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Ferrie, J., Shipley, M., Cappuccio, F., Brunner, E., Miller, M., Kumari, M., Marmot, M., Coenen, A., Castillo, J. L., Araya, F., Bustamante, G., Montecino, L., Torres, C., Oporto, S., Gronli, J., Fiske, E., Murison, R., Bjorvatn, B., Sorensen, E., Ursin, R., Portas, C. M., Rajaraman, S., Gribok, A., Wesensten, N., Balkin, T., Reifman, J., Dursunoglu, N., Ozkurt, S., Baser, S., Delen, O., Sarikaya, S., Sadler, P., Mitchell, P., Françon, D., Decobert, M., Herve, B., Richard, A., Griebel, G., Avenet, P., Scatton, B., Fur, G. L., Eckert, D., Jordan, A., Wellman, A., Smith, S., Malhotra, A., White, D., Bruck, D., Thomas, I., Kritikos, A., Oertel, W., Stiasny-Kolster, K., Garcia-Borreguero, D., Poewe, W., Hoegl, B., Kohnen, R., Schollmayer, E., Keffel, J., Trenkwalder, C., Valle, A., Roizenblatt, S., Fregni, F., Boggio, P., Tufik, S., Ward, K., Robertson, L., Palmer, L., Eastwood, P., Hillman, D., Lee, J., Mukherjee, S., de Padova, V., Barbato, G., Ficca, G., Zilli, I., Salzarulo, P., Veldi, M., Hion, T., Vasar, V., Kull, M., Nowak, L., Davis, J., Latzer, Y., Tzischinsky, O., Crowley, S., Carskadon, M., Anca-Herschkovitsch, M., Frey, D., Ortega, J., Wiseman, C., Farley, C., Wright, K., Campbell, A., Neill, A., Spiegel, K., Leproult, R., Tasali, E., Scherberg, N., van Cauter, E., Noradina, A. T., Karim, N. A., Norlinah, I., Raymond, A. A., Sahathevan, R., Hamidon, B., Werth, E., Poryazova, R., Khatami, R., Bassetti, C., Beran, R. G., Ainley, L., Holand, G., Duncan, J., Kinney, H., Davis, B., Hood, B., Frey, S., Schmidt, C., Hofstetter, M., Peigneux, P., Cajochen, C., Hu, W.-P., Li, J.-D., Zhang, C., Boehmer, L., Siegel, J., Zhou, Q.-Y., Sagawa, Y., Kondo, H., Takemura, T., Kanayama, H., Kaneko, Y., Sato, M., Kanbayashi, T., Hishikawa, Y., Shimizu, T., Viola, A., James, L., Schlangen, L., Dijk, D.-J., Andretic, R., Kim, Y.-C., Han, K.-A., Jones, F., Greenspan, R., Sanford, L., Yang, L., Tang, X., Dieter, K., Uta, E., Sven, H., Richard, M., Oyane, N., Pallesen, S., Holsten, F., Inoue, Y., Fujita, M., Emura, N., Kuroda, K., Uchimura, N., Johnston, A., Astbury, J., Kennedy, G., Hoedlmoser, K., Schabus, M., Pecherstorfer, T., Moser, S., Gruber, G., Anderer, P., Klimesch, W., Naidoo, N., Ferber, M., Pack, A., Neu, D., Mairesse, O., Hoffmann, G., Dris, A., Lambrecht, L., Linkowski, P., Verbanck, P., Le Bon, O., Matsuura, N., Yamao, M., Adachi, N., Aritomi, R., Komada, Y., Tanaka, H., Shirakawa, S., Kondoh, H., Takemura, F., Ohnuma, S., Suzuki, M., Uemura, S., Iskra-Golec, I., Smith, L., Thanh, D.-V., Boly, M., Phillips, C., Steven, L., Luxen, A., Maquet, M., Jay, S., Dawson, D., Lamond, N., Basner, M., Fomberstein, K., Dinges, D., Ogawa, K., Nittono, H., Yamazaki, K., Hori, T., Glamann, C., Hornung, O., Hansen, M.-L, Danker-Hopfe, H., Jung, C., Kecklund, G., Anund, A., Peters, B., Åkerstedt, T., Verster, J., Roehrs, T., Mets, M., de Senerpont Domis, L., Olivier, B., Volkerts, E., Knutson, K., Lauderdale, D., Rathouz, P., Christie, M., Chen, L., Bolortuya, Y., Lee, E., Mckenna, J., Mccarley, R., Strecker, R., Tamaki, M., Matsuoka, T., Aritake, S., Suzuki, H., Kuriyama, K., Ozaki, A., Abe, Y., Enomoto, M., Tagaya, H., Mishima, K., Matsuura, M., Uchiyama, M., Lima-Pacheco, E., Davis, K., Sabourin, C., Lortie-Lussier, M., de Koninck, J., van Der Werf, Y., van Der Helm, E., Schoonheim, M., van Someren, E., Tokley, M., Ball, M., Sato, T., Ghilardi, M. F., Moisello, C., Bove, M., Busi, M., Pelosin, E., Tononi, G., Eguchi, N., Sakata, M., Urade, Y., Doe, N., Yoshihara, K., Abe, K., Manabe, Y., Iwatsuki, K., Hayashi, T., Shoji, M., Kamiya, T., Gooley, J., Brainard, G., Rajaratnam, S., Kronauer, R., Czeisler, C., Lockley, S., Phillips, A., Robinson, P., Burgess, H., Revell, V., Eastman, C., Bihari, S., Ramakrishnan, N., Camerino, D., Conway, P. M., Costa, G., Vandewalle, G., Albouy, G., Sterpenich, V., Darsaud, A., Rauchs, G., Berken, P.-Y, Balteau, E., Maquet, P., Tendero, J. A., Domenech, M. P., Isern, F. S., Martínez, C., Roure, N., Sancho, E. E., Moreno, C. R., Silva, M., Marqueze, E. C., Waage, S., Bobko, N., Chernyuk, V., Yavorskiy, Y., Saxvig, I., Sørensen, E., de Mello, M. T., Esteves, A., Teixeira, C., Bittencourt, L. R., Silva, R., Pires, M. L., Mottram, V., Middelton, B., Arendt, J., Amaral, O., Rodrigues, M., Pereira, C., Tavares, I., Baba, K., Honma, S., Honma, K.-I., Yamanaka, Y., Hashimoto, S., Tanahashi, Y., Nishide, S.-Y, Honma, K.-I, Sletten, T., Middleton, B., Lederle, K., Skene, D., Roth, T., Walsh, J., Hogben, A., Ellis, J., Archer, S., von Schantz, M., Chen, N.-H., Wang, P.-C., Chen, C.-W., Lin, Y., Shih, T.-S., Armstrong, S., Redman, J., Stephan, E., David, M., Delanaud, S., Chardon, K., Libert, J.-P., Bach, V., Telliez, F., Reid, K., Jaksa, A., Eisengart, J., Kane, P., Naylor, E., Zee, P., Viola, A. U., de Valck, E., Hofmans, J., Theuns, P., Cluydts, R., Alexander, G., Karel, M., Christina, R., Sohn, I.-K., Cho, I. H., Kim, S. J., Yu, S.-H., Kim, H., Yoo, S. Y., Koh, S.-H., Cho, S.-J., Rotenberg, L., Silva-Costa, A., Griep, R. H., Amely, T., Kennedy, G. A., Pavlis, A., Thompson, B., Pierce, R., Howard, M., Briellmann, R., Venkateswaran, S., Blunden, S., Krawczyk, E., Blake, J., Gururajan, R., Kerr, D., Matuisi, T., Iwasaki, M., Yamasita, N., Iemura, A., Ohya, T., Yanagawa, T., Misa, R., Coleman, G., Conduit, R., Duce, B., Hukins, C., Nyandaiti, Y. W., Bamaki, S., Mohammed, A., Kwajarfa, S., Veeramachaneni, S. P., Murthy, A., Wilson, A., Maul, J., Hall, G., Stick, S., Moseley, L., Gradisar, M., Kurihara, T., Yamamoto, M., Yamamoto, S., Kuranari, M., Sparks, C. B., Bartle, A., Beckert, L., Latham-Smith, F. B., Hilton, J., Whitehead, B., Gulliver, T., Salvini, A., Grahame, S., Swift, M., Laybutt, N., Sharon, D., Mack, C., Hymell, B., Perrine, B., Ideshita, K., Taira, M., Matuo, A., Furutani, M., van Dongen, H., Mott, C., Huang, J.-K., Mollicone, D. J., Mckenzie, F., Dinges, David, Barnes, M., Rochford, P., Churchward, T., O’Donoghue, F., Penzel, T., Fietze, I., Canisius, S., Bekiaris, E., Terrill, P. I., Wilson, S., Suresh, S., Cooper, D., Suzuki, T., Ouchi, K., Moriya, A., Kameyama, K., Takahashi, M., Büttner, A., Rühle, K.-H., Wang, D., Wong, K., Dungan, II, G., Grunstein, R., Davidson, P., Jones, R., Gergely, V., Mashima, K., Miyazaki, S., Tanaka, T., Okawa, M., Yamada, N., Wyner, A., Raizen, D., Galante, R., Ng, A. K., Koh, T. S., Lim, L. L., Puvanendran, K., Peiris, M., Bones, P., Roebuck, T., Ho, S., Szollosi, I., Naughton, M., Williams, G., Parsley, C., Harris, M.-A., Thornton, A., Ruehland, W., Banks, S., Arroyo, S., Carroll, K., Pilmore, J., Stewart, C., Hamilton, G., van Acker, F., Cvetkovic, D., Holland, G., Cosic, I., Tolson, J., Worsnop, C., Cresswell, P., Hart, I., Bouarab, M., Delechelle, E., Drouot, X., Acebo, C., Singh, P., Lakey, T., Schachter, L., Rand, J., Collin, H., Snyder, E., Ma, J., Svetnick, V., Deacon, S., Dana, B., Konstanze, D., Uwe, M., Ingo, F., Thomas, P., Ivar, R., Mackiewicz, M., Shockley, K., Romer, M., Zimmerman, J., Baldwin, D., Jensen, S., Churchill, G., Paigen, B., Imeri, L., Ferrari, L., Bianchi, S., Dossena, S., Garofoli, A., Mangieri, M., Tagliavini, F., Forloni, G., Chiesa, R., Pedrazzoli, M., Pereira, D., Veauny, M., Bodenmann, S., Hohoff, C., Freitag, C., Deckert, J., Rétey, J., Landolt, H.-P., Strohl, K., Price, E., Yamauchi, M., Dostal, J., Feng, P., Han, F., Havekes, R., Novati, A., Hagewoud, R., Barf, P., van Der Borght, K., van Der Zee, E., Meerlo, P., Ruby, P., Caclin, A., Boulet, S., Delpuech, C., Morlet, D., Veasey, S., Aton, S., Jha, S., Coleman, T., Seibt, J., Frank, M., Lack, L., Churches, O., Feng, S. Y. S., Cassaglia, P., Yu, V. Y. H., Walker, A. M., Kohler, M., Kennedy, D., Martin, J., van Den Heuvel, C., Lushington, K., Herron, K., Khurana, C., Sterr, A., Olivadoti, M., Toth, L., Opp, M., Dang-Vu, T., Degueldre, C., Gais, S., Dang-Vu, T. T., Desseilles, M., Philips, C., Chijavadze, E., Babilodze, M., Chkhartishvili, E., Nachkebia, N., Mchedlidze, O., Dzadzamia, S., Griffiths, R., Walker, A., Horovitz, S., Fukunaga, M., Carr, W., Picchioni, D., de Zwart, J., van Gelderen, P., Braun, A., Duyn, J., Hanlon, E. H., Faraguna, U., Vyazovskiy, V., Cirelli, C., Ocampo-Garcés, A., Ibáñez, F., López, S., Vivaldi, E., Torrealba, F., Romanowski, C. P. N., Fenzl, T., Flachskamm, C., Deussing, J., Kimura, M., Tarokh, L., van Reen, E., Dorn, H., Velluti, R., Qu, W.-M., Huang, Z.-L., Hayaishi, O., Pedemonte, M., Drexler, D., Pol-Fernández, D., Bernhardt, V., Lopez, C., Rodriguez-Servetti, Z., Romanowski, C., Polta, S., Yassouridis, A., Abe, T., Takahashi, K., Koyama, Y., Kayama, Y., Lin, J.-S., Sakai, K., Gulia, K., Karashima, A., Shimazaki, M., Katayama, N., Nakao, M., Winsky-Sommerer, R., Knapman, A., Tobler, I., Altena, E., Sanz-Arigita, E., Chang, F.-C., Lu, C.-Y., Yi, P.-L., Hsiao, Y.-Z., Lowden, A., Nilsson, J., Hillert, L., Wiholm, C., Kuster, N., Arnetz, B., Szameitat, A., Shen, S., Daurat, A., Tiberge, M., Sok, N., D’Ortho, M. P. I. A., Karasinsky, P., Kohlmeier, K., Wess, J., Leonard, C., Kristensen, M., Kalinchuk, A., Porkka-Heiskanen, T., Mccarley, R. W., Basheer, R., Aizawa, R., Sunahara, H., Abe, S.-I., Iwaki, S., Houjyou, M., Satoh, M., Suda, H., Kheirandish-Gozal, L., Gozal, D., Walker, P., Noa, A., O’Driscoll, D., Ng, M., Yang, J., Davey, M., Anderson, V., Trinder, J., Horne, R., Sands, S., Kelly, V., Sia, K., Edwards, B., Skuza, E., Davidson, M., Berger, P. H. I. L. I. P., Wilkinson, M., Sánchez-Narváez, F., Gutiérrez, R., Camacho, L., Anaya, E., García-Campos, E., Labra, A., Domínguez, G., García-Polo, L., Haro, R., Verginis, N., Nixon, G., Baumert, M., Pamula, Y., Mihai, R., Wawurszak, M., Smith, N., Yiallourou, S., Andrew Ramsden, C., Williamson, B., Blecher, G., Teng, A., Dakin, C. Y. N., Yuil, M., Harris, M., Sadasivam, S., Bennison, J., Galland, B., Dawes, P., Taylor, B., Norman, M., Edwards, N., Harrison, H., Kol, C., Sullivan, C., Valladares, E., Macey, P., Kumar, R., Woo, M., Harper, R., Alger, J., Mcnamara, D., Tang, J., Goh, A., Teoh, O. H., Chiang, W. C., Chay, O. M., Marie Salvini, A., Riben, C., Blanck, A.-S., Marklund, M., Tourneux, P., Cardot, V., Leke, A., Iqbal, S. M., (Gus) Cooper, D., Witmans, M., Rodger, K., Thevasagayam, R., El-Hakim, H., Hill, C. M., Baya, A., Bucks, R., Kirkham, F., Virues-Ortega, J., Baldeweg, T., Paul, A., Hogan, A., Goodwin, J., Silva, G., Kaemingk, K., Sherrill, D., Morgan, W., Fregosi, R., Quan, S., Evans, C., Maclean, J., Waters, K., Fitzsimmons, D., Hayward, P., Fitzgerald, D., Terrill, G., O’Connell, A., Vannan, K., Richardson, H., Poluektov, M., Levin, I., Snegodskaya, M., Kolosova, N., Geppe, N., Nixon, G. Michelle, Thompson, J., Yhan, D., Becroft, D., Clark, P., Robinson, E., Waldie, K., Wild, C., Black, P., Stone, K., Britton, W., Chaves, Claudia, Tinoco, C., Goncalves, C., Ferreira, E., Santos, H., Boloto, J., Duarte, L., Paine, S., Wright, H., Slater, A., Rosen, G., Telliez, Frédéric, Djeddi, D., Kongolo, G., Degrugilliers, L., Horton, J., Buscemi, N., Vandermeer, B., Owens, J., Klassen, T., Gordon, J., King, N., Tripp, G., Oka, Y., Suzuki, S., de Lemos, M. C., Gonzaga, F. G., Shah, M. L., Bittencourt, L., Oliveira, L. V. Franco, Elshoff, J.-P., Braun, M., Andreas, J.-O., Strauss, B., Horstmann, R., Ahrweiler, S., Goldammer, N., Wada, M., Matsumoto, N., Rahman, M. D., Xu, X.-H., Makino, Y., Hashimoto, K., Zhang, M., Sastre, J.-P., Buda, C., Anaclet, C., Ohtsu, H., Danober, L., Desos, P., Cordi, A., Roger, A., Jacquet, A., Rogez, N., Thomas, J.-Y., Krentner, M., Boutin, J., Audinot-Bouchez, V., Baumann, C., Valko, P., Uhl, M., Hersberger, M., Rupp, T., Uchiyama, N., Nakamura, N., Konishi, T., Mcgrath, P., Fujiki, N., Tokunaga, J., Iijima, S., Nishino, S., Catherine, B.-R., Lely, F., Ralf, K., Oliver, N., François, J., Francois, J., Cedric, F., Changbin, Q., Patrick, H., Homanics, G., Heussler, H., Norris, R., Pache, D., Charles, B., Mcguire, T., Shelton, J., Bonaventure, P., Kelly, L., Aluisio, L., Lovenberg, T., Atack, J., Dugovic, C., Shapiro, C., Shen, J., Trajanovic, N., Chien, J., Verma, M., Fish, V., Wheatley, J., Amis, T., Alexiou, T., Wild, J., Bjursell, A., Solin, P., Sato, S., Matsubuchi, N., Gingras, M.-A., Labrosse, M., Chevrier, É, Lageix, P., Guay, M.-C., Braun, C., Godbout, R., Fatim, E. H., Loic, D., Stephane, D., Nathalie, L., Stéphane, D., Alain, G., Wiâm, R., Koabyashi, T., Tomita, S., Ishikawa, T., Manadai, O., Arakawa, K., Siato, Y., Bassi, A., Ocampo, A., Estrada, J., Blyton, D., O’Keeffe, K., Galletly, D., Larsen, P., Amatoury, J., Bilston, L., Kairaitis, K., Stephenson, R., Chu, K., Sekiguchi, Y., Suzuki, N., Yasuda, Y., Kodama, T., Honda, Y., Hsieh, K.-C., Lai, Y.-Y., Bannai, M., Kawai, N., Amici, R., Baracchi, F., Cerri, M., Del Sindaco, E., Dentico, D., Jones, C. A., Luppi, M., Martelli, D., Perez, E., Tazaki, M., Katayose, Y., Yasuda, K., Tokuyama, K., Maddison, K., Platt, P., Kirkness, J., Ware, J. C., May, J., Rosenthal, T., Park, G., Guibert, M., Allen, R. W., Cetin, T., Roman, V., Mollicone, D., Crummy, F., Cameron, P., Swann, P., Kossman, T., Taggart, F., Kandala, N.-B., Currie, A., Peile, E., Stranges, S., Marshall, N., Peltonen, M., Stenlof, K., Hedner, J., Sjostrom, L., Anderson, C., Platten, C., Jordan, K., Horne, J., Bjorkum, A., Kluge, B., Braseth, T., Gurvin, I., Kristensen, T., Nybo, R., Rosendahl, K., Nygaard, I., Biggs, S., Dollman, J., Kennedy, J. D., Martin, A. J., Haghighi, K. S., Bakht, N., Hyde, M., Harris, E., Zerouali, Y., Hosein, A., Jemel, B., Dodd, M., Rogers, N., Andersen, M., Martins, R., Alvarenga, T., Antunes, I., Papale, L., Killgore, W. S., Axelsson, J., Lekander, M., Ingre, M., Brismar, K., Dorrian, J., Ferguson, S., Jones, C., Buxton, O., Marcelli, E., Phipps-Nelson, J. O., Teixeira, L. R., de Castro Moreno, C., Turte, S. L., Nagai, R., do Rosário Dias De Oliveira Latorre, M., Marina, F., Paterson, J., Jackson, M., Johnston, P., Papafotiou, K., Croft, R., Dawson, S., Leenaars, C., Sandberg, H., Joosten, R., Dematteis, M., Feenstra, M., Wehrle, R., Rieger, M., Widmann, A., Dietl, T., Philipp, S., Wetter, T., Drummond, S., Czisch, M., Cairns, A., Lebourgeois, M., Harsh, J., Baulk, S., Vakulin, A., Catcheside, P., Antic, N., Mcevoy, D., Orff, H., Salamat, J., Meloy, M. J., Caron, A., Kostela, J., Purnell, M., Feyer, A.-M., Herbison, P., Saaresranta, T., Aittokallio, J., Karppinen, N., Toikka, J., Polo, O., Sallinen, M., Haavisto, M.-L., Hublin, C., Kiti, M., Jussi, V., Mikko, H., Chuah, L., Chee, M., Borges, F., Fischer, F., Moreno, C., Soares, N., Fonseca, M., Smolensky, M., Sackett-Lundeen, L., Haus, E., Nagata, N., Michael, N., Siccoli, M., Rogers, A., Hwang, W.-T., Scott, L., Dean, G., Geissler, E., Ametamey, S., Treyer, V., Wyss, M., Achermann, P., Schubiger, P., Theorell-Haglöw, J., Berne, C., Janson, C., Svensson, M., Lindberg, E., Caruso, H., Avinash, D., Minkel, J., Thompson, C., Wisor, J., Gerashchenko, D., Smith, K., Kuan, L., Pathak, S., Hawrylycz, M., Jones, A., Kilduff, T., Bergamo, C., Ecker, A., William, J., Niyogi, S., Coble, M., Goel, N., Lakhtman, L., Horswill, M., Whetton, M., Chambers, B., Signal, L., van Den Berg, M., Gander, P., Polotsky, V., Savransky, V., Bevans, S., Nanayakkara, A., Li, J.-G., Smith, P., Torbenson, M., Stockx, E., Brodecky, V., Berger, P., Chung-Mei Lam, J., Rial, R., Roca, C., Garau, C., Akaarir, M., Mccoy, J., Ward, C., Connolly, N., Tartar, J., Brown, R., Carberry, J., Bradford, A., O’Halloran, K., Mcguire, M., Nacher, M., Serrano-Mollar, A., Navajas, D., Farre, R., Montserrat, J., Fenik, V., Rukhadze, I., Kubin, L., Sivertsen, B., Overland, S., Mykletun, A., Czira, M., Fornádi, K., Lindner, A., Szeifert, L., Szentkirályi, A., Mucsi, I., Molnár, M., Novák, M., Zoller, R., Chin, K., Takegami, M., Oga, T., Nakayama-Asida, Y., Wakamura, T., Mishima, M., Fukuhara, S., Shepherd, K., Keir, G., Rixon, K., Makarie-Rofail, L., Unger, G., Svanborg, E., Harder, L., Sarberg, M., Broström, A., Josefsson, A., Herrera, A., Aguilera, L., Diaz, M., Fedson, A., Hung, J., Williams, C., Love, G., Middleton, S., Vermeulen, W., Middleton, P., Steinfort, D., Goldin, J., Eritaia, J., Dionysopoulos, P., Irving, L., Ciftci, T. U., Kokturk, O., Demirtas, S., Kanbay, A., Tavil, Y., Bukan, N., Demritas, S., Olsen, S., Douglas, J., Oei, T., Williams, S., Leung, S., Starmer, G., Lee, R., Chan, A., Dungan, G., Cistulli, P., Zeng, B., Bansal, A., Patial, K., Vijayan, V. K., Sonka, K., Fialova, L., Svarcova, J., Volna, J., Jiroutek, P., Pretl, M., Bartos, A., Hasegawa, R. A., Sasanabe, R., Nomura, A., Morita, M., Hori, R., Ohkura, Y., Shiomi, T. T., Collins, A., Jerums, G., Hare, D., Panagiotopoulos, S., Weatherhead, B., Bailey, M., Neil, C., Goldsworthy, U., Hill, C., Valencia-Flores, M., Resendiz, M., Juarez, S., Castano, A., Santiago, V., Aguilar, C., Ostrosky, F., Krum, H., Kaye, D., Neves, C., Decio, M., Monteiro, M., Cintra, F., Poyares, D., Viegas, C., Silva, C., Oliveira, H., Peixoto, T., Mikami, A., Watanabe, T., Kumano-Go, T., Adachi, H., Sugita, Y., Takeda, M., Oktay, B., Firat, H., Akbal, E., Ardic, S., Paim, S., Santos, R., Barrreto, A., Whitmore, H., Imperial, J., Temple, K., Rue, A., Hoffman, L., Liljenquist, D., Kazsa, K., Pavasovic, M., Copland, J., Ho, M., Jayamaha, J., Peverill, R., Hii, S., Hensley, M., Rowland, S., Windler, S., Johansson, M., Eriksson, P., Peker, Y., Råstam, L., Lindblad, U., Grote, L., Zou, D., Radlinski, J., Eder, D., Plens, C. M., Garcia Gonzaga, F. M., Farias Sa, P., Franco Oliveira, L. V., Faria Sa, P., Yoon, I.-Y., Chung, S., Hee Lee, C., Kim, J.-W., Faludi, B., Wang, X., Li, Q., Wan, H., Li, M., Pallayova, M., Donic, V., Tomori, Z., Ioacara, S., Olech, T., Mccallum, C., Bowes, M., Bowes, J., Chia, M., Gilbert, S. S., Sajkov, D., Teichtahl, H., Stevenson, I., Cunnington, D., Kalman, J., Szaboova, E., Higami, S., Kryger, M., Higami, Y., Suzuki, C., Kitano, H., Carin, S., Olof, S., Yngve, G., Gösta, B., Carlberg, B., Stenlund, H., Franklin, K. A., Oliveira, A., Vasconcelos, L., Martinez, D., Goncalves, S. C., Gus, M., Silva, E. O. A., Fuchs, S. C., Fuchs, F. D., Li, A., Au, J., Ho, C., Sung, R., Wing, Y., Tada, H., Terada, N., Togawa, K., Nakagawa, Y., Kishida, K., Kihara, S., Hirata, A., Sonoda, M., Nishizawa, H., Nakamura, T., Shimomura, I., Funahashi, T., Andrewartha, P., Sasse, A., Becker, M., Troester, N., Olschewski, H., Lisamayerkard, L., Glos, M., Blau, A., Peter, J.-G., Chesworth, W., Wilson, G., Piper, A., Chuang, L.-P., Lin, S.-W., Wang, C.-J., Li, H.-Y., Chou, Y.-T., Fu, J.-Y., Liao, Y.-F., Tsai, Y.-H., Chan, K., Laks, L., Nishibayashi, M., Miyamoto, M., Miyamoto, T., Hirata, K., Hoever, P., De Haas, S., Chiossi, E., Van Gerven, J., Dingemanse, J., Winkler, J., Cavallaro, M., Narui, K., Kasai, T., Dohl, T., Takaya, H., Kawana, F., Ueno, K., Panjwani, U., Thakur, L., Anand, J. P., Banerjee, P. K., Leigh, M., Paduch, A., Armstrong, J., Sampson, D., Kotajima, F., Mochizuki, T., Lorr, D., Harder, H., Chesworth, M., Becker, H., Abd-Elaty, N. M., Elprince, M., Ismail, N., Elserogi, W., Yeo, A., George, K., Thomson, K., Stadler, D., Bradley, J., Paul, D., Schwartz, A., Hagander, L., Harlid, R., Hultcrantz, E., Haraldsson, P., Cho, J.-G., Narayan, J., Nagarajah, M., Perri, R., Johnson, P., Burgess, K., Chau, N., Mcevoy, R. D., Arnardottir, E. S., Thorleifsdottir, B., Olafsson, I., Gislason, T., Tsuiki, S., Fujimatsu, S., Munezawa, T., Sato, Y., Subedi, P., Ainslie, P., Topor, Z., Whitelaw, W., Chan, M., So, H., Lam, H., Ng, S., Chan, I., Lam, C., Saigusa, H., Higurashi, N., He, Z. M., Cui, X. C., Li, J., Dong, X., Lv, Y., Zhou, M., Han, X., An, P., Wang, L., Macey, P. M., Serber, S., Cross, R., Yan-Go, F., Marshall, M., Rees, D., Lee, S. H., Ho Cho, J. I., Shin, C., Lee, J. Y., Kwon, S. Y., Kim, T.-H., Vedam, H., Barnes, D., Walter, H., Karin, J., Hermann, P., Belyavskiy, E., Galitsyn, P., Arbolishvili, G., Litvin, A., Chazova, I., Mareev, V., Ramar, K., Khan, A., Gay, P., Strömberg, A., Ulander, M., Fridlund, B., Mårtensson, J., Yee, B., Desai, A., Buchanan, P., Crompton, R., Melehan, K., Wong, P., Tee, A., Ng, A., Darendeliler, M. A., Ye, L., Maislin, G., Hurley, S., Mccluskey, S., Weaver, T., Yun, C.-H., Ji, K.-H., Ahn, J. Y., Lee, H.-W., Zhang, X., Yin, K., Zhaofang, G., Chong, L., Navailles, B., Zenou, E., Cheze, L., Pignat, J.-C., Tang, T., Remmers, J., Vasilakos, K., Denotti, A., Gilholme, J., Castronovo, V., Marelli, S., Aloia, M., Fantini, M. L., Kuo, T., Manconi, M., Zucconi, M., Ferini-Strambi, L., Livia Fantini, M., Giarolli, L., Oldani, A., Lee, Y., Trenell, M., Berend, N., Wang, M., Liang, Z., Lei, F., Komada, I., Nishikawa, M., Sriram, K., Mignone, L., Antic, R., Fujiwara, K., Beaudry, M., Gauthier, L., Laforte, M., Lavigne, G., Wylie, P., Orr, W., Grover, S., Geisler, P., Engelke, E., Cossa, G., Veitch, E., Brillante, R., Mcardle, N., Murphy, M., Singh, B., Gain, K., Maguire, C., Mutch, S., Brown, S., Asciuto, T., Newsam, C., Fransson, A., Ísacsson, G., Tsou, M.-C., Hsu, S.-P., Almendros, I., Acerbi, I., Vilaseca, I., Dcruz, O., Vaughn, B., Muenzer, J., Lacassagne, L., Montemayor, T., Roch-Paoli, J., Qian, J., Petocz, P., Chan, M. R., Munro, J., Zimmerman, M., Stanchina, M., Millman, R., Cassel, W., Ploch, T., Loh, A., Koehler, U., Jerrentrup, A., Greulich, T., Doyle, G., Pascoe, T., Jorgensen, G., Baglioni, C., Lombardo, C., Espie, C., Violani, C., Edell-Gustafsson, U., Swahn, E., Ejdeback, J., Tygesen, H., Johansson, A., Neckelmann, D., Hilde Nordhus, I., Zs-Kovács, Á., Vámos, E., Zs-Molnár, M., Maisuradze, L., Gugushvili, J., Darchia, N., Gvilia, I., Lortkipanidze, N., Oniani, N., Wang-Weigand, S., Mayer, G., Roth-Schechter, B., Hsu, S.-C., Yang, C.-M., Liu, C.-Y., Ito, H., Omvik, S., Nordhus, I. H., Farber, R., Scharf, M., Harris-Collazo, R., Pereira, J., Andras, S., Ohayon, M., David, B., Morgan, K., Voorn, T., Vis, J., Kuijer, J., Fortier-Brochu, E., Beaulieu-Bonneau, S., Ivers, H., Morin, C., Beaulieu-Benneau, S., Harris, J., Bartlett, D., Paisley, L., Moncada, S., Toelle, B., Bonnet, M. H., Arand, D., Bonnet, J., Bonnet, M., Doi, Y., Edéll-Gustafsson, U., Strijers, R., Fernando, A., Arroll, B., Warman, G., Funakura, M., Shikano, S., Unemoto, Y., Fujisawa, M., Hong, S.-C., Jeong, J.-H., Shin, Y.-K., Han, J.-H., Lee, S.-P., Lee, J.-H., Mignot, E., Nakajima, T., Hayashida, K., Honda, M., Ardestani, P., Etemadifar, M., Nejadnik, H., Maghzi, A. H., Basiri, K., Ebrahimi, A., Davoodi, M., Peraita-Adrados, R., Vicario, J. L., Shin, H.-B., Marti, I., Carriero, L., Fulda, S., Beitinger, P., Pollmacher, T., Lam, J. S. P., Fong, S. Y. Y., Tang, N. L. S., Ho, C. K. W., Li, A. M. C., Wing, Y. K., Guilleminault, C., Black, J., Wells, C., Kantor, S., Janisiewicz, A., Scammell, T., Tanaka, S., Smith, A., Neufing, P., Gordon, T., Fuller, P., Gompf, H., Pedersen, N., Saper, C., Lu, J., Sasai, T., Donjacour, C., Fronczek, R., Le Cessie, S., Lammers, G. J., van Dijk, J. G., Hayashi-Ogawa, Y., Okuda, M., Lam, V. K.-H., Chen, A. L., Ho, C. K.-W., Wing, Y.-K., Lehrhaft, B., Brilliante, R., van Der Zande, W., Overeem, S., van Dijk, G., Lammers, J. G., Opazo, C. J., Jeong, D.-U., Sung, Y. H., Lyoo, I. K., Takahashi, Y., Murasaki, M., Bloch, K., Jung, H., Dahab, M. M., Campos, T. F., Mccabe, S., Maravic, K., Wiggs, L., Connelly, V., Barnes, J., Saito, Y., Ogawa, M., Murata, M., Nadig, U., Rahman, A., Aritake, K., D’Cruz, O., Suzuki, K., Kaji, Y., Takekawa, H., Nomura, T., Yasui, K., Nakashima, K., Bahammam, A., Rab, M. G., Owais, S., Alsuwat, K., Hamam, K., Zs, M., Boroojerdi, B., Giladi, N., Wood, D., Sherman, D., Chaudhuri, R., Partinen, M., Abdo, F., Bloem, B., Kremer, B., Verbeek, M., Cronlein, T., Mueller, U., Hajak, G., Zulley, J., Namba, K., Li, L., Mtsuura, M., Kaneita, Y., Ohida, T., Cappeliez, B., Moutrier, R., De, S., Dwivedi, S., Chambers, D., Gabbay, E., Watanabe, A., Valle, C., Kauati, A., Watanabe, R., Chediek, F., Botte, S., Azevedo, E., Kempf, J., Cizza, G., Torvik, S., Brancati, G., Smirne, N., Bruni, A., Goff, E., Freilich, S., Malaweera, A., Simonds, A., Mathias, C., Morrell, M., Rinsky, B., Fonarow, G., Gradinger, F. P., Boldt, C., Geyh, S., Stucki, A., Dahlberg, A., Michel, F., Savard, M.-H., Savard, J., Quesnel, C., Hirose, K., Takahara, M., Mizuno, K., Sadachi, H., Nagashima, Y., Yada, Y., Cheung, C.-F., Lau, C., Lai, W., Sin, K., Tam, C., Hellgren, J., Omenaas, E., Gíslason, T., Jögi, R., Franklin, K., Torén, K., Wang, F., Kadono, M., Shigeta, M., Nakazawa, A., Ueda, M., Fukui, M., Hasegawa, G., Yoshikawa, T., de Niet, G., Tiemens, B., Lendemeijer, B., Hutschemaekers, G., Gauthier, A.-K., Chevrette, T., Chevrier, E., Bouvier, H., Parry, B., Meliska, C., Nowakowski, S., Lopez, A., Martinez, F., Sorenson, D., Lien, M. L., Lattova, Z., Maurovich-Horvat, E., Nia, S., Pollmächer, T., Poulin, J., Chouinard, S., Stip, E., Guillem, F., Venne, D., Caouette, M., Lamont, M.-E., Lázár, A., Lázár, Z., Bíró, A., Gyõri, M., Tárnok, Z., Prekop, C., Gádoros, J., Halász, P., Bódizs, R., Okun, M., Hanusa, B., Hall, M., Wisner, K., Pereira, M., Kumar, R. A. J. E. S. H., Macey, P. A. U. L., Woo, M. A. R. Y., Serber, S. T. A. C. Y., Valladares, E. D. W. I. N., Harper, R. E. B. E. C. C. A., Harper, R. O. N. A. L. D., Puttonen, S., Härmä, M., Vahtera, J., Kivimäki, M., Lamarche, L., Hemmeter, U. M., Thum, A., Rocamora, R., Giesler, M., Haag, A., Dodel, R., Krieg, J. C., Shechter, A., L’Esperance, P., Boivin, D. B., Vu, M.-T., and Richards, H.

Published
2007
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10. Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia

Author

Geyh, S, primary, Rodríguez-Paredes, M, additional, Jäger, P, additional, Khandanpour, C, additional, Cadeddu, R-P, additional, Gutekunst, J, additional, Wilk, C M, additional, Fenk, R, additional, Zilkens, C, additional, Hermsen, D, additional, Germing, U, additional, Kobbe, G, additional, Lyko, F, additional, Haas, R, additional, and Schroeder, T, additional

Published
2015
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13. International Spinal Cord Injury Quality Of Life Basic Data Set

Author

Charlifue, S, Post, M W, Biering-Sørensen, Fin, Catz, A, Dijkers, M, Geyh, S, Horsewell, J, Noonan, V, Noreau, L, Tate, D, Sinnott, K A, Charlifue, S, Post, M W, Biering-Sørensen, Fin, Catz, A, Dijkers, M, Geyh, S, Horsewell, J, Noonan, V, Noreau, L, Tate, D, and Sinnott, K A

Abstract

Survey of expert opinion, feedback, and development of final consensus.

Published
2012

14. Measuring Quality of Life in SCI:Development of an International Data Set.

Author

Tate, DG, Biering-Sørensen, Fin, Catz, A, Charliefue, Susan, Dijkers, M, Geyh, S, Horsewell, Jane, Kirchberger, I, Norreau, L, Noonan, V, Sinnot, A, Post, Marcel, Tate, DG, Biering-Sørensen, Fin, Catz, A, Charliefue, Susan, Dijkers, M, Geyh, S, Horsewell, Jane, Kirchberger, I, Norreau, L, Noonan, V, Sinnot, A, and Post, Marcel

Published
2010

15. P-230 MDS-derived mesenchymal stromal cells are phenotypically, structurally and epigenetically altered resulting in insufficient stromal support for CD34+ HSPC

Author

Geyh, S., primary, Cadeddu, R.P., additional, Fröbel, J., additional, Hünerlitürkoglu, A.N., additional, Kündgen, A., additional, Hermsen, D., additional, Zilkens, C., additional, Fenk, R., additional, Kobbe, G., additional, Germing, U., additional, Haas, R., additional, and Schroeder, T., additional

Published
2013
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27. Quality of life after spinal cord injury: a comparison across six countries.

Author

Geyh, S, Ballert, C, Sinnott, A, Charlifue, S, Catz, A, D'Andrea Greve, J M, and Post, M W M

Subjects
*QUALITY of life, *SPINAL cord injuries, *ANALYSIS of variance, *COMPARATIVE studies, *EMPLOYMENT, *MEDICAL cooperation, *QUESTIONNAIRES, *REGRESSION analysis, *RESEARCH, *RESEARCH funding, *STATISTICS, *ETHNOLOGY research, *DATA analysis, *INTER-observer reliability, *CROSS-sectional method, *DISEASE duration, *DESCRIPTIVE statistics, *PSYCHOLOGY
Abstract

Study design:An international cross-sectional study.Objective:To examine the quality of life (QoL) of people with spinal cord injury (SCI) across six countries worldwide, controlling for socio-demographic and lesion-related sample characteristics and using a cross-culturally valid assessment.Methods:Data from 243 persons with SCI from Australia, Brazil, Canada, Israel, South Africa and the United States were analyzed. QoL was measured using five satisfaction items from the World Health Organization Quality of Life Assessment. Cross-culturally valid, Rasch-transformed scores were used for comparison.Results:Analysis of variance showed a significant difference in QoL between countries (F=3.938; df=5; P=0.002). Shorter time since injury, no paid employment and living in Brazil were significant predictors of lower QoL, explaining 13% of variance in linear regression. Using multilevel regression with country as higher-order variable, time since injury and paid employment remained significant predictors and explained 18% of variance in QoL. The intraclass correlation coefficient (0.05) indicates that 5% of the variability can be accounted for by country.Conclusion:This study showed QoL differences between countries that could not be explained by differences in demographic and lesion-related characteristics. Results point to the relevance of reintegration of people with SCI into the workforce. Further international comparative research using larger samples is recommended. [ABSTRACT FROM AUTHOR]

Published
2013
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28. Psychological resources in spinal cord injury: a systematic literature review.

Author

Peter, C, Müller, R, Cieza, A, and Geyh, S

Subjects
SPINAL cord injuries, THERAPEUTICS, CONTROL (Psychology), PSYCHOLOGICAL adaptation, ANALYSIS of covariance, ANALYSIS of variance, CINAHL database, STATISTICAL correlation, EPIDEMIOLOGY, ERIC (Information retrieval system), HEALTH status indicators, MEDICAL information storage & retrieval systems, PSYCHOLOGY information storage & retrieval systems, INTELLECT, MEDLINE, MENTAL health, MOTIVATION (Psychology), ONLINE information services, OPTIMISM, HEALTH outcome assessment, PERSONALITY, QUALITY of life, REGRESSION analysis, RESEARCH funding, SATISFACTION, SCALES (Weighing instruments), SELF-efficacy, SELF-perception, SOCIAL participation, SPIRITUALITY, STATISTICS, SYSTEMATIC reviews, DATA analysis, DISABILITIES, QUANTITATIVE research, SOCIAL support, WELL-being, HEALTH literacy, DISEASE duration, DATA analysis software, DESCRIPTIVE statistics, PSYCHOLOGY
Abstract

Study design:Systematic literature review.Objectives:The purpose of this study was to gain a systematic overview of the role of psychological resources in the adjustment to spinal cord injury (SCI).Methods:A systematic literature review was performed. The literature search was conducted in the databases Pubmed, PsycINFO, the Social Sciences Citation Index, the Education Resources Information Center, Embase and the Citation Index of Nursing and Allied Health Literature. The assessed variables, measurement instruments, results and the methodological quality of the studies were extracted, summarized and evaluated.Results:A total of 83 mainly cross-sectional studies were identified. Psychological resources were categorized into seven groups: self-efficacy (SE), self-esteem, sense of coherence (SOC), spirituality, optimism, intellect and other personality characteristics. SE and self-esteem were consistently associated with positive adjustment indicators such as high well-being and better mental health. Interrelations between psychological resources and key rehabilitation outcome variables such as participation were rarely studied. Only a few interventions, which were aimed at strengthening psychological resources were identified. Longitudinal studies suggested that SE, SOC, spirituality and purpose in life were potential determinants of adjustment outcomes in the long term.Conclusion:Research on psychological resources in SCI is broad, but fragmented. Associations of psychological resources with mental health and well-being were frequently shown, while associations with participation were rarely studied. Further development of resource-based interventions to strengthen persons with SCI is indicated. This review can serve as guide for clinical practice and can add to the design of future SCI research. [ABSTRACT FROM AUTHOR]

Published
2012
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29. The role of social support and social skills in people with spinal cord injury-a systematic review of the literature.

Author

Müller, R, Peter, C, Cieza, A, and Geyh, S

Subjects
THERAPEUTICS, PSYCHOLOGICAL adaptation, CINAHL database, COMMUNICATIVE competence, ERIC (Information retrieval system), MEDICAL information storage & retrieval systems, PSYCHOLOGY information storage & retrieval systems, MEDLINE, MENTAL health, ONLINE information services, PROBLEM solving, QUALITY of life, RESEARCH funding, SATISFACTION, SOCIAL skills, SPINAL cord injuries, SYSTEMATIC reviews, SOCIAL support
Abstract

Study design:Systematic literature review.Objectives:To examine the current knowledge of how social support and social skills are associated with aspects of health, functioning and quality of life of persons living with spinal cord injury (SCI).Methods:A systematic literature review was conducted. The literature search was carried out in Pubmed, PsycINFO, ERIC (Educational Resources Information Centre), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase and SSCI (Social Sciences Citation Index). Publications were identified according to predefined eligibility criteria; study qualities were evaluated, study results extracted and a narrative synthesis was compiled.Results:In all, 58 publications about social support and SCI were included. Social support was positively related to physical and mental health, pain, coping, adjustment and life satisfaction. Social skills were assessed in 11 studies: social problem solving (n=7), assertiveness (n=3), verbal communication (n=1) and self-monitoring (n=1) were examined. Effective problem-solving skills were related to better mental health outcomes, health prevention behavior and less secondary conditions. Assertiveness was related to higher depression in rehabilitation setting. Interventions targeted at social support or social skills were scarcely studied. Only one study examined the relationship between social skills and social support in SCI.Conclusion:Social support is associated with better health and functioning in individuals with SCI. However, the full range of social skills has not yet been studied in people with SCI. Furthermore, the role of social skills in relation to social support, health and functioning remains unclear. Better understanding of social skills and social support in SCI could facilitate the development of targeted and effective interventions to enhance functioning of people with SCI. [ABSTRACT FROM AUTHOR]

Published
2012
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30. The utlity of the ICF to identify and evaluate problems and needs in participation in spinal cord injury rehabilitation.

Author

Rauch A, Bickenbach J, Reinhardt JD, Geyh S, and Stucki G

Abstract

The ultimate goal of spinal cord injury (SCI) rehabilitation is often described as reintegration into the community, which includes a person's full inclusion and participation in the physical and social environment. The International Classification of Functioning and Disability (ICF) is the international framework that explains the nature and role of 'participation.' Case studies have been used to illustrate the utility of the ICF to identify and evaluate problems and needs in participation during inpatient rehabilitation programs. It could be shown that the ICF allows for systematic data collection and, in particular, allows clinicians to more fully describe the extent to which a spinal cord-injured person's levels of activity and participation may be affected. In particular, differences between levels of capacity and performance could be shown to be affected by the impact of environmental factors. [ABSTRACT FROM AUTHOR]

Published
2010
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31. ICF linking rules: an update based on lessons learned.

Author

Cieza A, Geyh S, Chatterji S, Kostanjsek N, Üstün B, and Stucki G

Abstract

Objective: Outcome research seeks to understand the end results of health services. Researchers use a wide variety of outcome measures including technical, clinical and patient-oriented measures. The International Classification of Functioning, Disability and Health (ICF) as a common reference framework for functioning may contribute to improved outcome research. The objective of this paper is to provide an updated version of the linking rules published in 2002 and illustrate how these rules are applied to link technical and clinical measures, health-status measures and interventions to the ICF.Results: Three specific linking rules have been established to link health-status measures to the ICF and one specific linking rule has been created to link technical and clinical measures and interventions. A total of 8 linking rules have been established for use with all different outcome measures and with interventions.Conclusion: The newly updated linking rules will allow researchers systematically to link and compare meaningful concepts contained in them. This should prove extremely useful in selecting the most appropriate outcome measures among a number of candidate measures for the applied interventions. Further possible applications are the operationalization of concrete ICF categories using specific measures or the creation of ICF category-based item bankings. [ABSTRACT FROM AUTHOR]

Published
2005

32. Personal factors in systemic sclerosis and their coverage by patient-reported outcome measures: A multicentre European qualitative study and literature review

Author

Mattsson M, Boström C, Mihai C, Stöcker J, Geyh S, Stummvoll G, Gard G, Möller B, Hesselstrand R, Sandqvist G, Draghicescu O, Am, Gherghe, Voicu M, Distler O, Js, Smolen, Ta, Stamm, University of Zurich, and Mattsson, M

Subjects
Europe, Patient Outcome Assessment, 2742 Rehabilitation, Disability Evaluation, Scleroderma, Systemic, 10051 Rheumatology Clinic and Institute of Physical Medicine, Humans, Multicenter Studies as Topic, 610 Medicine & health, 3612 Physical Therapy, Sports Therapy and Rehabilitation, Qualitative Research
Abstract

Systemic sclerosis (SSc) is an autoimmune disease where thickening of the skin can lead to reduced body function and limitations in activities. Severe forms can also affect and seriously damage inner organs. Patient-centred rehabilitation emphasises considerations of patients' background, experience and behavior which highlights the need to know if patient-reported outcome measures (PROMs) include such personal factors.To identify and describe personal factors in the experiences of functioning and health of persons with SSc and to examine if and to what extent PROMs in SSc research cover these factors.Data from a qualitative study with focus group interviews were analysed. PROMs in SSc research were identified in a literature review between 2008-2013.Participants were recruited from outpatient clinics at rheumatology department.Sixty-three patients with SSc from four European countries participated.Data from interviews were analysed using a structure of personal factors developed by Geyh et al. Identified PROMs were analysed and linked to main concepts, related to the personal factors, found in the interview data.Nineteen main concepts were related to the area "patterns of experience and behaviour" in the personal factor structure, 16 to "thoughts and beliefs", nine to "feelings", one to "motives" and one to "personal history and biography", respectively. Among the 35 PROMs identified, 15 did not cover any of the identified concepts. Concepts within the area "feelings" were mostly covered by the PROMs. Five of the PROMs covered "patterns of experience and behaviour", while "motives" and "personal history and biography" were not covered at all. Four of the identified PROMs covered concepts within the areas "feelings", "thoughts and beliefs" and "patterns of experience and behaviour" in the same instrument. The Illness Cognition Questionnaire and Illness Behaviour Questionnaire were such PROMs.Patterns of experience and behaviour had the highest number of concepts related to personal factors, but few of the PROMs in SSc research covered these factors. Only a few PROMs covered several personal factors areas in the same instrument.The results would be of value when developing core sets for outcome measurements in SSc.

33. Cross-cultural validity of four quality of life scales in persons with spinal cord injury

Author

Geyh Szilvia, Fellinghauer Bernd AG, Kirchberger Inge, and Post Marcel WM

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Quality of life (QoL) in persons with spinal cord injury (SCI) has been found to differ across countries. However, comparability of measurement results between countries depends on the cross-cultural validity of the applied instruments. The study examined the metric quality and cross-cultural validity of the Satisfaction with Life Scale (SWLS), the Life Satisfaction Questionnaire (LISAT-9), the Personal Well-Being Index (PWI) and the 5-item World Health Organization Quality of Life Assessment (WHOQoL-5) across six countries in a sample of persons with spinal cord injury (SCI). Methods A cross-sectional multi-centre study was conducted and the data of 243 out-patients with SCI from study centers in Australia, Brazil, Canada, Israel, South Africa, and the United States were analyzed using Rasch-based methods. Results The analyses showed high reliability for all 4 instruments (person reliability index .78-.92). Unidimensionality of measurement was supported for the WHOQoL-5 (Chi2 = 16.43, df = 10, p = .088), partially supported for the PWI (Chi2 = 15.62, df = 16, p = .480), but rejected for the LISAT-9 (Chi2 = 50.60, df = 18, p = .000) and the SWLS (Chi2 = 78.54, df = 10, p = .000) based on overall and item-wise Chi2 tests, principal components analyses and independent t-tests. The response scales showed the expected ordering for the WHOQoL-5 and the PWI, but not for the other two instruments. Using differential item functioning (DIF) analyses potential cross-country bias was found in two items of the SWLS and the WHOQoL-5, three items of the LISAT-9 and four items of the PWI. However, applying Rasch-based statistical methods, especially subtest analyses, it was possible to identify optimal strategies to enhance the metric properties and the cross-country equivalence of the instruments post-hoc. Following the post-hoc procedures the WHOQOL-5 and the PWI worked in a consistent and expected way in all countries. Conclusions QoL assessment using the summary scores of the WHOQOL-5 and the PWI appeared cross-culturally valid in persons with SCI. In contrast, summary scores of the LISAT-9 and the SWLS have to be interpreted with caution. The findings of the current study can be especially helpful to select instruments for international research projects in SCI.

Published
2010
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34. Identification of candidate categories of the International Classification of Functioning Disability and Health (ICF) for a Generic ICF Core Set based on regression modelling

Author

Üstün Bedirhan T, Kostanjsek Nenad, Chatterji Somnath, Geyh Szilvia, Cieza Alarcos, and Stucki Gerold

Subjects
Medicine (General), R5-920
Abstract

Abstract Background The International Classification of Functioning, Disability and Health (ICF) is the framework developed by WHO to describe functioning and disability at both the individual and population levels. While condition-specific ICF Core Sets are useful, a Generic ICF Core Set is needed to describe and compare problems in functioning across health conditions. Methods The aims of the multi-centre, cross-sectional study presented here were: a) to propose a method to select ICF categories when a large amount of ICF-based data have to be handled, and b) to identify candidate ICF categories for a Generic ICF Core Set by examining their explanatory power in relation to item one of the SF-36. The data were collected from 1039 patients using the ICF checklist, the SF-36 and a Comorbidity Questionnaire. ICF categories to be entered in an initial regression model were selected following systematic steps in accordance with the ICF structure. Based on an initial regression model, additional models were designed by systematically substituting the ICF categories included in it with ICF categories with which they were highly correlated. Results Fourteen different regression models were performed. The variance the performed models account for ranged from 22.27% to 24.0%. The ICF category that explained the highest amount of variance in all the models was sensation of pain. In total, thirteen candidate ICF categories for a Generic ICF Core Set were proposed. Conclusion The selection strategy based on the ICF structure and the examination of the best possible alternative models does not provide a final answer about which ICF categories must be considered, but leads to a selection of suitable candidates which needs further consideration and comparison with the results of other selection strategies in developing a Generic ICF Core Set.

Published
2006
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35. Self-efficacy and self-esteem as predictors of participation in spinal cord injury--an ICF-based study

Author

D Stirnimann, F Michel, Claudio Peter, Szilvia Geyh, Peter Lude, E Nick, S Ehrat, University of Zurich, and Geyh, S

Subjects
Adult, Male, medicine.medical_specialty, Cross-sectional study, media_common.quotation_subject, Self-concept, 610 Medicine & health, Physical medicine and rehabilitation, International Classification of Diseases, Predictive Value of Tests, Surveys and Questionnaires, Humans, Medicine, Patient participation, Spinal cord injury, Spinal Cord Injuries, Aged, media_common, Self-efficacy, business.industry, Self-esteem, social sciences, General Medicine, Middle Aged, Spinal cord, medicine.disease, Self Concept, Self Efficacy, humanities, Cross-Sectional Studies, medicine.anatomical_structure, 2728 Neurology (clinical), Neurology, Predictive value of tests, 2808 Neurology, Physical therapy, Female, 10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center, Self Report, Neurology (clinical), Patient Participation, business, human activities
Abstract

A multi-centre cross-sectional study.To examine the relationship of self-efficacy and self-esteem with participation of persons with spinal cord injury (SCI) from a comprehensive bio-psycho-social perspective, based on the conceptual framework of the International Classification of Functioning, Disability and Health (ICF).Community-dwelling participants,5 years post discharge, recruited through three SCI rehabilitation centers in Switzerland.Data were collected by means of standardized self-report questionnaires sent to the eligible participants by postal mail. The questionnaires covered the different components of the ICF's bio-psycho-social model, namely health conditions, body functions, participation, environmental and personal factors. Bivariate correlations and multivariate linear regression analyses with participation as the dependent variable have been conducted.In all, 102 persons with SCI answered the survey, response rate 25.9%. Self-esteem (r=0.61) and self-efficacy (r=0.54) correlated highly with participation and were the strongest correlates of participation. They were stronger correlates of participation than symptoms of anxiety, depressive symptoms, pain, health conditions, social support, coping styles or sense of coherence. Participation seemed to be independent of gender, age, level or completeness of injury. Self-efficacy and self-esteem explained together with time since discharge and years of education 48% of the variance in participation adjusting for health condition, depressive symptoms, pain interference and social support.Considering self-efficacy and self-esteem within the comprehensive framework of the ICF can contribute to a better understanding of functioning, disability and health in SCI, which in turn may facilitate the development of interventions to support the persons' adjustment and reintegration.

Published
2012
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36. Biopsychosocial outcomes in individuals with and without spinal cord injury: a Swiss comparative study

Author

Rachel Müller, S Ehrat, F Michel, E Nick, Szilvia Geyh, D Stirnimann, University of Zurich, and Geyh, S

Subjects
Biopsychosocial model, Adult, Male, medicine.medical_specialty, Injury control, Accident prevention, Poison control, Pain, 610 Medicine & health, Physical medicine and rehabilitation, Surveys and Questionnaires, Injury prevention, medicine, Humans, Spinal cord injury, Spinal Cord Injuries, Aged, business.industry, Depression, Social Support, General Medicine, Middle Aged, medicine.disease, Self Concept, Self Efficacy, Treatment Outcome, 2728 Neurology (clinical), Neurology, 2808 Neurology, Physical therapy, Female, 10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center, Neurology (clinical), business, Switzerland
Abstract

Multicentre controlled study.To investigate if individuals with and without spinal cord injury (SCI) differ in biopsychosocial variables according to the International Classification of Functioning, Disability and Health (ICF).Participants were recruited through three major SCI rehabilitation centres in Switzerland.A convenience sample of people with SCI (N=102) and a matched non-SCI sample (N=73) were compared according to secondary conditions, pain, depressive symptoms, participation, social support, self-efficacy, self-esteem, coping and sense of coherence. Difference tests and multivariate logistic regression analyses to predict the likelihood of group membership were calculated.People with SCI reported more health conditions, higher levels of anxiety and depressive symptoms, worse pain and pain interference, lower level of participation and social support, lower self-efficacy, self-esteem and task- and emotion-oriented coping. The two samples did not differ in satisfaction with social support, in use of avoidance-oriented coping and in sense of coherence. Health conditions, pain interference, participation and age were found to be significant predictors of the likelihood of group membership. In the logistic regression models, the number of health conditions, limitations due to health conditions, pain interference, participation, task-oriented coping and age are significant predictors of group membership, accounting for 55% of variation.Health conditions, pain interference and participation seemed to be the areas of biopsychosocial functioning that are substantially influenced by SCI. Potential buffering resources seem to be diminished in individuals with SCI. In rehabilitation practice, prevention of secondary conditions, treatment of pain, enhancement of participation and strengthening resources should be addressed.

Published
2012

37. Antineoplastic therapy affects the in vitro phenotype and functionality of healthy human bone marrow-derived mesenchymal stromal cells.

Author

Scherer B, Bogun L, Koch A, Jäger P, Maus U, Schmitt L, Krings KS, Wesselborg S, Haas R, Schroeder T, and Geyh S

Abstract

While antineoplastic therapies aim to specifically target cancer cells, they may also exert adverse effects on healthy tissues, like healthy hematopoietic stem and progenitor cells (HSPC), leading to hematotoxicity as a common side effect. Mesenchymal stromal cells (MSC) are a major component of the bone marrow (BM) microenvironment, regulating normal hematopoiesis, while their susceptibility to anticancer therapies and contribution to therapy-related hematotoxicity remains largely unexplored. To address this, we investigated the effects of etoposide, temozolomide, 5-azacitidine, and venetoclax on healthy BM-derived MSC functionality. Doses below therapeutic effects of etoposide (0.1-0.25 µM) inhibited cellular growth and induced cellular senescence in healthy MSC, accompanied by an increased mRNA expression of CDKN1A, decreased trilineage differentiation capacity, and insufficient hematopoietic support. Pharmacological doses of 5-azacitidine (2.5 µM) shifted MSC differentiation capacity by inhibiting osteogenic capacity but enhancing the chondrogenic lineage, as demonstrated by histochemical staining and on mRNA level. At the highest clinically relevant dose, neither venetoclax (40 nM) nor temozolomide (100 µM) exerted any effects on MSC but clearly inhibited cellular growth of cancer cell lines and primary healthy HSPC, pointing to damage to hematopoietic cells as a major driver of hematotoxicity of these two compounds. Our findings show that besides HSPC, also MSC are sensitive to certain antineoplastic agents, resulting in molecular and functional alterations that may contribute to therapy-related myelosuppression. Understanding these interactions could be helpful for the development of strategies to preserve BM MSC functionality during different kinds of anticancer therapies., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (© 2024. The Author(s).)

Published
2024
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38. Overlapping Stromal Alterations in Myeloid and Lymphoid Neoplasms.

Author

Bogun L, Koch A, Scherer B, Germing U, Fenk R, Maus U, Bormann F, Köhrer K, Petzsch P, Wachtmeister T, Kobbe G, Dietrich S, Haas R, Schroeder T, Geyh S, and Jäger P

Abstract

Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms. We aimed to identify overlapping mechanisms in MSCs derived from myeloid and lymphoid neoplasms contributing to disease progression and suppression of HSPCs to develop interventions that target these mechanisms. MSCs derived from healthy donors ( n = 44) and patients diagnosed with myeloproliferative neoplasia ( n = 11), myelodysplastic syndromes ( n = 16), or acute myeloid leukemia ( n = 25) and B-Non-Hodgkin lymphoma ( n = 9) with BM infiltration and acute lymphoblastic leukemia ( n = 9) were analyzed for their functionality and by RNA sequencing. A reduced growth and differentiation capacity of MSCs was found in all entities. RNA sequencing distinguished both groups but clearly showed overlapping differentially expressed genes, including major players in the BMP/TGF and WNT-signaling pathway which are crucial for growth, osteogenesis, and hematopoiesis. Functional alterations in healthy MSCs were inducible by exposure to supernatants from malignant cells, implicating the involvement of these factors in disease progression. Overall, we were able to identify overlapping factors that pose potential future therapeutic targets.

Published
2024
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39. Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma.

Author

Bogun L, Koch A, Scherer B, Fenk R, Maus U, Bormann F, Köhrer K, Petzsch P, Wachtmeister T, Zukovs R, Dietrich S, Haas R, Schroeder T, Jäger P, and Geyh S

Subjects
Humans, Cell Differentiation, Male, Female, Aged, Monoclonal Gammopathy of Undetermined Significance genetics, Monoclonal Gammopathy of Undetermined Significance pathology, Multiple Myeloma genetics, Multiple Myeloma pathology, Mesenchymal Stem Cells metabolism, Smoldering Multiple Myeloma
Abstract

Abstract: The hallmark of multiple myeloma (MM) is a clonal plasma cell infiltration in the bone marrow accompanied by myelosuppression and osteolysis. Premalignant stages such as monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic stages such as smoldering myeloma (SMM) can progress to MM. Mesenchymal stromal cells (MSCs) are an integral component of the bone marrow microenvironment and play an important role in osteoblast differentiation and hematopoietic support. Although stromal alterations have been reported in MM contributing to hematopoietic insufficiency and osteolysis, it is not clear whether alterations in MSC already occur in MGUS or SMM. In this study, we analyzed MSCs from MGUS, SMM, and MM regarding their properties and functionality and performed messenger RNA sequencing to find underlying molecular signatures in different disease stages. A high number of senescent cells and a reduced osteogenic differentiation capacity and hematopoietic support were already present in MGUS MSC. As shown by RNA sequencing, there was a broad spectrum of differentially expressed genes including genes of the BMP/TGF-signaling pathway, detected already in MGUS and that clearly increases in patients with SMM and MM. Our data may help to block these signaling pathways in the future to hinder progression to MM., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Published
2024
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40. Allogeneic hematopoietic stem cell transplantation and pre-transplant strategies in patients with NPM1-mutated acute myeloid leukemia: a single center experience.

Author

Jäger P, Rautenberg C, Kaivers J, Kasprzak A, Geyh S, Baermann BN, Haas R, Germing U, Schroeder T, and Kobbe G

Subjects
Humans, Nuclear Proteins genetics, Nucleophosmin, Neoplasm, Residual genetics, Retrospective Studies, Mutation, Prognosis, Recurrence, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute drug therapy
Abstract

Patients with acute myeloid leukemia (AML) and nucleophosmin 1 gene mutations (NPM1 mut ) show a favorable prognosis with chemotherapy (CT) in the absence of negative prognostic genetic abnormalities. Between 2008 and 2021 64 patients with NPM1 mut AML received alloHSCT because of additional adverse prognostic factors (1st line), inadequate response to or relapse during or after CT (2nd line). To expand the evidence in alloTX in NPM1 mut AML, clinical and molecular data were retrospectively analyzed with respect to pre-transplant strategies and outcome. Patients with minimal residual disease negative (MRD-) CR at transplant had better 2-y-PFS and 2-y-OS (77% and 88%) than patients with minimal residual disease positive (MRD+) CR (41% and 71%) or patients with active disease (AD) at transplant (20% and 52%). The 2nd line patients with relapse after completing CT responded well to high dose cytarabine based salvage chemotherapy (salvage CT) in contrast to patients relapsing while still on CT (90% vs 20%, P = 0.0170). 2-y-PFS and 2-y-OS was 86% in patients who achieved a 2nd MRD- CR pre alloHSCT. Outcome in NPM1 mut AML depends on disease burden at alloHSCT. Time and type of relapse in relation to CT are predictive for response to salvage CT., (© 2023. The Author(s).)

Published
2023
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41. The mycotoxin viriditoxin induces leukemia- and lymphoma-specific apoptosis by targeting mitochondrial metabolism.

Author

Stuhldreier F, Schmitt L, Lenz T, Hinxlage I, Zimmermann M, Wollnitzke P, Schliehe-Diecks J, Liu Y, Jäger P, Geyh S, Teusch N, Peter C, Bhatia S, Haas R, Levkau B, Reichert AS, Stühler K, Proksch P, Stork B, and Wesselborg S

Subjects
Humans, Leukocytes, Mononuclear metabolism, Apoptosis, Mitochondria metabolism, Reactive Oxygen Species metabolism, Membrane Potential, Mitochondrial, Mycotoxins metabolism, Leukemia drug therapy, Leukemia metabolism, Lymphoma drug therapy, Lymphoma metabolism
Abstract

Inhibition of the mitochondrial metabolism offers a promising therapeutic approach for the treatment of cancer. Here, we identify the mycotoxin viriditoxin (VDT), derived from the endophytic fungus Cladosporium cladosporioides, as an interesting candidate for leukemia and lymphoma treatment. VDT displayed a high cytotoxic potential and rapid kinetics of caspase activation in Jurkat leukemia and Ramos lymphoma cells in contrast to solid tumor cells that were affected to a much lesser extent. Most remarkably, human hematopoietic stem and progenitor cells and peripheral blood mononuclear cells derived from healthy donors were profoundly resilient to VDT-induced cytotoxicity. Likewise, the colony-forming capacity was affected only at very high concentrations, which provides a therapeutic window for cancer treatment. Intriguingly, VDT could directly activate the mitochondrial apoptosis pathway in leukemia cells in the presence of antiapoptotic Bcl-2 proteins. The mitochondrial toxicity of VDT was further confirmed by inhibition of mitochondrial respiration, breakdown of the mitochondrial membrane potential (ΔΨm), the release of mitochondrial cytochrome c, generation of reactive oxygen species (ROS), processing of the dynamin-like GTPase OPA1 and subsequent fission of mitochondria. Thus, VDT-mediated targeting of mitochondrial oxidative phosphorylation (OXPHOS) might represent a promising therapeutic approach for the treatment of leukemia and lymphoma without affecting hematopoietic stem and progenitor cells., (© 2022. The Author(s).)

Published
2022
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42. Bone marrow stroma cells promote induction of a chemoresistant and prognostic unfavorable S100A8/A9high AML cell subset.

Author

Böttcher M, Panagiotidis K, Bruns H, Stumpf M, Völkl S, Geyh S, Dietel B, Schroeder T, Mackensen A, and Mougiakakos D

Subjects
Humans, Bone Marrow metabolism, Calgranulin A genetics, Calgranulin A metabolism, Prognosis, Interleukin-6, Leukemia, Myeloid, Acute metabolism
Abstract

The bone marrow (BM) stroma represents a protective niche for acute myeloid leukemia (AML) cells. However, the complex underlying mechanisms remain to be fully elucidated. We found 2 small, intracellular, calcium-sensing molecules, S100A8 and S100A9, among the top genes being upregulated in primary AML blasts upon stromal contact. As members of the S100 protein family, they can modulate such cellular processes as proliferation, migration, and differentiation. Dysregulation of S100 proteins is described as a predictor of poor survival in different human cancers, including increased S100A8 expression in de novo AML. Thus, we wanted to decipher the underlying pathways of stroma-mediated S100A8/A9 induction, as well as its functional consequences. Upregulation of S100A8/A9 after stromal cross talk was validated in AML cell lines, was contact independent and reversible and resulted in accumulation of S100A8/A9high cells. Accordingly, frequency of S100A8/A9high AML blasts was higher in the patients' BM than in peripheral blood. The S100A8/A9high AML cell population displayed enhanced utilization of free fatty acids, features of a more mature myeloid phenotype, and increased resilience toward chemotherapeutics and BCL2 inhibition. We identified stromal cell-derived interleukin-6 (IL-6) as the trigger for a Jak/STAT3 signaling-mediated S100A8/A9 induction. Interfering with fatty acid uptake and the IL-6-Jak/STAT3 pathway antagonized formation of S100A8/A9high cells and therapeutic resistance, which could have therapeutic implications as a strategy to interfere with the AML-niche dynamics., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Published
2022
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43. Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells.

Author

Jäger P, Geyh S, Twarock S, Cadeddu RP, Rabes P, Koch A, Maus U, Hesper T, Zilkens C, Rautenberg C, Bormann F, Köhrer K, Petzsch P, Wieczorek D, Betz B, Surowy H, Hildebrandt B, Germing U, Kobbe G, Haas R, and Schroeder T

Subjects
Antigens, CD34 metabolism, Bone Marrow metabolism, Hematopoiesis, Humans, Hematopoietic Stem Cells metabolism, Leukemia, Myeloid, Acute genetics
Abstract

Acute myeloid leukemia (AML) is characterized by an expansion of leukemic cells and a simultaneous reduction of normal hematopoietic precursors in the bone marrow (BM) resulting in hematopoietic insufficiency, but the underlying mechanisms are poorly understood in humans. Assuming that leukemic cells functionally inhibit healthy CD34+ hematopoietic stem and progenitor cells (HSPC) via humoral factors, we exposed healthy BM-derived CD34+ HSPC to cell-free supernatants derived from AML cell lines as well as from 24 newly diagnosed AML patients. Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation, and differentiation of healthy CD34+ HSPC. RNA sequencing of healthy CD34+ HSPC after exposure to leukemic conditions revealed a specific signature of genes related to proliferation, cell-cycle regulation, and differentiation, thereby reflecting their functional inhibition on a molecular level. Experiments with paired patient samples showed that these inhibitory effects are markedly related to the immunomagnetically enriched CD34+ leukemic cell population. Using PCR, ELISA, and RNA sequencing, we detected overexpression of TGFβ1 in leukemic cells on the transcriptional and protein level and, correspondingly, a molecular signature related to TGFβ1 signaling in healthy CD34+ HSPC. This inhibitory effect of TGFβ1 on healthy hematopoiesis was functionally corrobated and could be pharmacologically reverted by SD208, an inhibitor of TGFβ receptor 1 signaling. Overall, these data indicate that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through TGFβ1, suggesting that blockage of this pathway may improve hematopoiesis in AML., (© 2021 The Authors. STEM CELLS published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Published
2021
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44. Germline variants drive myelodysplastic syndrome in young adults.

Author

Feurstein S, Churpek JE, Walsh T, Keel S, Hakkarainen M, Schroeder T, Germing U, Geyh S, Heuser M, Thol F, Pohlkamp C, Haferlach T, Gao J, Owen C, Goehring G, Schlegelberger B, Verma D, Krause DS, Gao G, Cronin T, Gulsuner S, Lee M, Pritchard CC, Subramanian HP, Del Gaudio D, Li Z, Das S, Kilpivaara O, Wartiovaara-Kautto U, Wang ES, Griffiths EA, Döhner K, Döhner H, King MC, and Godley LA

Subjects
Adolescent, Adult, Anemia, Aplastic pathology, Female, Humans, Male, Myelodysplastic Syndromes pathology, Prognosis, Young Adult, Anemia, Aplastic genetics, Biomarkers analysis, Genetic Predisposition to Disease, Germ-Line Mutation, Myelodysplastic Syndromes genetics
Published
2021
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45. Influence of somatic mutations and pretransplant strategies in patients allografted for myelodysplastic syndrome or secondary acute myeloid leukemia.

Author

Rautenberg C, Germing U, Stepanow S, Lauseker M, Köhrer K, Jäger PS, Geyh S, Fan M, Haas R, Kobbe G, and Schroeder T

Subjects
Adult, Allografts, Female, Humans, Male, Middle Aged, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Mutation, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes therapy, Neoplasm Proteins genetics, Neoplasms, Second Primary genetics, Neoplasms, Second Primary therapy
Published
2021
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46. Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS.

Author

Rautenberg C, Germing U, Pechtel S, Lamers M, Fischermanns C, Jäger P, Geyh S, Haas R, Kobbe G, and Schroeder T

Subjects
Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Humans, Male, Middle Aged, Survival Rate, Gene Expression Regulation, Myelodysplastic Syndromes blood, Myelodysplastic Syndromes mortality, RNA, Messenger blood, WT1 Proteins blood
Abstract

Few reports suggested a prognostic impact of Wilms'Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Overall, 54 patients (57%) showed WT1-mRNA overexpression, while 40 patients (43%) had normal WT1-mRNA expression. This enabled discrimination between MDS and both healthy controls and non-MDS cytopenias. Furthermore, WT1-mRNA expression correlated with WHO 2016 subcategories and IPSS-R as indicated by mean WT1-mRNA expression and frequency of WT1-mRNA overexpressing patients within respective subgroups. Regarding the entire group, PB WT1-mRNA expression was associated with prognosis, as those patients showing WT1-mRNA overexpression had higher risk for disease progression and AML transformation and accordingly shorter progression-free, leukemia-free and overall survival in univariate analysis. In multivariate analysis, prognostic impact of PB WT1-mRNA expression status was independent of IPSS-R and enabled more precise prediction of PFS, but not OS, within IPSS-R very low/low and intermediate risk groups. Overall, measuring PB WT1-mRNA appears valuable to support diagnostics and refine prognostication provided by the IPSS-R.

Published
2019
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47. Representing and organizing information to describe the lived experience of health from a personal factors perspective in the light of the International Classification of Functioning, Disability and Health (ICF): a discussion paper.

Author

Geyh S, Schwegler U, Peter C, and Müller R

Subjects
Disability Evaluation, Humans, International Classification of Functioning, Disability and Health, Life Change Events, Disabled Persons psychology, Spinal Cord Injuries
Abstract

Purpose: To discuss the representation and organization of information describing persons' lived experience of health from a personal factors perspective in the light of the International Classification of Functioning, Disability and Health, using spinal cord injury as a case in point for disability., Methods: The scientific literature was reviewed, discussion rounds conducted, and qualitative secondary analyses of data carried out using an iterative inductive-deductive approach., Results: Conceptual considerations are explicated that distinguish the personal factors perspective from other components of the International Classification of Functioning, Disability and Health. A representation structure is developed that organizes health-related concepts describing the internal context of functioning. Concepts are organized as individual facts, subjective experiences, and recurrent patterns of experience and behavior specifying 7 areas and 211 concept groups., Conclusions: The article calls for further scientific debate on the perspective of personal factors in the light of the International Classification of Functioning, Disability and Health. A structure that organizes concepts in relation to a personal factors perspective can enhance the comprehensiveness, transparency and standardization of health information, and contribute to the empowerment of persons with disabilities. Implications for rehabilitation The present study collected data from scientific literature reviews, discussion rounds and qualitative secondary analyses in order to develop a representation and organization of information describing persons' lived experience of health from a personal factors perspective in the light of the International Classification of Functioning, Disability and Health. The following representation structure for health-related information from a personal factors perspective was developed: (i) Individuals facts (i.e., socio-demographical factors, position in the immediate social and physical context, personal history and biography), (ii) subjective experience (i.e., feelings, thoughts and beliefs, motives), and (iii) recurrent patterns of experience (i.e., feelings, thoughts and beliefs) and behavior. With this study, we aim to stimulate further scientific discussion about the personal factors component in the International Classification of Functioning, Disability and Health, including its application and subsequent validation for potential implementation into clinical practice.

Published
2019
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48. Secretome analysis of human bone marrow derived mesenchymal stromal cells.

Author

Baberg F, Geyh S, Waldera-Lupa D, Stefanski A, Zilkens C, Haas R, Schroeder T, and Stühler K

Subjects
Adult, Aged, Aged, 80 and over, Bone Marrow, Humans, Middle Aged, Proteome, Mesenchymal Stem Cells metabolism
Abstract

As an essential cellular component of the bone marrow (BM) microenvironment mesenchymal stromal cells (MSC) play a pivotal role for the physiological regulation of hematopoiesis, in particular through the secretion of cytokines and chemokines. Mass spectrometry (MS) facilitates the identification and quantification of a large amount of secreted proteins (secretome), but can be hampered by the false-positive identification of contaminating proteins released from dead cells or derived from cell medium. To reduce the likelihood of contaminations we applied an approach combining secretome and proteome analysis to characterize the physiological secretome of BM derived human MSC. Our analysis revealed a secretome consisting of 315 proteins. Pathway analyses of these proteins revealed a high abundance of proteins related to cell growth and/or maintenance, signal transduction and cell communication thereby representing key biological functions of BM derived MSC on protein level. Within the MSC secretome we identified several cytokines and growth factors such as VEGFC, TGF-β1, TGF-β2 and GDF6 which are known to be involved in the physiological regulation of hematopoiesis. By comparing the peptide patterns of secretomes and cell lysates 17 proteins were identified as candidates for proteolytic processing. Taken together, our combined MS work-flow reduced the likelihood of contaminations and enabled us to carve out a specific overview about the composition of the secretome from human BM derived MSC. This methodological approach and the specific secretome signature of BM derived MSC may serve as basis for future comparative analyses of the interplay of MSC and HSPC in patients with hematological malignancies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2019
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49. Perceived posttraumatic growth and depreciation after spinal cord injury: Actual or illusory?

Author

Kunz S, Joseph S, Geyh S, and Peter C

Subjects
Depreciation, Female, Humans, Male, Middle Aged, Retrospective Studies, Anxiety psychology, Depression psychology, Posttraumatic Growth, Psychological, Spinal Cord Injuries psychology
Abstract

Objective: This study examined whether retrospective reports of posttraumatic growth (PTG) and depreciation (PTD) of individuals recently diagnosed with a spinal cord injury (SCI) coincide with prospectively measured changes in the conceptually close domains of general self-efficacy (SE) and purpose in life (PIL). The study also tested whether PTG/D and changes in SE and PIL independently predict psychological adjustment to the injury (depressive symptoms, anxiety, life satisfaction)., Method: Adopting a longitudinal design, a sample of 206 newly injured patients admitted to one of the four Swiss SCI rehabilitation centers was analyzed. SE and PIL were assessed one month after injury diagnosis and at rehabilitation discharge, PTG/D and the adjustment indicators only at discharge. Structural equation modeling was used to calculate latent change scores for SE and PIL, to correlate these scores to PTG/D scores, and to regress the adjustment indicators on both of them., Results: PTG/D scores were weakly (rmax = .20, p = .033) correlated to changes in SE and PIL. In the multivariate analyses, positive changes in SE and PIL and PTG scores were all associated with better adjustment (e.g., fewer depressive symptoms). In contrast, PTD scores were related to lower adjustment., Conclusions: These results suggest that PTG/D in the initial time after a potentially traumatic medical event seem to be illusory to some degree, as indicated by their weak association with "actual" (i.e., longitudinally measured) changes. Nevertheless, both, PTG/D and actual changes, need to be considered by researchers and clinicians, as they seem to be independently related to psychological adjustment. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Published
2019
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50. Wilms' Tumor 1 Gene Expression Using a Standardized European LeukemiaNet-Certified Assay Compared to Other Methods for Detection of Minimal Residual Disease in Myelodysplastic Syndrome and Acute Myelogenous Leukemia after Allogeneic Blood Stem Cell Transplantation.

Author

Rautenberg C, Pechtel S, Hildebrandt B, Betz B, Dienst A, Nachtkamp K, Kondakci M, Geyh S, Wieczorek D, Haas R, Germing U, Kobbe G, and Schroeder T

Subjects
Adult, Aged, Europe, Female, Humans, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Myelodysplastic Syndromes pathology, Neoplasm, Residual pathology, Gene Expression genetics, Leukemia, Myeloid, Acute complications, Myelodysplastic Syndromes complications, Neoplasm, Residual diagnosis, Peripheral Blood Stem Cell Transplantation methods, Transplantation, Homologous methods, WT1 Proteins genetics
Abstract

Overexpression of the Wilms' tumor 1 (WT1) gene is informative in many patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) and is measurable in peripheral blood (PB). Despite these advantages, WT1 has not broadly been established as a marker for minimal residual disease (MRD) monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to limited patient numbers, differing sample sources, and nonstandardized in-house methods. To estimate the value of WT1 as an MRD marker, we serially quantified PB WT1 expression using a standardized European LeukemiaNet-certified assay in 59 patients with AML and MDS after allo-HSCT. We compared its performance with routine methods such as chimerism, XY-fluorescence in situ hybridization (FISH), disease-specific cytogenetic, and molecular analyses, which were accessible in 100%, 34%, 68%, and 37%, respectively. Twenty-four patients (41%) relapsed within a median of 126 days after allo-HSCT, and 20 of them showed at least 1 elevated WT1 value above the validated cutoff. The other 35 patients (59%) remained in complete remission, and only 1 patient had a transient increase in WT1 expression. This reflects a sensitivity of 83% and a specificity of 97% for WT1 and appears to be favorable compared with the sensitivities and specificities observed for chimerism (33% and 91%), XY-FISH (67% and 73%), cytogenetic (33% and 77%), and molecular (78% and 85%) analyses. Further supporting its predictive impact, elevated WT1 expression prompted an earlier BM biopsy and consecutively the diagnosis of relapse in 62% of patients. The results of this real-life experience imply that PB WT1 expression is measurable by a standardized assay and predicts imminent relapse after allo-HSCT with high sensitivity and specificity in most patients with AML and MDS., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Published
2018
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