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1. Partible paternity, the secondary sex ratio, and a possible Trivers-Willard effect

Author

Beckerman, S, Lizarralde, M, Peluso, D, Yvinec, C, Harris, N, Parker, D, Walker, R, and Hill, K

Subjects
Anthropology, Archaeology, Law
Abstract

Partible paternity, the belief that a child can have more than one biological father, is widespread in lowland South America. An analysis of demographic data sets from four lowland tribes (Aché, Barí, Ese Eja, and Surui) reveals a systematic variation in the sex ratios of live births with respect to the number of fathers to whom the births are attributed. Births attributed to only one father show a sex ratio that is unexceptional for South America; births with two fathers are highly male biased, while children with three or more fathers are female biased. This pattern may be a manifestation of a phenomenon predicted by the Trivers-Willard hypothesis, which proposes that, in many circumstances, females in good condition might bias their offspring toward males, whereas those in poor condition would produce a preponderance of females. If, as suggested below, a woman with a husband and a single extramarital lover tends to be better cared for before and during a pregnancy than other women, this difference might result in the improved maternal condition required by the Trivers-Willard hypothesis for excess males, whereas women who accept two or more lovers might be preponderantly those who are already in distress, thus tending to produce female-biased offspring.

Published
2017

3. Home infusion program with enzyme replacement therapy for Fabry disease: The experience of a large Italian collaborative group

Author

Concolino, D., Amico, L., Cappellini, M.D., Cassinerio, E., Conti, M., Donati, M.A., Falvo, F., Fiumara, A., Maccarone, M., Manna, R., Matucci, A., Musumeci, M.B., Nicoletti, A., Nisticò, R., Papadia, F., Parini, R., Peluso, D., Pensabene, L., Pisani, A., Pistone, G., Rigoldi, M., Romani, I., Tenuta, M., Torti, G., Veroux, M., and Zachara, E.

Published
2017
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5. Ethnic-Specific Normative Reference Values for Echocardiographic LA and LV Size, LV Mass, and Systolic Function: The EchoNoRMAL Study

Author

Poppe, K.K., Doughty, R.N., Gardin, J.M., Hobbs, F.D.R., McMurray, J.J.V., Nagueh, S.F., Senior, R., Thomas, L., Whalley, G.A., Aune, E., Brown, A., Badano, L.P., Cameron, V., Chadha, D.S., Chahal, N., Chien, K.L., Daimon, M., Dalen, H., Detrano, R., Akif Duzenli, M., Ezekowitz, J., de Simone, G., Di Pasquale, P., Fukuda, S., Gill, P.S., Grossman, E., Kim, H.-K., Kuznetsova, T., Leung, N.K.W., Linhart, A., McDonagh, T.A., McGrady, M., Mill, J.G., Mogelvang, R., Muiesan, M.L., Ng, A.C.T., Ojji, D., Otterstad, J.E., Petrovic, D.J., Prendergast, B., Rietzschel, E., Schirmer, H., Schvartzman, P., Simova, I., Sliwa, K., Stewart, S., Squire, I.B., Takeuchi, M., Altman, D.G., Perera, R., Triggs, C.M., Au Yeung, H., Beans Picón, G.A., Anderson, T., Dyck, J., Ezekowitz, J.A., Chirinos, J.A., De Buyzere, M.L., Gillebert, T.C., Segers, P., Van daele, C.M., Walsh, H.A., Izzo, R., De Luca, N., Trimarco, B., Goel, K., Misra, A., Chen, P.-C., Lin, H.-J., Su, T.-C., Richards, A.M., Troughton, R., Skov Jensen, J., Paterna, S., Davies, M.K., Davis, R.C., Roalfe, A., Calvert, M., Freemantle, N., Lip, G.Y.H., Staessen, J.A., Dargie, H.J., Ford, I., Galasko, G., Lahiri, A., Carrington, M., Krum, H., Zeitz, C., Blauwet, L., Moelmen Hansen, H.E., Støylen, A., Thorstensen, A., Watanabe, H., Yoshikawa, J., Chambers, J.C., Kooner, J., Davies, J., Loke, I., Ng, L., Leung, D.Y., Arnold, L., Coffey, S., d'Arcy, J., Hammond, C., Mabbett, C., Lima, C., Loudon, M., Pinheiro, N., Reynolds, R., Muraru, D., Peluso, D., Dal Bianco, L., Petrovic, J., Fuchs, F.D., Katova, T., Kaku, K., Boyd, A., Chia, E.M., Angelo, L.C., Pereira, A.C., Krieger, J.E., Rodrigues, S.L., Paini, A., Agabiti Rosei, E., and Salvetti, M.

Published
2015
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6. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden M, Wang D, Mason M, Szalai B, Bulusu K, Guan Y, Yu T, Kang J, Jeon M, Wolfinger R, Nguyen T, Zaslavskiy M, Jang I, Ghazoui Z, Ahsen M, Vogel R, Neto E, Norman T, Tang E, Garnett M, Di Veroli G, Fawell S, Stolovitzky G, Guinney J, Dry J, Saez-Rodriguez J, Abante J, Abecassis B, Aben N, Aghamirzaie D, Aittokallio T, Akhtari F, Al-lazikani B, Alam T, Allam A, Allen C, de Almeida M, Altarawy D, Alves V, Amadoz A, Anchang B, Antolin A, Ash J, Aznar V, Ba-alawi W, Bagheri M, Bajic V, Ball G, Ballester P, Baptista D, Bare C, Bateson M, Bender A, Bertrand D, Wijayawardena B, Boroevich K, Bosdriesz E, Bougouffa S, Bounova G, Brouwer T, Bryant B, Calaza M, Calderone A, Calza S, Capuzzi S, Carbonell-Caballero J, Carlin D, Carter H, Castagnoli L, Celebi R, Cesareni G, Chang H, Chen G, Chen H, Cheng L, Chernomoretz A, Chicco D, Cho K, Cho S, Choi D, Choi J, Choi K, Choi M, De Cock M, Coker E, Cortes-Ciriano I, Cserzo M, Cubuk C, Curtis C, Van Daele D, Dang C, Dijkstra T, Dopazo J, Draghici S, Drosou A, Dumontier M, Ehrhart F, Eid F, ElHefnawi M, Elmarakeby H, van Engelen B, Engin H, de Esch I, Evelo C, Falcao A, Farag S, Fernandez-Lozano C, Fisch K, Flobak A, Fornari C, Foroushani A, Fotso D, Fourches D, Friend S, Frigessi A, Gao F, Gao X, Gerold J, Gestraud P, Ghosh S, Gillberg J, Godoy-Lorite A, Godynyuk L, Godzik A, Goldenberg A, Gomez-Cabrero D, Gonen M, de Graaf C, Gray H, Grechkin M, Guimera R, Guney E, Haibe-Kains B, Han Y, Hase T, He D, He L, Heath L, Hellton K, Helmer-Citterich M, Hidalgo M, Hidru D, Hill S, Hochreiter S, Hong S, Hovig E, Hsueh Y, Hu Z, Huang J, Huang R, Hunyady L, Hwang J, Hwang T, Hwang W, Hwang Y, Isayev O, Walk O, Jack J, Jahandideh S, Ji J, Jo Y, Kamola P, Kanev G, Karacosta L, Karimi M, Kaski S, Kazanov M, Khamis A, Khan S, Kiani N, Kim A, Kim J, Kim K, Kim S, Kim Y, Kirk P, Kitano H, Klambauer G, Knowles D, Ko M, Kohn-Luque A, Kooistra A, Kuenemann M, Kuiper M, Kurz C, Kwon M, van Laarhoven T, Laegreid A, Lederer S, Lee H, Lee J, Lee Y, Leppaho E, Lewis R, Li J, Li L, Liley J, Lim W, Lin C, Liu Y, Lopez Y, Low J, Lysenko A, Machado D, Madhukar N, De Maeyer D, Malpartida A, Mamitsuka H, Marabita F, Marchal K, Marttinen P, Mason D, Mazaheri A, Mehmood A, Mehreen A, Michaut M, Miller R, Mitsopoulos C, Modos D, Van Moerbeke M, Moo K, Motsinger-Reif A, Movva R, Muraru S, Muratov E, Mushthofa M, Nagarajan N, Nakken S, Nath A, Neuvial P, Newton R, Ning Z, De Niz C, Oliva B, Olsen C, Palmeri A, Panesar B, Papadopoulos S, Park J, Park S, Pawitan Y, Peluso D, Pendyala S, Peng J, Perfetto L, Pirro S, Plevritis S, Politi R, Poon H, Porta E, Prellner I, Preuer K, Pujana M, Ramnarine R, Reid J, Reyal F, Richardson S, Ricketts C, Rieswijk L, Rocha M, Rodriguez-Gonzalvez C, Roell K, Rotroff D, de Ruiter J, Rukawa P, Sadacca B, Safikhani Z, Safitri F, Sales-Pardo M, Sauer S, Schlichting M, Seoane J, Serra J, Shang M, Sharma A, Sharma H, Shen Y, Shiga M, Shin M, Shkedy Z, Shopsowitz K, Sinai S, Skola D, Smirnov P, Soerensen I, Soerensen P, Song J, Song S, Soufan O, Spitzmueller A, Steipe B, Suphavilai C, Tamayo S, Tamborero D, Tang J, Tanoli Z, Tarres-Deulofeu M, Tegner J, Thommesen L, Tonekaboni S, Tran H, De Troyer E, Truong A, Tsunoda T, Turu G, Tzeng G, Verbeke L, Videla S, Vis D, Voronkov A, Votis K, Wang A, Wang H, Wang P, Wang S, Wang W, Wang X, Wennerberg K, Wernisch L, Wessels L, van Westen G, Westerman B, White S, Willighagen E, Wurdinger T, Xie L, Xie S, Xu H, Yadav B, Yau C, Yeerna H, Yin J, Yu M, Yun S, Zakharov A, Zamichos A, Zanin M, Zeng L, Zenil H, Zhang F, Zhang P, Zhang W, Zhao H, Zhao L, Zheng W, Zoufir A, Zucknick M, AstraZeneca-Sanger Drug Combinatio, Ege Üniversitesi, Gönen, Mehmet (ORCID 0000-0002-2483-075X & YÖK ID 237468), Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, de Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Romeo Aznar, Victoria, Ba-alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzo, Miklos, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham, van Engelen, Bo, Engin, Hatice Billur, de Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, de Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, Laszlo, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Walk, Oliver Bear Don't, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Leppaho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Angel Pujana, Miguel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, de Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong, De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gabor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, Zucknick, Manuela, College of Engineering, Department of Industrial Engineering, Institute of Data Science, RS: FSE DACS IDS, Bioinformatica, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: FHML MaCSBio, Promovendi NTM, Tero Aittokallio / Principal Investigator, Bioinformatics, Institute for Molecular Medicine Finland, Hu, Z, Fotso, DC, Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, Bosdriesz, E, Bougouffa, S, Bounova, G, Brouwer, T, Bryant, B, Calaza, M, Calderone, A, Calza, S, Capuzzi, S, Carbonell-Caballero, J, Carlin, D, Carter, H, Castagnoli, L, Celebi, R, Cesareni, G, Chang, H, Chen, G, Chen, H, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, Gestraud, P, Ghosh, S, Gillberg, J, Godoy-Lorite, A, Godynyuk, L, Godzik, A, Goldenberg, A, Gomez-Cabrero, D, Gonen, M, de Graaf, C, Gray, H, Grechkin, M, Guimera, R, Guney, E, Haibe-Kains, B, Han, Y, Hase, T, He, D, He, L, Heath, L, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, Moerbeke, M, Moo, K, Motsinger-Reif, A, Movva, R, Muraru, S, Muratov, E, Mushthofa, M, Nagarajan, N, Nakken, S, Nath, A, Neuvial, P, Newton, R, Ning, Z, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, Park, S, Pawitan, Y, Peluso, D, Pendyala, S, Peng, J, Perfetto, L, Pirro, S, Plevritis, S, Politi, R, Poon, H, Porta, E, Prellner, I, Preuer, K, Pujana, M, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden, Michael P. [0000-0003-0267-5792], Mason, Mike J. [0000-0002-5652-7739], Yu, Thomas [0000-0002-5841-0198], Kang, Jaewoo [0000-0001-6798-9106], Nguyen, Tin [0000-0001-8001-9470], Ahsen, Mehmet Eren [0000-0002-4907-0427], Stolovitzky, Gustavo [0000-0002-9618-2819], Guinney, Justin [0000-0003-1477-1888], Saez-Rodriguez, Julio [0000-0002-8552-8976], Apollo - University of Cambridge Repository, Menden, Michael P [0000-0003-0267-5792], Mason, Mike J [0000-0002-5652-7739], Pathology, CCA - Cancer biology and immunology, Medical oncology laboratory, Neurosurgery, Chemistry and Pharmaceutical Sciences, AIMMS, Medicinal chemistry, Universidade do Minho, Department of Computer Science, Professorship Marttinen P., Aalto-yliopisto, and Aalto University

Subjects
Drug Resistance, 02 engineering and technology, 13, PATHWAY, Antineoplastic Combined Chemotherapy Protocols, Molecular Targeted Therapy, Càncer, lcsh:Science, media_common, Cancer, Tumor, Settore BIO/18, Settore BIO/11, Drug combinations, High-throughput screening, Drug Synergism, purl.org/becyt/ford/1.2 [https], Genomics, Machine Learning, predictions, 3. Good health, ddc, Technologie de l'environnement, contrôle de la pollution, Benchmarking, 5.1 Pharmaceuticals, Cancer treatment, Farmacogenètica, Science & Technology - Other Topics, Development of treatments and therapeutic interventions, 0210 nano-technology, Human, Drug, media_common.quotation_subject, Science, 49/23, ADAM17 Protein, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, RESOURCE, Machine learning, Genetics, Chimie, Humans, BREAST-CANCER, CELL, 49/98, Science & Technology, Antineoplastic Combined Chemotherapy Protocol, 45, MUTATIONS, Computational Biology, Androgen receptor, Breast-cancer, Gene, Cell, Inhibition, Resistance, Pathway, Mutations, Landscape, Resource, 631/114/1305, medicine.disease, Drug synergy, 49, 030104 developmental biology, Pharmacogenetics, Mutation, Ciências Médicas::Biotecnologia Médica, lcsh:Q, 631/154/1435/2163, Biomarkers, RESISTANCE, 0301 basic medicine, ING-INF/06 - BIOINGEGNERIA ELETTRONICA E INFORMATICA, Statistical methods, Computer science, General Physics and Astronomy, Datasets as Topic, Drug resistance, purl.org/becyt/ford/1 [https], Phosphatidylinositol 3-Kinases, Biotecnologia Médica [Ciências Médicas], Neoplasms, Science and technology, Phosphoinositide-3 Kinase Inhibitors, Multidisciplinary, Biomarkers, Tumor, Cell Line, Tumor, Drug Antagonism, Drug Resistance, Neoplasm, Treatment Outcome, Pharmacogenetic, article, ANDROGEN RECEPTOR, 49/39, 631/114/2415, 021001 nanoscience & nanotechnology, 692/4028/67, Multidisciplinary Sciences, 317 Pharmacy, Patient Safety, Systems biology, 3122 Cancers, INHIBITION, Computational biology, Cell Line, medicine, LANDSCAPE, Physique, Human Genome, Data Science, General Chemistry, AstraZeneca-Sanger Drug Combination DREAM Consortium, Astronomie, GENE, Good Health and Well Being, Pharmacogenomics, Genomic, Neoplasm, 631/553, Phosphatidylinositol 3-Kinase
Abstract

PubMed: 31209238, The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. © 2019, The Author(s)., National Institute for Health Research, NIHR Wellcome Trust, WT: 102696, 206194 Magyar Tudományos Akadémia, MTA Bayer 668858 PrECISE AstraZeneca, We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194)., Competing interests: K.C.B., Z.G., G.Y.D., E.K.Y.T., S.F., and J.R.D. are AstraZeneca employees. K.C.B., Z.G., E.K.Y.T., S.F., and J.R.D. are AstraZeneca shareholders. Y.G. receives personal compensation from Eli Lilly and Company, is a shareholder of Cleerly, Inc., and Ann Arbor Algorithms, Inc. M.G. receives research funding from AstraZeneca and has performed consultancy for Sanofi. The remaining authors declare no competing interests.

Published
2019
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10. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, Bosdriesz, E, Bougouffa, S, Bounova, G, Brouwer, T, Bryant, B, Calaza, M, Calderone, A, Calza, S, Capuzzi, S, Carbonell-Caballero, J, Carlin, D, Carter, H, Castagnoli, L, Celebi, R, Cesareni, G, Chang, H, Chen, G, Chen, H, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, Gestraud, P, Ghosh, S, Gillberg, J, Godoy-Lorite, A, Godynyuk, L, Godzik, A, Goldenberg, A, Gomez-Cabrero, D, Gonen, M, de Graaf, C, Gray, H, Grechkin, M, Guimera, R, Guney, E, Haibe-Kains, B, Han, Y, Hase, T, He, D, He, L, Heath, L, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Hu, Z, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, Moerbeke, M, Moo, K, Motsinger-Reif, A, Movva, R, Muraru, S, Muratov, E, Mushthofa, M, Nagarajan, N, Nakken, S, Nath, A, Neuvial, P, Newton, R, Ning, Z, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, Park, S, Pawitan, Y, Peluso, D, Pendyala, S, Peng, J, Perfetto, L, Pirro, S, Plevritis, S, Politi, R, Poon, H, Porta, E, Prellner, I, Preuer, K, Pujana, M, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden M. P., Wang D., Mason M. J., Szalai B., Bulusu K. C., Guan Y., Yu T., Kang J., Jeon M., Wolfinger R., Nguyen T., Zaslavskiy M., Abante J., Abecassis B. S., Aben N., Aghamirzaie D., Aittokallio T., Akhtari F. S., Al-lazikani B., Alam T., Allam A., Allen C., de Almeida M. P., Altarawy D., Alves V., Amadoz A., Anchang B., Antolin A. A., Ash J. R., Aznar V. R., Ba-alawi W., Bagheri M., Bajic V., Ball G., Ballester P. J., Baptista D., Bare C., Bateson M., Bender A., Bertrand D., Wijayawardena B., Boroevich K. A., Bosdriesz E., Bougouffa S., Bounova G., Brouwer T., Bryant B., Calaza M., Calderone A., Calza S., Capuzzi S., Carbonell-Caballero J., Carlin D., Carter H., Castagnoli L., Celebi R., Cesareni G., Chang H., Chen G., Chen H., Cheng L., Chernomoretz A., Chicco D., Cho K. -H., Cho S., Choi D., Choi J., Choi K., Choi M., Cock M. D., Coker E., Cortes-Ciriano I., Cserzo M., Cubuk C., Curtis C., Daele D. V., Dang C. C., Dijkstra T., Dopazo J., Draghici S., Drosou A., Dumontier M., Ehrhart F., Eid F. -E., ElHefnawi M., Elmarakeby H., van Engelen B., Engin H. B., de Esch I., Evelo C., Falcao A. O., Farag S., Fernandez-Lozano C., Fisch K., Flobak A., Fornari C., Foroushani A. B. K., Fotso D. C., Fourches D., Friend S., Frigessi A., Gao F., Gao X., Gerold J. M., Gestraud P., Ghosh S., Gillberg J., Godoy-Lorite A., Godynyuk L., Godzik A., Goldenberg A., Gomez-Cabrero D., Gonen M., de Graaf C., Gray H., Grechkin M., Guimera R., Guney E., Haibe-Kains B., Han Y., Hase T., He D., He L., Heath L. S., Hellton K. H., Helmer-Citterich M., Hidalgo M. R., Hidru D., Hill S. M., Hochreiter S., Hong S., Hovig E., Hsueh Y. -C., Hu Z., Huang J. K., Huang R. S., Hunyady L., Hwang J., Hwang T. H., Hwang W., Hwang Y., Isayev O., Don't Walk O. B., Jack J., Jahandideh S., Ji J., Jo Y., Kamola P. J., Kanev G. K., Karacosta L., Karimi M., Kaski S., Kazanov M., Khamis A. M., Khan S. A., Kiani N. A., Kim A., Kim J., Kim K., Kim S., Kim Y., Kirk P. D. W., Kitano H., Klambauer G., Knowles D., Ko M., Kohn-Luque A., Kooistra A. J., Kuenemann M. A., Kuiper M., Kurz C., Kwon M., van Laarhoven T., Laegreid A., Lederer S., Lee H., Lee J., Lee Y. W., Lepp_aho E., Lewis R., Li J., Li L., Liley J., Lim W. K., Lin C., Liu Y., Lopez Y., Low J., Lysenko A., Machado D., Madhukar N., Maeyer D. D., Malpartida A. B., Mamitsuka H., Marabita F., Marchal K., Marttinen P., Mason D., Mazaheri A., Mehmood A., Mehreen A., Michaut M., Miller R. A., Mitsopoulos C., Modos D., Moerbeke M. V., Moo K., Motsinger-Reif A., Movva R., Muraru S., Muratov E., Mushthofa M., Nagarajan N., Nakken S., Nath A., Neuvial P., Newton R., Ning Z., Niz C. D., Oliva B., Olsen C., Palmeri A., Panesar B., Papadopoulos S., Park J., Park S., Pawitan Y., Peluso D., Pendyala S., Peng J., Perfetto L., Pirro S., Plevritis S., Politi R., Poon H., Porta E., Prellner I., Preuer K., Pujana M. A., Ramnarine R., Reid J. E., Reyal F., Richardson S., Ricketts C., Rieswijk L., Rocha M., Rodriguez-Gonzalvez C., Roell K., Rotroff D., de Ruiter J. R., Rukawa P., Sadacca B., Safikhani Z., Safitri F., Sales-Pardo M., Sauer S., Schlichting M., Seoane J. A., Serra J., Shang M. -M., Sharma A., Sharma H., Shen Y., Shiga M., Shin M., Shkedy Z., Shopsowitz K., Sinai S., Skola D., Smirnov P., Soerensen I. F., Soerensen P., Song J. -H., Song S. O., Soufan O., Spitzmueller A., Steipe B., Suphavilai C., Tamayo S. P., Tamborero D., Tang J., Tanoli Z. -U. -R., Tarres-Deulofeu M., Tegner J., Thommesen L., Tonekaboni S. A. M., Tran H., Troyer E. D., Truong A., Tsunoda T., Turu G., Tzeng G. -Y., Verbeke L., Videla S., Vis D., Voronkov A., Votis K., Wang A., Wang H. -Q. H., Wang P. -W., Wang S., Wang W., Wang X., Wennerberg K., Wernisch L., Wessels L., van Westen G. J. P., Westerman B. A., White S. R., Willighagen E., Wurdinger T., Xie L., Xie S., Xu H., Yadav B., Yau C., Yeerna H., Yin J. W., Yu M., Yu M. H., Yun S. J., Zakharov A., Zamichos A., Zanin M., Zeng L., Zenil H., Zhang F., Zhang P., Zhang W., Zhao H., Zhao L., Zheng W., Zoufir A., Zucknick M., Jang I. S., Ghazoui Z., Ahsen M. E., Vogel R., Neto E. C., Norman T., Tang E. K. Y., Garnett M. J., Veroli G. Y. D., Fawell S., Stolovitzky G., Guinney J., Dry J. R., Saez-Rodriguez J., Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, Bosdriesz, E, Bougouffa, S, Bounova, G, Brouwer, T, Bryant, B, Calaza, M, Calderone, A, Calza, S, Capuzzi, S, Carbonell-Caballero, J, Carlin, D, Carter, H, Castagnoli, L, Celebi, R, Cesareni, G, Chang, H, Chen, G, Chen, H, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, Gestraud, P, Ghosh, S, Gillberg, J, Godoy-Lorite, A, Godynyuk, L, Godzik, A, Goldenberg, A, Gomez-Cabrero, D, Gonen, M, de Graaf, C, Gray, H, Grechkin, M, Guimera, R, Guney, E, Haibe-Kains, B, Han, Y, Hase, T, He, D, He, L, Heath, L, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Hu, Z, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, Moerbeke, M, Moo, K, Motsinger-Reif, A, Movva, R, Muraru, S, Muratov, E, Mushthofa, M, Nagarajan, N, Nakken, S, Nath, A, Neuvial, P, Newton, R, Ning, Z, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, Park, S, Pawitan, Y, Peluso, D, Pendyala, S, Peng, J, Perfetto, L, Pirro, S, Plevritis, S, Politi, R, Poon, H, Porta, E, Prellner, I, Preuer, K, Pujana, M, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden M. P., Wang D., Mason M. J., Szalai B., Bulusu K. C., Guan Y., Yu T., Kang J., Jeon M., Wolfinger R., Nguyen T., Zaslavskiy M., Abante J., Abecassis B. S., Aben N., Aghamirzaie D., Aittokallio T., Akhtari F. S., Al-lazikani B., Alam T., Allam A., Allen C., de Almeida M. P., Altarawy D., Alves V., Amadoz A., Anchang B., Antolin A. A., Ash J. R., Aznar V. R., Ba-alawi W., Bagheri M., Bajic V., Ball G., Ballester P. J., Baptista D., Bare C., Bateson M., Bender A., Bertrand D., Wijayawardena B., Boroevich K. A., Bosdriesz E., Bougouffa S., Bounova G., Brouwer T., Bryant B., Calaza M., Calderone A., Calza S., Capuzzi S., Carbonell-Caballero J., Carlin D., Carter H., Castagnoli L., Celebi R., Cesareni G., Chang H., Chen G., Chen H., Cheng L., Chernomoretz A., Chicco D., Cho K. -H., Cho S., Choi D., Choi J., Choi K., Choi M., Cock M. D., Coker E., Cortes-Ciriano I., Cserzo M., Cubuk C., Curtis C., Daele D. V., Dang C. C., Dijkstra T., Dopazo J., Draghici S., Drosou A., Dumontier M., Ehrhart F., Eid F. -E., ElHefnawi M., Elmarakeby H., van Engelen B., Engin H. B., de Esch I., Evelo C., Falcao A. O., Farag S., Fernandez-Lozano C., Fisch K., Flobak A., Fornari C., Foroushani A. B. K., Fotso D. C., Fourches D., Friend S., Frigessi A., Gao F., Gao X., Gerold J. M., Gestraud P., Ghosh S., Gillberg J., Godoy-Lorite A., Godynyuk L., Godzik A., Goldenberg A., Gomez-Cabrero D., Gonen M., de Graaf C., Gray H., Grechkin M., Guimera R., Guney E., Haibe-Kains B., Han Y., Hase T., He D., He L., Heath L. S., Hellton K. H., Helmer-Citterich M., Hidalgo M. R., Hidru D., Hill S. M., Hochreiter S., Hong S., Hovig E., Hsueh Y. -C., Hu Z., Huang J. K., Huang R. S., Hunyady L., Hwang J., Hwang T. H., Hwang W., Hwang Y., Isayev O., Don't Walk O. B., Jack J., Jahandideh S., Ji J., Jo Y., Kamola P. J., Kanev G. K., Karacosta L., Karimi M., Kaski S., Kazanov M., Khamis A. M., Khan S. A., Kiani N. A., Kim A., Kim J., Kim K., Kim S., Kim Y., Kirk P. D. W., Kitano H., Klambauer G., Knowles D., Ko M., Kohn-Luque A., Kooistra A. J., Kuenemann M. A., Kuiper M., Kurz C., Kwon M., van Laarhoven T., Laegreid A., Lederer S., Lee H., Lee J., Lee Y. W., Lepp_aho E., Lewis R., Li J., Li L., Liley J., Lim W. K., Lin C., Liu Y., Lopez Y., Low J., Lysenko A., Machado D., Madhukar N., Maeyer D. D., Malpartida A. B., Mamitsuka H., Marabita F., Marchal K., Marttinen P., Mason D., Mazaheri A., Mehmood A., Mehreen A., Michaut M., Miller R. A., Mitsopoulos C., Modos D., Moerbeke M. V., Moo K., Motsinger-Reif A., Movva R., Muraru S., Muratov E., Mushthofa M., Nagarajan N., Nakken S., Nath A., Neuvial P., Newton R., Ning Z., Niz C. D., Oliva B., Olsen C., Palmeri A., Panesar B., Papadopoulos S., Park J., Park S., Pawitan Y., Peluso D., Pendyala S., Peng J., Perfetto L., Pirro S., Plevritis S., Politi R., Poon H., Porta E., Prellner I., Preuer K., Pujana M. A., Ramnarine R., Reid J. E., Reyal F., Richardson S., Ricketts C., Rieswijk L., Rocha M., Rodriguez-Gonzalvez C., Roell K., Rotroff D., de Ruiter J. R., Rukawa P., Sadacca B., Safikhani Z., Safitri F., Sales-Pardo M., Sauer S., Schlichting M., Seoane J. A., Serra J., Shang M. -M., Sharma A., Sharma H., Shen Y., Shiga M., Shin M., Shkedy Z., Shopsowitz K., Sinai S., Skola D., Smirnov P., Soerensen I. F., Soerensen P., Song J. -H., Song S. O., Soufan O., Spitzmueller A., Steipe B., Suphavilai C., Tamayo S. P., Tamborero D., Tang J., Tanoli Z. -U. -R., Tarres-Deulofeu M., Tegner J., Thommesen L., Tonekaboni S. A. M., Tran H., Troyer E. D., Truong A., Tsunoda T., Turu G., Tzeng G. -Y., Verbeke L., Videla S., Vis D., Voronkov A., Votis K., Wang A., Wang H. -Q. H., Wang P. -W., Wang S., Wang W., Wang X., Wennerberg K., Wernisch L., Wessels L., van Westen G. J. P., Westerman B. A., White S. R., Willighagen E., Wurdinger T., Xie L., Xie S., Xu H., Yadav B., Yau C., Yeerna H., Yin J. W., Yu M., Yu M. H., Yun S. J., Zakharov A., Zamichos A., Zanin M., Zeng L., Zenil H., Zhang F., Zhang P., Zhang W., Zhao H., Zhao L., Zheng W., Zoufir A., Zucknick M., Jang I. S., Ghazoui Z., Ahsen M. E., Vogel R., Neto E. C., Norman T., Tang E. K. Y., Garnett M. J., Veroli G. Y. D., Fawell S., Stolovitzky G., Guinney J., Dry J. R., and Saez-Rodriguez J.

Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

Published
2019

30. A meta-analysis of echocardiographic measurements of the left heart for the development of normative reference ranges in a large international cohort: the EchoNoRMAL study

Author

Anderson T., Dyck J., Ezekowitz J. A., Chirinos J. A., De Buyzere M. L., Gillebert T. C., Rietzschel E., Segers P., Van Daele C. M., Doughty R. N., Poppe K. K., Walsh H. A., Whalley G. A., Chen P. C., Chien K. L., Lin H. J., Su, T. C., Mogelvang R., Jensen J. S., Chadha D. S., Goel K., Misra A., Detrano R., Cameron V., Richards A. M., Troughton R., Di Pasquale P., Paterna S., Duzenli M. A., Hobbs F. D. R., Davies M. K., Davis R. C., Roalfe A., Calvert M., Freemantle N., Gill, P. S., Lip G. Y. H., Kuznetsova T., Staessen J. A., Dargie H. J., Ford I., McDonagh T. A., McMurray J. J. V., Grossman E., Galasko G., Lahiri A., Senior R., Blauwet L., Sliwa K., Stewart S., Brown A., Carrington M., Krum H., McGrady M., Zeitz C., Dalen H., Hansen H. E. M., Støylen A., Thorstensen A., Daimon M., Watanabe H., Yoshikawa J., Fukuda S., Kim H. K., Leung N. K. W., Linhart A., Chahal N., Chambers J. C., Kooner J., Davies J., Loke I., Ng, L., Squire I. B., Aune E., Otterstad J. E., Leung D. Y., Ng A. C. T., Ojji D., Arnold L., Coffey S., D'Arcy J., Hammond C., Mabbett C., Lima C., Loudon M., Pinheiro N., Prendergast B., Reynolds R., Badano L. P., Muraru D., Peluso D., Dal Bianco L., Petrovic D. J., Petrovic J., Schvartzman P., Fuchs F. D., Katova T., Simova I., Kaku K., Takeuchi M., Boyd A., Thomas L., Chia E. M., Schirmer H., Angelo L. C., Pereira A. C., Krieger J. E., Mill J. G., Rodrigues S. L., Muiesan M. L., Paini A., Rosei E. A., Salvetti M., Gardin J. M., Nagueh S. F., Altman D., Perera R., Triggs C. M., Au Yeung H., Beans Picon G. A., IZZO, RAFFAELE, DE LUCA, NICOLA, TRIMARCO, BRUNO, DE SIMONE, GIOVANNI, Anderson, T., Dyck, J., Ezekowitz, J. A., Chirinos, J. A., De Buyzere, M. L., Gillebert, T. C., Rietzschel, E., Segers, P., Van Daele, C. M., Doughty, R. N., Poppe, K. K., Walsh, H. A., Whalley, G. A., Izzo, Raffaele, DE LUCA, Nicola, Trimarco, Bruno, DE SIMONE, Giovanni, Chen, P. C., Chien, K. L., Lin, H. J., Su, T. C., Mogelvang, R., Jensen, J. S., Chadha, D. S., Goel, K., Misra, A., Detrano, R., Cameron, V., Richards, A. M., Troughton, R., Di Pasquale, P., Paterna, S., Duzenli, M. A., Hobbs, F. D. R., Davies, M. K., Davis, R. C., Roalfe, A., Calvert, M., Freemantle, N., Gill, P. S., Lip, G. Y. H., Kuznetsova, T., Staessen, J. A., Dargie, H. J., Ford, I., Mcdonagh, T. A., Mcmurray, J. J. V., Grossman, E., Galasko, G., Lahiri, A., Senior, R., Blauwet, L., Sliwa, K., Stewart, S., Brown, A., Carrington, M., Krum, H., Mcgrady, M., Zeitz, C., Dalen, H., Hansen, H. E. M., Støylen, A., Thorstensen, A., Daimon, M., Watanabe, H., Yoshikawa, J., Fukuda, S., Kim, H. K., Leung, N. K. W., Linhart, A., Chahal, N., Chambers, J. C., Kooner, J., Davies, J., Loke, I., Ng, L., Squire, I. B., Aune, E., Otterstad, J. E., Leung, D. Y., Ng, A. C. T., Ojji, D., Arnold, L., Coffey, S., D'Arcy, J., Hammond, C., Mabbett, C., Lima, C., Loudon, M., Pinheiro, N., Prendergast, B., Reynolds, R., Badano, L. P., Muraru, D., Peluso, D., Dal Bianco, L., Petrovic, D. J., Petrovic, J., Schvartzman, P., Fuchs, F. D., Katova, T., Simova, I., Kaku, K., Takeuchi, M., Boyd, A., Thomas, L., Chia, E. M., Schirmer, H., Angelo, L. C., Pereira, A. C., Krieger, J. E., Mill, J. G., Rodrigues, S. L., Muiesan, M. L., Paini, A., Rosei, E. A., Salvetti, M., Gardin, J. M., Nagueh, S. F., Altman, D., Perera, R., Triggs, C. M., Au Yeung, H., Beans Picon, G. A., and Badano, L

Subjects
Male, Pediatrics, International Cooperation, Left, Ethnic Group, Sex Factor, Ventricular Function, Left, Heart Ventricle, Cohort Studies, Echocardiography, Meta-analysis, Reference ranges, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Atrial Function, Left, Ethnic Groups, Female, Heart Atria, Heart Ventricles, Humans, Middle Aged, Reference Standards, Sex Factors, Young Adult, Cardiology and Cardiovascular Medicine, Radiology, Nuclear Medicine and Imaging, Nuclear Medicine and Imaging, 80 and over, Ethnicity, Ventricular Function, Age Factor, Young adult, education.field_of_study, General Medicine, Atrial Function, Parametric Regression Method, Cohort, Cardiology, Radiology, Human, Cohort study, medicine.medical_specialty, Population, Internal medicine, medicine, Meta-analysi, Radiology, Nuclear Medicine and imaging, education, business.industry, Reference range, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Quantile regression, Reference Standard, Normative, Cohort Studie, business
Abstract

Aim: To develop age-, sex-, and ethnic-Appropriate normative reference ranges for standard echocardiographic measurements of the left heart by combining echocardiographic measurements obtained from adult volunteers without clinical cardiovascular disease or significant cardiovascular risk factors, from multiple studies around the world.Methods and results: The Echocardiographic Normal Ranges Meta-Analysis of the Left heart (EchoNoRMAL) collaboration was established and population-based data sets of echocardiographic measurements combined to perform an individual person data meta-Analysis. Data from 43 studies were received, representing 51 222 subjects, of which 22 404 adults aged 18-80 years were without clinical cardiovascular or renal disease, hypertension or diabetes. Quantile regression or an appropriate parametric regression method will be used to derive reference values at the 5th and 95th centile of each measurement against age. Conclusion: This unique data set represents a large, multi-ethnic cohort of subjects resident in a wide range of countries. The resultant reference ranges will have wide applicability for normative data based on age, sex, and ethnicity. © The Author 2013.

Published
2013
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31. Sex- and method-specific reference values for right ventricular strain by 2-dimensional speckle-tracking echocardiography

Author

Muraru, D, Onciul, S, Peluso, D, Soriani, N, Cucchini, U, Aruta, P, Romeo, G, Cavalli, G, Iliceto, S, Badano, L, Muraru D., Onciul S., Peluso D., Soriani N., Cucchini U., Aruta P., Romeo G., Cavalli G., Iliceto S., Badano L., Muraru, D, Onciul, S, Peluso, D, Soriani, N, Cucchini, U, Aruta, P, Romeo, G, Cavalli, G, Iliceto, S, Badano, L, Muraru D., Onciul S., Peluso D., Soriani N., Cucchini U., Aruta P., Romeo G., Cavalli G., Iliceto S., and Badano L.

Abstract

Background - Despite the fact that assessment of right ventricular longitudinal strain (RVLS) carries important implications for patient diagnosis, prognosis, and treatment, its implementation in clinical settings has been hampered by the limited reference values and the lack of uniformity in software, method, and definition used for measuring RVLS. Accordingly, this study was designed to establish (1) the reference values for RVLS by 2-dimensional speckle-tracking echocardiography; and (2) their relationship with demographic, hemodynamic, and cardiac factors. Methods and Results - In 276 healthy volunteers (55% women; age, 18-76 years), free wall and septum RVLS (6 segments) and free wall RVLS (3 segments) using both 6- and 3-segment regions of interest were obtained. Feasibility of 6-segment RVLS was 92%. Free wall RVLS from 3- versus 6-segment regions of interest had similar values, yet 6-segment region of interest was more feasible (86% versus 73%; P<0.001) and reproducible. Reference values (lower limits of normality) were as follows: 6-segment RVLS, -24.7±2.6% (-20.0%) for men and -26.7±3.1% (-20.3%) for women; 3-segment RVLS, -29.3±3.4% (-22.5%) for men and -31.6±4.0% (-23.3%) for women (P<0.001). Free wall RVLS was 5±2 strain units (%) larger in magnitude than 6-segment RVLS, 10±4% larger than septal RVLS, and 2±4% larger in women than in men (P<0.001). At multivariable analysis, age, sex, pulmonary systolic pressure, right atrial minimal volume, as well as right atrial and left ventricular longitudinal strain resulted as correlates of RVLS values. Conclusions - This is the largest study providing sex- and method-specific reference values for RVLS. Our data may foster the implementation of 2-dimensional speckle-tracking echocardiography-derived RV analysis in clinical practice.

Published
2016

32. Left atrial volumes and function by three-dimensional echocardiography: Reference values, accuracy, reproducibility, and comparison with two-dimensional echocardiographic measurements

Author

Badano, L, Miglioranza, M, Mihaila, S, Peluso, D, Xhaxho, J, Marra, M, Cucchini, U, Soriani, N, Iliceto, S, Muraru, D, Badano L., Miglioranza M. H., MihAilA S., Peluso D., Xhaxho J., Marra M. P., Cucchini U., Soriani N., Iliceto S., Muraru D., Badano, L, Miglioranza, M, Mihaila, S, Peluso, D, Xhaxho, J, Marra, M, Cucchini, U, Soriani, N, Iliceto, S, Muraru, D, Badano L., Miglioranza M. H., MihAilA S., Peluso D., Xhaxho J., Marra M. P., Cucchini U., Soriani N., Iliceto S., and Muraru D.

Abstract

Background - Our study sought to (1) identify reference values for left atrial (LA) volumes and phasic function indices by 3-dimensional echocardiography (3DE) and compare them with those measured by 2-dimensional echocardiography (2DE) and (2) analyze their relationship with age, sex, body size, and left ventricular function. Accuracy and reproducibility of 3DE and 2DE have been also tested to evaluate the robustness of our data. Methods and Results - We obtained maximal, minimal, and preA LA volumes by 3DE and 2DE in 276 healthy volunteers (18-79 years; 57% women). Limits of normality for LA volumes and total LA emptying fraction were larger with 3DE than with 2DE (maximal LA volume: 43 versus 35 mL/m2; preA LA volume: 31 versus 25 mL/m2; minimal LA volume: 18 versus 14 mL/m2; 53 versus 48%, respectively; P<0.001). 3DE LA volumes indexed by body surface area were similar in men and women and increased with age. On multivariable analysis, age, weight, and left ventricular systolic and diastolic function indices resulted as correlates of LA 3DE indices. LA volumes were tightly correlated with cardiac magnetic resonance measurements, yet more underestimated by 2DE versus 3DE (bias±SD: -17±16 versus -7±15 mL, respectively). Among all LA parameters, maximal LA volume and total emptying fraction were the most reproducible, including at test-retest and at expert versus trainee comparisons. Conclusions - This study provides reference values for LA 3DE volumes and function from a relatively large cohort of healthy subjects with a wide age range. Our data may help clinicians to identify LA remodeling and dysfunction.

Published
2016

33. Physiologic Determinants of Left Atrial Longitudinal Strain: A Two-Dimensional Speckle-Tracking and Three-Dimensional Echocardiographic Study in Healthy Volunteers

Author

Miglioranza, M, Badano, L, Mihaila, S, Peluso, D, Cucchini, U, Soriani, N, Iliceto, S, Muraru, D, Miglioranza M. H., Badano L., Mihaila S., Peluso D., Cucchini U., Soriani N., Iliceto S., Muraru D., Miglioranza, M, Badano, L, Mihaila, S, Peluso, D, Cucchini, U, Soriani, N, Iliceto, S, Muraru, D, Miglioranza M. H., Badano L., Mihaila S., Peluso D., Cucchini U., Soriani N., Iliceto S., and Muraru D.

Abstract

Background Left atrial (LA) longitudinal strain (LS) using two-dimensional speckle-tracking echocardiography has emerged as an important diagnostic and prognostic parameter in various cardiovascular conditions. However, its reference values, their correlations with demographics characteristics, and its physiologic determinants remain to be established. Methods Accordingly, 171 healthy volunteers (mean age, 45 ± 12 years; 61% women) in whom LS was obtained from both apical four- and two-chamber dedicated views of the left atrium, considering the P-P interval on the electrocardiogram as the reference cardiac cycle, were prospectively studied. From the LA LS curve we measured the extent of the negative deflection (LSneg), representing LA active contraction, the positive deflection (LSpos) during LA filling, and total LS (LStot), as the sum of LSneg and LSpos values. Results Average values for biplane LA LSpos, LSneg, and LStot were 19.7%, −14.5%, and 33.3%, respectively. On multivariate analysis, age, left ventricular (LV) global LS and volume, and LV diastolic function were the main physiologic determinants of LA LSpos (R2 = 0.57) and LStot (R2 = 0.40), whereas systolic blood pressure, E/A ratio, global LS, and LV stroke volume were the main determinants of LA LSneg (R2 = 0.20). Women had higher LSpos and LStot than men, particularly before 50 years of age. LA LSpos and LStot decreased with aging, with different trends in men and women. Conclusions LA LS values are different in men and women and should be interpreted taking into account patient age and LV function as well. These reference values may help identify subclinical LA dysfunction in several cardiovascular or systemic conditions.

Published
2016

35. Evaluation of right ventricular function performed by 3d-echocardiography in scleroderma patients

Author

Pigatto, E, Peluso, D, Zanatta, E, Polito, P, Miatton, P, Bourji, K, Badano, L, Punzi, L, Cozzi, F, Pigatto E., Peluso D., Zanatta E., Polito P., Miatton P., Bourji K., Badano L., Punzi L., Cozzi F., Pigatto, E, Peluso, D, Zanatta, E, Polito, P, Miatton, P, Bourji, K, Badano, L, Punzi, L, Cozzi, F, Pigatto E., Peluso D., Zanatta E., Polito P., Miatton P., Bourji K., Badano L., Punzi L., and Cozzi F.

Abstract

The impairment of the right ventricle (RV) in systemic sclerosis (SSc) is usually related to pulmonary arterial hypertension (PAH). New echocardiographic techniques, such as 3-dimensional echocardiography (3DE) and 2-dimensional speckle tracking (2DSTE), allow an accurate evaluation of the RV function. The aim of this study was to evaluate the RV function using 3DE and 2DSTE in SSc patients with no history of heart disease and no PAH. Forty-five SSc patients, 42 females and 3 males, 28 with limited cutaneous SSc (lcSSc) and 17 with diffuse cutaneous SSc (dcSSc), were studied. Forty-three age- and gender-matched healthy subjects were enrolled as controls. All of them underwent a 3DE and 2DSTE ecocardiographic evaluation of the RV function. Systolic pulmonary arterial pressure (sPAP) and total pulmonary vascular resistance (tPVR) were also estimated by power doppler. RV echocardiographic parameters were compared in the different subsets of SSc patients. A statistical analysis was performed by t-test, ANOVA and multiple logistic regression. RV areas in 2DSTE and volumes in 3DE were higher and RV function parameters were reduced in SSc patients compared with controls. Also sPAP and tVPR were higher, but they did not reach pathological values. Echocardiographic alterations were more pronounced in patients with lcSSc. 3DE and 2DSTE echocardiography allowed us to detect morphological and functional alterations of the RV in a group of SSc patients with no clinical signs of heart disease and no PAH. These patients had significantly higher sPAP and tPVR than healthy controls without reporting values compatible with PAH. These data suggest that RV alterations are related to a pressure overload rather than to an intrinsic myocardial involvement in SSc.

Published
2015

40. Poster Session Saturday 14 December - AM: 14/12/2013 08:30-12:30 * Location: Poster area

Author

Muraru, D., Addetia, K., Veronesi, F., Corsi, C., Mor-Avi, V., Yamat, M., Weinert, L., Lang, R., Badano, L., Faita, F., Di Lascio, N., Bruno, R., Bianchini, E., Ghiadoni, L., Sicari, R., Gemignani, V., Angelis, A., Ageli, K., Ioakimidis, N., Chrysohoou, C., Agelakas, A., Felekos, I., Vaina, S., Aznaourides, K., Vlachopoulos, C., Stefanadis, C., Nemes, A., Szolnoky, G., Gavaller, H., Gonczy, A., Kemeny, L., Forster, T., Ramalho, A., Placido, R., Marta, L., Menezes, M., Magalhaes, A., Cortez Dias, N., Martins, S., Almeida, A., Pinto, F., Nunes Diogo, A., Botezatu, C.-D., Enache, R., Popescu, B., Nastase, O., Coman, M., Ghiorghiu, I., Calin, A., Rosca, M., Beladan, C., Ginghina, C., Grapsa, J., Cabrita, I., Durighel, G., O'regan, D., Dawson, D., Nihoyannopoulos, P., Pellicori, P., Kallvikbacka-Bennett, A., Zhang, J., Lukaschuk, E., Joseph, A., Bourantas, C., Loh, H., Bragadeesh, T., Clark, A., Cleland, J., Lomax, S., Putzu, P., Diercx, R., Parsons, S., Dicken, B., Vered, Z., Adirevitz, L., Dragu, R., Blatt, A., Karev, E., Malca, Y., Roytvarf, A., Marek, D., Sovova, E., Berkova, M., Cihalik, C., Taborsky, M., Lindqvist, P., Tossavainen, E., Soderberg, S., Gonzales, M., Gustavsson, S., Henein, M., Sonne, C., Bott-Fluegel, L., Hauck, S., Lesevic, H., Hadamitzky, M., Wolf, P., Kolb, C., Bandera, F., Pellegrino, M., Generati, G., Donghi, V., Alfonzetti, E., Castelvecchio, S., Menicanti, L., Guazzi, M., Buchyte, S., Rinkuniene, D., Jurkevicius, R., Smarz, K., Zaborska, B., Jaxa-Chamiec, T., Maciejewski, P., Budaj, A., Santoro, A., Federico Alvino, F., Giovanni Antonelli, G., Roberta Molle, R., Matteo Bertini, M., Stefano Lunghetti, S., Sergio Mondillo, S., Henri, C., Magne, J., Dulgheru, R., Laaraibi, S., Voilliot, D., Kou, S., Pierard, L., Lancellotti, P., Szulik, M., Stabryla-Deska, J., Kalinowski, M., Sliwinska, A., Szymala, M., Lenarczyk, R., Kalarus, Z., Kukulski, T., Yiangou, K., Azina, C., Yiangou, A., Ioannides, M., Chimonides, S., Baysal, S., Pirat, B., Okyay, K., Bal, U., Muderrisoglu, H., Popovic, D., Ostojic, M., Petrovic, M., Vujisic-Tesic, B., Arandjelovic, A., Petrovic, I., Banovic, M., Popovic, B., Vukcevic, V., Damjanovic, S., Velasco Del Castillo, S., Onaindia Gandarias, J., Arana Achaga, X., Laraudogoitia Zaldumbide, E., Rodriguez Sanchez, I., Cacicedo De Bobadilla, A., Romero Pereiro, A., Aguirre Larracoechea, U., Salinas, T., Subinas, A., Elzbieciak, M., Wita, K., Grabka, M., Chmurawa, J., Doruchowska, A., Turski, M., Filipecki, A., Wybraniec, M., Mizia-Stec, K., Varho, V., Karjalainen, P., Lehtinen, T., Airaksinen, J., Ylitalo, A., Kiviniemi, T., Gargiulo, P., Galderisi, M., D' Amore, C., Lo Iudice, F., Savarese, G., Casaretti, L., Pellegrino, A., Fabiani, I., La Mura, L., Perrone Filardi, P., Kim, J. Y., Chung, W., Yu, J., Choi, Y., Park, C., Youn, H., Lee, M., Nagy, A., Manouras, A., Gunyeli, E., Gustafsson, U., Shahgaldi, K., Winter, R., Johnsson, J., Zagatina, A., Krylova, L., Zhuravskaya, N., Vareldzyan, Y., Tyurina, T., Clitsenko, O., Khalifa, E. A., Ashour, Z., Elnagar, W., Jung, I., Seo, H., Lee, S., Lim, D., Mizariene, V., Verseckaite, R., Janenaite, J., Jonkaitiene, R., Sanchez Espino, A., Bonaque Gonzalez, J., Merchan Ortega, G., Bolivar Herrera, N., Ikuta, I., Macancela Quinones, J., Gomez Recio, M., Silva Fazendas Adame, P. R., Caldeira, D., Stuart, B., Almeida, S., Cruz, I., Ferreira, A., Freire, G., Lopes, L., Cotrim, C., Pereira, H., Mediratta, A., Moss, J., Nayak, H., Al Amri, I., Debonnaire, P., Van Der Kley, F., Schalij, M., Bax, J., Ajmone Marsan, N., Delgado, V., Schmidt, F. P., Gniewosz, T., Jabs, A., Munzel, T., Jansen, T., Kaempfner, D., Hink, U., Von Bardeleben, R., Jose, J., George, O., Joseph, G., Adawi, S., Najjar, R., Ahronson, D., Shiran, A., Van Riel, A., Boerlage - Van Dijk, K., De Bruin - Bon, H., Araki, M., Meregalli, P., Koch, K., Vis, M., Mulder, B., Baan, J., Bouma, B., Marciniak, A., Elton, D., Glover, K., Campbell, I., Sharma, R., Batalha, S., Lourenco, C., Oliveira Da Silva, C., Caballero, L., Garcia-Lara, J., Gonzalez-Carrillo, J., Oliva, M., Saura, D., Garcia-Navarro, M., Espinosa, M., Pinar, E., Valdes, M., De La Morena, G., Barreiro Perez, M., Lopez Perez, M., Roy, D., Brecker, S., Venkateshvaran, A., Dash, P. K., Sola, S., Barooah, B., Govind, S. C., Brodin, L. A., Saura Espin, D., Caballero Jimenez, L., Gonzalez Carrillo, J., Oliva Sandoval, M., Lopez Ruiz, M., Garcia Navarro, M., Espinosa Garcia, M., Valdes Chavarri, M., De La Morena Valenzuela, G., Gatti, G., Dell'angela, L., Pinamonti, B., Benussi, B., Sinagra, G., Pappalardo, A., Hernandez, V., Saavedra, J., Gonzalez, A., Iglesias, P., Civantos, S., Guijarro, G., Monereo, S., Ikeda, M., Toh, N., Oe, H., Tanabe, Y., Watanabe, N., Ito, H., Ciampi, Q., Cortigiani, L., Pratali, L., Rigo, F., Villari, B., Picano, E., Yoon, J., Sohn, J., Kim, Y., Chang, H., Hong, G., Kim, T., Ha, J., Choi, B., Rim, S., Choi, E., Tibazarwa, K., Sliwa, K., Wonkam, A., Mayosi, B., Oryshchyn, N., Ivaniv, Y., Pavlyk, S., Lourenco, M. R., Azevedo, O., Moutinho, J., Nogueira, I., Fernandes, M., Pereira, V., Quelhas, I., Lourenco, A., Sunbul, M., Tigen, K., Karaahmet, T., Dundar, C., Ozben, B., Guler, A., Cincin, A., Bulut, M., Sari, I., Basaran, Y., Baydar, O., Kadriye Kilickesmez, K., Ugur Coskun, U., Polat Canbolat, P., Veysel Oktay, V., Umit Yasar Sinan, U., Okay Abaci, O., Cuneyt Kocas, C., Sinan Uner, S., Serdar Kucukoglu, S., Zaroui, A., Mourali, M., Ben Said, R., Asmi, M., Aloui, H., Kaabachi, N., Mechmeche, R., Saberniak, J., Hasselberg, N., Borgquist, R., Platonov, P., Holst, A., Edvardsen, T., Haugaa, K., Eran, A., Yueksel, D., Er, F., Gassanov, N., Rosenkranz, S., Baldus, S., Guedelhoefer, H., Faust, M., Caglayan, E., Matveeva, N., Nartsissova, G., Chernjavskij, A., Ippolito, R., De Palma, D., Muscariello, R., Santoro, C., Raia, R., Schiano-Lomoriello, V., Gargiulo, F., Lipari, P., Bonapace, S., Zenari, L., Valbusa, F., Rossi, A., Lanzoni, L., Canali, G., Molon, G., Campopiano, E., Barbieri, E., Ikonomidis, I., Varoudi, M., Papadavid, E., Theodoropoulos, K., Papadakis, I., Pavlidis, G., Triantafyllidi, H., Anastasiou - Nana, M., Rigopoulos, D., Lekakis, J., Ozen, G., Durmus, E., Kivrak, T., Atas, H., Direskeneli, H., Stevanovic, A., Dekleva, M., Trajic, S., Paunovic, N., Simic, A., Khan, S., Mushemi-Blake, S., Jouhra, F., Dennes, W., Monaghan, M., Melikian, N., Shah, A., Maceira Gonzalez, A. M., Lopez-Lereu, M., Monmeneu, J., Igual, B., Estornell, J., Boraita, A., Kosmala, W., Rojek, A., Bialy, D., Mysiak, A., Przewlocka-Kosmala, M., Popescu, I., Mancas, S., Mornos, C., Serbescu, I., Ionescu, G., Ionac, A., Gaudron, P., Niemann, M., Herrmann, S., Hu, K., Liu, D., Wojciech, K., Frantz, S., Bijnens, B., Ertl, G., Weidemann, F., Cosin-Sales, J., Ruvira, J., Diago, J., Aguilar, J., Cruz, C., Pinho, T., Madureira, A., Lebreiro, A., Dias, C., Ramos, I., Silva Cardoso, J., Julia Maciel, M., De Meester, P., Van De Bruaene, A., Herijgers, P., Voigt, J.-U., Budts, W., Franzoso, F., Voser, E., Wohlmut, C., Kellenberger, C., Valsangiacomo Buechel, E., Carrero, C., Benger, J., Parcerisa, M., Falconi, M., Oberti, P., Granja, M., Cagide, A., Del Pasqua, A., Secinaro, A., Antonelli, G., Iacomino, M., Toscano, A., Chinali, M., Esposito, C., Carotti, A., Pongiglione, G., Rinelli, G., Youssef Moustafa, A., Al Murayeh, M., Al Masswary, A., Al Sheikh, K., Moselhy, M., Dardir, M., Deising, J., Butz, T., Suermeci, G., Liebeton, J., Wennemann, R., Tzikas, S., Van Bracht, M., Prull, M., Trappe, H.-J., Martin Hidalgo, M., Delgado Ortega, M., Ruiz Ortiz, M., Mesa Rubio, D., Carrasco Avalos, F., Seoane Garcia, T., Pan Alvarez-Ossorio, M., Lopez Aguilera, J., Puentes Chiachio, M., Suarez De Lezo Cruz Conde, J., Petrovic, M. T., Giga, V., Stepanovic, J., Tesic, M., Jovanovic, I., Djordjevic-Dikic, A., Piatkowski, R., Kochanowski, J., Scislo, P., Opolski, G., Vareldzhyan, Y., Bombardini, T., Gherardi, S., Leone, O., Michelotto, E., Ciccarone, A., Tarantino, N., Ostuni, V., Rubino, M., Genco, W., Santoro, G., Carretta, D., Romito, R., Colonna, P., Cameli, M., Lunghetti, S., Lisi, M., Curci, V., Cameli, P., Focardi, M., Favilli, R., Mondillo, S., Hoffmann, R., Barletta, G., Von Bardeleben, S., Kasprzak, J., Greis, C., Vanoverschelde, J., Becher, H., Machida, T., Izumo, M., Suzuki, K., Kaimijima, R., Mizukoshi, K., Manabe-Uematsu, M., Takai, M., Harada, T., Akashi, Y., Martin Garcia, A., Arribas-Jimenez, A., Cruz-Gonzalez, I., Nieto, F., Iscar, A., Merchan, S., Martin-Luengo, C., Brecht, A., Theres, L., Spethmann, S., Dreger, H., Baumann, G., Knebel, F., Jasaityte, R., Heyde, B., Rademakers, F., Claus, P., D'hooge, J., Lervik Nilsen, L. C., Lund, J., Brekke, B., Stoylen, A., Giraldeau, G., Duchateau, N., Gabrielli, L., Penela, D., Evertz, R., Mont, L., Brugada, J., Berruezo, A., Sitges, M., Kordybach, M., Kowalski, M., Hoffman, P., Pilichowska, E., Baran, J., Kulakowski, P., Wahi, S., Vollbon, W., Leano, R., Thomas, A., Bricknell, K., Holland, D., Napier, S., Stanton, T., Teferici, D., Qirko, S., Petrela, E., Dibra, A., Bajraktari, G., Bara, P., Sanchis Ruiz, L., Andrea, R., Falces, C., Perez-Villa, F., Sulemane, S., Panoulas, V., Bratsas, A., Tam, F., Abduch, M., Alencar, A., Coracin, F., Barban, A., Saboya, R., Dulley, F., Mathias, W., Vieira, M., Buccheri, S., Mangiafico, S., Arcidiacono, A., Bottari, V., Leggio, S., Tamburino, C., Monte, I. P., Spitzer, E., Beitzke, D., Kaneider, A., Pavo, N., Gottsauner-Wolf, M., Wolf, F., Loewe, C., Mushtaq, S., Andreini, D., Pontone, G., Bertella, E., Conte, E., Baggiano, A., Annoni, A., Cortinovis, S., Fiorentini, C., Pepi, M., Gustafsson, M., Alehagen, U., Dahlstrom, U., Johansson, P., Faden, G., Faggiano, P., Albertini, L., Reverberi, C., Gaibazzi, N., Taylor, R. J., Moody, W., Umar, F., Edwards, N., Townend, J., Steeds, R., Leyva, F., Mihaila, S., Piasentini, E., Peluso, D., Casablanca, S., Naso, P., Puma, L., Iliceto, S., Vinereanu, D., Ciciarello, F. L., Agati, L., Cimino, S., De Luca, L., Petronilli, V., Fedele, F., and Tsverava, M.

Subjects
medicine.medical_specialty, Bundle branch block, business.industry, Left bundle branch block, Speckle tracking echocardiography, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Radial function, Ventricle, Internal medicine, Cardiology, medicine, Radiology, Nuclear Medicine and imaging, In patient, Cardiology and Cardiovascular Medicine, business
Published
2013
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41. Right ventricular geometry and function in pulmonary hypertension: non-invasive evaluation

Author

Peluso, D, Tona, F, Muraru, D, Romeo, G, Cucchini, U, Marra, M, Iliceto, S, Badano, L, PELUSO D, TONA F, MURARU D, ROMEO G, CUCCHINI U, MARRA MP, ILICETO S, BADANO L, Peluso, D, Tona, F, Muraru, D, Romeo, G, Cucchini, U, Marra, M, Iliceto, S, Badano, L, PELUSO D, TONA F, MURARU D, ROMEO G, CUCCHINI U, MARRA MP, ILICETO S, and BADANO L

Abstract

Pulmonary hypertension (PH) is a rare disease, which still carries a poor prognosis. PH is characterized by a pressure overload on the right ventricle (RV), which develops hypertrophy, followed by a progressive failure. Accordingly, recent evidence showed that RV function has an important prognostic role in patients with PH. Echocardiography, cardiac magnetic resonance (CMR), computed tomography, and nuclear imaging allow a non-invasive evaluation of the RV size and function, but only the first two are routinely used in the clinical arena. Some conventional echocardiographic parameters, such as TAPSE (tricuspid anular plane systolic excursion), have demonstrated prognostic value in patients with PH. Moreover, there are some new advanced echo techniques, which can provide a more detailed assessment of RV function. Three-dimensional (3D) echocardiography allows measurement of RV volumes and ejection fraction, and two-dimensional (2D) speckle tracking (STE), allows assessment of RV myocardial mechanics. CMR provides accurate measurement of RV volumes, ejection fraction, and mass and allows the characterization of the RV wall composition by identifying the presence of fibrosis by late gadolinium enhancement. Although CMR seems to hold promise for both initial assessment and follow-up of patients with PH, its main role has been restricted to diagnostic work-up only

Published
2014

42. Static and dynamic analysis of the mitral valve annulus in normal subjects: a three-dimensional transthoracic echocardiography study

Author

Mihaila, S, Muraru, D, Piasentini, E, Peluso, D, Casablanca, S, Naso, P, Puma, L, Iliceto, S, Vinereanu, D, Badano, L, Mihaila S, Muraru D, Piasentini E, Peluso D, Casablanca S, Naso P, Puma L, Iliceto S, Vinereanu D, Badano L, Mihaila, S, Muraru, D, Piasentini, E, Peluso, D, Casablanca, S, Naso, P, Puma, L, Iliceto, S, Vinereanu, D, Badano, L, Mihaila S, Muraru D, Piasentini E, Peluso D, Casablanca S, Naso P, Puma L, Iliceto S, Vinereanu D, and Badano L

Abstract

Reference values for mitral valve annulus (MVA) by 3D transthoracic echo (3D-TTE) are lacking. Thus, we acquired 3D-TTE data sets ofMV (33+4 vps) in 119 healthy volunteers (44+14 yrs; 55 M). A prototype software for 3D TTE (4D MVanalysis 2.3, TomTec, D) was used to measure MVA parameters atMV closure, peak-minim,mid- and end- systole.We excluded 9 subjects due to poor MV tracking (feasibility 93%). MVA reached lowest area close afterMVclosure (MVAareachange=29+5%), mostlydue to antero-posteriordiameter shortening (20+7%) (Figure). Lateral-medial diameter and circumference showed smaller changes (12+4% and 11+3%). MVA size differed between genders, being related to body size but not to age (table, figures). MVA static and dynamic sizing by 3D-TTE are highly feasible. Our data may foster their implementation in clinical settings

Published
2013

43. Reference values for aortic diameters obtained using both inner-­edge-­to-­inner-­edge and leading­-edge-­to-­leading-­edge methods in 190 healthy subjects

Author

Kocabay, G, Dal Bianco, L, Muraru, D, Peluso, D, Segafredo, B, Iliceto, S, Badano, L, Kocabay GK, Dal Bianco L, Muraru D, Peluso D, Segafredo B, Iliceto S, Badano L, Kocabay, G, Dal Bianco, L, Muraru, D, Peluso, D, Segafredo, B, Iliceto, S, Badano, L, Kocabay GK, Dal Bianco L, Muraru D, Peluso D, Segafredo B, Iliceto S, and Badano L

Abstract

ASE/EAE guidelines suggest to measure aortic diameters (AoD) using the leading edge-to-leading edge method (LEM), whereas ACC/AHA ones favor the inner edge-to-inner edge method (IEM) to increase reproducibility and consistency with MRI and CT. To obtain reference values of the AoD by transthoracic echocardiography using both LEM and IEM and to compare them, we prospectively studied 190 healthy volunteers (82 men, 44 + 14 years, range 18-80 years), using a Vivid E9 (GE Healthcare, Horten, Norway) with M5S probe and 2nd-harmonic imaging. On 2D images optimized for the aortic root and ascending aorta, a single observer performed offline measurements using LEM and IEM at the level of the aortic root (Ao-R), sino-tubular junction (STJ) and ascending aorta (AscAo, 1 cm from the STJ) at end-diastole (at R-wave on ECG). Reference AoD with both methods are reported in Table. As expected, at Bland-Altman’s analysis all AoD measured using LEM were significantly larger than those measured using IEM: Ao-R (bias= 3.1 mm; 95% LOA 0.9 – 5.3); STJ (bias=3.5 mm; 95% LOA 0.7 – 6.3), and AscAo (bias= 3.2 mm; 95% LOA 0.7 – 5.7). At multivariable regression analysis (including age, gender, body surface area (BSA), height, systolic blood pressure), age and BSA (adjusted R2= 0.42), were independent predictors of Ao-R diameters with both methods, while age, BSA and gender (adjusted R2 = 0.44) were independent predictors of AscAo diameter. Intra- and inter-observer variability was similar between LEM and IEM methods (2% vs 2%, p= 0.63, and 4% vs 5%, p=0.23 for AoR, respectively; and 3% vs 2%, p= 0.26, and 4% vs 6%, p= 0.15 for AscAo, respectively). This is the first report about reference values of the AoD obtained using both LEM and IEM, the difference in diameter measurement between the two methods, and the independent determinants of them in a largee population of healthy subjects.

Published
2012

44. Quantitative analysis of mitral valve geometry by transthoracic three-dimensional echocardiography: reference values, feasibility and reproducibility

Author

Muraru, D, Cattarina, M, Dal Bianco, L, Peluso, D, Zoppellaro, G, Segafredo, B, Calore, C, Cucchini, U, Iliceto, S, Badano, L, Muraru D, Cattarina M, Dal Bianco L, Peluso D, Zoppellaro G, Segafredo B, Calore C, Cucchini U, Iliceto S, Badano L, Muraru, D, Cattarina, M, Dal Bianco, L, Peluso, D, Zoppellaro, G, Segafredo, B, Calore, C, Cucchini, U, Iliceto, S, Badano, L, Muraru D, Cattarina M, Dal Bianco L, Peluso D, Zoppellaro G, Segafredo B, Calore C, Cucchini U, Iliceto S, and Badano L

Abstract

Background: Quantitative analysis of mitral valve (MV) can discriminate among various mechanisms causing valve insufficiency. There are no established reference values for MV geometry, nor data on its feasibility and reproducibility with latest transthoracic 3D echocardiography (3DTTE). Methods: Eighty-one consecutive healthy volunteers (43+13 years, range 18-70; 33 men) with good apical window underwent a 3D full-volume acquisition of MV apparatus (32+2 vps) using Vivid E9 (BT 12, GE Healthcare, Horten, N). MV datasets were analyzed offline using a software recently developed for 3DTTE (TomTec MV assessment 2.0, Unterschleissheim, D). Intra- and inter-observer reproducibility were assessed in 15 subjects and expressed as intraclass correlation coefficients (ICC). Results: Five subjects were excluded due to low quality of 3D dataset with poor MV tracking (feasibility 94%). The average analysis time of one dataset (including manual editing) was 2’. Reference values of MV parameters and their reproducibility are reported in Table. Leaflet tenting and annulus measures were positively correlated with body surface area (BSA, r=0.34-0.53, p , 0.001), but not with age. After correcting for BSA, there were no gender differences in MV parameters. Conclusion: Quantitative analysis of MV by 3DTTE is highly feasible and reproducible, and reference values are reported. Our findings may support the implementation of MV quantitative analysis by 3DTTE in clinical settings.

Published
2012

45. Quantitation of cardiac chamber geometry and function using transthoracic three-dimensional echocardiography

Author

Muraru, D, Boccalini, F, Cattarina, M, Peluso, D, DAL BIANCO, L, Zoppellaro, G, Segafredo, B, Nour, A, Sarais, C, Badano, L, MURARU D, BOCCALINI F, CATTARINA M, PELUSO D, DAL BIANCO L, ZOPPELLARO G, SEGAFREDO B, NOUR A, SARAIS C, BADANO L, Muraru, D, Boccalini, F, Cattarina, M, Peluso, D, DAL BIANCO, L, Zoppellaro, G, Segafredo, B, Nour, A, Sarais, C, Badano, L, MURARU D, BOCCALINI F, CATTARINA M, PELUSO D, DAL BIANCO L, ZOPPELLARO G, SEGAFREDO B, NOUR A, SARAIS C, and BADANO L

Abstract

Quantification of cardiac chambers size, geometry and function represent the most frequent indications for an echocardiographic study and are pivotal for patient evaluation and management. Three-dimensional echocardiography (3DE) enables an easier, more accurate and reproducible interpretation of the complex geometry of cardiac chambers, overcoming the intrinsic limitations of conventional two-dimensional echocardiography (2DE). One major advantage of the third dimension is the improvement in the accuracy and reproducibility of chamber volume measurement by eliminating geometric assumptions and errors caused by foreshortened views. This feature render the technique feasible and reliable even in patients with asymmetric or distorted cardiac chambers, paradoxically the subjects in whom an accurate quantification is most needed. The purpose of this review is to analyze the role of 3DE in chamber quantification, emphasizing the incremental benefits of 3DE over conventional 2DE.

Published
2012

46. Two-dimensional assessment of tricuspid annulus dynamics and diameters: study for new reference values

Author

Miglioranza, MH, Muraru, D, Peluso, D, Cucchini, U, Mihaila, S, Naso, P, Puma, L, Kocabay, G, Iliceto, S, Badano, L, Miglioranza, M, Muraru, D, Peluso, D, Cucchini, U, Mihaila, S, Naso, P, Puma, L, Kocabay, G, Iliceto, S, and Badano, L

Abstract

Background: Tricuspid annulus (TA) size and function plays an important role in decision-making process about the need of associated TA annuloplasty during left sided cardiac surgery. Recommendations about echo assessment of TA don't indicate the view and the timing where TA should be measured. Our aim was to study TA diameters and shortening in different 2D TTE views to assess the extent of their variability. Methods: Cross-sectional study of normal volunteers. TA was measured from 3 2DTTE views (apical 4-CH, LAX-RV inflow, SAX basal) at 5 time points during cardiac cycle. TA fractional shortening diameter was obtained as (TV opening early-filling – Mid-systole) / TV opening early-filling. Result: 100pts; 42%male; 44±13yrs. TA diameters are in the Table. Fractional shortening of TA was 22±7%, 18±8%, 31±16% in 4-CH, LAX-RV inflow and SAX basal views respectively. Conclusion: This study support new references values for TA evaluation using 2D TTE. Values vary according to 2D TTE view and cardiac cycle time, showing the dynamism and complex geometry of TA

Published
2013

47. Static and dynamic analysis of the mitral valve annulus in normal subjects: a three-dimensional transthoracic echocardiography study

Author

Mihaila S, Muraru D, Piasentini E, Peluso D, Casablanca S, Naso P, Puma L, Iliceto S, Vinereanu D, Badano L, Mihaila, S, Muraru, D, Piasentini, E, Peluso, D, Casablanca, S, Naso, P, Puma, L, Iliceto, S, Vinereanu, D, and Badano, L

Subjects
Echocardiography, Mitral annulu, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE
Abstract

Reference values for mitral valve annulus (MVA) by 3D transthoracic echo (3D-TTE) are lacking. Thus, we acquired 3D-TTE data sets ofMV (33+4 vps) in 119 healthy volunteers (44+14 yrs; 55 M). A prototype software for 3D TTE (4D MVanalysis 2.3, TomTec, D) was used to measure MVA parameters atMV closure, peak-minim,mid- and end- systole.We excluded 9 subjects due to poor MV tracking (feasibility 93%). MVA reached lowest area close afterMVclosure (MVAareachange=29+5%), mostlydue to antero-posteriordiameter shortening (20+7%) (Figure). Lateral-medial diameter and circumference showed smaller changes (12+4% and 11+3%). MVA size differed between genders, being related to body size but not to age (table, figures). MVA static and dynamic sizing by 3D-TTE are highly feasible. Our data may foster their implementation in clinical settings

Published
2013

48. Reference values for aortic diameters obtained using both inner-­edge-­to-­inner-­edge and leading­-edge-­to-­leading-­edge methods in 190 healthy subjects

Author

Kocabay GK, Dal Bianco L, Muraru D, Peluso D, Segafredo B, Iliceto S, Badano L, Kocabay, G, Dal Bianco, L, Muraru, D, Peluso, D, Segafredo, B, Iliceto, S, and Badano, L

Subjects
aorta, echocardiography, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, reference values
Abstract

ASE/EAE guidelines suggest to measure aortic diameters (AoD) using the leading edge-to-leading edge method (LEM), whereas ACC/AHA ones favor the inner edge-to-inner edge method (IEM) to increase reproducibility and consistency with MRI and CT. To obtain reference values of the AoD by transthoracic echocardiography using both LEM and IEM and to compare them, we prospectively studied 190 healthy volunteers (82 men, 44 + 14 years, range 18-80 years), using a Vivid E9 (GE Healthcare, Horten, Norway) with M5S probe and 2nd-harmonic imaging. On 2D images optimized for the aortic root and ascending aorta, a single observer performed offline measurements using LEM and IEM at the level of the aortic root (Ao-R), sino-tubular junction (STJ) and ascending aorta (AscAo, 1 cm from the STJ) at end-diastole (at R-wave on ECG). Reference AoD with both methods are reported in Table. As expected, at Bland-Altman’s analysis all AoD measured using LEM were significantly larger than those measured using IEM: Ao-R (bias= 3.1 mm; 95% LOA 0.9 – 5.3); STJ (bias=3.5 mm; 95% LOA 0.7 – 6.3), and AscAo (bias= 3.2 mm; 95% LOA 0.7 – 5.7). At multivariable regression analysis (including age, gender, body surface area (BSA), height, systolic blood pressure), age and BSA (adjusted R2= 0.42), were independent predictors of Ao-R diameters with both methods, while age, BSA and gender (adjusted R2 = 0.44) were independent predictors of AscAo diameter. Intra- and inter-observer variability was similar between LEM and IEM methods (2% vs 2%, p= 0.63, and 4% vs 5%, p=0.23 for AoR, respectively; and 3% vs 2%, p= 0.26, and 4% vs 6%, p= 0.15 for AscAo, respectively). This is the first report about reference values of the AoD obtained using both LEM and IEM, the difference in diameter measurement between the two methods, and the independent determinants of them in a largee population of healthy subjects.

Published
2012

49. Quantitative analysis of mitral valve geometry by transthoracic three-dimensional echocardiography: reference values, feasibility and reproducibility

Author

Muraru D, Cattarina M, Dal Bianco L, Peluso D, Zoppellaro G, Segafredo B, Calore C, Cucchini U, Iliceto S, Badano L, Muraru, D, Cattarina, M, Dal Bianco, L, Peluso, D, Zoppellaro, G, Segafredo, B, Calore, C, Cucchini, U, Iliceto, S, and Badano, L

Subjects
mitral valve, healthy volunteers
Abstract

Background: Quantitative analysis of mitral valve (MV) can discriminate among various mechanisms causing valve insufficiency. There are no established reference values for MV geometry, nor data on its feasibility and reproducibility with latest transthoracic 3D echocardiography (3DTTE). Methods: Eighty-one consecutive healthy volunteers (43+13 years, range 18-70; 33 men) with good apical window underwent a 3D full-volume acquisition of MV apparatus (32+2 vps) using Vivid E9 (BT 12, GE Healthcare, Horten, N). MV datasets were analyzed offline using a software recently developed for 3DTTE (TomTec MV assessment 2.0, Unterschleissheim, D). Intra- and inter-observer reproducibility were assessed in 15 subjects and expressed as intraclass correlation coefficients (ICC). Results: Five subjects were excluded due to low quality of 3D dataset with poor MV tracking (feasibility 94%). The average analysis time of one dataset (including manual editing) was 2’. Reference values of MV parameters and their reproducibility are reported in Table. Leaflet tenting and annulus measures were positively correlated with body surface area (BSA, r=0.34-0.53, p , 0.001), but not with age. After correcting for BSA, there were no gender differences in MV parameters. Conclusion: Quantitative analysis of MV by 3DTTE is highly feasible and reproducible, and reference values are reported. Our findings may support the implementation of MV quantitative analysis by 3DTTE in clinical settings.

Published
2012

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