetta, R., Quaretti, P., Thyrion, F. Z., Cappelli, A., Benevento, D., De Donato, G., Mele, M. A., Palasciano, G., Pieragalli, D., Rossi, A., Setacci, C., Setacci, F., Palombo, D., Perfumo, M. C., Martelli, E., Paolucci, A., Trimarchi, S., Grassi, V., Grimaldi, L., La Rosa, G., Mirabella, D., Scialabba, M., Sichel, L., D'Angelo, C. L., Fadda, G. F., Kasemi, H., Marino, M., Burzotta, Francesco, Codispoti, F. A., Ferrante, A., Tinelli, Giovanni, Tshomba, Yamume, Vincenzoni, Claudio, Amis, D., Anderson, D., Catterson, M., Clarke, M., Davis, M., Dixit, A., Dyker, A., Ford, G., Jackson, R., Kappadath, S., Lambert, D., Lees, T., Louw, S., Mccaslin, J., Parr, N., Robson, R., Stansby, G., Wales, L., Wealleans, V., Wilson, L., Wyatt, M., Baht, H., Balogun, I., Burger, I., Cosier, T., Cowie, L., Gunathilagan, G., Hargroves, D., Insall, R., Jones, S., Rudenko, H., Schumacher, N., Senaratne, J., Thomas, G., Thomson, A., Webb, T., Brown, E., Esisi, B., Mehrzad, A., Macsweeney, S., Mcconachie, N., Southam, A., Sunman, W., Abdul-Hamiq, A., Bryce, J., Chetter, I., Ettles, D., Lakshminarayan, R., Mitchelson, K., Rhymes, C., Robinson, G., Scott, P., Vickers, A., Ashleigh, R., Butterfield, S., Gamble, E., Ghosh, J., Mccollum, C. N., Welch, M., Welsh, S., Wolowczyk, L., Donnelly, M., D'Souza, S., Egun, A. A., Gregary, B., Joseph, T., Kelly, C., Punekar, S., Rahi, M. A., Raj, S., Seriki, D., Thomson, G., Brown, J., Durairajan, R., Grunwald, I., Guyler, P., Harman, P., Jakeways, M., Khuoge, C., Kundu, A., Loganathan, T., Menon, N., Prabakaran, R. O., Sinha, D., Thompson, V., Tysoe, S., Briley, D., Darby, C., Hands, L., Howard, D., Kuker, W., Schulz, U., Teal, R., Barer, D., Brown, A., Crawford, S., Dunlop, P., Krishnamurthy, R., Majmudar, N., Mitchell, D., Myint, M. P., O'Brien, R., O'Connell, J., Sattar, N., Vetrivel, S., Beard, J., Cleveland, T., Gaines, P., Humphreys, J., Jenkins, A., King, C., Kusuma, D., Lindert, R., Lonsdale, R., Nair, R., Nawaz, S., Okhuoya, F., Turner, D., Venables, G., Dorman, P., Hughes, A., Jones, D., Mendelow, D., Rodgers, H., Raudoniitis, A., Enevoldson, P., Nahser, H., O'Brien, I., Torella, F., Watling, D., White, R., Brown, P., Dutta, D., Emerson, L., Hilltout, P., Kulkarni, S., Morrison, J., Poskitt, K., Slim, F., Smith, S., Tyler, A., Waldron, J., Whyman, M., Bajoriene, M., Baker, L., Colston, A., Eliot-Jones, B., Gramizadeh, G., Lewis-Clarke, C., Mccafferty, L., Oliver, D., Palmer, D., Patil, A., Pegler, S., Ramadurai, G., Roberts, A., Sargent, T., Siddegowda, S., Singh-Ranger, R., Williams, A., Williams, L., Windebank, S., Zuromskis, T., Alwis, L., Angus, J., Asokanathan, A., Fornolles, C., Hardy, D., Hunte, S., Justin, F., Phiri, D., Mitabouana-Kibou, M., Sekaran, L., Sethuraman, S., Tate, M. L., Akyea-Mensah, J., Ball, S., Chrisopoulou, A., Keene, E., Phair, A., Rogers, S., Smyth, J. V., Bicknell, C., Chataway, J., Cheshire, N., Clifton, A., Eley, C., Gibbs, R., Hamady, M., Hazel, B., James, A., Jenkins, M., Khanom, N., Lacey, A., Mireskandari, M., O'Reilly, J., Pereira, A., Sachs, T., Wolfe, J., Davey, P., Rogers, G., Smith, G., Tervit, G., Nichol, I., Parry, A., Young, G., Ashley, S., Barwell, J., Dix, F., Nor, A. M., Parry, C., Birt, A., Davies, P., George, J., Graham, A., Jonker, L., Kelsall, N., Potts, C., Wilson, T., Crinnion, J., Cuenoud, L., Aleksic, N., Babic, S., Ilijevski, N., Radak, Sagic, D., Tanaskovic, S., Colic, M., Cvetic, V., Davidovic, L., Jovanovic, D. R., Koncar, I., Mutavdzic, P., Sladojevic, M., Tomic, I., Debus, E. S., Grzyska, U., Otto, D., Thomalla, G., Barlinn, J., Gerber, J., Haase, K., Hartmann, C., Ludwig, S., Putz, V., Reeps, C., Schmidt, C., Weiss, N., Werth, S., Winzer, S., Gemper, J., Gunther, A., Heiling, B., Jochmann, E., Karvouniari, P., Klingner, C., Mayer, T., Schubert, J., Schulze-Hartung, F., Zanow, J., Bausback, Y., Borger, F., Botsios, S., Branzan, D., Braunlich, S., Holzer, H., Lenzer, J., Piorkowski, C., Richter, N., Schuster, J., Scheinert, D., Schmidt, A., Staab, H., Ulrich, M., Werner, M., Berger, H., Biro, G., Eckstein, H. -H., Kallmayer, M., Kreiser, K., Zimmermann, A., Berekoven, B., Frerker, K., Gordon, V., Torsello, G., Arnold, S., Dienel, C., Storck, M., Biermaier, B., Gissler, H. M., Klotzsch, C., Pfeiffer, T., Schneider, R., Sohl, L., Wennrich, M., Alonso, A., Keese, M., Groden, C., Coster, A., Engelhardt, A., Ratusinski, C. -M., Berg, B., Delle, M., Formgren, J., Gillgren, P., Jarl, L., Kall, T. B., Konrad, P., Nyman, N., Skioldebrand, C., Steuer, J., Takolander, R., Malmstedt, J., Acosta, S., Bjorses, K., Brandt, K., Dias, N., Gottsater, A., Holst, J., Kristmundsson, T., Kuhme, T., Kolbel, T., Lindblad, B., Lindh, M., Malina, M., Ohrlander, T., Resch, T., Ronnle, V., Sonesson, B., Warvsten, M., Zdanowski, Z., Campbell, E., Kjellin, P., Lindgren, H., Nyberg, J., Petersen, B., Plate, G., Parsson, H., Qvarfordt, P., Ignatenko, P., Karpenko, A., Starodubtsev, V., Chernyavsky, M. A., Golovkova, M. S., Komakha, B. B., Zherdev, N. N., Belyasnik, A., Chechulov, P., Kandyba, D., Stepanishchev, I., Csobay-Novak, C., Dosa, E., Entz, L., Nemes, B., Szeberin, Z., Barzo, P., Bodosi, M., Fako, E., Fulop, B., Nemeth, T., Pazdernyik, S., Skoba, K., Voros, E., Chatzinikou, E., Giannoukas, A., Karathanos, C., Koutsias, S., Kouvelos, G., Matsagkas, M., Ralli, S., Rountas, C., Rousas, N., Spanos, K., Brountzos, E., Kakisis, J. D., Lazaris, A., Moulakakis, K. G., Stefanis, L., Tsivgoulis, G., Vasdekis, S., Antonopoulos, C. N., Bellenis, I., Maras, D., Polydorou, A., Polydorou, V., Tavernarakis, A., Ioannou, N., Terzoudi, M., Lazarides, M., Mantatzis, M., Vadikolias, K., Dzieciuchowicz, L., Gabriel, M., Krasinski, Z., Oszkinis, G., Pukacki, F., Slowinski, M., Stanisic, M. -G., Staniszewski, R., Tomczak, J., Zielinski, M., Myrcha, P., Rozanski, D., Drelichowski, S., Iwanowski, W., Koncewicz, K., Bialek, P., Biejat, Z., Czepel, W., Czlonkowska, A., Dowzenko, A., Jedrzejewska, J., Kobayashi, A., Leszczynski, J., Malek, A., Polanski, J., Proczka, R., Skorski, M., Szostek, M., Andziak, P., Dratwicki, M., Gil, R., Nowicki, M., Pniewski, J., Rzezak, J., Seweryniak, P., Dabek, P., Juszynski, M., Madycki, G., Pacewski, B., Raciborski, W., Slowinski, P., Staszkiewicz, W., Bombic, M., Chlouba, V., Fiedler, J., Hes, K., Kostal, P., Sova, J., Kriz, Z., Privara, M., Reif, M., Staffa, R., Vlachovsky, R., Vojtisek, B., Hrbac, T., Kuliha, M., Prochazka, V., Roubec, M., Skoloudik, D., Netuka, D., Steklacova, A., Benes III, V., Buchvald, P., Endrych, L., Sercl, M., Campos, W., Casella, I. B., de Luccia, N., Estenssoro, A. E. V., Presti, C., Puech-Leao, P., Neves, C. R. B., da Silva, E. S., Sitrangulo, C. J., Monteiro, J. A. T., Tinone, G., Bellini Dalio, M., Joviliano, E. E., Pontes Neto, O. M., Serra Ribeiro, M., Cras, P., Hendriks, J. M. H., Hoppenbrouwers, M., Lauwers, P., Loos, C., Yperzeele, L., Geenens, M., Hemelsoet, D., van Herzeele, I., Vermassen, F., Astarci, P., Hammer, F., Lacroix, V., Peeters, A., Verhelst, R., Cirelli, S., Dormal, P., Grimonprez, A., Lambrecht, B., Lerut, P., Thues, E., De Koster, G., Desiron, Q., Maertens de Noordhout, A., Malmendier, D., Massoz, M., Saad, G., Bosiers, M., Callaert, J., Deloose, K., Blanco Canibano, E., Garcia Fresnillo, B., Guerra Requena, M., Morata Barrado, P. C., Muela Mendez, M., Yusta Izquierdo, A., Aparici Robles, F., Blanes Orti, P., Garcia Dominguez, L., Martinez Lopez, R., Miralles Hernandez, M., Tembl Ferrairo, J. I., Chamorro, A., Macho, J., Obach, V., Riambau, V., San Roman, L., Ahlhelm, F. J., Blackham, K., Engelter, S., Eugster, T., Gensicke, H., Gurke, L., Lyrer, P., Mariani, L., Maurer, M., Mujagic, E., Muller, M., Psychogios, M., Stierli, P., Stippich, C., Traenka, C., Wolff, T., Wagner, B., Wiegert, M. M., Clarke, S., Diepers, M., Grochenig, E., Gruber, P., Isaak, A., Kahles, T., Marti, R., Nedeltchev, K., Remonda, L., Tissira, N., Valenca Falcao, M., de Borst, G. J., Lo, R. H., Moll, F. L., Toorop, R., van der Worp, B. H., Vonken, E. J., Kappelle, J. L., Jahrome, O., Vos, F., Schuiling, W., van Overhagen, H., Keunen, R. W. M., Knippenberg, B., Wever, J. J., Lardenoije, J. W., Reijnen, M., Smeets, L., van Sterkenburg, S., Fraedrich, G., Gizewski, E., Gruber, I., Knoflach, M., Kiechl, S., Rantner, B., Abdulamit, T., Bergeron, P., Padovani, R., Trastour, J. -C., Cardon, J. -M., Le Gallou-Wittenberg, A., Allaire, E., Becquemin, J. -P., Cochennec-Paliwoda, F., Desgranges, P., Hosseini, H., Kobeiter, H., Marzelle, J., Almekhlafi, M. A., Bal, S., Barber, P. A., Coutts, S. B., Demchuk, A. M., Eesa, M., Gillies, M., Goyal, M., Hill, M. D., Hudon, M. E., Jambula, A., Kenney, C., Klein, G., Mcclelland, M., Mitha, A., Menon, B. K., Morrish, W. F., Peters, S., Ryckborst, K. J., Samis, G., Save, S., Smith, E. E., Stys, P., Subramaniam, S., Sutherland, G. R., Watson, T., Wong, J. H., Zimmel, L., Flis, V., Matela, J., Miksic, K., Milotic, F., Mrdja, B., Stirn, B., Tetickovic, E., Gasparini, M., Grad, A., Kompara, I., Milosevic, Z., Palmiste, V., Toomsoo, T., Aidashova, B., Kospanov, N., Lyssenko, R., Mussagaliev, D., Beyar, R., Hoffman, A., Karram, T., Kerner, A., Nikolsky, E., Nitecki, S., Andonova, S., Bachvarov, C., Petrov, V., Cvjetko, I., Vidjak, V., Haluzan, D., Petrunic, M., Liu, B., Liu, C. -W., Bartko, D., Beno, P., Rusnak, F., Zelenak, K., Ezura, M., Inoue, T., Kimura, N., Kondo, R., Matsumoto, Y., Shimizu, H., Endo, H., Furui, E., Bakke, S., Krohg-Sorensen, K., Nome, T., Skjelland, M., Tennoe, B., Albuquerque e Castro, J., Alves, G., Bastos Goncalves, F., de Aragao Morais, J., Garcia, A. C., Valentim, H., Vasconcelos, L., Belcastro, F., Cura, F., Zaefferer, P., Abd-Allah, F., Eldessoki, M. H., Heshmat Kassem, H., Soliman Gharieb, H., Colgan, M. P., Haider, S. N., Harbison, J., Madhavan, P., Moore, D., Shanik, G., Kazan, V., Nazzal, M., Ramsey-Williams, V., Burzotta F. (ORCID:0000-0002-6569-9401), Tinelli G. (ORCID:0000-0002-2212-3226), Tshomba Y. (ORCID:0000-0001-7304-7553), Vincenzoni C., Halliday, A., Bulbulia, R., Bonati, L. H., Chester, J., Cradduck-Bamford, A., Peto, R., Pan, H., Potter, J., Henning Eckstein, H., Farrell, B., Flather, M., Mansfield, A., Mihaylova, B., Rahimi, K., Simpson, D., Thomas, D., Sandercock, P., Gray, R., Molyneux, A., Shearman, C. P., Rothwell, P., Belli, A., Herrington, W., Judge, P., Leopold, P., Mafham, M., Gough, M., Cao, P., Macdonald, S., Bari, V., Berry, C., Bradshaw, S., Brudlo, W., Clarke, A., Cox, R., Fathers, S., Gaba, K., Gray, M., Hayter, E., Holliday, C., Kurien, R., Lay, M., le Conte, S., Mcmanus, J., Madgwick, Z., Morris, D., Munday, A., Pickworth, S., Ostasz, W., Poorthuis, M., Richards, S., Teixeira, L., Tochlin, S., Tully, L., Wallis, C., Willet, M., Young, A., Casana, R., Malloggi, C., Odero, A., Silani, V., Parati, G., Malchiodi, G., Malferrari, G., Strozzi, F., Tusini, N., Vecchiati, E., Coppi, G., Lauricella, A., Moratto, R., Silingardi, R., Veronesi, J., Zini, A., Ferrero, E., Ferri, M., Gaggiano, A., Labate, C., Nessi, F., Psacharopulo, D., Viazzo, A., Malacrida, G., Mazzaccaro, D., Meola, G., Modafferi, A., Nano, G., Occhiuto, M. T., Righini, P., Stegher, S., Chiarandini, S., Griselli, F., Lepidi, S., Pozzi Mucelli, F., Naccarato, M., D'Oria, M., Ziani, B., Stella, A., Dieng, M., Faggioli, G., Gargiulo, M., Palermo, S., Pini, R., Puddu, G. M., Vacirca, A., Angiletta, D., Desantis, C., Marinazzo, D., Mastrangelo, G., Regina, G., Pulli, R., Bianchi, P., Cireni, L., Coppi, E., Pizzirusso, R., Scalise, F., Sorropago, G., Tolva, V., Caso, V., Cieri, E., Derango, P., Farchioni, L., Isernia, G., Lenti, M., Parlani, G. B., Pupo, G., Pula, G., Simonte, G., Verzini, F., Carimati, F., Delodovici, M. L., Fontana, F., Piffaretti, G., Tozzi, M., Civilini, E., Poletto, G., Reimers, B., Praquin, B., Ronchey, S., Capoccia, L., Mansour, W., Sbarigia, E., Speziale, F., Sirignano, P., Toni, D., Galeotti, R., Gasbarro, V., Mascoli, F., Rocca, T., Tsolaki, E., Bernardini, G., Demarco, E., Giaquinta, A., Patti, F., Veroux, M., Veroux, P., Virgilio, C., Mangialardi, N., Orrico, M., Di Lazzaro, V., Montelione, N., Spinelli, F., Stilo, F., Cernetti, C., Irsara, S., Maccarrone, G., Tonello, D., Visona, A., Zalunardo, B., Chisci, E., Michelagnoli, S., Troisi, N., Masato, M., Dei Negri, M., Pacchioni, A., Sacca, S., Amatucci, G., Cannizzaro, A., Accrocca, F., Ambrogi, C., Barbazza, R., Marcucci, G., Siani, A., Bajardi, G., Savettieri, G., Argentieri, A., Corbetta, R., Quaretti, P., Thyrion, F. Z., Cappelli, A., Benevento, D., De Donato, G., Mele, M. A., Palasciano, G., Pieragalli, D., Rossi, A., Setacci, C., Setacci, F., Palombo, D., Perfumo, M. C., Martelli, E., Paolucci, A., Trimarchi, S., Grassi, V., Grimaldi, L., La Rosa, G., Mirabella, D., Scialabba, M., Sichel, L., D'Angelo, C. L., Fadda, G. F., Kasemi, H., Marino, M., Burzotta, Francesco, Codispoti, F. A., Ferrante, A., Tinelli, Giovanni, Tshomba, Yamume, Vincenzoni, Claudio, Amis, D., Anderson, D., Catterson, M., Clarke, M., Davis, M., Dixit, A., Dyker, A., Ford, G., Jackson, R., Kappadath, S., Lambert, D., Lees, T., Louw, S., Mccaslin, J., Parr, N., Robson, R., Stansby, G., Wales, L., Wealleans, V., Wilson, L., Wyatt, M., Baht, H., Balogun, I., Burger, I., Cosier, T., Cowie, L., Gunathilagan, G., Hargroves, D., Insall, R., Jones, S., Rudenko, H., Schumacher, N., Senaratne, J., Thomas, G., Thomson, A., Webb, T., Brown, E., Esisi, B., Mehrzad, A., Macsweeney, S., Mcconachie, N., Southam, A., Sunman, W., Abdul-Hamiq, A., Bryce, J., Chetter, I., Ettles, D., Lakshminarayan, R., Mitchelson, K., Rhymes, C., Robinson, G., Scott, P., Vickers, A., Ashleigh, R., Butterfield, S., Gamble, E., Ghosh, J., Mccollum, C. N., Welch, M., Welsh, S., Wolowczyk, L., Donnelly, M., D'Souza, S., Egun, A. A., Gregary, B., Joseph, T., Kelly, C., Punekar, S., Rahi, M. A., Raj, S., Seriki, D., Thomson, G., Brown, J., Durairajan, R., Grunwald, I., Guyler, P., Harman, P., Jakeways, M., Khuoge, C., Kundu, A., Loganathan, T., Menon, N., Prabakaran, R. O., Sinha, D., Thompson, V., Tysoe, S., Briley, D., Darby, C., Hands, L., Howard, D., Kuker, W., Schulz, U., Teal, R., Barer, D., Brown, A., Crawford, S., Dunlop, P., Krishnamurthy, R., Majmudar, N., Mitchell, D., Myint, M. P., O'Brien, R., O'Connell, J., Sattar, N., Vetrivel, S., Beard, J., Cleveland, T., Gaines, P., Humphreys, J., Jenkins, A., King, C., Kusuma, D., Lindert, R., Lonsdale, R., Nair, R., Nawaz, S., Okhuoya, F., Turner, D., Venables, G., Dorman, P., Hughes, A., Jones, D., Mendelow, D., Rodgers, H., Raudoniitis, A., Enevoldson, P., Nahser, H., O'Brien, I., Torella, F., Watling, D., White, R., Brown, P., Dutta, D., Emerson, L., Hilltout, P., Kulkarni, S., Morrison, J., Poskitt, K., Slim, F., Smith, S., Tyler, A., Waldron, J., Whyman, M., Bajoriene, M., Baker, L., Colston, A., Eliot-Jones, B., Gramizadeh, G., Lewis-Clarke, C., Mccafferty, L., Oliver, D., Palmer, D., Patil, A., Pegler, S., Ramadurai, G., Roberts, A., Sargent, T., Siddegowda, S., Singh-Ranger, R., Williams, A., Williams, L., Windebank, S., Zuromskis, T., Alwis, L., Angus, J., Asokanathan, A., Fornolles, C., Hardy, D., Hunte, S., Justin, F., Phiri, D., Mitabouana-Kibou, M., Sekaran, L., Sethuraman, S., Tate, M. L., Akyea-Mensah, J., Ball, S., Chrisopoulou, A., Keene, E., Phair, A., Rogers, S., Smyth, J. V., Bicknell, C., Chataway, J., Cheshire, N., Clifton, A., Eley, C., Gibbs, R., Hamady, M., Hazel, B., James, A., Jenkins, M., Khanom, N., Lacey, A., Mireskandari, M., O'Reilly, J., Pereira, A., Sachs, T., Wolfe, J., Davey, P., Rogers, G., Smith, G., Tervit, G., Nichol, I., Parry, A., Young, G., Ashley, S., Barwell, J., Dix, F., Nor, A. M., Parry, C., Birt, A., Davies, P., George, J., Graham, A., Jonker, L., Kelsall, N., Potts, C., Wilson, T., Crinnion, J., Cuenoud, L., Aleksic, N., Babic, S., Ilijevski, N., Radak, Sagic, D., Tanaskovic, S., Colic, M., Cvetic, V., Davidovic, L., Jovanovic, D. R., Koncar, I., Mutavdzic, P., Sladojevic, M., Tomic, I., Debus, E. S., Grzyska, U., Otto, D., Thomalla, G., Barlinn, J., Gerber, J., Haase, K., Hartmann, C., Ludwig, S., Putz, V., Reeps, C., Schmidt, C., Weiss, N., Werth, S., Winzer, S., Gemper, J., Gunther, A., Heiling, B., Jochmann, E., Karvouniari, P., Klingner, C., Mayer, T., Schubert, J., Schulze-Hartung, F., Zanow, J., Bausback, Y., Borger, F., Botsios, S., Branzan, D., Braunlich, S., Holzer, H., Lenzer, J., Piorkowski, C., Richter, N., Schuster, J., Scheinert, D., Schmidt, A., Staab, H., Ulrich, M., Werner, M., Berger, H., Biro, G., Eckstein, H. -H., Kallmayer, M., Kreiser, K., Zimmermann, A., Berekoven, B., Frerker, K., Gordon, V., Torsello, G., Arnold, S., Dienel, C., Storck, M., Biermaier, B., Gissler, H. M., Klotzsch, C., Pfeiffer, T., Schneider, R., Sohl, L., Wennrich, M., Alonso, A., Keese, M., Groden, C., Coster, A., Engelhardt, A., Ratusinski, C. -M., Berg, B., Delle, M., Formgren, J., Gillgren, P., Jarl, L., Kall, T. B., Konrad, P., Nyman, N., Skioldebrand, C., Steuer, J., Takolander, R., Malmstedt, J., Acosta, S., Bjorses, K., Brandt, K., Dias, N., Gottsater, A., Holst, J., Kristmundsson, T., Kuhme, T., Kolbel, T., Lindblad, B., Lindh, M., Malina, M., Ohrlander, T., Resch, T., Ronnle, V., Sonesson, B., Warvsten, M., Zdanowski, Z., Campbell, E., Kjellin, P., Lindgren, H., Nyberg, J., Petersen, B., Plate, G., Parsson, H., Qvarfordt, P., Ignatenko, P., Karpenko, A., Starodubtsev, V., Chernyavsky, M. A., Golovkova, M. S., Komakha, B. B., Zherdev, N. N., Belyasnik, A., Chechulov, P., Kandyba, D., Stepanishchev, I., Csobay-Novak, C., Dosa, E., Entz, L., Nemes, B., Szeberin, Z., Barzo, P., Bodosi, M., Fako, E., Fulop, B., Nemeth, T., Pazdernyik, S., Skoba, K., Voros, E., Chatzinikou, E., Giannoukas, A., Karathanos, C., Koutsias, S., Kouvelos, G., Matsagkas, M., Ralli, S., Rountas, C., Rousas, N., Spanos, K., Brountzos, E., Kakisis, J. D., Lazaris, A., Moulakakis, K. 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N., Bellenis, I., Maras, D., Polydorou, A., Polydorou, V., Tavernarakis, A., Ioannou, N., Terzoudi, M., Lazarides, M., Mantatzis, M., Vadikolias, K., Dzieciuchowicz, L., Gabriel, M., Krasinski, Z., Oszkinis, G., Pukacki, F., Slowinski, M., Stanisic, M. -G., Staniszewski, R., Tomczak, J., Zielinski, M., Myrcha, P., Rozanski, D., Drelichowski, S., Iwanowski, W., Koncewicz, K., Bialek, P., Biejat, Z., Czepel, W., Czlonkowska, A., Dowzenko, A., Jedrzejewska, J., Kobayashi, A., Leszczynski, J., Malek, A., Polanski, J., Proczka, R., Skorski, M., Szostek, M., Andziak, P., Dratwicki, M., Gil, R., Nowicki, M., Pniewski, J., Rzezak, J., Seweryniak, P., Dabek, P., Juszynski, M., Madycki, G., Pacewski, B., Raciborski, W., Slowinski, P., Staszkiewicz, W., Bombic, M., Chlouba, V., Fiedler, J., Hes, K., Kostal, P., Sova, J., Kriz, Z., Privara, M., Reif, M., Staffa, R., Vlachovsky, R., Vojtisek, B., Hrbac, T., Kuliha, M., Prochazka, V., Roubec, M., Skoloudik, D., Netuka, D., Steklacova, A., Benes III, V., Buchvald, P., Endrych, L., Sercl, M., Campos, W., Casella, I. B., de Luccia, N., Estenssoro, A. E. V., Presti, C., Puech-Leao, P., Neves, C. R. B., da Silva, E. S., Sitrangulo, C. J., Monteiro, J. A. T., Tinone, G., Bellini Dalio, M., Joviliano, E. E., Pontes Neto, O. M., Serra Ribeiro, M., Cras, P., Hendriks, J. M. H., Hoppenbrouwers, M., Lauwers, P., Loos, C., Yperzeele, L., Geenens, M., Hemelsoet, D., van Herzeele, I., Vermassen, F., Astarci, P., Hammer, F., Lacroix, V., Peeters, A., Verhelst, R., Cirelli, S., Dormal, P., Grimonprez, A., Lambrecht, B., Lerut, P., Thues, E., De Koster, G., Desiron, Q., Maertens de Noordhout, A., Malmendier, D., Massoz, M., Saad, G., Bosiers, M., Callaert, J., Deloose, K., Blanco Canibano, E., Garcia Fresnillo, B., Guerra Requena, M., Morata Barrado, P. C., Muela Mendez, M., Yusta Izquierdo, A., Aparici Robles, F., Blanes Orti, P., Garcia Dominguez, L., Martinez Lopez, R., Miralles Hernandez, M., Tembl Ferrairo, J. I., Chamorro, A., Macho, J., Obach, V., Riambau, V., San Roman, L., Ahlhelm, F. J., Blackham, K., Engelter, S., Eugster, T., Gensicke, H., Gurke, L., Lyrer, P., Mariani, L., Maurer, M., Mujagic, E., Muller, M., Psychogios, M., Stierli, P., Stippich, C., Traenka, C., Wolff, T., Wagner, B., Wiegert, M. M., Clarke, S., Diepers, M., Grochenig, E., Gruber, P., Isaak, A., Kahles, T., Marti, R., Nedeltchev, K., Remonda, L., Tissira, N., Valenca Falcao, M., de Borst, G. J., Lo, R. H., Moll, F. L., Toorop, R., van der Worp, B. H., Vonken, E. J., Kappelle, J. L., Jahrome, O., Vos, F., Schuiling, W., van Overhagen, H., Keunen, R. W. M., Knippenberg, B., Wever, J. J., Lardenoije, J. W., Reijnen, M., Smeets, L., van Sterkenburg, S., Fraedrich, G., Gizewski, E., Gruber, I., Knoflach, M., Kiechl, S., Rantner, B., Abdulamit, T., Bergeron, P., Padovani, R., Trastour, J. -C., Cardon, J. -M., Le Gallou-Wittenberg, A., Allaire, E., Becquemin, J. -P., Cochennec-Paliwoda, F., Desgranges, P., Hosseini, H., Kobeiter, H., Marzelle, J., Almekhlafi, M. A., Bal, S., Barber, P. A., Coutts, S. B., Demchuk, A. M., Eesa, M., Gillies, M., Goyal, M., Hill, M. D., Hudon, M. E., Jambula, A., Kenney, C., Klein, G., Mcclelland, M., Mitha, A., Menon, B. K., Morrish, W. F., Peters, S., Ryckborst, K. J., Samis, G., Save, S., Smith, E. E., Stys, P., Subramaniam, S., Sutherland, G. R., Watson, T., Wong, J. H., Zimmel, L., Flis, V., Matela, J., Miksic, K., Milotic, F., Mrdja, B., Stirn, B., Tetickovic, E., Gasparini, M., Grad, A., Kompara, I., Milosevic, Z., Palmiste, V., Toomsoo, T., Aidashova, B., Kospanov, N., Lyssenko, R., Mussagaliev, D., Beyar, R., Hoffman, A., Karram, T., Kerner, A., Nikolsky, E., Nitecki, S., Andonova, S., Bachvarov, C., Petrov, V., Cvjetko, I., Vidjak, V., Haluzan, D., Petrunic, M., Liu, B., Liu, C. -W., Bartko, D., Beno, P., Rusnak, F., Zelenak, K., Ezura, M., Inoue, T., Kimura, N., Kondo, R., Matsumoto, Y., Shimizu, H., Endo, H., Furui, E., Bakke, S., Krohg-Sorensen, K., Nome, T., Skjelland, M., Tennoe, B., Albuquerque e Castro, J., Alves, G., Bastos Goncalves, F., de Aragao Morais, J., Garcia, A. C., Valentim, H., Vasconcelos, L., Belcastro, F., Cura, F., Zaefferer, P., Abd-Allah, F., Eldessoki, M. H., Heshmat Kassem, H., Soliman Gharieb, H., Colgan, M. P., Haider, S. N., Harbison, J., Madhavan, P., Moore, D., Shanik, G., Kazan, V., Nazzal, M., Ramsey-Williams, V., Burzotta F. (ORCID:0000-0002-6569-9401), Tinelli G. (ORCID:0000-0002-2212-3226), Tshomba Y. (ORCID:0000-0001-7304-7553), and Vincenzoni C.
- Abstract
Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA
- Published
- 2021
3. Assessment of acute stroke CT examinations by anaesthesiologists: O18
- Author
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Hov, M. R., Nome, T., Zakariassen, E., Røislien, J., Lossius, H. M., Russell, D., and Lund, C. G.
- Published
- 2014
4. Genome-wide association mapping in Norwegian Red cattle identifies quantitative trait loci for fertility and milk production on BTA12
- Author
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Olsen, H. G., Hayes, B. J., Kent, M. P., Nome, T., Svendsen, M., Larsgard, A. G., and Lien, S.
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- 2011
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5. A genome wide association study for QTL affecting direct and maternal effects of stillbirth and dystocia in cattle
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Olsen, H. G., Hayes, B. J., Kent, M. P., Nome, T., Svendsen, M., and Lien, S.
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- 2010
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6. Characterization of a QTL region affecting clinical mastitis and protein yield on BTA6
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Nilsen, H., Olsen, H. G., Hayes, B., Nome, T., Sehested, E., Svendsen, M., Meuwissen, T. H. E., and Lien, S.
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- 2009
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7. MR ANGIOGRAPHY IN THE FOLLOW-UP OF COILED CEREBRAL ANEURYSMS AFTER TREATMENT WITH GUGLIELMI DETACHABLE COILS
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NOME, T., BAKKE, S. J., and NAKSTAD, P. H.
- Published
- 2002
8. 508 Identification of Fusion Transcripts in Colorectal Cancer by Combined RNA-seq and Exon Microarray Analyses
- Author
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Skotheim, R., primary, Nome, T., additional, Thomassen, G.O.S., additional, Johannessen, B., additional, Bakken, A.C., additional, Bruun, J., additional, Ahlquist, T.C., additional, Meza-Zepeda, L.A., additional, Myklebost, O., additional, and Lothe, R.A., additional
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- 2012
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9. Revealing genetic relationships between compounds affecting boar taint and reproduction in pigs1
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Grindflek, E., primary, Meuwissen, T. H. E., additional, Aasmundstad, T., additional, Hamland, H., additional, Hansen, M. H. S., additional, Nome, T., additional, Kent, M., additional, Torjesen, P., additional, and Lien, S., additional
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- 2011
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10. Histogram Analysis of MR Imaging–Derived Cerebral Blood Volume Maps: Combined Glioma Grading and Identification of Low-Grade Oligodendroglial Subtypes
- Author
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Emblem, K.E., primary, Scheie, D., additional, Due-Tonnessen, P., additional, Nedregaard, B., additional, Nome, T., additional, Hald, J.K., additional, Beiske, K., additional, Meling, T.R., additional, and Bjornerud, A., additional
- Published
- 2008
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11. Casein haplotypes and their association with milk production traits in Norwegian Red cattle
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Nome Torfinn, Svendsen Morten, Sehested Erling, Hayes Ben, Olsen Hanne, Nilsen Heidi, Meuwissen Theo, and Lien Sigbjørn
- Subjects
Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract A high resolution SNP map was constructed for the bovine casein region to identify haplotype structures and study associations with milk traits in Norwegian Red cattle. Our analyses suggest separation of the casein cluster into two haplotype blocks, one consisting of the CSN1S1, CSN2 and CSN1S2 genes and another one consisting of the CSN3 gene. Highly significant associations with both protein and milk yield were found for both single SNPs and haplotypes within the CSN1S1-CSN2-CSN1S2 haplotype block. In contrast, no significant association was found for single SNPs or haplotypes within the CSN3 block. Our results point towards CSN2 and CSN1S2 as the most likely loci harbouring the underlying causative DNA variation. In our study, the most significant results were found for the SNP CSN2_67 with the C allele consistently associated with both higher protein and milk yields. CSN2_67 calls a C to an A substitution at codon 67 in β-casein gene resulting in histidine replacing proline in the amino acid sequence. This polymorphism determines the protein variants A1/B (CSN2_67 A allele) versus A2/A3 (CSN2_67 C allele). Other studies have suggested that a high consumption of A1/B milk may affect human health by increasing the risk of diabetes and heart diseases. Altogether these results argue for an increase in the frequency of the CSN2_67 C allele or haplotypes containing this allele in the Norwegian Red cattle population by selective breeding.
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- 2009
- Full Text
- View/download PDF
12. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy
- Author
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Alison Halliday, Richard Bulbulia, Leo H Bonati, Johanna Chester, Andrea Cradduck-Bamford, Richard Peto, Hongchao Pan, John Potter, Hans Henning Eckstein, Barbara Farrell, Marcus Flather, Averil Mansfield, Boby Mihaylova, Kazim Rahimi, David Simpson, Dafydd Thomas, Peter Sandercock, Richard Gray, Andrew Molyneux, Cliff P Shearman, Peter Rothwell, Anna Belli, Will Herrington, Parminder Judge, Peter Leopold, Marion Mafham, Michael Gough, Piergiorgio Cao, Sumaira MacDonald, Vasha Bari, Clive Berry, S Bradshaw, Wojciech Brudlo, Alison Clarke, Robin Cox, Susan Fathers, Kamran Gaba, Mo Gray, Elizabeth Hayter, Constance Holliday, Rijo Kurien, Michael Lay, Steffi le Conte, Jessica McManus, Zahra Madgwick, Dylan Morris, Andrew Munday, Sandra Pickworth, Wiktor Ostasz, Michiel Poorthuis, Sue Richards, Louisa Teixeira, Sergey Tochlin, Lynda Tully, Carol Wallis, Monique Willet, Alan Young, Renato Casana, Chiara Malloggi, Andrea Odero Jr, Vincenzo Silani, Gianfranco Parati, Giuseppe Malchiodi, Giovanni Malferrari, Francesco Strozzi, Nicola Tusini, Enrico Vecchiati, Gioacchino Coppi, Antonio Lauricella, Roberto Moratto, Roberto Silingardi, Jessica Veronesi, Andrea Zini, Emanuele Ferrero, Michelangelo Ferri, Andrea Gaggiano, Carmelo Labate, Franco Nessi, Daniele Psacharopulo, Andrea Viazzo, Giovanni Malacrida, Daniela Mazzaccaro, Giovanni Meola, Alfredo Modafferi, Giovanni Nano, Maria Teresa Occhiuto, Paolo Righini, Silvia Stegher, Stefano Chiarandini, Filippo Griselli, Sandro Lepidi, Fabio Pozzi Mucelli, Marcello Naccarato, Mario D'Oria, Barbara Ziani, Andrea Stella, Mortalla Dieng, Gianluca Faggioli, Mauro Gargiulo, Sergio Palermo, Rodolfo Pini, Giovanni Maria Puddu, Andrea Vacirca, Domenico Angiletta, Claudio Desantis, Davide Marinazzo, Giovanni Mastrangelo, Guido Regina, Raffaele Pulli, Paolo Bianchi, Lea Cireni, Elisabetta Coppi, Rocco Pizzirusso, Filippo Scalise, Giovanni Sorropago, Valerio Tolva, Valeria Caso, Enrico Cieri, Paola DeRango, Luca Farchioni, Giacomo Isernia, Massimo Lenti, Gian Battista Parlani, Guglielmo Pupo, Grazia Pula, Gioele Simonte, Fabio Verzini, Federico Carimati, Maria Luisa Delodovici, Federico Fontana, Gabriele Piffaretti, Matteo Tozzi, Efrem Civilini, Giorgio Poletto, Bernhard Reimers, Barbara Praquin, Sonia Ronchey, Laura Capoccia, Wassim Mansour, Enrico Sbarigia, Francesco Speziale, Pasqualino Sirignano, Danilo Toni, Roberto Galeotti, Vincenzo Gasbarro, Francesco Mascoli, Tiberio Rocca, Elpiniki Tsolaki, Giulia Bernardini, Ester DeMarco, Alessia Giaquinta, Francesco Patti, Massimiliano Veroux, Pierfrancesco Veroux, Carla Virgilio, Nicola Mangialardi, Matteo Orrico, Vincenzo Di Lazzaro, Nunzio Montelione, Francesco Spinelli, Francesco Stilo, Carlo Cernetti, Sandro Irsara, Giuseppe Maccarrone, Diego Tonello, Adriana Visonà, Beniamino Zalunardo, Emiliano Chisci, Stefano Michelagnoli, Nicola Troisi, Maela Masato, Massimo Dei Negri, Andrea Pacchioni, Salvatore Saccà, Giovanni Amatucci, Alfredo Cannizzaro, Federico Accrocca, Cesare Ambrogi, Renzo Barbazza, Giustino Marcucci, Andrea Siani, Guido Bajardi, Giovanni Savettieri, Angelo Argentieri, Riccardo Corbetta, Attilio Odero, Pietro Quaretti, Federico Z Thyrion, Alessandro Cappelli, Domenico Benevento, Gianmarco De Donato, Maria Agnese Mele, Giancarlo Palasciano, Daniela Pieragalli, Alessandro Rossi, Carlo Setacci, Francesco Setacci, Domenico Palombo, Maria Cecilia Perfumo, Edoardo Martelli, Aldo Paolucci, Santi Trimarchi, Viviana Grassi, Luigi Grimaldi, Giuliana La Rosa, Domenico Mirabella, Matteo Scialabba, Leonildo Sichel, Costantino L D'Angelo, Gian Franco Fadda, Holta Kasemi, Mario Marino, Francesco Burzotta, Francesco Alberto Codispoti, Angela Ferrante, Giovanni Tinelli, Yamume Tshomba, Claudio Vincenzoni, Deborah Amis, Dawn Anderson, Martin Catterson, Mike Clarke, Michelle Davis, Anand Dixit, Alexander Dyker, Gary Ford, Ralph Jackson, Sreevalsan Kappadath, David Lambert, Tim Lees, Stephen Louw, James McCaslin, Noala Parr, Rebecca Robson, Gerard Stansby, Lucy Wales, Vera Wealleans, Lesley Wilson, Michael Wyatt, Hardeep Baht, Ibrahim Balogun, Ilse Burger, Tracy Cosier, Linda Cowie, Gunaratnam Gunathilagan, David Hargroves, Robert Insall, Sally Jones, Hannah Rudenko, Natasha Schumacher, Jawaharlal Senaratne, George Thomas, Audrey Thomson, Tom Webb, Ellen Brown, Bernard Esisi, Ali Mehrzad, Shane MacSweeney, Norman McConachie, Alison Southam, Wayne Sunman, Ahmed Abdul-Hamiq, Jenny Bryce, Ian Chetter, Duncan Ettles, Raghuram Lakshminarayan, Kim Mitchelson, Christopher Rhymes, Graham Robinson, Paul Scott, Alison Vickers, Ray Ashleigh, Stephen Butterfield, Ed Gamble, Jonathan Ghosh, Charles N McCollum, Mark Welch, Sarah Welsh, Leszek Wolowczyk, Mary Donnelly, Stephen D'Souza, Anselm A Egun, Bindu Gregary, Thomas Joseph, Christine Kelly, Shuja Punekar, M Asad Rahi, Sonia Raj, Dare Seriki, George Thomson, James Brown, Ragunath Durairajan, Iris Grunwald, Paul Guyler, Paula Harman, Matthew Jakeways, Christopher Khuoge, Ashish Kundu, Thayalini Loganathan, Nisha Menon, Raji O Prabakaran, Devesh Sinha, Vicky Thompson, Sharon Tysoe, Dennis Briley, Chris Darby, Linda Hands, Dominic Howard, Wilhelm Kuker, Ursula Schulz, Rachel Teal, David Barer, Andrew Brown, Susan Crawford, Paul Dunlop, Ramesh Krishnamurthy, Nikhil Majmudar, Duncan Mitchell, Min P Myint, Richard O'Brien, Janice O'Connell, Naweed Sattar, Shanmugam Vetrivel, Jonathan Beard, Trevor Cleveland, Peter Gaines, John Humphreys, Alison Jenkins, Craig King, Daniel Kusuma, Ralph Lindert, Robbie Lonsdale, Raj Nair, Shah Nawaz, Faith Okhuoya, Douglas Turner, Graham Venables, Paul Dorman, Andrea Hughes, Deborah Jones, David Mendelow, Helen Rodgers, Aidas Raudoniitis, Peter Enevoldson, Hans Nahser, Imelda O'Brien, Francesco Torella, Dave Watling, Richard White, Pauline Brown, Dipankar Dutta, Lorraine Emerson, Paula Hilltout, Sachin Kulkarni, Jackie Morrison, Keith Poskitt, Fiona Slim, Sarah Smith, Amanda Tyler, Joanne Waldron, Mark Whyman, Milda Bajoriene, Lucy Baker, Amanda Colston, Bekky Eliot-Jones, Gita Gramizadeh, Catherine Lewis-Clarke, Laura McCafferty, Deborah Oliver, Debbie Palmer, Abhijeet Patil, Suzannah Pegler, Gopi Ramadurai, Aisling Roberts, Tracey Sargent, Shivaprasad Siddegowda, Ravi Singh-Ranger, Akintunde Williams, Lucy Williams, Steve Windebank, Tadas Zuromskis, Lanka Alwis, Jane Angus, Asaipillai Asokanathan, Caroline Fornolles, Diana Hardy, Sophy Hunte, Frances Justin, Duke Phiri, Marie Mitabouana-Kibou, Lakshmanan Sekaran, Sakthivel Sethuraman, Margaret L Tate, Joyce Akyea-Mensah, Stephen Ball, Angela Chrisopoulou, Elizabeth Keene, Alison Phair, Steven Rogers, John V Smyth, Colin Bicknell, Jeremy Chataway, Nicholas Cheshire, Andrew Clifton, Caroline Eley, Richard Gibbs, Mohammad Hamady, Beth Hazel, Alex James, Michael Jenkins, Nyma Khanom, Austin Lacey, Maz Mireskandari, Joanna O'Reilly, Antony Pereira, Tina Sachs, John Wolfe, Philip Davey, Gill Rogers, Gemma Smith, Gareth Tervit, Ian Nichol, Andrew Parry, Gavin Young, Simon Ashley, James Barwell, Francis Dix, Azlisham M Nor, Chris Parry, Angela Birt, Paul Davies, Jim George, Anne Graham, Leon Jonker, Nicci Kelsall, Caroline Potts, Toni Wilson, Jamie Crinnion, Larissa Cuenoud, Nikola Aleksic, Srdan Babic, Nenad Ilijevski, Đorde Radak, Dragan Sagic, Slobodan Tanaskovic, Momcilo Colic, Vladimir Cvetic, Lazar Davidovic, Dejana R Jovanovic, Igor Koncar, Perica Mutavdžic, Miloš Sladojevic, Ivan Tomic, Eike S Debus, Ulrich Grzyska, Dagmar Otto, Götz Thomalla, Jessica Barlinn, Johannes Gerber, Kathrin Haase, Christian Hartmann, Stefan Ludwig, Volker Pütz, Christian Reeps, Christine Schmidt, Norbert Weiss, Sebastian Werth, Simon Winzer, Janine Gemper, Albrecht Günther, Bianka Heiling, Elisabeth Jochmann, Panagiota Karvouniari, Carsten Klingner, Thomas Mayer, Julia Schubert, Friederike Schulze-Hartung, Jürgen Zanow, Yvonne Bausback, Franka Borger, Spiridon Botsios, Daniela Branzan, Sven Bräunlich, Henryk Hölzer, Janin Lenzer, Christopher Piorkowski, Nadine 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E., Bernardini G., DeMarco E., Giaquinta A., Patti F., Veroux M., Veroux P., Virgilio C., Mangialardi N., Orrico M., Di Lazzaro V., Montelione N., Spinelli F., Stilo F., Cernetti C., Irsara S., Maccarrone G., Tonello D., Visona A., Zalunardo B., Chisci E., Michelagnoli S., Troisi N., Masato M., Dei Negri M., Pacchioni A., Sacca S., Amatucci G., Cannizzaro A., Accrocca F., Ambrogi C., Barbazza R., Marcucci G., Siani A., Bajardi G., Savettieri G., Argentieri A., Corbetta R., Quaretti P., Thyrion F.Z., Cappelli A., Benevento D., De Donato G., Mele M.A., Palasciano G., Pieragalli D., Rossi A., Setacci C., Setacci F., Palombo D., Perfumo M.C., Martelli E., Paolucci A., Trimarchi S., Grassi V., Grimaldi L., La Rosa G., Mirabella D., Scialabba M., Sichel L., D'Angelo C.L., Fadda G.F., Kasemi H., Marino M., Burzotta F., Codispoti F.A., Ferrante A., Tinelli G., Tshomba Y., Vincenzoni C., Amis D., Anderson D., Catterson M., Clarke M., Davis M., Dixit A., Dyker A., Ford G., Jackson R., Kappadath 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Golovkova M.S., Komakha B.B., Zherdev N.N., Belyasnik A., Chechulov P., Kandyba D., Stepanishchev I., Csobay-Novak C., Dosa E., Entz L., Nemes B., Szeberin Z., Barzo P., Bodosi M., Fako E., Fulop B., Nemeth T., Pazdernyik S., Skoba K., Voros E., Chatzinikou E., Giannoukas A., Karathanos C., Koutsias S., Kouvelos G., Matsagkas M., Ralli S., Rountas C., Rousas N., Spanos K., Brountzos E., Kakisis J.D., Lazaris A., Moulakakis K.G., Stefanis L., Tsivgoulis G., Vasdekis S., Antonopoulos C.N., Bellenis I., Maras D., Polydorou A., Polydorou V., Tavernarakis A., Ioannou N., Terzoudi M., Lazarides M., Mantatzis M., Vadikolias K., Dzieciuchowicz L., Gabriel M., Krasinski Z., Oszkinis G., Pukacki F., Slowinski M., Stanisic M.-G., Staniszewski R., Tomczak J., Zielinski M., Myrcha P., Rozanski D., Drelichowski S., Iwanowski W., Koncewicz K., Bialek P., Biejat Z., Czepel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Leszczynski J., Malek A., Polanski J., Proczka R., Skorski M., 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Noordhout A., Malmendier D., Massoz M., Saad G., Bosiers M., Callaert J., Deloose K., Blanco Canibano E., Garcia Fresnillo B., Guerra Requena M., Morata Barrado P.C., Muela Mendez M., Yusta Izquierdo A., Aparici Robles F., Blanes Orti P., Garcia Dominguez L., Martinez Lopez R., Miralles Hernandez M., Tembl Ferrairo J.I., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Ahlhelm F.J., Blackham K., Engelter S., Eugster T., Gensicke H., Gurke L., Lyrer P., Mariani L., Maurer M., Mujagic E., Muller M., Psychogios M., Stierli P., Stippich C., Traenka C., Wolff T., Wagner B., Wiegert M.M., Clarke S., Diepers M., Grochenig E., Gruber P., Isaak A., Kahles T., Marti R., Nedeltchev K., Remonda L., Tissira N., Valenca Falcao M., de Borst G.J., Lo R.H., Moll F.L., Toorop R., van der Worp B.H., Vonken E.J., Kappelle J.L., Jahrome O., Vos F., Schuiling W., van Overhagen H., Keunen R.W.M., Knippenberg B., Wever J.J., Lardenoije J.W., Reijnen M., Smeets L., van Sterkenburg S., Fraedrich G., Gizewski E., Gruber I., Knoflach M., Kiechl S., Rantner B., Abdulamit T., Bergeron P., Padovani R., Trastour J.-C., Cardon J.-M., Le Gallou-Wittenberg A., Allaire E., Becquemin J.-P., Cochennec-Paliwoda F., Desgranges P., Hosseini H., Kobeiter H., Marzelle J., Almekhlafi M.A., Bal S., Barber P.A., Coutts S.B., Demchuk A.M., Eesa M., Gillies M., Goyal M., Hill M.D., Hudon M.E., Jambula A., Kenney C., Klein G., McClelland M., Mitha A., Menon B.K., Morrish W.F., Peters S., Ryckborst K.J., Samis G., Save S., Smith E.E., Stys P., Subramaniam S., Sutherland G.R., Watson T., Wong J.H., Zimmel L., Flis V., Matela J., Miksic K., Milotic F., Mrdja B., Stirn B., Tetickovic E., Gasparini M., Grad A., Kompara I., Milosevic Z., Palmiste V., Toomsoo T., Aidashova B., Kospanov N., Lyssenko R., Mussagaliev D., Beyar R., Hoffman A., Karram T., Kerner A., Nikolsky E., Nitecki S., Andonova S., Bachvarov C., Petrov V., Cvjetko I., Vidjak V., Haluzan D., Petrunic M., Liu B., Liu C.-W., Bartko D., Beno P., Rusnak F., Zelenak K., Ezura M., Inoue T., Kimura N., Kondo R., Matsumoto Y., Shimizu H., Endo H., Furui E., Bakke S., Krohg-Sorensen K., Nome T., Skjelland M., Tennoe B., Albuquerque e Castro J., Alves G., Bastos Goncalves F., de Aragao Morais J., Garcia A.C., Valentim H., Vasconcelos L., Belcastro F., Cura F., Zaefferer P., Abd-Allah F., Eldessoki M.H., Heshmat Kassem H., Soliman Gharieb H., Colgan M.P., Haider S.N., Harbison J., Madhavan P., Moore D., Shanik G., Kazan V., Nazzal M., Ramsey-Williams V., and Gargiulo M
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Male ,medicine.medical_specialty ,Time Factors ,Time Factor ,medicine.medical_treatment ,Carotid Stenosi ,MEDLINE ,Carotid endarterectomy ,Rate ratio ,Risk Assessment ,Asymptomatic ,law.invention ,Randomized controlled trial ,law ,Risk Factors ,carotid artery stenting (CAS) ,carotid endarterectomy (CEA) ,Stent ,medicine ,Humans ,Carotid Stenosis ,Stroke ,Endarterectomy ,Aged ,Endarterectomy, Carotid ,business.industry ,carotid artery ,Risk Factor ,Articles ,General Medicine ,trial ,medicine.disease ,Settore MED/22 - CHIRURGIA VASCOLARE ,Surgery ,Stenosis ,Treatment Outcome ,Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,Female ,Stents ,Human medicine ,medicine.symptom ,business ,Human - Abstract
Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.
- Published
- 2021
13. External validation of clinical risk prediction score for elderly treated with endovascular thrombectomy.
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Enriquez BAB, Skattør TH, Laugesen NG, Truelsen T, Lund CG, Nome T, Beyer MK, Skjelland M, and Aamodt AH
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- Aged, Aged, 80 and over, Female, Humans, Male, Follow-Up Studies, Outcome Assessment, Health Care, Prognosis, Risk Assessment, Endovascular Procedures, Ischemic Stroke diagnostic imaging, Ischemic Stroke surgery, Ischemic Stroke therapy, Thrombectomy
- Abstract
Background and Aim: The thrombectomy in the elderly prediction score (TERPS) for functional outcome after anterior circulation endovascular therapy (EVT) in patients ≥ 80 years was recently developed. The aim of this study was to assess predictors of functional outcome in the elderly and validate the prediction model., Methods: Consecutive patients treated with EVT from the Oslo Acute Reperfusion Stroke Study were evaluated for inclusion. Clinical and radiological parameters were used to calculate the TERPS, and functional outcome were assessed at 3-month follow-up., Results: Out of 1028 patients who underwent EVT for acute ischemic stroke from January 2017 to July 2022, 218 (21.2%) patients ≥ 80 years with anterior ischemic stroke were included. Fair outcome, defined as modified Rankin scale ≤ 3 (mRS), was achieved in 117 (53.7%). In bivariate analyses, male sex (p 0.035), age (p 0.025), baseline National Institute of Health Stroke Scale (NIHSS, p < 0.001), pre-stroke mRS (p 0.002) and Alberta Stroke Program Early Computed Tomography score (ASPECTS, p 0.001) were associated with fair outcome. Significant predictors for fair outcome in regression analyses were lower pre-stroke mRS, adjusted odd ratio, (aOR) 0.67 (95% CI 0.50-0.91, p 0.01), NIHSS, aOR 0.92 (95% CI 0.87-0.97, p 0.002), and higher ASPECTS, aOR 1.22 (95% CI 1.03-1.44, p 0.023). The area under the curve (AUC) using TERPS was 0.74 (95% CI 0.67-0.80)., Conclusions: The risk prediction score TERPS showed moderate performance in this external validation. Other variables may still be included to improve the model and validation using other cohorts is recommended., Trial Registration: NCT06220981., (© 2024. The Author(s).)
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- 2024
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14. Clinical outcome after thrombectomy in patients with MeVO stroke: importance of clinical and technical factors.
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Nome T, Enriquez B, Nome CG, Tennøe B, Lund CG, Skjelland M, Aamodt AH, and Beyer M
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- Male, Humans, Female, Aged, 80 and over, Thrombectomy adverse effects, Cerebral Infarction complications, Treatment Outcome, Retrospective Studies, Stroke surgery, Stroke complications, Ischemic Stroke complications, Arterial Occlusive Diseases complications, Endovascular Procedures adverse effects, Brain Ischemia diagnostic imaging, Brain Ischemia surgery
- Abstract
Background and Aims: Whereas high-level evidence has been proven for safety and efficacy of endovascular treatment (EVT) in large vessel occlusion (LVO) stroke, the evidence for EVT in medium vessel occlusion (MeVO) in both sexes and different age groupremains to be answered. The aim of this study was to evaluate the importance of clinical and technical parameters, focusing on sex, age and EVT procedural factors, on functional outcome in primary MeVO (pMeVO) strokes., Methods: 144 patients with pMeVO in the MCA territory from the Oslo Acute Reperfusion Stroke Study (OSCAR) were included. Clinical and radiological data were collected including 90-day mRS follow-up., Results: Successful reperfusion with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 123 patients (84%). Good functional outcome (mRS ≤ 2) at 90-day follow-up was achieved in 84 patients (61.8%). Two or more passes with stent retriever was associated with increased risk of SAH, poor mTICI and poor functional outcome. In average, women had 62 min longer ictus to recanalization time compared to men. Age over 80 years was significantly associated with poor outcome and death., Conclusion: In pMeVO patients, TICI score and number of passes with stent retriever were the main technical factors predicting mRS ≤ 2. Good clinical outcome occurred almost twice as often in patients under 80 years of age compared to patients over 80 years. Women with MeVO strokes had significant longer time from ictus to recanalization; however, this did not affect the clinical outcome., (© 2023. The Author(s).)
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- 2024
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15. Predictors of outcome after endovascular treatment for tandem occlusions: a single center retrospective analysis.
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Enriquez BAB, Nome T, Nome CG, Tennøe B, Lund CG, Beyer MK, Skjelland M, and Aamodt AH
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- Humans, Retrospective Studies, Intracranial Hemorrhages, Cerebral Infarction, Anesthesia, General, Stroke epidemiology, Stroke surgery, Ischemic Stroke
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Background: The endovascular treatment procedure in tandem occlusions (TO) is complex compared to single occlusion (SO) and optimal management remains uncertain. The aim of this study was to identify clinical and procedural factors that may be associated to efficacy and safety in the management of TO and compare functional outcome in TO and SO stroke patients., Methods: This is a retrospective single center study of medium (MeVO) and large vessel occlusion (LVO) of the anterior circulation. Clinical, imaging, and interventional data were analyzed to identify predictive factors for symptomatic intracranial hemorrhage (sICH) and functional outcome after endovascular treatment (EVT) in TO. Functional outcome in TO and SO patients was compared., Results: Of 662 anterior circulation stroke patients with MeVO and LVO stroke, 90 (14%) had TO. Stenting was performed in 73 (81%) of TO patients. Stent thromboses occurred in 8 (11%) patients. Successful reperfusion with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 82 (91%). SICH occurred in seven (8%). The strongest predictors for sICH were diabetes mellitus and number of stent retriever passes. Good functional clinical outcome (mRS ≤ 2) at 90-day follow up was similar in TO and SO patients (58% vs 59% respectively). General anesthesia (GA) was associated with good functional outcome whereas hemorrhage in the infarcted tissue, lower mTICI score and history of smoking were associated with poor outcome., Conclusions: The risk of sICH was increased in patients with diabetes mellitus and those with extra stent-retriever attempts. Functional clinical outcomes in patients with TO were comparable to patients with SO., (© 2023. The Author(s).)
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- 2023
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16. Dissecting the loci underlying maturation timing in Atlantic salmon using haplotype and multi-SNP based association methods.
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Sinclair-Waters M, Nome T, Wang J, Lien S, Kent MP, Sægrov H, Florø-Larsen B, Bolstad GH, Primmer CR, and Barson NJ
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- Animals, Haplotypes, Polymorphism, Single Nucleotide, Bayes Theorem, Phenotype, Salmo salar genetics
- Abstract
Characterizing the role of different mutational effect sizes in the evolution of fitness-related traits has been a major goal in evolutionary biology for a century. Such characterization in a diversity of systems, both model and non-model, will help to understand the genetic processes underlying fitness variation. However, well-characterized genetic architectures of such traits in wild populations remain uncommon. In this study, we used haplotype-based and multi-SNP Bayesian association methods with sequencing data for 313 individuals from wild populations to test the mutational composition of known candidate regions for sea age at maturation in Atlantic salmon (Salmo salar). We detected an association at five loci out of 116 candidates previously identified in an aquaculture strain with maturation timing in wild Atlantic salmon. We found that at four of these five loci, variation explained by the locus was predominantly driven by a single SNP suggesting the genetic architecture of this trait includes multiple loci with simple, non-clustered alleles and a locus with potentially more complex alleles. This highlights the diversity of genetic architectures that can exist for fitness-related traits. Furthermore, this study provides a useful multi-SNP framework for future work using sequencing data to characterize genetic variation underlying phenotypes in wild populations., (© 2022. The Author(s).)
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- 2022
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17. The emergence of supergenes from inversions in Atlantic salmon.
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Stenløkk K, Saitou M, Rud-Johansen L, Nome T, Moser M, Árnyasi M, Kent M, Barson NJ, and Lien S
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- Alleles, Animals, Chromosome Inversion, Genotype, Polymorphism, Genetic, Salmo salar genetics
- Abstract
Supergenes link allelic combinations into non-recombining units known to play an essential role in maintaining adaptive genetic variation. However, because supergenes can be maintained over millions of years by balancing selection and typically exhibit strong recombination suppression, both the underlying functional variants and how the supergenes are formed are largely unknown. Particularly, questions remain over the importance of inversion breakpoint sequences and whether supergenes capture pre-existing adaptive variation or accumulate this following recombination suppression. To investigate the process of supergene formation, we identified inversion polymorphisms in Atlantic salmon by assembling eleven genomes with nanopore long-read sequencing technology. A genome assembly from the sister species, brown trout, was used to determine the standard state of the inversions. We found evidence for adaptive variation through genotype-environment associations, but not for the accumulation of deleterious mutations. One young 3 Mb inversion segregating in North American populations has captured adaptive variation that is still segregating within the standard arrangement of the inversion, while some adaptive variation has accumulated after the inversion. This inversion and two others had breakpoints disrupting genes. Three multigene inversions with matched repeat structures at the breakpoints did not show any supergene signatures, suggesting that shared breakpoint repeats may obstruct supergene formation. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
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- 2022
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18. Mechanical thrombectomy in acute ischaemic stroke.
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Enriquez BA, Tennøe B, Nome T, Gjertsen Ø, Nedregaard B, Sletteberg R, Skattør T, Sökjer M, Johansen H, Skagen KR, Skjelland M, Aamodt AH, and Lund CG
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- Acute Disease, Cerebral Infarction, Humans, Retrospective Studies, Stents, Thrombectomy methods, Treatment Outcome, Brain Ischemia diagnostic imaging, Brain Ischemia surgery, Endovascular Procedures, Stroke diagnostic imaging, Stroke surgery
- Abstract
Mechanical thrombectomy is now the standard treatment for acute ischaemic stroke with occlusion of a carotid or intercranial artery. With occlusions of this type, thrombolytic treatment often has limited effect. The therapeutic outcome with the use of thrombectomy is time-dependent, and a personalised approach to indication is always necessary. To achieve the best possible results, the main prerequisites are good clinical procedures, an optimal patient pathway, high neuroradiological competence and coordinated, interdisciplinary teams.
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- 2022
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19. Microsurgery as first-line treatment in acute hemorrhagic cranial dural arteriovenous fistulas (dAVFs) and ruptured intracranial aneurysms-anachronism or duty?
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Sorteberg W, Sorteberg A, Jacobsen EA, Rønning P, Nome T, and Eide PK
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- Humans, Microsurgery, Retrospective Studies, Skull surgery, Treatment Outcome, Aneurysm, Ruptured surgery, Central Nervous System Vascular Malformations complications, Central Nervous System Vascular Malformations surgery, Embolization, Therapeutic, Intracranial Aneurysm diagnostic imaging, Intracranial Aneurysm surgery
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- 2022
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20. Early surgical versus endovascular repair of ruptured blood-blister aneurysm of the internal carotid artery: a single-center 20-year experience.
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Eide PK, Sorteberg A, Nome T, Rønning PA, and Sorteberg W
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- Humans, Carotid Artery, Internal surgery, Prospective Studies, Cerebral Angiography, Treatment Outcome, Retrospective Studies, Intracranial Aneurysm diagnostic imaging, Intracranial Aneurysm surgery, Carotid Artery Diseases surgery, Aneurysm, Ruptured diagnostic imaging, Aneurysm, Ruptured surgery, Endovascular Procedures, Embolization, Therapeutic
- Abstract
Objective: Early repair of ruptured blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) remains challenging. Although both surgical and endovascular therapies have been established, their relative superiority remains debated. The authors assessed their single-center experience and compared early deconstructive versus reconstructive repair and early reconstructive surgical versus endovascular repair of ruptured BBAs of the ICA., Methods: The study included patients who underwent repair of ruptured BBAs of the ICA within 1 week after the ictus during a 20-year period. Multiple variables were recorded, including clinical state, severity of subarachnoid hemorrhage (SAH), characteristics of the BBA, treatment details, complication profile, need for secondary treatment, and clinical outcome., Results: In total, 27 patients underwent early surgical (n = 16) or endovascular (n = 11) repair of BBAs at a median of 24 hours (range 9-120 hours) after the ictus during the period from September 2000 to June 2021 (20.4 years). Primary deconstructive repair (n = 6) without bypass was accompanied by middle cerebral artery (MCA) territory infarction in 5 of 6 (83%) patients and a high mortality rate (4/6 [67%]). Among the 21 patients who underwent early reconstructive repair, surgery was performed in 11 patients (clipping in 6 and clip-wrapping in 5 patients) and endovascular repair in 10 patients (flow diversion in 7 and stent/stent-assisted coiling in 3 patients). No differences were found in complication profiles or clinical outcomes between the surgical and endovascular groups. The mortality rate was low (2/21 [9.5%]), with 1 fatality in each group., Conclusions: From the authors' experience, both surgical and endovascular approaches permitted reconstructive repair of ruptured BBAs of the ICA, with no modality proving superior. Reconstructive treatment is preferable to ICA sacrifice, and if sacrifice is chosen, it should be accompanied with bypass surgery or delayed to the phase when cerebral vasospasm has resumed. The rare occurrence of this disease calls for prospective multicenter studies to improve treatment and delineate which modality is preferable in individual cases.
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- 2022
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21. Endovascular versus surgical treatment of cranial dural arteriovenous fistulas: a single-center 8-year experience.
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Sorteberg W, Sorteberg A, Jacobsen EA, Rønning P, Nome T, and Eide PK
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- Angiography, Female, Humans, Male, Retrospective Studies, Skull, Treatment Outcome, Central Nervous System Vascular Malformations diagnostic imaging, Central Nervous System Vascular Malformations surgery, Embolization, Therapeutic
- Abstract
Background: Cranial dural arteriovenous fistulas (dAVFs) are rare lesions managed mainly with endovascular treatment (EVT) and/or surgery. We hypothesize that there may be subtypes of dAVFs responding better to a specific treatment modality in terms of successful obliteration and cessation of symptoms and/or risks., Methods: All dAVFs treated during 2011-2018 at our hospital were analyzed retrospectively. Presenting symptoms, radiological variables, treatment modality, complications, and residual symptoms were related to dAVF type using the original Djindjian classification., Results: We treated 112 dAVFs in 107 patients (71, 66% males). They presented with hemorrhage (n = 23; 21%), non-hemorrhagic symptoms (n = 75; 70%), or were discovered incidentally (n = 9; 8%). There were 25 (22%) type I, 29 (26%) type II, 26 (23%) type III, and 32 (29%) type IV fistulas. EVT was the primary treatment modality in 72/112 (64%) dAVFs whereas 40/112 (36%) underwent primary surgery with angiographic obliteration rates of 60% and 90%, respectively. Using a secondary treatment modality in 23 dAVFs, we obtained a final obliteration rate of 93%, including all type III/IV and 26/27 (96%) type II dAVFs. Except for headache, residual symptoms were rare and minor. Permanent neurological complications consisted of five cranial nerve deficits., Conclusions: We recommend EVT as first treatment modality in types I, II, and in non-hemorrhagic type III/IV dAVFs. We recommend surgery as first treatment choice in acute hemorrhagic dAVFs and as secondary choice in type III/IV dAVFs not successfully occluded by EVT. Combining the two modalities provides obliteration in 9/10 dAVF cases at a low procedural risk., (© 2021. The Author(s).)
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- 2022
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22. Immunologic Profiling of the Atlantic Salmon Gill by Single Nuclei Transcriptomics.
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West AC, Mizoro Y, Wood SH, Ince LM, Iversen M, Jørgensen EH, Nome T, Sandve SR, Martin SAM, Loudon ASI, and Hazlerigg DG
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- Animal Migration, Animals, Gene Expression Regulation, Gills cytology, RNA-Seq, Salt Tolerance, Seawater, Fish Proteins genetics, Gene Expression Profiling, Gills immunology, Salmo salar genetics, Salmo salar immunology, Single-Cell Analysis, Transcriptome
- Abstract
Anadromous salmonids begin life adapted to the freshwater environments of their natal streams before a developmental transition, known as smoltification, transforms them into marine-adapted fish. In the wild, smoltification is a photoperiod-regulated process, involving radical remodeling of gill function to cope with the profound osmotic and immunological challenges of seawater (SW) migration. While prior work has highlighted the role of specialized "mitochondrion-rich" cells (MRCs) and accessory cells (ACs) in delivering this phenotype, recent RNA profiling experiments suggest that remodeling is far more extensive than previously appreciated. Here, we use single-nuclei RNAseq to characterize the extent of cytological changes in the gill of Atlantic salmon during smoltification and SW transfer. We identify 20 distinct cell clusters, including known, but also novel gill cell types. These data allow us to isolate cluster-specific, smoltification-associated changes in gene expression and to describe how the cellular make-up of the gill changes through smoltification. As expected, we noted an increase in the proportion of seawater mitochondrion-rich cells, however, we also identify previously unknown reduction of several immune-related cell types. Overall, our results provide fresh detail of the cellular complexity in the gill and suggest that smoltification triggers unexpected immune reprogramming., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 West, Mizoro, Wood, Ince, Iversen, Jørgensen, Nome, Sandve, Martin, Loudon and Hazlerigg.)
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- 2021
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23. The structural variation landscape in 492 Atlantic salmon genomes.
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Bertolotti AC, Layer RM, Gundappa MK, Gallagher MD, Pehlivanoglu E, Nome T, Robledo D, Kent MP, Røsæg LL, Holen MM, Mulugeta TD, Ashton TJ, Hindar K, Sægrov H, Florø-Larsen B, Erkinaro J, Primmer CR, Bernatchez L, Martin SAM, Johnston IA, Sandve SR, Lien S, and Macqueen DJ
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- Animals, DNA Transposable Elements genetics, Fisheries, Gene Duplication, Gene Frequency, Genetic Variation, Genetics, Population, Genotyping Techniques, Male, Molecular Sequence Annotation, Phylogeography, Whole Genome Sequencing, Workflow, Animals, Wild genetics, Domestication, Genome, Genomic Structural Variation, Salmo salar genetics
- Abstract
Structural variants (SVs) are a major source of genetic and phenotypic variation, but remain challenging to accurately type and are hence poorly characterized in most species. We present an approach for reliable SV discovery in non-model species using whole genome sequencing and report 15,483 high-confidence SVs in 492 Atlantic salmon (Salmo salar L.) sampled from a broad phylogeographic distribution. These SVs recover population genetic structure with high resolution, include an active DNA transposon, widely affect functional features, and overlap more duplicated genes retained from an ancestral salmonid autotetraploidization event than expected. Changes in SV allele frequency between wild and farmed fish indicate polygenic selection on behavioural traits during domestication, targeting brain-expressed synaptic networks linked to neurological disorders in humans. This study offers novel insights into the role of SVs in genome evolution and the genetic architecture of domestication traits, along with resources supporting reliable SV discovery in non-model species.
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- 2020
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24. Direct visual targeting versus preset coordinates for ANT-DBS in epilepsy.
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Nome T, Herrman H, Lehtimäki K, Egge A, Konglund A, Ramm-Pettersen J, Taubøll E, and Dietrichs E
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- Adult, Double-Blind Method, Drug Resistant Epilepsy therapy, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging methods, Randomized Controlled Trials as Topic, Tomography, X-Ray Computed, Anterior Thalamic Nuclei physiology, Deep Brain Stimulation methods, Epilepsy therapy
- Abstract
Objectives: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) may be used against refractory focal epilepsy, but only two randomized double-blinded trials have been performed. The Oslo study was discontinued prematurely since reduction in seizure frequency was less than expected. The aim of the present study was to review the targeting used in the Oslo study and to identify the actual positions of the contacts used for stimulation., Material and Methods: BrainLab MRI data were available from 12 Oslo study patients. Based on MRI the coordinates of the center of the ANT were identified. The coordinates were considered as the visually identified preferred target and were compared with the target originally used for ANT electrode implantation and with the actual electrode positions estimated from post-operative CT scans., Results: We found considerable differences between the visually identified preferred target, the originally planned target, and the actual electrode position. The total distance between the active electrode position and the visually identified preferred target was on average 3.3 mm on the right and 2.9 mm on the left side., Conclusion: Indirect targeting based on preset coordinates may contribute to explain the modest effect of ANT-DBS on seizure frequency seen in the Oslo study. Observed differences between the center of the ANT and the actual electrode position may at least in part be explained by variations in position and size of the ANT. Direct identification of the target using better MRI imaging protocols is recommended for future ANT-DBS surgery., (© 2020 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)
- Published
- 2020
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25. Publisher Correction: Sex-dependent dominance maintains migration supergene in rainbow trout.
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Pearse DE, Barson NJ, Nome T, Gao G, Campbell MA, Abadía-Cardoso A, Anderson EC, Rundio DE, Williams TH, Naish KA, Moen T, Liu S, Kent M, Moser M, Minkley DR, Rondeau EB, Brieuc MSO, Sandve SR, Miller MR, Cedillo L, Baruch K, Hernandez AG, Ben-Zvi G, Shem-Tov D, Barad O, Kuzishchin K, Garza JC, Lindley ST, Koop BF, Thorgaard GH, Palti Y, and Lien S
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
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26. Sex-dependent dominance maintains migration supergene in rainbow trout.
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Pearse DE, Barson NJ, Nome T, Gao G, Campbell MA, Abadía-Cardoso A, Anderson EC, Rundio DE, Williams TH, Naish KA, Moen T, Liu S, Kent M, Moser M, Minkley DR, Rondeau EB, Brieuc MSO, Sandve SR, Miller MR, Cedillo L, Baruch K, Hernandez AG, Ben-Zvi G, Shem-Tov D, Barad O, Kuzishchin K, Garza JC, Lindley ST, Koop BF, Thorgaard GH, Palti Y, and Lien S
- Subjects
- Animals, Female, Male, Phenotype, Sex Chromosomes, Oncorhynchus mykiss
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Males and females often differ in their fitness optima for shared traits that have a shared genetic basis, leading to sexual conflict. Morphologically differentiated sex chromosomes can resolve this conflict and protect sexually antagonistic variation, but they accumulate deleterious mutations. However, how sexual conflict is resolved in species that lack differentiated sex chromosomes is largely unknown. Here we present a chromosome-anchored genome assembly for rainbow trout (Oncorhynchus mykiss) and characterize a 55-Mb double-inversion supergene that mediates sex-specific migratory tendency through sex-dependent dominance reversal, an alternative mechanism for resolving sexual conflict. The double inversion contains key photosensory, circadian rhythm, adiposity and sex-related genes and displays a latitudinal frequency cline, indicating environmentally dependent selection. Our results show sex-dependent dominance reversal across a large autosomal supergene, a mechanism for sexual conflict resolution capable of protecting sexually antagonistic variation while avoiding the homozygous lethality and deleterious mutations associated with typical heteromorphic sex chromosomes.
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- 2019
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27. SalMotifDB: a tool for analyzing putative transcription factor binding sites in salmonid genomes.
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Mulugeta TD, Nome T, To TH, Gundappa MK, Macqueen DJ, Våge DI, Sandve SR, and Hvidsten TR
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- Animals, DNA chemistry, Gene Duplication genetics, Gene Regulatory Networks, Lipid Metabolism genetics, Nucleotide Motifs, Protein Binding, Databases, Genetic, Genomics methods, Salmonidae genetics, Transcription Factors metabolism
- Abstract
Background: Recently developed genome resources in Salmonid fish provides tools for studying the genomics underlying a wide range of properties including life history trait variation in the wild, economically important traits in aquaculture and the evolutionary consequences of whole genome duplications. Although genome assemblies now exist for a number of salmonid species, the lack of regulatory annotations are holding back our mechanistic understanding of how genetic variation in non-coding regulatory regions affect gene expression and the downstream phenotypic effects., Results: We present SalMotifDB, a database and associated web and R interface for the analysis of transcription factors (TFs) and their cis-regulatory binding sites in five salmonid genomes. SalMotifDB integrates TF-binding site information for 3072 non-redundant DNA patterns (motifs) assembled from a large number of metazoan motif databases. Through motif matching and TF prediction, we have used these multi-species databases to construct putative regulatory networks in salmonid species. The utility of SalMotifDB is demonstrated by showing that key lipid metabolism regulators are predicted to regulate a set of genes affected by different lipid and fatty acid content in the feed, and by showing that our motif database explains a significant proportion of gene expression divergence in gene duplicates originating from the salmonid specific whole genome duplication., Conclusions: SalMotifDB is an effective tool for analyzing transcription factors, their binding sites and the resulting gene regulatory networks in salmonid species, and will be an important tool for gaining a better mechanistic understanding of gene regulation and the associated phenotypes in salmonids. SalMotifDB is available at https://salmobase.org/apps/SalMotifDB .
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- 2019
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28. A New Single Nucleotide Polymorphism Database for Rainbow Trout Generated Through Whole Genome Resequencing.
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Gao G, Nome T, Pearse DE, Moen T, Naish KA, Thorgaard GH, Lien S, and Palti Y
- Abstract
Single-nucleotide polymorphisms (SNPs) are highly abundant markers, which are broadly distributed in animal genomes. For rainbow trout ( Oncorhynchus mykiss ), SNP discovery has been previously done through sequencing of restriction-site associated DNA (RAD) libraries, reduced representation libraries (RRL) and RNA sequencing. Recently we have performed high coverage whole genome resequencing with 61 unrelated samples, representing a wide range of rainbow trout and steelhead populations, with 49 new samples added to 12 aquaculture samples from AquaGen (Norway) that we previously used for SNP discovery. Of the 49 new samples, 11 were double-haploid lines from Washington State University (WSU) and 38 represented wild and hatchery populations from a wide range of geographic distribution and with divergent migratory phenotypes. We then mapped the sequences to the new rainbow trout reference genome assembly (GCA_002163495.1) which is based on the Swanson YY doubled haploid line. Variant calling was conducted with FreeBayes and SAMtools mpileup , followed by filtering of SNPs based on quality score, sequence complexity, read depth on the locus, and number of genotyped samples. Results from the two variant calling programs were compared and genotypes of the double haploid samples were used for detecting and filtering putative paralogous sequence variants (PSVs) and multi-sequence variants (MSVs). Overall, 30,302,087 SNPs were identified on the rainbow trout genome 29 chromosomes and 1,139,018 on unplaced scaffolds, with 4,042,723 SNPs having high minor allele frequency (MAF > 0.25). The average SNP density on the chromosomes was one SNP per 64 bp, or 15.6 SNPs per 1 kb. Results from the phylogenetic analysis that we conducted indicate that the SNP markers contain enough population-specific polymorphisms for recovering population relationships despite the small sample size used. Intra-Population polymorphism assessment revealed high level of polymorphism and heterozygosity within each population. We also provide functional annotation based on the genome position of each SNP and evaluate the use of clonal lines for filtering of PSVs and MSVs. These SNPs form a new database, which provides an important resource for a new high density SNP array design and for other SNP genotyping platforms used for genetic and genomics studies of this iconic salmonid fish species.
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- 2018
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29. Evolution of Sex Determination Loci in Atlantic Salmon.
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Kijas J, McWilliam S, Naval Sanchez M, Kube P, King H, Evans B, Nome T, Lien S, and Verbyla K
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- Animals, Female, Genome, Genomics, Male, Whole Genome Sequencing, Chromosomes, Evolution, Molecular, Genetic Loci, Polymorphism, Single Nucleotide, Salmo salar genetics, Sex Determination Processes genetics
- Abstract
Teleost fish exhibit a remarkable diversity in the control of sex determination, offering the opportunity to identify novel differentiation mechanisms and their ecological consequences. Here, we perform GWAS using 4715 fish and 46,501 SNP to map sex determination to three separate genomic locations in Atlantic salmon (Salmo salar). To characterize each, whole genome sequencing was performed to 30-fold depth of coverage using 20 fish representing each of three identified sex lineages. SNP polymorphism reveals male fish carry a single copy of the male specific region, consistent with an XX/XY or male heterogametric sex system. Haplotype analysis revealed deep divergence between the putatively ancestral locus on chromosome 2, compared with loci on chromosomes 3 and 6. Haplotypes in fish carrying either the chromosome 3 or 6 loci were nearly indistinguishable, indicating a founding event that occurred following the speciation event that defined Salmo salar from other salmonids. These findings highlight the evolutionarily fluid state of sex determination systems in salmonids, and resolve to the sequence level differences in animals with divergent sex lineages.
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- 2018
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30. Erratum.
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Kirubakaran TG, Grove H, Kent MP, Sandve SR, Baranski M, Nome T, De Rosa MC, Righino B, Johansen T, Otterå H, Sonesson A, Lien SR, and Andersen Ø
- Published
- 2018
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31. CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension.
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Celestino R, Nome T, Pestana A, Hoff AM, Gonçalves AP, Pereira L, Cavadas B, Eloy C, Bjøro T, Sobrinho-Simões M, Skotheim RI, and Soares P
- Subjects
- Adenocarcinoma, Follicular genetics, Adenocarcinoma, Follicular pathology, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Complement C1q genetics, Diagnosis, Differential, Extracellular Matrix Proteins genetics, Female, Gene Expression Regulation, Neoplastic, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Neoplasm Invasiveness genetics, Neoplasm Invasiveness pathology, Prognosis, Pyrophosphatases genetics, Transcriptome genetics, Adenocarcinoma, Follicular diagnosis, Lipocalin-2 genetics, Receptors, Retinoic Acid genetics
- Abstract
Background: The prognostic variability of thyroid carcinomas has led to the search for accurate biomarkers at the molecular level. Follicular thyroid carcinoma (FTC) is a typical example of differentiated thyroid carcinomas (DTC) in which challenges are faced in the differential diagnosis., Methods: We used high-throughput paired-end RNA sequencing technology to study four cases of FTC with different degree of capsular invasion: two minimally invasive (mFTC) and two widely invasive FTC (wFTC). We searched by genes differentially expressed between mFTC and wFTC, in an attempt to find biomarkers of thyroid cancer diagnosis and/or progression. Selected biomarkers were validated by real-time quantitative PCR in 137 frozen thyroid samples and in an independent dataset (TCGA), evaluating the diagnostic and the prognostic performance of the candidate biomarkers., Results: We identified 17 genes significantly differentially expressed between mFTC and wFTC. C1QL1, LCN2, CRABP1 and CILP were differentially expressed in DTC in comparison with normal thyroid tissues. LCN2 and CRABP1 were also differentially expressed in DTC when compared with follicular thyroid adenoma. Additionally, overexpression of LCN2 and C1QL1 were found to be independent predictors of extrathyroidal extension in DTC., Conclusions: We conclude that the underexpression of CRABP1 and the overexpression of LCN2 may be useful diagnostic biomarkers in thyroid tumours with questionable malignity, and the overexpression of LCN2 and C1QL1 may be useful for prognostic purposes.
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- 2018
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32. Interpretation of Brain CT Scans in the Field by Critical Care Physicians in a Mobile Stroke Unit.
- Author
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Hov MR, Zakariassen E, Lindner T, Nome T, Bache KG, Røislien J, Gleditsch J, Solyga V, Russell D, and Lund CG
- Subjects
- Critical Care, Humans, Neuroimaging methods, Pilot Projects, Point-of-Care Systems, Retrospective Studies, Tomography Scanners, X-Ray Computed, Brain diagnostic imaging, Mobile Health Units, Stroke diagnostic imaging, Tomography, X-Ray Computed
- Abstract
Background and Purpose: In acute stroke, thromboembolism or spontaneous hemorrhage abruptly reduces blood flow to a part of the brain. To limit necrosis, rapid radiological identification of the pathological mechanism must be conducted to allow the initiation of targeted treatment. The aim of the Norwegian Acute Stroke Prehospital Project is to determine if anesthesiologists, trained in prehospital critical care, may accurately assess cerebral computed tomography (CT) scans in a mobile stroke unit (MSU)., Methods: In this pilot study, 13 anesthesiologists assessed unselected acute stroke patients with a cerebral CT scan in an MSU. The scans were simultaneously available by teleradiology at the receiving hospital and the on-call radiologist. CT scan interpretation was focused on the radiological diagnosis of acute stroke and contraindications for thrombolysis. The aim of this study was to find inter-rater agreement between the pre- and in-hospital radiological assessments. A neuroradiologist evaluated all CT scans retrospectively. Statistical analysis of inter-rater agreement was analyzed with Cohen's kappa., Results: Fifty-one cerebral CT scans from the MSU were included. Inter-rater agreement between prehospital anesthesiologists and the in-hospital on-call radiologists was excellent in finding radiological selection for thrombolysis (kappa .87). Prehospital CT scans were conducted in median 10 minutes (7 and 14 minutes) in the MSU, and median 39 minutes (31 and 48 minutes) before arrival at the receiving hospital., Conclusion: This pilot study shows that anesthesiologists trained in prehospital critical care may effectively assess cerebral CT scans in an MSU, and determine if there are radiological contraindications for thrombolysis., (© 2017 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.)
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- 2018
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33. SalmoBase: an integrated molecular data resource for Salmonid species.
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Samy JKA, Mulugeta TD, Nome T, Sandve SR, Grammes F, Kent MP, Lien S, and Våge DI
- Subjects
- Animals, Polymorphism, Single Nucleotide, User-Computer Interface, Databases, Genetic, Genomics, Salmonidae genetics
- Abstract
Background: Salmonids are ray-finned fishes which constitute 11 genera and at least 70 species including Atlantic salmon, whitefishes, graylings, rainbow trout, and char. The common ancestor of all Salmonidae experienced a whole genome duplication (WGD) ~80 million years ago, resulting in an autotetraploid genome. Genomic rediplodization is still going on in salmonid species, providing an unique system for studying evolutionary consequences of whole genome duplication. In recent years, high quality genome sequences of Atlantic salmon and Rainbow trout has been established, due to their scientific and commercial values. In this paper we introduce SalmoBase ( http://www.salmobase.org/ ), a tool for making molecular resources for salmonids public available in a framework of visualizations and analytic tools., Results: SalmoBase has been developed as a part of the ELIXIR.NO project. Currently, SalmoBase contains molecular resources for Atlantic salmon and Rainbow trout. Data can be accessed through BLAST, Genome Browser (GBrowse), Genetic Variation Browser (GVBrowse) and Gene Expression Browser (GEBrowse)., Conclusions: To the best of our knowledge, SalmoBase is the first database which integrates salmonids data and allow users to study salmonids in an integrated framework. The database and its tools (e.g., comparative genomics tools, synteny browsers) will be expanded as additional public resources describing other Salmonidae genomes become available.
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- 2017
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34. Genome-wide association mapping for milk fat composition and fine mapping of a QTL for de novo synthesis of milk fatty acids on bovine chromosome 13.
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Olsen HG, Knutsen TM, Kohler A, Svendsen M, Gidskehaug L, Grove H, Nome T, Sodeland M, Sundsaasen KK, Kent MP, Martens H, and Lien S
- Subjects
- Animals, Chromosome Mapping, Chromosomes genetics, Fatty Acids analysis, Fatty Acids genetics, Female, Genome-Wide Association Study, Milk chemistry, Cattle genetics, Fatty Acids biosynthesis, Milk metabolism, Quantitative Trait Loci
- Abstract
Background: Bovine milk is widely regarded as a nutritious food source for humans, although the effects of individual fatty acids on human health is a subject of debate. Based on the assumption that genomic selection offers potential to improve milk fat composition, there is strong interest to understand more about the genetic factors that influence the biosynthesis of bovine milk and the molecular mechanisms that regulate milk fat synthesis and secretion. For this reason, the work reported here aimed at identifying genetic variants that affect milk fatty acid composition in Norwegian Red cattle. Milk fatty acid composition was predicted from the nation-wide recording scheme using Fourier transform infrared spectroscopy data and applied to estimate heritabilities for 36 individual and combined fatty acid traits. The recordings were used to generate daughter yield deviations that were first applied in a genome-wide association (GWAS) study with 17,343 markers to identify quantitative trait loci (QTL) affecting fatty acid composition, and next on high-density and sequence-level datasets to fine-map the most significant QTL on BTA13 (BTA for Bos taurus chromosome)., Results: The initial GWAS revealed 200 significant associations, with the strongest signals on BTA1, 13 and 15. The BTA13 QTL highlighted a strong functional candidate gene for de novo synthesis of short- and medium-chained saturated fatty acids; acyl-CoA synthetase short-chain family member 2. However, subsequent fine-mapping using single nucleotide polymorphisms (SNPs) from a high-density chip and variants detected by resequencing showed that the effect was more likely caused by a second nearby gene; nuclear receptor coactivator 6 (NCOA6). These findings were confirmed with results from haplotype studies. NCOA6 is a nuclear receptor that interacts with transcription factors such as PPARγ, which is a major regulator of bovine milk fat synthesis., Conclusions: An initial GWAS revealed a highly significant QTL for de novo-synthesized fatty acids on BTA13 and was followed by fine-mapping of the QTL within NCOA6. The most significant SNPs were either synonymous or situated in introns; more research is needed to uncover the underlying causal DNA variation(s).
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- 2017
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35. Fine mapping of a QTL on bovine chromosome 6 using imputed full sequence data suggests a key role for the group-specific component (GC) gene in clinical mastitis and milk production.
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Olsen HG, Knutsen TM, Lewandowska-Sabat AM, Grove H, Nome T, Svendsen M, Arnyasi M, Sodeland M, Sundsaasen KK, Dahl SR, Heringstad B, Hansen HH, Olsaker I, Kent MP, and Lien S
- Subjects
- Alleles, Animals, Cattle, Chromosome Mapping, Female, Gene Frequency, Haplotypes, Lactation genetics, Linkage Disequilibrium, Mammary Glands, Animal physiology, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Mastitis, Bovine genetics, Milk, Quantitative Trait Loci, Vitamin D-Binding Protein genetics
- Abstract
Background: Clinical mastitis is an inflammation of the mammary gland and causes significant costs to dairy production. It is unfavourably genetically correlated to milk production, and, thus, knowledge of the mechanisms that underlie these traits would be valuable to improve both of them simultaneously through breeding. A quantitative trait locus (QTL) that affects both clinical mastitis and milk production has recently been fine-mapped to around 89 Mb on bovine chromosome 6 (BTA6), but identification of the gene that underlies this QTL was not possible due to the strong linkage disequilibrium between single nucleotide polymorphisms (SNPs) within this region. Our aim was to identify the gene and, if possible, the causal polymorphism(s) responsible for this QTL through association analysis of high-density SNPs and imputed full sequence data in combination with analyses of transcript and protein levels of the identified candidate gene., Results: Associations between SNPs and the studied traits were strongest for SNPs that were located within and immediately upstream of the group-specific component (GC) gene. This gene encodes the vitamin D-binding protein (DBP) and has multiple roles in immune defense and milk production. A 12-kb duplication that was identified downstream of this gene covered its last exon and segregated with the QTL allele that is associated with increased mastitis susceptibility and milk production. However, analyses of GC mRNA levels on the available samples revealed no differences in expression between animals having or lacking this duplication. Moreover, we detected no differences in the concentrations of DBP and its ligand vitamin D between the animals with different GC genotypes that were available for this study., Conclusions: Our results suggest GC as the gene that underlies the QTL for clinical mastitis and milk production. However, since only healthy animals were sampled for transcription and expression analyses, we could not draw any final conclusion on the absence of quantitative differences between animals with different genotypes. Future studies should investigate GC RNA expression and protein levels in cows with different genotypes during an infection.
- Published
- 2016
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36. The Atlantic salmon genome provides insights into rediploidization.
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Lien S, Koop BF, Sandve SR, Miller JR, Kent MP, Nome T, Hvidsten TR, Leong JS, Minkley DR, Zimin A, Grammes F, Grove H, Gjuvsland A, Walenz B, Hermansen RA, von Schalburg K, Rondeau EB, Di Genova A, Samy JK, Olav Vik J, Vigeland MD, Caler L, Grimholt U, Jentoft S, Våge DI, de Jong P, Moen T, Baranski M, Palti Y, Smith DR, Yorke JA, Nederbragt AJ, Tooming-Klunderud A, Jakobsen KS, Jiang X, Fan D, Hu Y, Liberles DA, Vidal R, Iturra P, Jones SJ, Jonassen I, Maass A, Omholt SW, and Davidson WS
- Subjects
- Animals, DNA Transposable Elements genetics, Female, Genomics, Male, Models, Genetic, Mutagenesis genetics, Phylogeny, Reference Standards, Salmo salar classification, Sequence Homology, Diploidy, Evolution, Molecular, Gene Duplication genetics, Genes, Duplicate genetics, Genome genetics, Salmo salar genetics
- Abstract
The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.
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- 2016
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37. Two adjacent inversions maintain genomic differentiation between migratory and stationary ecotypes of Atlantic cod.
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Kirubakaran TG, Grove H, Kent MP, Sandve SR, Baranski M, Nome T, De Rosa MC, Righino B, Johansen T, Otterå H, Sonesson A, Lien S, and Andersen Ø
- Subjects
- Animals, Genetic Linkage, Genetics, Population, Genotype, Haplotypes, Linkage Disequilibrium, Norway, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Animal Migration, Chromosome Inversion, Ecotype, Gadus morhua genetics, Selection, Genetic
- Abstract
Atlantic cod is composed of multiple migratory and stationary populations widely distributed in the North Atlantic Ocean. The Northeast Arctic cod (NEAC) population in the Barents Sea undertakes annual spawning migrations to the northern Norwegian coast. Although spawning occurs sympatrically with the stationary Norwegian coastal cod (NCC), phenotypic and genetic differences between NEAC and NCC are maintained. In this study, we resolve the enigma by revealing the mechanisms underlying these differences. Extended linkage disequilibrium (LD) and population divergence were demonstrated in a 17.4-Mb region on linkage group 1 (LG1) based on genotypes of 494 SNPs from 192 parents of farmed families of NEAC, NCC or NEACxNCC crosses. Linkage analyses revealed two adjacent inversions within this region that repress meiotic recombination in NEACxNCC crosses. We identified a NEAC-specific haplotype consisting of 186 SNPs that was fixed in NEAC sampled from the Barents Sea, but segregating under Hardy-Weinberg equilibrium in eight NCC stocks. Comparative genomic analyses determine the NEAC configuration of the inversions to be the derived state and date it to ~1.6-2.0 Mya. The haplotype block harbours 763 genes, including candidates regulating swim bladder pressure, haem synthesis and skeletal muscle organization conferring adaptation to long-distance migrations and vertical movements down to large depths. Our results suggest that the migratory ecotype experiences strong directional selection for the two adjacent inversions on LG1. Despite interbreeding between NEAC and NCC, the inversions are maintaining genetic differentiation, and we hypothesize the co-occurrence of multiple adaptive alleles forming a 'supergene' in the NEAC population., (© 2016 John Wiley & Sons Ltd.)
- Published
- 2016
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38. Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations.
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Lorenz S, Barøy T, Sun J, Nome T, Vodák D, Bryne JC, Håkelien AM, Fernandez-Cuesta L, Möhlendick B, Rieder H, Szuhai K, Zaikova O, Ahlquist TC, Thomassen GO, Skotheim RI, Lothe RA, Tarpey PS, Campbell P, Flanagan A, Myklebost O, and Meza-Zepeda LA
- Subjects
- Genes, Tumor Suppressor, Genomics, Humans, Osteosarcoma pathology, Translocation, Genetic, DNA Repair genetics, Genes, p53 genetics, Osteosarcoma genetics
- Abstract
In contrast to many other sarcoma subtypes, the chaotic karyotypes of osteosarcoma have precluded the identification of pathognomonic translocations. We here report hundreds of genomic rearrangements in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fused transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which was further supported by typical trans-splicing characteristics. By combining genomic and transcriptomic analysis, certain recurrent rearrangements were identified and further validated in patient biopsies, including a PMP22-ELOVL5 gene fusion, genomic structural variations affecting RB1, MTAP/CDKN2A and MDM2, and, most frequently, rearrangements involving TP53. Most cell lines (7/11) and a large fraction of tumor samples (10/25) showed TP53 rearrangements, in addition to somatic point mutations (6 patient samples, 1 cell line) and MDM2 amplifications (2 patient samples, 2 cell lines). The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors. Although rampant rearrangements appear to be a phenotype of osteosarcomas, we demonstrate that among the huge number of probable passenger rearrangements, specific recurrent, possibly oncogenic, events are present. For the first time the genomic chaos of osteosarcoma is characterized so thoroughly and delivered new insights in mechanisms involved in osteosarcoma development and may contribute to new diagnostic and therapeutic strategies.
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- 2016
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39. Cerebral foreign body reaction after carotid aneurysm stenting.
- Author
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Lorentzen AO, Nome T, Bakke SJ, Scheie D, Stenset V, and Aamodt AH
- Subjects
- Blood Vessel Prosthesis adverse effects, Brain Edema pathology, Carotid Artery Diseases complications, Carotid Artery Diseases pathology, Endovascular Procedures instrumentation, Female, Foreign-Body Reaction pathology, Humans, Intracranial Aneurysm complications, Intracranial Aneurysm pathology, Middle Aged, Treatment Outcome, Brain Edema etiology, Carotid Artery Diseases surgery, Endovascular Procedures adverse effects, Foreign-Body Reaction etiology, Intracranial Aneurysm surgery, Stents adverse effects
- Abstract
Flow diverter stents are new important tools in the treatment of large, giant, or wide-necked aneurysms. Their delivery and positioning may be difficult due to vessel tortuosity. Common adverse events include intracranial hemorrhage and ischemic stroke, which usually occurs within the same day, or the next few days after the procedure. We present a case where we encountered an unusual intracerebral complication several months after endovascular treatment of a large left internal carotid artery aneurysm, and where brain biopsy revealed foreign body reaction to hydrophilic polymer fragments distally to the stent site. Although previously described, embolization of polymer material from intravascular equipment is rare. We could not identify any other biopsy verified case in the literature, with this particular presentation of intracerebral polymer embolization--a multifocal inflammation spread out through the white matter of one hemisphere without hemorrhage or ischemic changes., (© The Author(s) 2015.)
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- 2016
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40. Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon.
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Barson NJ, Aykanat T, Hindar K, Baranski M, Bolstad GH, Fiske P, Jacq C, Jensen AJ, Johnston SE, Karlsson S, Kent M, Moen T, Niemelä E, Nome T, Næsje TF, Orell P, Romakkaniemi A, Sægrov H, Urdal K, Erkinaro J, Lien S, and Primmer CR
- Subjects
- Animals, Biological Evolution, Female, Fish Proteins metabolism, Genome-Wide Association Study, Humans, Male, Models, Biological, Phenotype, Reproduction genetics, Reproduction physiology, Transcription Factors genetics, Transcription Factors metabolism, Aging genetics, Body Size genetics, Fish Proteins genetics, Genetic Variation genetics, Growth genetics, Salmo salar genetics, Sex Characteristics
- Abstract
Males and females share many traits that have a common genetic basis; however, selection on these traits often differs between the sexes, leading to sexual conflict. Under such sexual antagonism, theory predicts the evolution of genetic architectures that resolve this sexual conflict. Yet, despite intense theoretical and empirical interest, the specific loci underlying sexually antagonistic phenotypes have rarely been identified, limiting our understanding of how sexual conflict impacts genome evolution and the maintenance of genetic diversity. Here we identify a large effect locus controlling age at maturity in Atlantic salmon (Salmo salar), an important fitness trait in which selection favours earlier maturation in males than females, and show it is a clear example of sex-dependent dominance that reduces intralocus sexual conflict and maintains adaptive variation in wild populations. Using high-density single nucleotide polymorphism data across 57 wild populations and whole genome re-sequencing, we find that the vestigial-like family member 3 gene (VGLL3) exhibits sex-dependent dominance in salmon, promoting earlier and later maturation in males and females, respectively. VGLL3, an adiposity regulator associated with size and age at maturity in humans, explained 39% of phenotypic variation, an unexpectedly large proportion for what is usually considered a highly polygenic trait. Such large effects are predicted under balancing selection from either sexually antagonistic or spatially varying selection. Our results provide the first empirical example of dominance reversal allowing greater optimization of phenotypes within each sex, contributing to the resolution of sexual conflict in a major and widespread evolutionary trade-off between age and size at maturity. They also provide key empirical evidence for how variation in reproductive strategies can be maintained over large geographical scales. We anticipate these findings will have a substantial impact on population management in a range of harvested species where trends towards earlier maturation have been observed.
- Published
- 2015
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41. Novel RNA variants in colorectal cancers.
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Hoff AM, Johannessen B, Alagaratnam S, Zhao S, Nome T, Løvf M, Bakken AC, Hektoen M, Sveen A, Lothe RA, and Skotheim RI
- Subjects
- HCT116 Cells, HT29 Cells, Humans, Survival Rate, Transcriptome, Colorectal Neoplasms genetics, RNA Splicing genetics, RNA, Neoplasm genetics
- Abstract
With an annual estimated incidence of 1.4 million, and a five-year survival rate of 60%, colorectal cancer (CRC) is a major clinical burden. To identify novel RNA variants in CRC, we analyzed exon-level microarray expression data from a cohort of 202 CRCs. We nominated 25 genes with increased expression of their 3' parts in at least one cancer sample each. To efficiently investigate underlying transcript structures, we developed an approach using rapid amplification of cDNA ends followed by high throughput sequencing (RACE-seq). RACE products from the targeted genes in 23 CRC samples were pooled together and sequenced. We identified VWA2-TCF7L2, DHX35-BPIFA2 and CASZ1-MASP2 as private fusion events, and novel transcript structures for 17 of the 23 other candidate genes. The high-throughput approach facilitated identification of CRC specific RNA variants. These include a recurrent read-through fusion transcript between KLK8 and KLK7, and a splice variant of S100A2. Both of these were overrepresented in CRC tissue and cell lines from external RNA-seq datasets.
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- 2015
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42. Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer.
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Bruun J, Kolberg M, Ahlquist TC, Røyrvik EC, Nome T, Leithe E, Lind GE, Merok MA, Rognum TO, Bjørkøy G, Johansen T, Lindblom A, Sun XF, Svindland A, Liestøl K, Nesbakken A, Skotheim RI, and Lothe RA
- Subjects
- Age Factors, Aged, Aged, 80 and over, Biomarkers, Tumor biosynthesis, Cell Line, Tumor, Chromosomal Proteins, Non-Histone biosynthesis, Chromosomes genetics, Colorectal Neoplasms pathology, DNA Mutational Analysis, Disease-Free Survival, Female, Guanine Nucleotide Exchange Factors biosynthesis, Humans, Male, Middle Aged, Neoplasm Staging, Prognosis, Biomarkers, Tumor genetics, Chromosomal Proteins, Non-Histone genetics, Colorectal Neoplasms genetics, Guanine Nucleotide Exchange Factors genetics, Microsatellite Instability
- Abstract
Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis., Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903)., Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 5' UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical high-risk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (>75 years), stage II patients, and those with rectal cancer., Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays., (©2015 American Association for Cancer Research.)
- Published
- 2015
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43. A novel transcript, VNN1-AB, as a biomarker for colorectal cancer.
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Løvf M, Nome T, Bruun J, Eknaes M, Bakken AC, Mpindi JP, Kilpinen S, Rognum TO, Nesbakken A, Kallioniemi O, Lothe RA, and Skotheim RI
- Subjects
- Adenoma pathology, Colon metabolism, Colon pathology, Colorectal Neoplasms pathology, GPI-Linked Proteins genetics, Gene Expression Profiling, Humans, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, Prognosis, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Adenoma genetics, Alternative Splicing genetics, Amidohydrolases genetics, Biomarkers, Tumor genetics, Colorectal Neoplasms genetics, Exons genetics
- Abstract
Colorectal cancer is a global health challenge with high incidence rate and mortality. The patients' prognosis is strongly associated with disease stage and currently there is a need for improved prognostic and predictive biomarkers. In this study, novel colorectal cancer-specific transcript structures were nominated from whole transcriptome sequencing of seven colorectal cancer cell lines, two primary colorectal carcinomas with corresponding normal colonic mucosa and 16 normal tissues. The nominated transcripts were combined with gene level outlier expression analyses in a cohort of 505 colorectal cancers to identify biomarkers with capacity to stratify colorectal cancer subgroups. The transcriptome sequencing data and outlier expression analysis revealed 11 novel colorectal cancer-specific exon-exon junctions, of which 3 were located in the gene VNN1. The junctions within VNN1 were further characterized using rapid amplification of cDNA ends (RACE) and the prevalence of the subsequently characterized novel transcript, VNN1-AB, was investigated by real-time RT-PCR in 291 samples of miscellaneous origins. VNN1-AB was not present in any of the 43 normal colorectal tissue samples investigated, but in 5 of the 6 polyps, and 102 of the 136 (75%) colorectal cancers. We have identified a novel transcript of the VNN1 gene, with an organ-confined complete specificity for colorectal neoplasia., (© 2014 UICC.)
- Published
- 2014
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44. Mechanical embolectomy in cerebral infarction.
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Jusufovic M, Nome T, Skjelland M, and Jacobsen EA
- Subjects
- Aged, Cerebral Angiography, Cerebral Arteries diagnostic imaging, Female, Humans, Male, Stroke diagnostic imaging, Cerebral Arteries surgery, Embolectomy, Stroke surgery
- Published
- 2014
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- View/download PDF
45. High frequency of fusion transcripts involving TCF7L2 in colorectal cancer: novel fusion partner and splice variants.
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Nome T, Hoff AM, Bakken AC, Rognum TO, Nesbakken A, and Skotheim RI
- Subjects
- Base Sequence, Exons genetics, Gene Rearrangement genetics, Genetic Loci, Genome, Human genetics, HCT116 Cells, Humans, Molecular Sequence Data, RNA Splice Sites genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Reproducibility of Results, Transcription Factor 7-Like 2 Protein metabolism, Colorectal Neoplasms genetics, Oncogene Proteins, Fusion genetics, RNA Splicing genetics, Transcription Factor 7-Like 2 Protein genetics
- Abstract
VTI1A-TCF7L2 was reported as a recurrent fusion gene in colorectal cancer (CRC), found to be expressed in three out of 97 primary cancers, and one cell line, NCI-H508, where a genomic deletion joins the two genes [1]. To investigate this fusion further, we analyzed high-throughput DNA and RNA sequencing data from seven CRC cell lines, and identified the gene RP11-57H14.3 (ENSG00000225292) as a novel fusion partner for TCF7L2. The fusion was discovered from both genome and transcriptome data in the HCT116 cell line. By triplicate nested RT-PCR, we tested both the novel fusion transcript and VTI1A-TCF7L2 for expression in a series of 106 CRC tissues, 21 CRC cell lines, 14 normal colonic mucosa, and 20 normal tissues from miscellaneous anatomical sites. Altogether, 42% and 45% of the CRC samples expressed VTI1A-TCF7L2 and TCF7L2-RP11-57H14.3 fusion transcripts, respectively. The fusion transcripts were both seen in 29% of the normal colonic mucosa samples, and in 25% and 75% of the tested normal tissues from other organs, revealing that the TCF7L2 fusion transcripts are neither specific to cancer nor to the colon and rectum. Seven different splice variants were detected for the VTI1A-TCF7L2 fusion, of which three are novel. Four different splice variants were detected for the TCF7L2-RP11-57H14.3 fusion. In conclusion, we have identified novel variants of VTI1A-TCF7L2 fusion transcripts, including a novel fusion partner gene, RP11-57H14.3, and demonstrated detectable levels in a large fraction of CRC samples, as well as in normal colonic mucosa and other tissue types. We suggest that the fusion transcripts observed in a high frequency of samples are transcription induced chimeras that are expressed at low levels in most samples. The similar fusion transcripts induced by genomic rearrangements observed in individual cancer cell lines may yet have oncogenic potential as suggested in the original study by Bass et al.
- Published
- 2014
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46. Common fusion transcripts identified in colorectal cancer cell lines by high-throughput RNA sequencing.
- Author
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Nome T, Thomassen GO, Bruun J, Ahlquist T, Bakken AC, Hoff AM, Rognum T, Nesbakken A, Lorenz S, Sun J, Barros-Silva JD, Lind GE, Myklebost O, Teixeira MR, Meza-Zepeda LA, Lothe RA, and Skotheim RI
- Abstract
Colorectal cancer (CRC) is the third most common cancer disease in the Western world, and about 40% of the patients die from this disease. The cancer cells are commonly genetically unstable, but only a few low-frequency recurrent fusion genes have so far been reported for this disease. In this study, we present a thorough search for novel fusion transcripts in CRC using high-throughput RNA sequencing. From altogether 220 million paired-end sequence reads from seven CRC cell lines, we identified 3391 candidate fused transcripts. By stringent requirements, we nominated 11 candidate fusion transcripts for further experimental validation, of which 10 were positive by reverse transcription-polymerase chain reaction and Sanger sequencing. Six were intrachromosomal fusion transcripts, and interestingly, three of these, AKAP13-PDE8A, COMMD10-AP3S1, and CTB-35F21.1-PSD2, were present in, respectively, 18, 18, and 20 of 21 analyzed cell lines and in, respectively, 18, 61, and 48 (17%-58%) of 106 primary cancer tissues. These three fusion transcripts were also detected in 2 to 4 of 14 normal colonic mucosa samples (14%-28%). Whole-genome sequencing identified a specific genomic breakpoint in COMMD10-AP3S1 and further indicates that both the COMMD10-AP3S1 and AKAP13-PDE8A fusion transcripts are due to genomic duplications in specific cell lines. In conclusion, we have identified AKAP13-PDE8A, COMMD10-AP3S1, and CTB-35F21.1-PSD2 as novel intrachromosomal fusion transcripts and the most highly recurring chimeric transcripts described for CRC to date. The functional and clinical relevance of these chimeric RNA molecules remains to be elucidated.
- Published
- 2013
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47. Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly.
- Author
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Heck A, Ringstad G, Fougner SL, Casar-Borota O, Nome T, Ramm-Pettersen J, and Bollerslev J
- Subjects
- Acromegaly diagnosis, Acromegaly epidemiology, Acromegaly etiology, Adenoma complications, Adult, Age of Onset, Antineoplastic Agents, Hormonal therapeutic use, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Pituitary Neoplasms complications, Radiography, Retrospective Studies, Signal Processing, Computer-Assisted, Acromegaly drug therapy, Adenoma diagnostic imaging, Adenoma drug therapy, Magnetic Resonance Imaging methods, Octreotide therapeutic use, Pituitary Neoplasms diagnostic imaging, Pituitary Neoplasms drug therapy
- Abstract
Background: Primary, preoperative medical treatment is an option in selected patients with acromegaly, but a subset of patients respond poorly. Valid prediction of response to somatostatin analogues (SA) might thus alter treatment stratification. The aims of this study were to assess whether T2 signal intensity could determine long-term response to first-line SA treatment and to assess clinical and biochemical baseline characteristics, as well as histological subtype in relation to the magnetic resonance imaging (MRI) appearances., Methods: In 45 newly diagnosed patients, T2-weighted signal intensity of the tumour was classified into hypo-, iso- or hyperintense. Biochemical and clinical baseline variables for the three groups were compared. In 25 patients primarily treated with long-acting SA for a median of 6 months [interquartile range (IQR):155-180 days], GH and IGF-1 reduction was assessed, and in 34 cases, immunohistochemical granulation pattern was evaluated., Results: The results showed that 12 (27%) adenomas were hypointense, 15 (33%) isointense and 18 (40%) hyperintense. Median IGF-1 [ratio IGF-1/ULN; (upper limit of normal)] was 3·5 (2·3-4·9), 2·9 (2·6-3·8) and 1·9 (1·3-2·6), respectively (P = 0·006 for difference between groups). Median GH values (μg/l) of a 3- to 5-point profile were 17·5 (6·1-35), 9·3 (6·0-32·5) and 4·1 (1·5-8·3), (P = 0·025). Median IGF-1 reduction (% of baseline) after first-line SA treatment was 51 (49-70), 36 (19-74) and 13 (5-42) (P = 0·03); median reduction in GH (% of baseline) was 86 (72-94), 78 (62-85) and 46 (1-70) (P = 0·02). T2 hyperintensity was associated with sparse granulation pattern on immunohistochemistry., Conclusion: In patients with acromegaly, T2 signal intensity at diagnosis correlates with histological features and predicts biochemical outcome of first-line SA treatment., (© 2012 Blackwell Publishing Ltd.)
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- 2012
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48. Whole-transcriptome sequencing identifies novel IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma.
- Author
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Nyquist KB, Panagopoulos I, Thorsen J, Haugom L, Gorunova L, Bjerkehagen B, Fosså A, Guriby M, Nome T, Lothe RA, Skotheim RI, Heim S, and Micci F
- Subjects
- Adult, Biopsy, Child, Chromosome Aberrations, Chromosome Banding, Chromosomes, Artificial, Bacterial, DNA-Binding Proteins, Female, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Middle Aged, Models, Genetic, Transcription Factors, Carrier Proteins genetics, Chondrosarcoma, Mesenchymal genetics, Homeodomain Proteins genetics, Nuclear Proteins genetics, Transcriptome
- Abstract
Mesenchymal chondrosarcomas (MCs) account for 3-10% of primary chondrosarcomas. The cytogenetic literature includes only ten such tumours with karyotypic information and no specific aberrations have been identified. Using a purely molecular genetic approach a HEY1-NCOA2 fusion gene was recently detected in 10 of 15 investigated MCs. The fusion probably arises through intrachromosomal rearrangement of chromosome arm 8 q. We report a new case of MC showing a t(1;5)(q42;q32) as the sole karyotypic aberration. Through FISH and whole transcriptome sequencing analysis we found a novel fusion between the IRF2BP2 gene and the transcription factor CDX1 gene arising from the translocation. The IRF2BP2-CDX1 has not formerly been described in human neoplasia. In our hospital's archives three more cases of MC were found, and we examined them looking for the supposedly more common HEY1-NCOA2 fusion, finding it in all three tumours but not in the case showing t(1;5) and IRF2BP2-CDX1 gene fusion. This demonstrates that genetic heterogeneity exists in mesenchymal chondrosarcoma.
- Published
- 2012
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49. Multiparametric analysis of magnetic resonance images for glioma grading and patient survival time prediction.
- Author
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Garzón B, Emblem KE, Mouridsen K, Nedregaard B, Due-Tønnessen P, Nome T, Hald JK, Bjørnerud A, Håberg AK, and Kvinnsland Y
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Brain Neoplasms mortality, Brain Neoplasms pathology, Glioma mortality, Glioma pathology, Magnetic Resonance Imaging, Neoplasm Grading methods
- Abstract
Background: A systematic comparison of magnetic resonance imaging (MRI) options for glioma diagnosis is lacking., Purpose: To investigate multiple MR-derived image features with respect to diagnostic accuracy in tumor grading and survival prediction in glioma patients., Material and Methods: T1 pre- and post-contrast, T2 and dynamic susceptibility contrast scans of 74 glioma patients with histologically confirmed grade were acquired. For each patient, a set of statistical features was obtained from the parametric maps derived from the original images, in a region-of-interest encompassing the tumor volume. A forward stepwise selection procedure was used to find the best combinations of features for grade prediction with a cross-validated logistic model and survival time prediction with a cox proportional-hazards regression., Results: Presence/absence of enhancement paired with kurtosis of the FM (first moment of the first-pass curve) was the feature combination that best predicted tumor grade (grade II vs. grade III-IV; median AUC = 0.96), with the main contribution being due to the first of the features. A lower predictive value (median AUC = 0.82) was obtained when grade IV tumors were excluded. Presence/absence of enhancement alone was the best predictor for survival time, and the regression was significant (P < 0.0001)., Conclusion: Presence/absence of enhancement, reflecting transendothelial leakage, was the feature with highest predictive value for grade and survival time in glioma patients.
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- 2011
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50. Automatic glioma characterization from dynamic susceptibility contrast imaging: brain tumor segmentation using knowledge-based fuzzy clustering.
- Author
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Emblem KE, Nedregaard B, Hald JK, Nome T, Due-Tonnessen P, and Bjornerud A
- Subjects
- Adolescent, Adult, Aged, Area Under Curve, Echo-Planar Imaging methods, Female, Humans, Image Processing, Computer-Assisted methods, Imaging, Three-Dimensional methods, Male, Middle Aged, Observer Variation, Organometallic Compounds, Reproducibility of Results, Risk Factors, Sensitivity and Specificity, Survival Analysis, Young Adult, Brain Neoplasms pathology, Contrast Media, Fuzzy Logic, Glioma pathology, Image Enhancement methods, Magnetic Resonance Imaging methods
- Abstract
Purpose: To assess whether glioma volumes from knowledge-based fuzzy c-means (FCM) clustering of multiple MR image classes can provide similar diagnostic efficacy values as manually defined tumor volumes when characterizing gliomas from dynamic susceptibility contrast (DSC) imaging., Materials and Methods: Fifty patients with newly diagnosed gliomas were imaged using DSC MR imaging at 1.5 Tesla. To compare our results with manual tumor definitions, glioma volumes were also defined independently by four neuroradiologists. Using a histogram analysis method, diagnostic efficacy values for glioma grade and expected patient survival were assessed., Results: The areas under the receiver operator characteristics curves were similar when using manual and automated tumor volumes to grade gliomas (P = 0.576-0.970). When identifying a high-risk patient group (expected survival <2 years) and a low-risk patient group (expected survival >2 years), a higher log-rank value from Kaplan-Meier survival analysis was observed when using automatic tumor volumes (14.403; P < 0.001) compared with the manual volumes (10.650-12.761; P = 0.001-0.002)., Conclusion: Our results suggest that knowledge-based FCM clustering of multiple MR image classes provides a completely automatic, user-independent approach to selecting the target region for presurgical glioma characterization., ((c) 2009 Wiley-Liss, Inc.)
- Published
- 2009
- Full Text
- View/download PDF
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