11,349 results on '"Department of Gynaecology"'
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2. Predicting Response In Cervical Intraepithelial Neoplasia to Topical Imiquimod Treatment (PRedICT-TOPIC)
- Author
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ZonMw: The Netherlands Organisation for Health Research and Development, Stichting Olijf: Dutch patient association for women with gynaecological cancer, Leids Universitair Medisch Centrum: Department of Medical Oncology and Department of Pathology, Maastricht Universitair Medisch Centrum: Department of Gynaecology and Department of Pathology, Erasmus Medisch Centrum: Department of Gynaecology, Radboud Medisch Centrum: Department of Gynaecology, and Edith van Esch, Principal Investigator, gynaecologist
- Published
- 2023
3. Study of Offspring of Women With Type 1 Diabetes (EPICOM)
- Author
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University of Copenhagen, Department of Gynaecology and Obstetrics, Rigshospitalet, Copenhagen, Rigshospitalet, Denmark, University of Southern Denmark, University of Aarhus, Aarhus University Hospital, and Zuzana Vlachová, MD, Cand. med.
- Published
- 2018
4. Elective Cancer Surgery in COVID-19-Free Surgical Pathways during the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study
- Author
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Writing Group (denotes joint first author) James, C Glasbey (UK), Dmitri Nepogodiev (UK), Joana FF Simoes (Portugal), Omar Omar (UK), Elizabeth Li (UK), Mary, L Venn (UK), Mohammad Abou Chaar (Jordan), Vita Capizzi (Italy), Daoud Chaudhry (UK), Anant Desai (UK), Jonathan, G Edwards (UK), Jonathan, P Evans (UK), Marco Fiore (Italy), Jose Flavio Videria (Portugal), Samuel, J Ford (UK), Ian Ganyli (USA), Ewen, A Griffiths (UK), Rohan, R Gujjuri (UK), Angelos, G Kolias (UK), Haytham MA Kaafarani (USA), Ana Minaya-Bravo (Spain), Siobhan, C McKay (UK), Helen, M Mohan (Ireland), Keith Roberts (UK), Carlos San Miguel-Mé, ndez (Spain), Peter Pockney (Australia), Richard Shaw (UK), Neil, J Smart (UK), Grant, D Stewart (UK), Sudha Sundar (UK), Raghavan Vidya (UK), Aneel, A Bhangu (UK, Statistical analysis Glasbey JC, Overall guarantor)., Omar, O (Lead statistician), Bhangu, A CovidSurg Operations Committee Kwabena Siaw-Acheampong, Ruth, A Benson, Edward, Bywater, Daoud, Chaudhry, Brett, E Dawson, Jonathan, P Evans, James, C Glasbey, Rohan, R Gujjuri, Emily, Heritage, Conor, S Jones, Sivesh, K Kamarajah, Chetan, Khatri, Rachel, A Khaw, James, M Keatley, Andrew, Knight, Samuel, Lawday, Elizabeth, Li, Harvinder, S Mann, Ella, J Marson, Kenneth, A McLean, Siobhan, C Mckay, Emily, C Mills, Dmitri, Nepogodiev, Gianluca, Pellino, Maria, Picciochi, Elliott, H Taylor, Abhinav, Tiwari, Joana FF Simoes, Isobel, M Trout, Mary, L Venn, Richard JW Wilkin, International Cancer Leads (denotes specialty Principal Investigators) James C Glasbey (Chair), Aneel Bhangu., Colorectal: Neil, J Smart, Ana, Minaya-Bravo, Susan, Moug, Dale, Vimalchandran, Abigail, Vallance, Peter, Pockney, Oesophagogastric: Ewen, A Griffiths, Richard PT Evans, Philip, Townend, Hepatopancreatobilary: Keith Roberts, Siobhan, McKay, John, Isaac, Sohei, Satoi, Thoracic: John Edwards, Aman, S Coonar, Adrian, Marchbank, Edward, J Caruana, Georgia, R Layton, Akshay, Patel, Alessandro, Brunelli, Sarcoma: Samuel Ford, Anant, Desai, Alessandro, Gronchi, Marco, Fiore, Max, Almond, Fabio, Tirotta, Sinziana, Dumitra, Neurosurgery: Angelos Kolias, Stephen, J Price, Daniel, M Fountain, Michael, D Jenkinson, Peter, Hutchinson, Hani, J Marcus, Rory, J Piper, Laura, Lippa, Franco, Servadei, Ignatius, Esene, Christian, Freyschlag, Iuri, Neville, Gail, Rosseau, Karl, Schaller, Andreas, K Demetriades, Faith, Robertson, Alex, Alamri, Head and neck: Richard Shaw, Andrew, G Schache, Stuart, C Winter, Michael, Ho, Paul, Nankivell, Juan Rey Biel, Martin, Batstone, Ian, Ganly, Breast: Raghavan Vidya, Alex, Wilkins, Jagdeep, K Singh, Dinesh, Thekinkattil, Gynaecology: Sudha Sundar, Christina, Fotopoulou, Elaine, Leung, Tabassum, Khan, Luis, Chiva, Jalid, Sehouli, Anna, Fagotti, Paul, Cohen, Murat, Gutelkin, Rahel, Ghebre, Thomas, Konney, Rene, Pareja, Rob, Bristow, Sean, Dowdy, Shylasree TS Rajkumar, Joe, Ng, Keiiji, Fujiwara, Urology: Grant, D Stewart, Benjamin, Lamb, Krishna, Narahari, Alan, McNeill, Alexandra, Colquhoun, John, McGrath, Steve, Bromage, Ravi, Barod, Veeru, Kasivisvanathan, Dissemination Committee Joana FF Simoes (Chair), Tobias Klatte., Tom EF Abbott, Michel, Adamina, Adesoji, O Ademuyiwa, Arnav, Agarwal, Ehab, Alameer, Derek, Alderson, Felix, Alakaloko, Markus, Albertsmeiers, Osaid, Alser, Muhammad, Alshaar, Sattar, Alshryda, Alexis, P Arnaud, Knut Magne Augestad, Faris, Ayasra, José, Azevedo, Brittany, K Bankhead-Kendall, Emma, Barlow, Ruth, Blanco-Colino, Amanpreet, Brar, Kerry, A Breen, Chris, Bretherton, Igor Lima Buarque, Joshua, Burke, Mohammad, Chaar, Sohini, Chakrabortee, Peter, Christensen, Daniel, Cox, Moises, Cukier, Miguel, F Cunha, Giana, H Davidson, Salomone Di Saverio, Thomas, M Drake, John, G Edwards, Muhammed, Elhadi, Sameh, Emile, Shebani, Farik, J Edward Fitzgerald, Samuel, Ford, Tatiana, Garmanova, Gaetano, Gallo, Dhruv, Ghosh, Gustavo Mendonç, a Ataí, de Gomes, Gustavo, Grecinos, Ewen, A Griffiths, Madalegna, Grü, ndl, Constantine, Halkias, Ewen, M Harrison, Intisar, Hisham, Peter, J Hutchinson, Shelley, Hwang, Arda, Isik, Pascal, Jonker, Haytham MA Kaafarani, Angelos, Kolias, Schelto, Kruijff, Ismail, Lawani, Hans, Lederhuber, Sezai, Leventoglu, Andrey, Litvin, Andrew, Loehrer, Markus, W Lö, ffler, Maria Aguilera Lorena, Maria Marta Madolo, Piotr, Major, Janet, Martin, Hassan, N Mashbari, Dennis, Mazingi, Symeon, Metallidis, Helen, M Mohan, Rachel, Moore, David, Moszkowicz, Joshua, S Ng-Kamstra, Mayaba, Maimbo, Milagros, Niquen, Faustin, Ntirenganya, Maricarmen, Olivos, Kacimi, Oussama, Oumaima, Outani, Marie Dione Parreno-Sacdalanm, Francesco, Pata, Carlos Jose Perez Rivera, Thomas, D Pinkney, Willemijn van der Plas, Ahmad, Qureshi, Dejan, Radenkovic, Antonio Ramos- De la Medina, Keith, Roberts, April, C Roslani, Martin, Rutegå, Irè, ne, Santos, Raza, Sayyed, Andrew, Schache, Andreas, A Schnitzbauer, Seyi-Olajide, Justina O., Neil, Sharma, Richard, Shaw, Sebastian, Shu, Kjetil, Soreide, Antonino, Spinelli, Grant, D Stewart, Malin, Sund, Sudha, Sundar, Stephen, Tabiri, Georgios, Tsoulfas, Gabrielle, H van Ramshorst, Raghavan, Vidya, Dale, Vimalachandran, Oliver, J Warren, Duane, Wedderburn, Naomi, Wright, EuroSurg, European Society of Coloproctology (ESCP), Global Initiative for Children’, s Surgery (GICS), GlobalSurg, GlobalPaedSurg, ItSURG, PTSurg, SpainSurg, Italian Society of Colorectal Surgery (SICCR), Association of Surgeons in Training (ASiT), Irish Surgical Research Collaborative (ISRC), Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), Collaborators (denotes Site Principal Investigators) Argentina: Allemand C, Italian Society of Surgical Oncology (SICO)., Boccalatte, L, Figari, M, Lamm, M, Larrañ, aga, J, Marchitelli, C, Noll, F, Odetto, D, Perrotta, M, Saadi, J, Zamora, L (Hospital Italiano De Buenos Aires), Alurralde, C, Caram, El, Eskinazi, D, Mendoza, Jp, Usandivaras M (Sanatorio, 9 De Julio Sa), Badra, R, Esteban, A, Garcí, a, Js, a, Pm, Gerchunoff, Ji, Lucchini, Sm, NIgra, Ma, Armenia: Hovhannisyan T, Vargas L (Sanatorio Allende)., Australia: Gould T, Stepanyan A (Nairi Medical Center)., Gourlay, R, Griffiths, B (Calvary Mater Newcastle), Gananadha S, McLaren M (Canberra Hospital), Cecire, J, Joshi, N, Salindera, S, Sutherland, A (Coffs Harbour Health Campus), Ahn, Jh, Charlton, G, Chen, S, Gauri, N, Hayhurst, R, Jang, S, Jia, F, Mulligan, C, Yang, W, Ye, G, Zhang, H (Concord Repatriation General Hospital), Ballal, M, Gibson, D, Hayne, D, Moss, J, Richards, T, Viswambaram, P, Vo UG (Fiona Stanley Hospital), Bennetts, J, Bright, T, Brooke-Smith, M, Fong, R, Gricks, B, Lam, Yh, Ong, Bs, Szpytma, M, Watson, D (Flinders Medical Centre), Bagraith, K, Caird, S, Chan, E, Dawson, C, Ho, D, Jeyarajan, E, Jordan, S, Lim, A, Nolan, Gj, Oar, A, Parker, D, Puhalla, H, Quennell, A, Rutherford, L, Townend, P, Von Papen, M, Wullschleger, M (Gold Coast University Hospital), Blatt, A, Cope, D, Egoroff, N, Fenton, M, Gani, J, Lott, N, Pockney, P, Shugg, N (John Hunter Hospital), Elliott M, Phung D (Lifehouse), Phan D, Townend D (Lismore Base Hospital), Bong C, Gundara J (Logan Hospital), Frankel, A (Princess Alexandra Hospital), Bowman S, Guerra GR (Queen Elizabeth Ii Jubilee Hospital), Bolt, J, Buddingh, K, Dudi-Venkata, Nn, Jog, S, Kroon, Hm, Sammour, T, Smith, R, Stranz, C (Royal Adelaide Hospital), Batstone, M, Lah, K, McGahan, W, Mitchell, D, Morton, A, Pearce, A, Roberts, M, Sheahan, G, Swinson, B (Royal Brisbane And Women’, s Hospital), Alam, N, Banting, S, Chong, L, Choong, P, Clatworthy, S, Foley, D, Fox, A, Hii, Mw, Knowles, B, Mack, J, Read, M, Rowcroft, A, Ward, S, Austria: Lanner M (Kardinal Schwarzenberg Klinikum), Wright G (St Vincent’, s Hospital)., Kö, nigsrainer, I (Landeskrankenhaus Feldkirch), Bauer, M, Freyschlag, C, Kafka, M, Messner, F, 214, fner, D, Tsibulak, I (Medical University Of Innsbruck), Emmanuel, K, Grechenig, M, Gruber, R, Harald, M, hlberger, L, Presl, J, Azerbaijan: Namazov İ, Wimmer A (Paracelsus Medical University Salzburg)., Barbados: Barker D, Samadov E (Leyla Medical Centerl)., Boyce, R, Corbin, S, Doyle, A, Eastmond, A, Gill, R, Haynes, A, Millar, S, O’, Shea, M, Padmore, G, Paquette, N, Phillips, E, John S, St., Belgium: Flamey N, Walkes K (Queen Elizabeth Hospital)., Pattyn, P (Az Delta), Oosterlinck, W, Van den Eynde, J, Brazil: Gatti A, Van den Eynde R (Uz Leuven)., Nardi, C, Oliva, R (Hospital Geral De Pirajussara), De Cicco, R (Instituto De Câ, ncer Dr Arnaldo Vieira De Carvalho), Cecconello, I, Gregorio, P, Pontual Lima, L, Ribeiro Junior, U, Takeda, F, Canada: Kidane B, Terra RM (Instituto Do Câ, ncer De Estado De Sã, o Paulo). Bulgaria: Sokolov M (University Hospital Alexandrovska)., Srinathan, S (Health Sciences Centre), Boutros, M, Caminsky, N, Ghitulescu, G, Jamjoum, G, Moon, J, Pelletier, J, Vanounou, T, Wong, S (Jewish General Hospital), Dumitra, S, Kouyoumdjian, A (Mcgill University Health Center), Johnston B, Russell C (Saint John Regional Hospital), Demyttenaere, S, Mary’, s Hospital), Garfinkle R (St., Abou-Khalil, J, Nessim, C, Colombia: Almeciga A, Stevenson J (The Ottawa Hospital). Chile: Heredia F (Clí, nica Universitaria De Concepció, n)., Fletcher, A, Merchan A (Centro De Investigaciones Oncoló, gicas Clí, nica San Diego, - Ciosad), Puentes LO (Hospital San José, Croatia: Bač, ić, G, Mendoza Quevedo J (Subred Sur Occidente De Kennedy (Hospital De Kennedy))., Karlović, D, Krš, ul, D, Zelić, M (University Hospital Center Rijeka), Luksic I, Mamic M (University Hospital Dubrava), Bakmaz, B, 262, oza, I, Dijan, E, Katusic, Z, Mihanovic, J, Cyprus: Frantzeskou K, Rakvin I (Zadar General Hospital)., Gouvas, N, Kokkinos, G, Papatheodorou, P, Pozotou, I, Stavrinidou, O, Czechia: Martinek L, Yiallourou A (Nicosia General Hospital)., Skrovina, M, Szubota, I (Hospital &, amp, Oncological Centre Novy Jicin), 381, atecký, J (Slezská, Nemocnice V Opavě, P. o. ), Javurkova, V, Denmark: Avlund T, Klat J (University Hospital Ostrava)., Christensen, P, Harbjerg, Jl, Iversen, Lh, Kjaer, Dw, Kristensen, Hø, Mekhael, M (Aarhus University Hospital), Ebbehø, j, Al, Krarup, P, Schlesinger, N, Egypt: Abdelsamed A, Smith H (Bispebjerg Hospital)., Azzam, Ay, Salem, H, Seleim, A (Al Azhar University Hospitals), Abdelmajeed, A, Abdou, M, Abosamak, Ne, AL Sayed, M, Ashoush, F, Atta, R, Elazzazy, E, Elhoseiny, M, Elnemr, M, Elqasabi, Ms, Elsayed Hewalla ME, Elsherbini, I, Essam, E, Eweda, M, Ghallab, I, Hassan, E, Ibrahim, M, Metwalli, M, Mourad, M, Qatora, Ms, Ragab, M, Sabry, A, Saifeldin, H, Saleh Mesbah Mohamed Elkaffas, M, Samih, A, Samir Abdelaal, A, Shehata, S, Shenit, K (Alexandria Main University Hospital), Attia, D, Kamal, N, Osman, N (Alexandria Medical Research Institute), Abbas, Am, Abd Elazeem HAS, Abdelkarem, Mm, Alaa, S, Ali, Ak, Ayman, A, Azizeldine, Mg, Elkhayat, H, elghazaly S, M., Monib, Fa, Nageh, Ma, Saad, Mm, Salah, M, Shahine, M, Yousof, Ea, Youssef, A (Assiut University Hospital), Eldaly, A (El-Menshawy Hospital), ElFiky, M, Nabil, A (Kasr Alainy Faculty Of Medicine, Cairo, University), Amira, G, Sallam, I, Sherief, M, Sherif, A (Misr Cancer Center), Abdelrahman, A, Aboulkassem, H, Ghaly, G, Hamdy, R, Morsi, A, Sherif, G (National Cancer Institute), Abdeldayem, H, Abdelkader Salama, I, Balabel, M, Fayed, Y, Sherif AE (National Liver Institute, Finland: Kauppila J, Menoufia University). Ethiopia: Bekele D (Maddawalabu University Goba Referral Hospital)., Sarjanoja, E (Lä, nsi-Pohja Central Hospital), Helminen, O, Huhta, H, France: Beyrne C, Kauppila JH (Oulu University Hospital)., Jouffret, L, Lugans, L, Marie-Macron, L (Centre Hospitalier Avignon), Chouillard E, De Simone B (Centre Hospitalier Intercommunal Poissy Saint Germain En Laye), Bettoni, J, Dakpé, S, Devauchelle, B, Lavagen, N, Testelin, S (Chu Amiens), Boucher, S, Breheret, R, Gueutier, A, Kahn, A, Kü, n-Darbois, J (Chu Angers), Barrabe, A, Lakkis, Z, Louvrier, A, Manfredelli, S, Mathieu, P (Chu Besanç, on), Chebaro, A, Drubay, V, El amrani, M, Eveno, C, Lecolle, K, Legault, G, Martin, L, Piessen, G, Pruvot, Fr, Truant, S, Zerbib, P (Chu Lille), Ballouhey, Q, Barrat, B, Laloze, J, Salle, H, Taibi, A, Usseglio, J (Chu Limoges), Bergeat D, Merdrignac A (Chu Rennes - General Surgery), Le Roy, B, Perotto, Lo, Scalabre, A (Chu Saint Etienne), Aimé, A, Ezanno, A, Malgras, B (Hia Begin), Bouche P, Tzedakis S (Hô, pital Cochin - Aphp), Cotte, E, Glehen, O, Lifante, J (Hopital Lyon Sud), D’, Urso, A, Felli, E, Mutter, D, Pessaux, P, Seeliger, B (Hus, Pole Hé, pato-Digestif, / Ihu- Strasbourg), Bardet, J, Berry, R, Boddaert, G, Bonnet, S, Brian, E, Denet, C, Fuks, D, Gossot, D, Grigoroiu, M, Laforest, A, Levy-Zauberman, Y, Louis-Sylvestre, C, Moumen, A, Pourcher, G, Seguin-givelet, A, Tribillon, E (Institut Mutualiste Montsouris), Duchalais, E, Espitalier, F, Ferron, C, Germany: Bork U, Malard O (Nantes University Hospital)., Distler, M, Fritzmann, J, Kirchberg, J, Praetorius, C, Riediger, C, Weitz, J, Welsch, T, Wimberger, P (Carl-Gustav-Carus University, Dresden), Tu, Beyer, K, Kamphues, C, Lauscher, J, Loch, Fn, Schineis, C (Charité, University Medicine, Campus Benjamin Franklin), Albertsmeier, M, Angele, M, Kappenberger, A, Niess, H, Schiergens, T, Werner, J (Department of General, Visceral and Transplantation Surgery, Ludwig- Maximilians-Universitat Munich), Becker R, Jonescheit J (Heilig-Geist Hospital Bensheim), Pergolini I, Reim D (Klinikum Rechts Der Isar Tum School Of Medicine), Boeker, C, Hakami, I, Mall, J (Krh Nordstadt-Siloah Hospitals), Liokatis P, Smolka W (LMU Klinikum Campus Innenstadt), Nowak K, Reinhard T (Romed Klinikum Rosenheim), Hö, lzle, F, Modabber, A, Winnand, P (University Hospital Aachen), Knitschke, M (University Hospital Giessen And Marburg), Kauffmann P, Wolfer S (University Hospital Goettingen / Universitä, tsmedizin Goettingen), Kleeff, J, Lorenz, K, Michalski, C, Ronellenfitsch, U, Schneider, R (University Hospital Halle (Saale)), Bertolani, E, nigsrainer, A, Lö, ffler, Mw, Quante, M, Steidle, C, 220, berrü, ck, L, Yurttas, C (University Hospital Tuebingen), Betz, Cs, Bewarder, J, Bö, ttcher, A, Burg, S, Busch, C, Gosau, M, Heuer, A, Izbicki, J, Klatte, To, Koenig, D, Moeckelmann, N, Nitschke, C, Priemel, M, Smeets, R, Speth, U, Thole, S, Uzunoglu, Fg, Vollkommer, T, Zeller, N (University Medical Center Hamburg- Eppendorf), Battista, Mj, Gillen, K, Hasenburg, A, Krajnak, S, Linz, V, Schwab, R (University Of Mainz, Greece: Angelou K, Department Of Gynaecology And Obstetrics)., Haidopoulos, D, Rodolakis, A (Alexandra General Hospital), Antonakis, P, Bramis, K, Chardalias, L, Contis, I, Dafnios, N, Dellaportas, D, Fragulidis, G, Gklavas, A, Konstadoulakis, M, Memos, N, Papaconstantinou, I, Polydorou, A, Theodosopoulos, T, Vezakis, A (Aretaieion Hospital), Antonopoulou, Mi, Manatakis, Dk, Tasis, N (Athens Naval And Veterans Hospital), Arkadopoulos, N, Danias, N, Economopoulou, P, Kokoropoulos, P, Larentzakis, A, Michalopoulos, N, Selmani, J, Sidiropoulos, T, Tsaousis, V, Vassiliu, P (Attikon University General Hospital), Bouchagier, K, Klimopoulos, S, Paspaliari, D, Stylianidis, G (Evaggelismos General Hospital), Baxevanidou, K, Bouliaris, K, Chatzikomnitsa, P, Efthimiou, M, Giaglaras, A, Kalfountzos, C, Koukoulis, G, Ntziovara, Am, Petropoulos, K, Soulikia, K, Tsiamalou, I, Zervas, K, Zourntou, S (General Hospital Of Larissa “, Koutlimpaneio And Triantafylleio”, Baloyiannis, I, Diamantis, A, Gkrinia, E, Hajiioannou, J, Korais, C, Koukoura, O, Perivoliotis, K, Saratziotis, A, Skoulakis, C, Symeonidis, D, Tepetes, K, Tzovaras, G, Zacharoulis, D (General University Hospital Of Larissa), Alexoudi, V, Antoniades, K, Astreidis, I, Christidis, P, Deligiannidis, D, Grivas, T, Ioannidis, O, Kalaitsidou, I, Loutzidou, L, Mantevas, A, Michailidou, D, Paraskevopoulos, K, Politis, S, Stavroglou, A, Tatsis, D, Tilaveridis, I, Vahtsevanos, K, Venetis, G (George Papanikolaou General Hospital Of Thessaloniki), Karaitianos I, Tsirlis T (Henry Dunant Hospital Center), Charalabopoulos, A, Liakakos, T, Mpaili, E, Schizas, D, Spartalis, E, Syllaios, A, Zografos, C (Laiko University Hospital), Anthoulakis, C, Christou, C, Papadopoulos, V, Tooulias, A, Tsolakidis, D, Tsoulfas, G, Zouzoulas, D (Papageorgiou General Hospital), Athanasakis, E, Chrysos, E, Tsiaousis, J, Xenaki, S, Hong Kong: Futaba K, Xynos E (University Hospital Of Heraklion Crete And Interclinic Hospital Of Crete)., Ho, Mf, Hon, Sf, Mak, Twc, Ng SSM (Prince Of Wales Hospital), Hungary: Banky B, Foo CC (Queen Mary Hospital)., Ireland: Aremu M, Susztá, k N (Szent Borbá, la Kó, rhá, z)., Canas-Martinez, A, Cullivan, O, Murphy, C, Owens, P, Pickett, L (Connolly Hospital Blanchardstown), Akmenkalne, L, Byrne, J, Corrigan, M, Cullinane, C, Daly, A, Fleming, C, Jordan, P, Killeen, S, Lynch, N, McCarthy, A, Mustafa, H, Brien, S, Leary, P, Syed, Was, Vernon, L (Cork University Hospital), Callanan, D, Huang, L, Ionescu, A, Sheahan, P (South Infirmary Victoria University Hospital), Balasubramanian, I, Boland, M, Conlon, K, Evoy, D, Fearon, N, Gallagher, T, Geraghty, J, Heneghan, H, Kennedy, N, Maguire, D, McCartan, D, McDermott, Ew, Prichard, Rs, Winter, D (St Vincent’, s University Hospital), Alazawi, D, Barry, C, Boyle, T, Butt, W, Connolly, Em, Donlon, N, Donohue, C, Fahey, Ba, Farrell, R, Fitzgerald, C, Kinsella, J, Larkin, Jo, Lennon, P, Maguire, Pj, Mccormick, P, Mehigan, Bj, Mohan, H, Nugent, T, Sullivan, H, Ravi, N, Reynolds, Jv, Rogers, A, Shokuhi, P, Smith, J, Smith, La, James’, s Hospital), Timon C (St., Bashir, Y, Bass, G, Connelly, T, Earley, H, Elliott, Ja, Gillis, A, Kavanagh, D, Neary, P, riordan, J, Reynolds, Is, Rice, D, Ridgway, P, Umair, M, Whelan, M (Tallaght Hospital), Carroll, P, Collins, C, Corless, K, Finnegan, L, Fowler, A, Hogan, A, Kerin, M, Lowery, A, McAnena, P, McKevitt, K, Nizami, K, Ryan, É, Samy, A (University Hospital Galway), Coffey, Jc, Cunningham, R, Devine, M, Nally, D, Peirce, C, Tormey, S (University Hospital Limerick), Hardy, N, Malley, S, Italy: Macina S (Asst Mantua), Ryan M (University Hospital Waterford/University College Cork)., Mariani, Nm, Opocher, E, Pisani Ceretti A (Asst Santi Paolo, E Carlo), Ferrari, F, Odicino, F, Sartori, E (Asst Spedali Civili, Ospedale Di Brescia), Cotsoglou C, Granieri S (Asst Vimercate), Bianco, F, Camillo’, Colledan, M, Tornese, S, Zambelli MF (Asst-Papa Giovanni Xxiii- Bergamo), Bissolotti, G, Fusetti, S, Lemma, F (Azienda Ospedaliera Di Padova), Marino, M, Mirabella, A, Vaccarella, G (Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo), Agostini, C, Alemanno, G, Bartolini, I, Bergamini, C, Bruscino, A, Checcucci, C, De Vincenti, R, Di Bella, A, Fambrini, M, Fortuna, L, Maltinti, G, Muiesan, P, Petraglia, F, Prosperi, P, Ringressi, Mn, Risaliti, M, Sorbi, F, Taddei, A, Tucci, R (Azienda Ospedaliera Universitaria Careggi), Bassi, C, Campagnaro, T, Casetti, L, De Pastena, M, Esposito, A, Fontana, M, Guglielmi, A, Landoni, L, Malleo, G, Marchegiani, G, Nobile, S, Paiella, S, Pedrazzani, C, Rattizzato, S, Ruzzenente, A, Salvia, R, Turri, G, Tuveri, M (Azienda Ospedaliera Universitaria Integrata Di Verona), Bellora, P, Aloisio, G, Ferrari, M, Francone, E, Gentilli, S, Nikaj, H (Azienda Ospedaliero Universitaria Maggiore Della Carità, Bianchini, M, Chiarugi, M, Coccolini, F, Di Franco, G, Furbetta, N, Gianardi, D, Guadagni, S, Morelli, L, Palmeri, M, Tartaglia, D (Azienda Ospedaliero Universitaria Pisana), Anania, G, Carcoforo, P, Chiozza, M, De Troia, A, Koleva Radica, M, Portinari, M, Sibilla, Mg, Urbani, A (Azienda Ospedaliero Universitaria Sant’, anna), Fabbri, N, Feo, Cv, Gennari, S, Parini, S, Righini E (Azienda Unità, Sanitaria Locale di Ferrara, - University of Ferrara), Ampollini, L, Bellanti, L, Bergonzani, M, Bertoli, G, Bocchialini, G, Angelo, G, Lanfranco, D, Musini, L, Poli, T, Santoro, Gp, Varazzani, A (Azienda Ospedaliero-Universitaria Di Parma), Aguzzoli, L, Borgonovo, G, Castro Ruiz, C, Coiro, S, Falco, G, Mandato, Vd, Mastrofilippo, V, Montella, Mt, Annessi, V, Zizzo M (Azienda Unità, Sanitaria Locale, - Irccs Di Reggio Emilia), Grossi, U, Novello, S, Romano, M, Rossi, S, Zanus, G (Ca’, Foncello Treviso-DISCOG-Universit Di Padova), Esposito, G, Frongia, F, Pisanu, A, Podda, M (Cagliari University Hospital), Belluco, C, Lauretta, A, Montori, G, Moras, L, Olivieri, M (Centro Di Riferimento Oncologico Di Aviano (Cro) Irccs), Bussu, F, Carta, Ag, Cossu, Ml, Cottu, P, Fancellu, A, Feo, Cf, Ginesu, Gc, Giuliani, G, Madonia, M, Perra, T, Piras, A, Porcu, A, Rizzo, D, Scanu, Am, Tedde, A, Tedde, M (Cliniche San Pietro, Sassari), A. o. u., Delrio, P, Rega D (Colorectal Surgical Oncology Unit, - Istituto Nazionale Tumori Fondazione, Pascale-I. r. c. c. s., ), Badalamenti, G, Campisi, G, Cordova, A, Franza, M, Maniaci, G, Rinaldi, G, Toia, F (Department Of Surgical, University Of Palermo), Oncological And Oral Sciences., Calabrò, M, Farnesi, F, Lunghi, Eg, Muratore, A, Pipitone Federico NS (Edoardo Agnelli), Bà, mbina, F, Andrea, G, Familiari, P, Picotti, V (Fabrizio Spaziani), De Palma, G, Luglio, G, Pagano, G, Tropeano FP (Federico Ii University Hospital), Baldari, L, Beltramini, Ga, Boni, L, Cassinotti, E, Gianni’, Pignataro, L, Torretta S (Fondazione Irccs Ca’, Granda, - Ospedale Maggiore Policlinico), Abatini, C, Baia, M, Biasoni, D, Bogani, G, Cadenelli, P, Capizzi, V, Cioffi, Spb, Citterio, D, Comini, Lv, Cosimelli, M, Fiore, M, Folli, S, Gennaro, M, Giannini, L, Gronchi, A, Guaglio, M, Macchi, A, Martinelli, F, Mazzaferro, V, Mosca, A, Pasquali, S, Piazza, C, Raspagliesi, F, Rolli, L, Salvioni, R, Sarpietro, G, Sarre, C, Sorrentino, L (Fondazione Irccs Istituto Nazionale Dei Tumori, Milano), Agnes, A, Alfieri, S, Belia, F, Biondi, A, Cozza, V, Amore, A, Ugo, D, De Simone, V, Fagotti, A, Gasparini, G, Gordini, L, Litta, F, Lombardi, Cp, Lorenzon, L, Marra, Aa, Marzi, F, Moro, A, Parello, A, Perrone, E, Persiani, R, Ratto, C, Rosa, F, Saponaro, G, Scambia, G, Scrima, O, Sganga, G, Tudisco, R (Fondazione Policlinico Universitario Agostino Gemelli), Belli, A, Granata, V, Izzo, F, Palaia, R, Patrone R (Hpb Surgical Oncology Unit, - Istituto Nazionale Tumori Fondazione, Pascale- I. r. c. c. s., ), Carrano, Fm, Carvello, Mm, De Virgilio, A, Di Candido, F, Ferreli, F, Gaino, F, Mercante, G, Rossi, V, Spinelli, A, Spriano, G (Humanitas Clinical And Research Center Irccs, Rozzano (Mi) &, Humanitas, University, Department Of Biomedical Sciences, Pieve Emanuele (Mi)), Donati, Dm, Frisoni, T, Palmerini, E (Irccs Istituto Ortopedico Rizzoli), Aprile, A, Barra, F, Batistotti, P, Ferrero, S, Fregatti, P, Scabini, S, Sparavigna, M (Irccs Ospedale Policlinico San Martino), Asti, E, Bernardi, D, Bonavina, L, Lovece, A (University of Milan, IRCCS Policlinico San Donato), Adamoli, L, Ansarin, M, Cenciarelli, S, Chu, F, De Berardinis, R, Fumagalli Romario, U, Mastrilli, F, Pietrobon, G, Tagliabue M (Istituto Europeo Di Oncologia, - Irccs -Milano), Badellino, E, Ferrero, A, Massobrio, R (Mauriziano Hospital Torino, Italy), De Manzoni Garberini, A (Ospedale Civile Spirito Santo), Federico, P, Maida, P, Marra, E, Marte, G, Petrillo, A, Tammaro, T, Tufo, A (Ospedale Del Mare), Berselli, M, Borroni, G, Cocozza, E, Conti, L, Desio, M, Livraghi, L, Quintodei, V, Rizzi, A, Zullo A (Ospedale Di Circolo, E Fondazione Macchi (Varese)), Baldi, C, Corbellini, C, Sampietro GM (Ospedale Di Rho, - Asst Rhodense), Cellerino P (Ospedale Fatebenefratelli, E Oftalmico), Baldini, E, Capelli, P, Isolani, Sm, Ribolla, M (Ospedale Guglielmo Da Saliceto Piacenza), Bondurri, A, Colombo, F, Ferrario, L, Guerci, C, Maffioli, A (Ospedale Luigi Sacco Milano), Armao, T, Ballabio, M, Bisagni, P, Gagliano, A, Longhi, M, Madonini, M, Pizzini, P (Ospedale Maggiore Di Lodi), Baietti, Am, Biasini, M, Maremonti, P, Neri, F, Prucher, Gm, Ricci, S, Ruggiero, F, Zarabini AG (Ospedale Maggiore/Bellaria Carlo Alberto Pizzardi Ausl Bologna), Barmasse, R, Mochet, S, Usai, A (Ospedale Regionale Umberto Parini), Leonardo - Asl Napoli 3 Sud, Incollingo P (Ospedale S., Castellammare Di Stabia), Mancini, S, Marino Cosentino, L, Sagnotta, A (Ospedale San Filippo Neri), Fruscio, R, Grassi, T, Nespoli, Lc, Tamini, N (Ospedale San Gerardo), Anastasi, A, Bartalucci, B, Bellacci, A, Canonico, G, Capezzuoli, L, Di Martino, C, Ipponi, P, Linari, C, Montelatici, M, Nelli, T, Spagni, G, Tirloni, L, Vitali, A (Ospedale San Giovanni Di Dio), Abate, E, Casati, M, Casiraghi, T, Laface, L, Schiavo M (Ospedale Vittorio Emanuele Iii, - Carate Brianza), Arminio, A, Cotoia, A, Lizzi, V, Vovola, F (Ospedali Riuniti Azienda Ospedaliera Universitaria Foggia), Vergari, R (Ospedali Riuniti Di Ancona), Ugo, S, Depalma, N, 8220, Vito Fazzi”, Spampinato MG (P. o., Bartolucci, P, Brachini, G, Bruzzaniti, P, Chiappini, A, Chiarella, V, Ciccarone, F, Cicerchia, Pm, Cirillo, B, De Toma, G, Di bartolomeo, A, Fiori, E, Fonsi, Gb, Franco, G, Frati, A, Giugliano, M, Iannone, I, La Torre, F, Lapolla, P, Leonardo, C, Marruzzo, G, Meneghini, S, Mingoli, A, Ribuffo, D, Salvati, M, Santoro, A, Sapienza, P, Scafa, Ak, Simonelli, L, Zambon M (Policlinico Umberto, I Sapienza University Of Rome), Capolupo, Gt, Carannante, F, Caricato, M, Mascianà, G, Mazzotta, E (Policlinico Universitario Campus Bio Medico Of Rome), Gattolin, A, Migliore, M, Rimonda, R, Sasia, D, Travaglio, E (Regina Montis Regalis Hospital, Mondovì, Cervellera, M, Gori, A, Sartarelli, L, orsola-Malpighi Hospital), Tonini V (S., Giacometti, M, Zonta, S (Ospedale San Biagio, Asl, VCO), Chessa, A, Fiorini, A, Norcini, C (San Giovanni Di Dio), Colletti, G, Confalonieri, M, Costanzi, A, Frattaruolo, C, Mari, G, Monteleone, M (San Leopoldo Mandic), Bandiera, A, Bocciolone, L, Bonavina, G, Candiani, M, De Nardi, P, Gagliardi, F, Medone, M, Mortini, P, Negri, G, Ottolina, J, Parise, P, Piloni, M, Sileri, P, Vignali, A (San Raffaele Scientific Institute, Milan), Belvedere, A, Bernante, P, Bertoglio, P, Boussedra, S, Brunocilla, E, Cipriani, R, Cisternino, G, De Crescenzo, E, De Iaco, P, Dondi, G, Frio, F, Jovine, E, Mineo Bianchi, F, Neri, J, Parlanti, D, Perrone, Am, Pezzuto, Ap, Pignatti, M, Pinto, V, Poggioli, G, Ravaioli, M, Rottoli, M, Schiavina, R, Serenari, M, Serra, M, Solli, P, Taffurelli, M, Tanzanu, M, Tesei, M, Violante, T, Zanotti, S (Sant’, orsola Hospital, Alma Mater Studiorum University Of Bologna, Borghi, F, Cianflocca, D, Di Maria Grimaldi, S, Donati, D, Gelarda, E, Geretto, P, Giraudo, G, Giuffrida, Mc, Marano, A, Palagi, S, Pellegrino, L, Peluso, C, Testa V (Santa Croce, E Carle Hospital, Cuneo), Agresta, F, Prando, D, Zese M (Santa Maria Degli Angeli Hospital Ulss5, - Adria), Aquila, F, Gambacciani, C, Lippa, L, Pieri, F, Santonocito OS (Spedali Riuniti Di Livorno), Armatura, G, Bertelli, G, Frena, A, Marinello, P, Notte, F, Patauner, S, Moritz Hospital), Scotton G (St., Fulginiti, Sf, Gallo, G, Sammarco, G, Vescio, G (University ‘, Magna Graecia’, Of Catanzaro), Balercia, P, Catarzi, L, Consorti G (University Hospital Umberto, I Ancona), Di Marzo, F (Valtiberina), Japan: Daiko H, Fontana T (Vittorio Emanuele)., Ishikawa, M, Ishiyama, K, Iwata, S, Kanematsu, K, Kanemitsu, Y, Kato, T, Kawai, A, Kobayashi, E, Kobayashi Kato, M, Moritani, K, Nakatani, F, Oguma, J, Tanase, Y, Jordan: Al Abdallah M, Uno M (National Cancer Center Hospital)., Ayasra, F, Ayasra, Y, Qasem, A (Al-Basheer Hospital), Abu Za’, nouneh FJ, Fahmawee, T, Hmedat, A, Ibrahim, A, Obeidat, K (King Abdullah University Hospital), Abdel Al, S, Abdel Jalil, R, Abou Chaar MK, Al-Masri, M, Al-Najjar, H, Alawneh, F, Alsaraireh, O, Elayyan, M, Ghanem, R, Libya: Alkadeeki G (Al-Jalaa Hospital), Lataifeh I (King Hussein Cancer Center)., Aldokali, N, Senossi, O, Subhi MT (Alkhadra Hospital), Burgan, D, Kamoka, E, Kilani, Ai, Salamah, A, Salem, M, Shuwayyah, A (National Cancer Institute, Sabratha, - Libya), Abdulwahed, E, Alshareea, E, Aribi, N, Aribi, S, Biala, M, Ghamgh, R, Morgom, M (Tripoli Central Hospital), Aldayri, Z, Ellojli, I, Lithuania: Bradulskis S, Kredan A (Tripoli University Hospital)., Dainius, E, Kubiliute, E, Kutkevič, ius, J, Parseliunas, A, Subocius, A, Madagascar: Rasoaherinomenjanahary F, Venskutonis D (Lithuanian University Of Health Sciences Kaunas Clinical Hospital)., Razafindrahita, Jb, Malaysia: Ong EC (Bintulu), Samison LH (Joseph Ravoahangy Andrianavalona Hospital)., Hamdan, Kh, Ibrahim, Mr, Tan, Ja, Thanapal MR (Hospital Kuala Lumpur), Amin Sahid, N, Hayati, F, Jayasilan, J, Sriram, Rk, Subramaniam, S (Queen Elizabeth Hospital &, Universiti Malaysia Sabah, Kota, Kinabalu, Sabah, Malaysia), Che Jusoh, A, Hussain, Ah, Mohamed Sidek AS, Mohd Yunus MF, Soh, Jy, Wong, Mpk, Zakaria, Ad, Zakaria, Z (School Of Medical Sciences &, Hospital, Universiti Sains Malaysia), Fadzli, A, Fathi, Nq, Koh, Ps, Liew, Yt, Roslani, Ac, Tang, Cy, Teoh, Ly, Wong, Wj, Mexico: Alvarez MR, Yahaya AS (University Malaya Medical Centre)., Arrangoiz, R, Cordera, F, De la Rosa Abaroa MA, Gó, mez-Pedraza, A, Hernandez, R, Maffuz-Aziz, A, Posada JA (Abc Medical Center), Becerra Garcí, a FC (Hospital San Á, ngel Inn Chapultepec), Alfaro-Goldaracena, A, Buerba, Ga, Castillejos- Molina RA, Chan, C, Dominguez-Rosado, I, Medina-Franco, H, Mercado, Má, Oropeza- Aguilar, M, Peñ, a Gó, mez Portugal, E, Posadas-Trujillo, Oe, Rodriguez-Covarrubias, F, Salgado-Nesme, N, Morocco: Arkha Y, Vilatoba M (Instituto Nacional De Ciencias Mé, dicas Y Nutrició, n “, Salvador Zubirá, n”, Bechri, H, El Ouahabi, A, Oudrhiri MY (Centre Hospitalier Universitaire Ibn Sina Rabat), Derkaoui hassani F, El abbadi N (Cheikh Zaid International University Hospital), Amrani, L, Belkhadir, Zh, Benkabbou, A, Chakib, O, El Ahmadi, B, El Bouazizi, Y, Essangri, H, Ghannam, A, Majbar, Am, Mohsine, R, Netherlands: Hompes R, Souadka A (Institut National D’, oncologie)., Meima-van Praag, E, Pronk, Ajm, Sharabiany, S (Amsterdam Umc, University Of Amsterdam), Grotenhuis, B, Hartveld, L, Reijers, S, Van Houdt, W (Antoni Van Leeuwenhoek Ziekenhuis), Baaij, J, Bolster-van Eenennaam, M, De Graaff, M, Sloothaak, D, Van Duijvendijk, P (Gelre Ziekenhuis), Posma-Bouman, L (Slingeland Ziekenhuis), Derksen, T, Franken, J, Oosterling, S (Spaarne Gasthuis), De Bree, R (University Medical Center Utrecht), Konsten, J, Nigeria: Fidelis L, Van Heinsbergen M (Viecuri Medisch Centrum)., Sholadoye, Tt, Tolani, M (Ahmadu Bello University Teaching Hospital), Olaogun, J (Ekiti State University Teaching Hospital), Egbuchulem, Ik, Lawal, Ta, Ogundoyin, O, Olulana DI (University College Hospital), Abdur-Rahman, L, Adeyeye, A, Aremu, I, Bello, J, Olasehinde, O, Oman: Massoud J, Popoola A (University Of Ilorin Teaching Hospital)., Massoud, R, Pakistan: Jamal A, Sorour TM (Khoula Hospital)., Kerawala AA (Cancer Foundation Hospital), Memon, As, Nafees Ahmed, R, Pfau Civil Hospital), Rai L (Dr Ruth K. m., Ayub, B, Hassan, N, Martins, Rs, Ramesh, P, Sayyed, R (Patel Hospital), Butt, U, Kashif, M, Khan, Wh, Qureshi, A, Umar, M, Waris Farooka, M, Wasim, T (Services Hospital Lahore), Ayubi, A, Rashid, I, Peru: Falcon GM, Waqar SH (The Pakistan Institute Of Medical Sciences)., Philippines: Jocson R, Robles R (Instituto Regional De Enfermedades Neoplá, sicas Del Sur)., Teh, C (National Kidney &, Poland: Major P (Jagiellonian University Medical College), Transplant Institute)., Bobiń, ski, M, Kotarski, J, Rasoul-Peliń, ska, K (Medical University Of Lublin, Portugal: Azevedo C, Chair And Department Of Gynaecological Oncology And Gynaecology)., Machado, D, Mendes, F (Centro Hospitalar Cova Da Beira), De Sousa, X (Centro Hospitalar De Setú, bal), Fernandes, U, Ferreira, C, Guidi, G, Leal, C, Març, al, A, Marques, R, Martins, D, Melo, A, Tenreiro, N, Vaz Pereira, R, Vieira B (Centro Hospitalar De Trá, s-Os-Montes, E Alto Douro, E. p. e., ), Almeida, Ji, Correia de Sá, T, Costa, Mjma, Fernandes, V, Ferraz, I, Gil, Cg, Lima da Silva, C, Lopes, L, Machado, N, Marialva, J, Nunes Coelho, M, Pedro, J, Pereira, C, Reis, R, Ribeiro, A, Santos, R, Saraiva, P, Silva, R, Tavares, F, Teixeira M (Centro Hospitalar Do Tamega, E Sousa), Almeida, Ac, Amaral, Mj, Andrade, R, Athayde Nemé, sio, R, Breda, D, Camacho, C, Canhoto, C, Colino, M, Correia, S, Costa, M, De Barros, J, De Oliveira Ló, pez AL, Duque, M, Garrido, S, Guerreiro, P, Guimarã, es, A, Lá, zaro, A, Lopes, C, Martins, R, Nogueira, O, Oliveira, A, Oliveira, Jm, Rodrigues, M, Ruivo, A, Santos, E, Silva, M, Simõ, es, J, Valente da Costa A (Centro Hospitalar, E Universitá, rio De Coimbra), Almeida, A, Cavaleiro, S, Devezas, V, Faria, Cs, Já, come, F, Magalhã, es Maia, M, Nogueiro, J, Pereira, A, Pereira-Neves, A, Pina-Vaz, T, Santos-Sousa, H, Silveira, H, Vaz, S, Vieira P (Centro Hospitalar, E Universitá, rio De Sã, o Joã, Gomes da Costa A, Lobo Antunes I (Centro Hospitalar Lisboa Norte), Pinto J, Tojal A (Centro Hospitalar Tondela-Viseu), Cardoso, N, Cardoso, P, Domingues, Jc, Henriques, P, Manso, Mi, Martins dos Santos, G, Morais, H, Pereira, R, Revez, T, Ribeiro, R, Ribeiro, Vi, Soares, A, Sousa, S, Teixeira J (Centro Hospitalar Universitá, rio Do Algarve, - Unidade De Faro), Amorim, E, Baptista, Vh, Cunha, Mf, Dias, B, Fazenda, A, Melo Neves JP, Policarpo, F, Sampaio da Nó, voa Gomes Miguel II, Veiga D (Centro Hospitalar Universitario Do Algarve, - Unidade De Portimã, Andrade, Ak, Bandovas, Jp, Borges, N, Branquinho, A, Chumbinho, B, Correia, J, Fidalgo, H, Figueiredo de Barros, I, Frade, S, Gomes, J, Maciel, J, Pina, S, Rodrigues, A, Silva, N, Silveira Nunes, I, Sousa, R (Centro Hospitalar Universitá, rio Lisboa Central), Ascensã, o, J, Azevedo, P, Costeira, B, Cunha, C, Garrido, R, Gomes, H, Lourenç, o, I, Mendinhos, G, Miranda, P, Nobre Pinto, A, Peralta Ferreira, M, Ribeiro, J, Rio Rodrigues, L, Sousa Fernandes, M (Hospital Beatriz Angelo), Azevedo J (Hospital Da Horta, E. p. e. ), Galvã, o, D, Soares, Ac, Vieira, A, Vieira, B (Hospital De Santo Espirito Da Ilha Terceira), Patrí, cio, B, Santos, Pmdd, Vieira Paiva Lopes AC (Hospital De Torres Vedras, - Centro Hospitalar Do Oeste), Cunha, R, Faustino, A, Freitas, A, Martins, Ab, Mendes, Jr, Parreira, R, Rosa, J, Teves, M (Hospital Do Divino Espí, rito Santo), Abreu da Silva, A, Claro, M, Costa Santos, D, Deus, Ac, Grilo JV (Hospital Do Litoral Alentejano), Borges, F, Corte Real, J, Henriques, S, Lima, Mj, Matos Costa, P (Hospital Garcia De Orta), Brito da Silva, F, Caiado, A, Fonseca, F (Instituto Portuguê, s De Oncologia De Lisboa Francisco Gentil), 194, ngelo, M, Baiao, Jm, Martins Jordã, Vieira Caroç, o, T (Ipo Coimbra), Messias, J, Millan, A, Salgado, I, Santos, P (Ipo Lisboa), Baí, a, C, Canotilho, R, Correia, Am, Ferreira Pinto AP, Peyroteo, M, Puerto Rico: Escobar P, Videira JF (Ipo Porto)., Ré, union: Kassir R, Maldonado Santiago M (Instituto Gineco Oncologico)., Romania: Bezede C, Sauvat F (Chu Reunion)., Chitul, A, Ciofic, E, Cristian, D, Grama, F (Coltea Clinical Hospital), Pirtea L, Secosan C (Emergency Clinical City Hospital), Bonci, E, Gata, V, Ion Chiricuta Institute Of Oncology), Titu S (Prof. Dr., Ginghina, O, Iordache, N, Russia: Garmanova T, Iosifescu RV (Saint John Emergency Hospital)., Kazachenko, E, Markaryan, D, Rodimov, S, Tsarkov, P, Tulina, I (Clinic Of Coloproctology And Minimally Invasive Surgery, Sechenov Medical State University), Litvina, Y, Provozina, A (Immanuel Kant Baltic Federal University, Regional Clinical Hospital), Agapov, M, Galliamov, E, Kakotkin, V, Kubyshkin, V, 1050, 1072, 1084, 1083, 1086, 1074, А, (Moscow Research And Educational Center, Saudi Arabia: Alshahrani M, Lomonosov Moscow State University)., Alsharif, F, Eskander, M (Aseer Central Hospital), Al Raddadi, R, Majrashi, S, Mashat, A (East Jeddah General Hospital), Akeel, N, Alharthi, M, Aljiffry, M, Basendowah, M, Farsi, A, Ghunaim, M, Khoja, A, Maghrabi, A, Malibary, N, Nassif, M, Nawawi, A, Saleem, A, Samkari, A, Trabulsi, N (King Abdulaziz University Hospital), Al Awwad, S, Alghamdi, M, Alnumani, T, Nasser, M, Said bayazeed, A (King Fahad General Hospital), Alhefdhi, A, Almalik, O, Alomair, A, Alotaibi, N, Alresaini, F, Alsalamah, R, Alsobhi, S, Mahasin, Z, Othman, E, Velagapudi, S (King Faisal Specialist Hospital), Al Habes, H, Alamri, A, Alkarak, S, Alqannas, M, Alyami, M, Alzamanan, M, Corté, s Guiral, D, Elawad, A (King Khalid Hospital), AlAamer, O, Alriyees, L, Alselaim, N (King Saud Bin Abdulaziz University For Health Sciences, King Abdullah International Medical Research Center, Ministry Of National Guard, Health, Affairs, General Surgery Department., ), Abdulkareem, A, Ajlan, A, Akkour, K, Al-Habib, A, Al-Khayal, K, Alatar, A, Alburakan, A, Alhalal, H, Alhassan, B, Alhassan, N, Alobeed, O, Alsaif, A, Alsaif, F, Alshammari, S, Alshaygy, I, Barry, M, Bin Nasser, A, Bin Traiki, T, Bokhari, A, Elwatidy, S, Helmi, H, Madkhali, A, Nouh, T, Rabah, Pd, Serbia: Paunovic I, Zubaidi A (King Saud University)., Slijepcevic, N (Centre For Endocrine Surgery, Clinical Centre Of Serbia), Aleksić, L, Antic, A, Barisic, G, Ceranic, M, Galun, D, Grubač, Ž, Jelenkovic, J, Kecmanović, Kmezić, Knezevic, D, Krivokapic, Z, Latinč, Markovic, V, Matić, Miladinov, M, Pavlov, M, Pejovic, I, Radenkovic, D, Tadic, B, Vasljević, J, Velickovic, D, Zivanovic, M (Clinic For Digestive Surgery, Perovic M, Srbinovic L (Clinic For Gynecology And Obstetrics Narodni Front), Andrijasevic, S, Bozanovic, T, Cerovic Popovic, R, Dokic, M, Janjic, T, Jeremic, K, Kadija, S, Ladjevic Likic, I, Mirkovic, L, Pantovic, S, Pilic, I, Radojevic, M, Stefanovic, A, Vidakovic, S, Vilendecic, Z (Clinic For Gynecology And Obstetrics, Clinical Center Of Serbia), Antic, S, Dunđ, erović, Jelovac, D, Jezdic, Z, Konstantinovic, V, Kotlar, B, Kuzmanovic, C, Lazić, Petrovic, M, Popovic, F, Pucar, A, Romic, M, Sumrak, S, Vujanac, V (Clinic For Maxillofacial Surgery, School Of Dental Medicine, University Of Belgrade), Bascarevic, V, Bogdanović, I, Grujič, Ilic, R, Milić, ević, Milisavljević, F, Miljković, Paunovic, A, 352, 263, epanović, V, Stanimirovic, A, Todorovic, M (Clinic For Neurosurgery, Jotic, A, Milovanovic, J, Trivic, A (Clinic For Otorhinolaryngology And Maxillofacial Surgery, Bumbasirevic, U, Dzamic, Z, Kajmaković, B, Prijović, N, Zivkovic, M (Clinic Of Urology, Buta, M, Cvetkovic, A, Djurisic, I, Gacic, S, Goran, M, Inic, Z, Jeftic, N, Jevric, M, Jokic, V, Markovic, I, Milanović, Nikolic, S, Pejnovic, L, Savković, Spurnic, I, Stevic, D, Stojiljkovic, D, Vucic, N, Zegarac, M (Institute For Oncology And Radiology Of Serbia), Karamarkovic, A, Kenic, M, Kovacevic, B, Krdzic, I, Singapore: Chan CW, Milutinović, V (Zvezdara University Medical Center)., Slovakia: Gá, lis B, Lieske B (National University Hospital)., South Africa: Almgla N, Š, imko K (University Hospital Bratislava)., Bernon, M, Boutall, A, Cairncross, L, Herman, A, Hilton, T, Jonas, E, Kloppers, C, Malherbe, F, Mugla, W, Nel, D, Rayamajhi, S, Van Wyngaard, T, Spain: Castañ, o-Leon AM, Vogel J (Groote Schuur Hospital)., Delgado Fernandez, J, Eiriz Fernandez, C, Espino Segura-Illa, M, Esteban Sinovas, O, Garcia Perez, D, Gomez, P, Jimenez-Roldan, L, Lagares, A, Moreno- Gomez, L, Paredes, I, Pé, rez Nú, 241, ez, A, Sá, nchez Aniceto, G, Santas, M (12 De Octubre University Hospital), Ferná, ndez Rodrí, guez, P, Paniagua Garcí, a Señ, orans, M, Sanchez- Santos, R, Vigorita, V (Á, lvaro Cunqueiro Hospital), Acrich, E, Baena Sanfeliu, E, Barrios, O, Golda, T, Santanach, C, Serrano-Navidad, M, Sorribas Grifell, M, Vives RV (Bellvitge University Hospital), Escolà, D, Jimé, nez A (Comarcal Alt Penedé, Cayetano Paniagua L, Gó, mez Ferná, ndez L (Consorci Sanitari De Terrassa), Artigues, E, Bernal-Sprekelsen, Jc, Catalá, Bauset JC (Consorcio Hospital General Universitario), Collera, P, Diaz Del Gobbo, R, Farre Font, R, Flores Clotet, R, mez Dí, az CJ, Guà, rdia, N, Guariglia, Ca, Osorio, A, Sanchez Jimenez, R, Sanchon, L, Soto Montesinos C (Fundació, Althaia, - Xarxa Assistencial Università, ria De Manresa), Albi Martin B, Garcí, a Villayzá, n JE (Fundació, n Jimenez Diaz University Hospital), Alonso-Lamberti, L, Assaf, M, Baeza Pintado, N, Carabias, A, a-Quijada, J, Huertas Fernandez MA, Jimenez Miramó, n, J, Jimenez, V, Jover, Jm, Landeo Agü, ero SA, Leon, R, Martí, n Salamanca MB, rez Simó, n, V, Ponce, S, Rodriguez, Jl, Salazar, A, Valle Rubio, A (Getafe University Hospital), Aguado, H (Hellí, n Hospital), Aldecoa Ansorregui, I, Bravo Infante, R, De Lacy FB, Di Somma, A, Dí, az-Feijoo, B, Enseñ, at Nora, J, Fabregas, N, Ferré, s, A, Gil Ibañ, ez, B, Gonzalez Sanchez JJ, Gracia, I, Hoyos Castro JA, Lacy, Am, Langdon, C, Momblá, n, D, Morales, X, Oleaga, L, Otero, A, Pedrosa, L, Poblete Carrizo, J, Reyes Figueroa LA, Roldan Ramos, P, Rumia-Arboix, J, Tercero-Uribe, Ai, Topczewski, Te, Torales, J, Torne, A, Torné, R, Turrado-Rodriguez, V, Valero, R, Valverde, S (Hospital Clinic Barcelona), Anula, R, Cano-Valderrama, O, Del Campo Martí, n, M, ez-Valladares, L, Domí, nguez, I, Dziakova, J, a Alonso, M, a Romero, E, mez Latorre, L, Muguerza, Jm, Pizarro, Mj, Saez Carlin, P, nchez del Pueblo, C, nchez-Pernaute, A, Sanz Ortega, G, Sanz-Lopez, R, Torres, A (Hospital Clí, nico De Madrid), Garcé, s-Albir, M, Lopez, F, n-Aré, valo, J, Moro-Valdezate, D, Pla-Marti, V (Hospital Clí, nico Universitario De Valencia), Beltrá, n de Heredia, J, De André, s Asenjo, B, mez Sanz, T, Jezieniecki, C, Nuñ, ez Del Barrio, H, Ortiz de Soló, rzano Aurusa FJ, Romero de Diego, A, Ruiz Soriano, M, Trujillo Dí, az, J, Vazquez fernandez, A (Hospital Clí, nico Universitario De Valladolid), Lora-Cumplido P, Sosa MV (Hospital De Cabueñ, es), Gonzalez-Gonzalez E, Minaya Bravo AM (Hospital Del Henares), Alonso de la Fuente, N, Cazador Labat, M, Cecchini, L, Espinosa, Ca, Jimenez Toscano, M, Ló, pez Campillo, A, Mancebo, G, Martorell, P, Munarriz, M (Hospital Del Mar), Grau-Talens EJ, Martin-Perez B (Hospital Don Benito-Villanueva), Benavides Buleje JA, Carrasco Prats, M, ndez, Pv, ndez-Ló, pez, A, a Escudero, D, a Porcel VJ, Garcia Soria, V, Gimé, nez Francé, s, C, Gonzá, lez Valverde FM, Gurrea, E, pez-Morales, P, Marco Garrido, A, nez Alonso JA, Medina, E, Muñ, oz Camarena JM, Parra Bañ, os PA, a Ros, E, Ramirez Faraco, M, Ruiz-Marí, Sanchez Rodriguez, C, Valero Soriano, M (Hospital General Reina Sofí, Estaire Gó, mez, M, ndez Camuñ, as, Á, Garcia Santos EP, Jimenez Higuera, E, nez-Pinedo, C, oz-Atienza, V, Padilla-Valverde, D, Picó, n Rodrí, guez, R, Redondo Calvo FJ, nchez-Garcí, a, S, Sanchez-Pelaez, D (Hospital General Universitario De Ciudad Real), Colombari, Rc, Del valle, E, ndez, M, Lozano Lominchar, P, n, L, Rey Valcarcel, C, Steiner, Ma, Tudela, M, Zorrilla Ortú, zar, J (Hospital General Universitario Gregorio Marañ, 243, Alcaide Matas, F, a Pé, rez JM, Troncoso Pereira, P (Hospital Mateu Orfila), Mora-Guzmá, n, I (Hospital Santa Bá, rbara), Abellá, Achalandabaso Boira, M, Jorba, R, Memba Ikuga, R, Olona, C, Sales Mallafré, R (Hospital Universitari De Tarragona Joan Xxiii), Cavallé, Busquets, P, Gavalda Pellice MGP, Salinas Peñ, a, J (Hospital Universitari Sant Joan), Aragon Achig EJ, Barbier, L, Caja Vivancos, P, Gainza, A, a Gutierrez JJ, Mallabiabarrena Ormaechea, G, Marí, n, H, Martin Playa, P, Melchor Corcó, stegui, I, Prieto Calvo, M, Rodriguez Fraga, A, Villalabeitia Ateca, I (Hospital Universitario Cruces), De Andres Olabarria, U, Durá, n Ballesteros, M, ndez Pablos FJ, Ibá, ez-Aguirre, Fj, Sanz Larrainzar, A, Ugarte-Sierra, B (Hospital Universitario De Galdakao), De la Hoz Rodrí, guez, Á, Di Martino, M, a Septiem, J, Martin-Perez, E, oz de Nova JL (Hospital Universitario De La Princesa), Calvo Espino P, Guillamot Ruano P (Hospital Universitario De Mó, stoles), Colao Garcí, a, L, az Pé, rez, D, Esteban Agustí, E, Galindo Jara, P, Gutierrez Samaniego, M, Hernandez Bartolome MA, Serrano Gonzá, lez, J (Hospital Universitario De Torrejó, n De Ardoz), Alonso Poza, A, Dié, guez, B, a-Conde, M, Herná, ndez-Garcí, a, M, Losada, M (Hospital Universitario Del Sureste), Chiesa-Estomba, Cm, lez Garcí, a JÁ, Larruscain, E, Sistiaga-Suá, rez JA (Hospital Universitario Donostia), Alvarez, E, Chavarrias, N, Frí, as, L, a Pineda, V, Gegú, ndez Simó, n, A, Gortá, zar, S, Gracia, M, Guevara, J, ndez Gutierrez, A, Loayza, A, a Dolores DT, C, Melendez, M, Moreno-Palacios, E, Perez, Y, Prieto Nieto MI, Ramos- Martí, n, P, Rubio-Perez, I, Saavedra, J, Sanchez-Mendez, Ji, Siegrist Ridruejo, J, Urbieta, A, Zapardiel, I (Hospital Universitario La Paz), Cantalejo diaz, M, De Miguel Ardevines MDC, Duque-Mallé, Gascon Ferrer, I, lez-Nicolá, s Tré, bol MT, Gracia-Roche, C, Herrero Lopez, M, Jariod Ferrer UM, Lanzon, A, Martinez German, A, Matute, M, Redondo, C, nchez Fuentes, N, nchez-Rubio, M, Santero-Ramirez, Ms, Saudí, Simó, n Sanz MV, Uson-Bouthelier, T (Hospital Universitario Miguel Servet), Blazquez Martin, A, Diez Alonso, M, a Rico, E, Garcia-Loarte Gomez, E, Garcia-Moreno Nisa, F, Gutierrez Calvo, A, Hernandez, P, Lasa, I, Mendoza-Moreno, F, Morales Palacios, N, Ovejero Merino, E, Vera Mansilla, C (Hospital Universitario Principe De Asturias), Acebes Garcí, a, F, Bailó, Bueno Cañ, ones AD, Choolani Bhojwani, E, Marcos-Santos, P, Miguel, T, Pacheco Sá, nchez, D, rez-Saborido, B, Sanchez Gonzalez, J, Tejero-Pintor FJ (Hospital Universitario Rí, o Hortega), Alconchel, F, Conesa, A, Gil Martí, nez, J, Gutié, rrez Ferná, ndez AI, Lopez Abad, A, Nicolá, s-Ló, pez, T, Ramirez Romero, P, Roca Calvo MJ, Rodrigues, K, Ruiz Manzanera JJ, Soriano AI (Hospital Universitario Virgen De La Arrixaca), Cano, A, Capitan-Morales, L, Cintas Catena, J, Gomez-Rosado, J, Oliva Mompean, F, rez Sá, nchez MA, Rí, o Lafuente FD, Torres Arcos, C, Valdes-Hernandez, J (Hospital Universitario Virgen Macarena), Cholewa, H, Domingo, S, Frasson, M, Lago, V, Marina Martin, T, nez Chicote, C, Sancho-Muriel J (Hospital Universitario, Y Polité, cnico La Fe), Landaluce-olavarria A, Lecumberri D (Hospital Urduliz), Abad Gurumeta, A, Abad-Motos, A, nez-Hurtado, E, Ripollé, s-Melchor, J, Ruiz Escobar, A (Infanta Leonor University Hospital), Cuadrado- Garcí, a, A, Garcia-Sancho Tellez, L, Heras Aznar, J, Maté, P, Ortega Vá, zquez, I, Picardo, Al, Rojo Ló, pez JA, Sanchez Cabezudo Noguera, F, Serralta de Colsa, D (Infanta Sofí, a University Hospital), Anchuelo Latorre, J, Cagigas Fernandez, C, Caiñ, a Ruiz, R, Gomez Ruiz, M, Hernanz, F, Jimeno Fraile, J, nez-Pé, rez, P, Poch, C, Santarrufina Martinez, S, Valbuena Jabares, V (Marqué, s De Valdecilla University Hospital), Moliner-Sá, nchez, C, Pingarron-Martin, L, Rey-Biel, J, Ruiz Martin, I (Rey Juan Carlos University Hospital), Blas Laina JL, Cros, B, Escartin, J, Garcia Egea, J, Nogué, Talal El-Abur, I, Yá, nez, C (Royo Villanova), Cagigal Ortega EP, Cervera, I, az Peñ, a, P, Elena, Gdcr, Enjuto, D, ndez Bernabé, s Garcí, a, R, Gonzalez, J, ndez, I, Herrera-Merino, N, Marqueta De Salas, M, Martinez Pascual, P, Perez Gonzalez, M, Ramos Bonilla, A, Rodrí, guez Gó, mez, L (Severo Ochoa University Hospital), Bescó, Blanco-Colino, R, Brana, I, Caimari, B, De Pablo Garcí, a-Cuenca, A, Duran-Valles, F, Espin-Basany, E, Giralt Ló, pez de Sagredo, J, Pamias, J, Pellino, G, Prat, N, Pujol Pina, R, Sri Lanka: Arulanantham A, Saez barba M (Vall D’, hebron University Hospital)., Bandara, Gbk, Jayarajah, U, Ravindrakumar, S, Rodrigo VS (District General Hospital Chilaw), Srishankar S (Teaching Hospital Anuradhapura). Sudan: Ali karar AA (Al-Rajhi). Sweden: Elbe P, Lindqvist EK (Karolinska University Hospital), Taflin, H (Sahlgrenska University Hospital), 196, lgå, Heinius, G, Nordberg, M, Pieniowski, E (South General Hospital), Gkekas, I, fgren, N, Rutegå, rd, M, Switzerland: Arigoni M, Sund M (Umea University Hospital)., Bernasconi, M, Christoforidis, D, Di Giuseppe, M, La Regina, D, Mongelli, F (Ente Ospedaliero Cantonale), Chevallay, M, Dwidar, O, Gialamas, E, Sauvain, M (Hopital De Pourtales), Klenke, F, Kollà, r, A, Kurze, C (Inselspital, Bern University Hospital, University Of Bern), Adamina, M, Bä, chler, T, Crugnale, As, Giardini, M, Guglielmetti, L, Peros, G, Turkey: Aghayeva A, Solimene F (Kantonsspital Winterthur)., Hamzaoglu, I, Sahin, I (Acibadem Altunizade Hospital), Akaydin, E, Aliyeva, Z, Aytac, E, Baca, B, Dü, lgeroğ, lu, O, Ozben, V, Ozmen, Bb, Uras, C (Acibadem Atakent Hospital), Arikan, Ae, Bilgin, Ia, Bozkı, rlı, Ceyhan, Go, Kara, H, Karahasanoğ, lu, T, Uras, C (Acibadem Maslak Hospital), Celik, H (Adana Baskent University), Meydanli MM (Ankara City Hospital), Akilli, H, Ayhan, A, Kuscu, E (Baskent University), Onan MA (Gazi University Medical Faculty Hospital), Akgor, U, Dincer, Ha, Erol, T, Gultekin, M, Orhan, N, Ozgul, N, Salman, Mc, Soyak, B (Hacettepe University Hospital), Alhamed, A, Ergü, n, S, OZcelı, k, Mf, Sanli, An, Uludağ, Velidedeoglu, M, Zengin AK (Istanbul Universty, - Cerrahpaş, a Medical Faculty), Bozkurt, Ma, Kara, Y, Kocataş, A (Kanuni Sultan Suleyman Training And Research Hospital), Cimenoglu, B, Demirhan, R, Lutfi Kirdar Training And Research Hospital), Saracoglu K (Kartal Dr., Azamat, İ, f, Balik, E, Buğ, ra, D, Giray, B, Kulle, Cb, Taskiran, C, Vatansever, D (Koç, University Medical School), Gö, zal, K, Gü, ler, Sa, ken, H, Tatar, Oc, Utkan, Nz, Yı, ldı, rı, m, A, Yü, ksel, E (Kocaeli University Teaching Hospital), Akin, E, Altintoprak, F, Bayhan, Z, Cakmak, G, 199, apoğ, lu, R, elebi, F, Demir, H, Dikicier, E, Firat, N, nü, llü, Kamburoğ, lu, Mb, Kocer, B, 231, 252, k, If, Mantoglu, B (Sakarya University Faculty Of Medicine), olak, E, Kucuk, Go, Uyanik MS (Samsun Training And Research Hospital), 304, lhan Varank Training And Research Hospital), Gö, ksoy B (Sehit Prof. dr., Bozkurt, E, Citgez, B, Mihmanli, M, Tanal, M, Yetkin, G (Sisli Hamidiye Etfal Training And Research Hospital), Akalin, M, Arican, C, Avci, Ek, Aydin, C, Demirli Atı, cı, Emiroglu, M, Kaya, T, Kebabç, 305, Kilinc, G, Kirmizi, Y, 287, cü, H, Salimoğ, lu, S, Sert, İ, Tugmen, C, Tuncer, K, Uslu, G, Yeş, ilyurt, D (University Of Health Sciences Tepecik Training And Research Hospital), Karaman, E, Kolusarı, A (Van Yuzuncu Yil University, Medical, Faculty), Uganda: Benson O, Yildiz A (Yildirim Beyazit University Yenimahalle Training And Research Hospital)., United Kingdom: Agilinko J, Lule H (Kampala International University Teaching Hospital)., Ahmeidat, A, Barabasz, M, Bekheit, M, Cheung, Lk, Colloc, T, Cymes, W, Elhusseini, M, Gradinariu, G, Hannah, A, Kamera, Bs, Mignot, G, Shaikh, S, Sharma, P (Aberdeen Royal Infirmary), Abu-Nayla, I, Agrawal, A, Al-Mohammad, A, Ali, S, Ashcroft, J, Azizi, A, Baker, O, Balakrishnan, A, Byrne, M, Colquhoun, A, Cotter, A, Coughlin, P, Davies, Rj, Durrani, A, Elshaer, M, Fordington, S, Forouhi, P, Georgiades, F, Grimes, H, Habeeb, A, Hudson, V, Hutchinson, P, Irune, E, Jah, A, Khan, Dz, Kolias, A, Kyriacou, H, Lamb, B, Liau, S, Luke, L, Mahmoud, R, Mannion, R, Masterson, L, Mitrofan, Cg, Mohan, M, Morris, A, Murphy, S, Neill, R, Price, S, Pushpa-rajah, J, Raby-Smith, W, Ramzi, J, Rooney, S, Santarius, T, Singh, A, Stewart, Gd, Tan, Xs, Townson, A, Tweedle, E, Walker, C, Waseem, S, Yordanov, S (Addenbrooke’, Jones, T, Kattakayam, A, Loh, C, Lunevicius, R, Pringle, S, Schache, A, Shaw, R, Sheel, A (Aintree University Hospital), Rossborough, C (Altnagelvin Area Hospital), Angelou, D, Choynowski, M, McAree, B, McCanny, A, Neely, D (Antrim Area Hospital- Northern Health And Social Care Trust), Tutoveanu, G (Barnsley Hospital Nhs Foundation Trust), Ahad, S, De La Cruz Monroy MFI, Mosley, F, Oktseloglou, V (Bradford Royal Infirmary), Alanbuki, A, Patel, M, Shabana, A (Brighton And Sussex Nhs Trust, Princess Royal Hospital), Perera, E, Raveendran, D, Ravi- Shankar, K, Thiruchelvam, J (Broomfield Hospital), Arrowsmith L, Campbell W (Causeway Hospital), Grove, T, Kontovounisios, C, Warren, O (Chelsea And Westminster Hospital), Rolland, P (Cheltenham General Hospital), Aggarwal, A, Brown, S, Jelley, C, Neal, N (Churchill Hospital), Clifford, R, Eardley, N, Krishnan, E, Manu, N, Martin, E, Roy Mahapatra, S, Serevina, Ol, Smith, C, Vimalachandran, D (Countess Of Chester Hospital), Bordenave, M, Houston, R, Putnam, G, Robson, A, Tustin, H (Cumberland Infirmary), Emslie, K, Labib, Pl, Marchbank, A, Miller, D, Minto, G, Natale, J, Nwinee, H, Panahi, P, Rogers, L (Derriford Hospital), Abubakar, A, Akhter Rahman MM, Kyk, Ko, Brien, H, Sasapu, K, Woodun, H (Diana Princess Of Wales Hospital Grimsby), Inglis R, Ng HJ (Dumfries And Galloway Royal Infirmary), De Gea Rico, A, Ghazali, N, Lambert, J, Markose, G, Math, S, Sarantitis, I, Shrestha, D, Sultana, A, Taggarsi, M, Timbrell, S, Vaz, Op, Vitone, L (East Lancashire Hospitals Nhs Trust), Day, A, Dent, H, Fahim, M, Waheed, S (East Surrey Hospital), Hunt A, Laskar N (East Sussex Healthcare (Conquest Hospital And Eastbourne District General Hospital)), Gupta, A, Steinke, J, Thrumurthy, S (Epsom &, St Helier University Hospitals Nhs Trust), Massie, E, McGivern, K, Rutherford, D, Wilson, M (Forth Valley Royal Hospital), Hardie J, Kazzaz S (Frimley Health Nhs Ft - Frimley Park), Handa, S, Kaushal, M, Kler, A, Patel, P, Redfern, J, Tezas, S (Furness General Hospital), Aawsaj, Y, Amonkar, S, Blackwell, L, Blake, D, Carter, J, Emerson, H, Fisher, A, Katory, M, Korompelis, P, McCormick, W, Mustafa, A, Pearce, L, Ratnavelu, N, Reehal, R (Gateshead Health Nhs Foundation Trust), Kretzmer, L, Lalou, L, Manku, B, Parwaiz, I, Stafford, J (George Eliot Hospital), Abdelkarim, M, Asqalan, A, Gala, T, Ibrahim, S, Maw, A, Mithany, R, Morgan, R, Sundaram Venkatesan, G (Glan Clwyd Hospital), Ang, K, Caruana, Ej, Chowdhry, Mf, Mohammad, A, Nakas, A, Rathinam, S (Glenfield Hospital), Boal, M, Brown, O, Dwerryhouse, S, Higgs, S, Vallance, A (Gloucestershire Royal Hospital), Boyd, E, Irvine, V, Kirk, A (Golden Jubilee National Hospital), Bakolas, G, Boulton, A, Chandock, A, Khan, T, Kumar, M (Good Hope Hospital), Agoston, P, Billè, Challacombe, B, Fraser, S, Harrison-Phipps, K, King, J, Mehra, G, Mills, L, Najdy, M, Nath, R, Okiror, L, Pilling, J, Rizzo, V, Routledge, T, Sayasneh, A, Stroman, L, Wali, A (Guy’, Fehervari, M, Fotopoulou, C, Habib, N, Hamrang-Yousefi, S, Jawad, Z, Jiao, L, Pai, M, Ploski, J, Rajagopal, P, Saso, S, Sodergren, M, Spalding, D (Hammersmith Hospital), Laws, S (Hampshire Hospitals Nhs Trust), Hardie C, McNaught C (Harrogate District Hospital), Alam, R, Budacan, A, Cahill, J, Kalkat, M, Karandikar, S, Kenyon, L, Naumann, D, Patel, A (Heartlands Hospital), Ayorinde, J, Chase, T, Cuming, T, Ghanbari, A, Humphreys, L, Tayeh, S (Homerton University Hospital), Aboelkassem Ibrahim, A, Bichoo, R, Cao, H, Chai, Akw, Choudhury, J, Evans, C, Fitzjohn, H, Ikram, H, Langstroth, M, Loubani, M, McMillan, A, Nazir, S, Qadri, Ssa, Robinson, A, Ross, E, Sehgal, T, Wilkins, A (Hull University Teaching Hospitals Nhs Trust), Dixon, J, Dunning, J, Freystaetter, K, Jha, M, Lester, S, Madhavan, A, Thulasiraman, Sv, Viswanath, Y (James Cook University Hospital), Curl-Roper, T, Delimpalta, C, Liao, Ccl, Velchuru, V, Westwood, E (James Paget Univeristy Nhs Foundation Trust Hospital), Belcher, E, Bond-Smith, G, Chidambaram, S, Di Chiara, F, Fasanmade, K, Fraser, L, Fu, H, Ganau, M, Gore, S, Graystone, J, Jeyaretna, D, Khatkar, H, Lami, M, Maher, M, Mastoridis, S, Mihai, R, Piper, R, Prabhu, S, Risk, Obf, Selbong, U, Shah, K, Smillie, R, Soleymani majd, H, Sravanam, S, Stavroulias, D, Tebala, Gd, Vatish, M, Verberne, C, Wallwork, K, Winter, S (John Radcliffe Hospital), Bhatti, Mi, Boyd-Carson, H, Elsey, E, Gemmill, E, Herrod, P, Jibreel, M, Lenzi, E, Saafan, T, Sapre, D, Sian, T, Watson, N (King’, s Mill Hospital), Athanasiou, A, Bourke, G, Bradshaw, L, Brunelli, A, Burke, J, Coe, P, Costigan, F, Elkadi, H, Ho, M, Johnstone, J, Kanatas, A, Kantola, V, Kaufmann, A, Laios, A, Lam, S, MacInnes, E, Munot, S, Nahm, C, Otify, M, Pompili, C, Smith, I, Theophilou, G, Toogood, G, Wade, R, Ward, D, West, C (Leeds Teaching Hospitals Trust), Annamalai, S, Ashmore, C, Boddy, A, Hossain, T, Kourdouli, A (Leicester Royal Infirmary), Gvaramadze, A, Jibril, A, Prusty, L, Thekkinkattil, D (Lincoln County Hospital), Harky A, Shackcloth M (Liverpool Heart And Chest Hospital), Askari, A, Cirocchi, N, Kudchadkar, S, Patel, K, Sagar, J, Shaw, S, Talwar, R (Luton And Dunstable University Hospital), Abdalla, M, Edmondson, R, Ismail, O, Jones, D, Newton, K, Stylianides, N (Manchester Royal Infirmary), Aderombi, A, Andaleeb, U, Bajomo, O, Beatson, K, Garrett, W, Mehmood, M, V (Medway Hospital), Ng, Al-Habsi, R, Divya, Gs, Keeler, B (Milton Keynes University Hospital), Al- Sarireh, B, Egan, R, Harries, R, Henry, A, Kittur, M, Li, Z, Parkins, K, Soliman, F, Spencer, N, Thompson, D (Morriston Hospital Swansea), Burgess, C, Gemmell, C, Grieco, C, Hollyman, M, Hunt, L, Morrison, J, Ojha, S, Ryan, N (Musgrove Park Hospital), Abbadessa, F, Barnard, S, Dawe, N, Hammond, J, Mahmoud Ali, F, McPherson, I, Mellor, C, Moir, J, Pandanaboyana, S, Powell, J, Rai, B, Roy, C, Sachdeva, A, Saleh, C, Tingle, S, Williams T (Newcastle Upon Tyne Hospitals Nhs Foundation Trust., ), Manickavasagam, J, McDonald, C, McGrath, N, McSorley, N, Ragupathy, K, Ramsay, L, Solth, A (Ninewells Hospital), Kakisi, O, Seebah, K, Shaikh, I, Sreedharan, L, Youssef, M (Norfolk And Norwich University Hospital), Shah, J (North Manchester General Hospital), Ameerally, P (Northampton General Hospital), McLarty, N, Mills, S, Shenfine, A (Northumbria Nhs Hospital Trust), Sahnan, K (Northwick Park Hospital), Abu, J, Addae-Boateng, E, Bratt, D, Brock, L, Burnside, N, Cadwell-Sneath, S, Gajjar, K, Gan, C, Grundy, C, Hallam, K, Hassell, K, Hawari, M, Joshi, A, Khout, H, Konstantinidi, K, Lee, Rxn, Nunns, D, Schiemer, R, Walton, T, Weaver, H, Whisker, L, Williamson, K (Nottingham City Hospital), McVeigh, J, Myatt, R, Williams MA (Nuffield Orthopaedic Centre), Kaur, R, Leung, E, Sundar, S (Pan- Birmingham Gynaecological Cancer Centre), Michel, M, Patil, S, Ravindran, S, Sarveswaran, J, Scott, L (Pinderfields Hospital), Edmond M, King E (Poole Hospital), Almond, M, Bhangu, A, Breik, O, Cato, Ld, Desai, A, Ford, S, Griffiths, E, Idle, M, Kamal, M, Kisiel, A, Kulkarni, R, Mak, Jkc, Martin, T, Nankivell, P, Parente, A, Parmar, S, Pathanki, Am, Phelan, L, Praveen, P, Saeed, S, Sharma, N, Singh, J, Tirotta, F, Vijayan, D (Queen Elizabeth Hospital Birmingham), Geddes, A, McCaul, J, McMahon, J (Queen Elizabeth University Hospital), Khan, Ah, Khan, F, Mansuri, A, Mukherjee, S, Sarigul, M, Singh, S, Tan, Kl, Woodham, A (Queen’, s Hospital Romford), Adiamah, A, Brewer, H, Chowdhury, A, Evans, J, Humes, D, Jackman, J, Koh, A, Lewis-Lloyd, C, Oyende, O, Reilly, J, Worku, D (Queens Medical Centre), Cool, P, Cribb, G, Shepherd, K (Robert Jones And Agnes Hunt Orthopaedic Hospital), Bisset C, Moug S (Royal Alexandra Hospital), Elson, N, Faulkner, G, Saleh, P, Underwood, C (Royal Bolton Hospital), Brixton, G, Findlay, L, Klatte, T, Majkowska, A, Manson, J, Potter, R (Royal Bournemouth Hospital), Bhalla, A, Chia, Z, Daliya, P, Goyal, A, Grimley, E, Hamad, A, Kumar, A, Malcolm, Fl, Theophilidou, E (Royal Derby Hospital), Bowden, J, Campain, N, Daniels, I, Fowler, G, John, J, Massey, L, McDermott, F, McGrath, J, McLennan, A, Ng, M, Pascoe, J, Rajaretnam, N (Royal Devon And Exeter Hospital), Bulathsinhala, S, Davidson, B, Fusai, G, Hidalgo Salinas, C, Machairas, N, Pissanou, T, Pollok, Jm, Raptis, Da, Soggiu, F, Tzerbinis, H, Xyda SE (Royal Free Hospital), Beamish, A, Davies, E, Foulkes, R, Magowan, D, Nassa, H, Ooi, R, Price, C, Smith, L, Solari, F, Tang, A, Williams, G (Royal Gwent Hospital), Al-Tamimi, Y, Bacon, A, Beasley, N, Chew, D, Crank, M, Ilenkovan, N, Macdonald, M, Narice, B, Rominiyi, O, Thompson, A, Varley, I (Royal Hallamshire Hospital), Drake, T, Harrison, E, Linder, G, Mayes, J, McGregor, R, Skipworth, R, Zamvar, V (Royal Infirmary Of Edinburgh), Hawkin, P, Raymond, T, Ryska, O (Royal Lancaster Infirmary), Baron, R, Dunne, D, Gahunia, S, Halloran, C, Howes, N, McKinney, R, McNicol, F, Russ, J, Szatmary, P, Tan, Jr, Thomas, A, Whelan, P (Royal Liverpool University Hospital), Anzak, A, Banerjee, A, Fuwa, O, Hughes, F, Jayasinghe, Jd, Knowles, C, Kocher, H, Leal Silva, I, Ledesma, Fs, Minicozzi, A, Navaratne, L, Rahman, R, Ramamoorthy, R, Sohrabi, C, Thaha, M, Thakur, B, Venn, M, Yip, V (Royal London Hospital), Baumber R, Parry J (Royal National Orthopaedic Hospital), Evans, S, Jeys, L, Morris, G, Parry, M, Stevenson, J (Royal Orthopaedic Hospital), Ahmadi, N, Aresu, G, Barrett-Brown, Zm, Coonar, As, Durio Yates, H, Gearon, D, Hogan, J, King, M, Peryt, A, Pradeep, Is, Smith, C (Royal Papworth Hospital), Adishesh, M, Atherton, R, Baxter, K, Brocklehurst, M, Chaudhury, M, Krishnamohan, N, McAleer, J, Owens, G, Parkin, E, Patkar, P, Phang, I (Royal Preston Hospital), Aladeojebi, A, Ali, M, Barmayehvar, B, Gaunt, A, Gowda, M, Halliday, E, Kitchen, M, Mansour, F, Thomas, M, Zakai, D (Royal Stoke University Hospital), Abbassi-Ghadi, N, Assalaarachchi, H, Currie, A, Flavin, M, Frampton, A, Hague, M, Hammer, C, Hopper, J, Horsnell, J, Humphries, S, Kamocka, A, Madhuri, Tk, Preston, S, Singh, P, Stebbing, J, Tailor, A, Walker, D (Royal Surrey County Hospital), Aljanadi, F, Jones, M, Mhandu, P, Donnell, C, Turkington, R (Royal Victoria Hospital, Belfast), Al-Ishaq, Z, Bhasin, S, Bodla, As, Burahee, A, Crichton, A, Fossett, R, Pigadas, N, Rahman, E, Snee, D, Vidya, R, Yassin, N (Royal Wolverhampton Nhs Trust), Fountain, D, Hasan, Mt, Karabatsou, K, Laurente, R, Pathmanaban, O (Salford Royal Hospital), Al-mukhtar, A, Edwards, J, Giblin, A, Kelty, C, Lee, M, Lye, G, Newman, T, Sharkey, A, Steele, C, Sureshkumar Shah, N, Whitehall, E (Sheffield Teaching Hospital Nhs Foundation Trust), Athwal, R, Baker, A, Jones, L, Konstantinou, C, Ramcharan, S, Vatish, J, Wilkin, R (South Warwickshire Nhs Foundation Trust), Ethunandan, M, Sekhon, Gk, Shields, H, Singh, R, Wensley, F (Southampton General Hospital), Lawday S, Lyons A (Southmead Hospital), Abbott, T, Anwar, S, Ghufoor, K, Sohrabi, C (St Bartholomew’, s Hospital (Non-Cardiac Unit)), Chung, E, Hagger, R, Hainsworth, A, Karim, A, Owen, H, Ramwell, A, Williams, K (St George’, Baker, C, Davies, A, Gossage, J, Kelly, M, Knight, W (St Thomas’, Hospital), Hall, J (Stepping Hill Hospital), Harris, G, James, G, Kang, C, Lin, Dj, Rajgor, Ad, Royle, T, Scurrah, R, Steel, B, Watson LJ (Sunderland Royal Hospital), Choi, D, Hutchison, R, Jain, A, Luoma, V, Marcus, H, May, R, Menon, A, Pramodana, B, Webber, L (The National Hospital For Neurology And Neurosurgery), Aneke, Ia, Asaad, P, Brown, B, Collis, J, Duff, S, Khan, A, Moura, F, Wadham, B, Warburton, H (The University Hospital Of South Manchester), Elmoslemany, T, Jenkinson, M, Millward, C, Zakaria, R (The Walton Centre Nhs Foundation Trust), Mccluney, S, Parmar, C, Shah, S (The Whittington Hospital), Allison, J, Babar, Ms, Collard, B, Goodrum, S, Lau, K, Patel, A, Scott, R, Thomas, E, Whitmore, H (Torbay And South Devon Nhs Trust), Balasubramaniam, D, Jayasankar, B, Kapoor, S, Ramachandran, A (Tunbridge Wells Hospital), Elhamshary, A, Imam, Smb, Kapriniotis, K, Kasivisvanathan, V, Lindsay, J, Rakhshani-Moghadam, S (University College London Hospital At Westmoreland Street), Beech, N, Chand, M, Green, L, Kalavrezos, N, Kiconco, H, McEwen, R, Schilling, C, Sinha, D (University College London Hospital), Pereca J, Singh J (University Hospital Ayr), Chopra, S, Egbeare, D, Thomas, R (University Hospital Llandough), Combellack, T, Jones, Sef, Kornaszewska, M, Mohammed, M, Sharma, A, Tahhan, G, Valtzoglou, V, Williams, J (University Hospital Of Wales), Eskander, P, Gash, K, Gourbault, L, Hanna, M, Maccabe, T, Newton, C, Olivier, J, Rozwadowski, S, Teh, E, West, D (University Hospitals Bristol NHS Foundation Trust), Al-omishy, H, Baig, M, Bates, H, Di Taranto, G, Dickson, K, Dunne, N, Gill, C, Howe, D, Jeevan, D, Khajuria, A, Martin-Ucar, A, McEvoy, K, Naredla, P, Ng, V, Robertson, S, Sait, M, Sarma, Dr, Shanbhag, S, Shortland, T, Simmonds, S, Skillman, J, Tewari, N, Walton, G (University Hospitals Coventry And Warwickshire Nhs Trusts), Akhtar, Ma, Brunt, A, McIntyre, J, Milne, K, Rashid, Mm, Sgrò, Stewart, Ke, Turnbull, A (Victoria Hospital Kirkcaldy), Aguilar Gonzalez M, Talukder S (West Suffolk Hospital), Boyle, C, Fernando, D, Gallagher, K, Laird, A, Tham, D (Western General Hospital), Bath, M, Patki, P, Tanabalan, C (Whipps Cross University Hospital), Arif, T, Magee, C, Nambirajan, T, Powell, S, Vinayagam, R (Wirral University Teaching Hospital), Flindall, I, Hanson, A, Mahendran, V (Worcestershire Royal Hospital), Green, S, Lim, M, MacDonald, L, Miu, V, Onos, L, Sheridan, K, Young, R (York Teaching Hospitals Nhs Trust), Alam, F, Griffiths, O, Houlden, C, Jones, R, Kolli, Vs, Lala, Ak, Leeson, S, Peevor, R, United States of America: Chen L, Seymour Z (Ysbyty Gwynedd)., Henderson, E, Loehrer, A (Dartmouth-Hitchcock Medical Center), Brown, K, Fleming, D, Heron, C, Hill, C, Kay, H, Leede, E, McElhinney, K, Olson, K, Osterberg, Ec, Riley, C, Srikanth, P, Thornhill, M (Dell Seton Medical Center At The University Of Texas), Blazer, D, DiLalla, G, Hwang, Es, Lee, W, Lidsky, M, Plichta, J, Rosenberger, L, Scheri, R, Turnage, K, Visgauss, J, Zani, S (Duke University Medical Center), Farma, J (Fox Chase Cancer Center), Clark J, Kwon D (Henry Ford Hospital), Etchill, E, Gabre-Kidan, A, Jenny, He, Kent, A, Ladd, M, Long, C, Malapati, H, Margalit, A, Rapaport, S, Rose, J, Stevens, K, Tsai, L, Vervoort, D, Yesantharao, P (Johns Hopkins Hospital), Dehal, A (Kaiser Permanente Panorama City Medical Center), Klaristenfeld, D (Kaiser Permanente San Diego Medical Center), Huynh, K (Kaiser Permanente West Los Angeles), Brown L, Ganly I (Memorial Sloan Kettering Cancer Center), Mullinax, J (Moffitt Cancer Center), Gusani, N, Hazelton, J, Maines, J, Oh, Js, Ssentongo, A, Ssentongo, P (Pennsylvania State University), Azam, M, Choudhry, A, Marx, W (Suny Upstate University Hospital), Fleming, J, Fuson, A, Gigliotti, J, Ovaitt, A, Ying, Y (University Of Alabama Birmingham), Abel, Mk, Boeck, Ma, Chern, H, Corvera, C, El- sayed, I, Glencer, A, Ha, P, Hamilton, Bcs, Heaton, C, Hirose, K, Jablons, Dm, Kirkwood, K, Kornblith, Lz, Kratz, Jr, Lee, R, Miller, Pn, Nakakura, E, Nunez-Garcia, B, Ozgediz, D, Sarin, A, Sheu, B, Varma, M, Wai, K, Xu MJ (University Of California, San Francisco (UCSF)), Beswick, D, Goddard, J, Manor, J, Song, J (University Of Colorado Hospital/Memorial Hospital/Medical Center Of The Rockies (All Within Uchealth System)), Fullmer, T, Gaskill, C, Gross, N, Kiong, K, Roland, Cl, Zafar SN (University Of Texas Md Anderson Cancer Center), Abdallah, M, Abouassi, A, Almasri, M, Kulkarni, G, Marwan, H, Mehdi, M (University Of Texas Medical Branch), Aoun, S, Ban, Vs, Batjer, Hh, Caruso, J (University Of Texas Southwestern), Abbott, D, Acher, A, Aiken, T, Barrett, J, Foley, E, Schwartz, P, Zafar SN (University Of Wisconsin), Hawkins, A, Uruguay: Laufer J, Maiga A (Vanderbilt University Medical Center)., Scasso, S (Hospital Pereira Rossell, Montevideo, )., Glasbey, J. C., Nepogodiev, D., Simoes, J. F. F., Omar, O., Li, E., Venn, M. L., Chaar, M. K. A., Capizzi, V., Chaudhry, D., Desai, A., Edwards, J. G., Evans, J. P., Fiore, M., Videria, J. F., Ford, S. J., Ganly, I., Griffiths, E. A., Gujjuri, R. R., Kolias, A. G., Kaafarani, H. M. A., Minaya-Bravo, A., Mckay, S. C., Mohan, H. M., Roberts, K. J., Miguel-Mendez, C. S., Pockney, P. G., Shaw, R., Smart, N. J., Stewart, G. D., Sundar, S., Vidya, R., Bhangu, A. A., Allemand, C., Boccalatte, L., Figari, M., Lamm, M., Larranaga, J., Marchitelli, C., Noll, F., Odetto, D., Perrotta, M., Saadi, J., Zamora, L., Alurralde, C., Caram, E. L., Eskinazi, D., Mendoza, J. P., Usandivaras, M., Badra, R., Esteban, A., Garcia, J. S., Garcia, P. M., Gerchunoff, J. I., Lucchini, S. M., Nigra, M. A., Vargas, L., Hovhannisyan, T., Stepanyan, A., Gould, T., Gourlay, R., Griffiths, B., Gananadha, S., Mclaren, M., Cecire, J., Joshi, N., Salindera, S., Sutherland, A., Ahn, J. H., Charlton, G., Chen, S., Gauri, N., Hayhurst, R., Jang, S., Jia, F., Mulligan, C., Yang, W., Ye, G., Zhang, H., Ballal, M., Gibson, D., Hayne, D., Moss, J., Richards, T., Viswambaram, P., Vo, U. G., Bennetts, J., Bright, T., Brooke-Smith, M., Fong, R., Gricks, B., Lam, Y. H., Ong, B. S., Szpytma, M., Watson, D., Bagraith, K., Caird, S., Chan, E., Dawson, C., Ho, D., Jeyarajan, E., Jordan, S., Lim, A., Nolan, G. J., Oar, A., Parker, D., Puhalla, H., Quennell, A., Rutherford, L., Townend, P., Von Papen, M., Wullschleger, M., Blatt, A., Cope, D., Egoroff, N., Fenton, M., Gani, J., Lott, N., Shugg, N., Elliott, M., Phung, D., Phan, D., Townend, D., Bong, C., Gundara, J., Frankel, A., Bowman, S., Guerra, G. R., Bolt, J., Buddingh, K., Dudi-Venkata, N. N., Jog, S., Kroon, H. M., Sammour, T., Smith, R., Stranz, C., Batstone, M., Lah, K., Mcgahan, W., Mitchell, D., Morton, A., Pearce, A., Roberts, M., Sheahan, G., Swinson, B., Alam, N., Banting, S., Chong, L., Choong, P., Clatworthy, S., Foley, D., Fox, A., Hii, M. W., Knowles, B., Mack, J., Read, M., Rowcroft, A., Ward, S., Wright, G., Lanner, M., Konigsrainer, I., Bauer, M., Freyschlag, C., Kafka, M., Messner, F., Ofner, D., Tsibulak, I., Emmanuel, K., Grechenig, M., Gruber, R., Harald, M., Ohlberger, L., Presl, J., Wimmer, A., Namazov, I., Samadov, E., Barker, D., Boyce, R., Corbin, S., Doyle, A., Eastmond, A., Gill, R., Haynes, A., Millar, S., O'Shea, M., Padmore, G., Paquette, N., Phillips, E., S, t. John S., Walkes, K., Flamey, N., Pattyn, P., Oosterlinck, W., Van Den Eynde, J., Van Den Eynde, R., Gatti, A., Nardi, C., Oliva, R., De Cicco, R., Cecconello, I., Gregorio, P., Pontual Lima, L., Ribeiro, U., Takeda, F., Terra, R. M., Sokolov, M., Kidane, B., Srinathan, S., Boutros, M., Caminsky, N., Ghitulescu, G., Jamjoum, G., Moon, J., Pelletier, J., Vanounou, T., Wong, S., Dumitra, S., Kouyoumdjian, A., Johnston, B., Russell, C., Demyttenaere, S., Garfinkle, R., Abou-Khalil, J., Nessim, C., Stevenson, J., Heredia, F., Almeciga, A., Fletcher, A., Merchan, A., Puentes, L. O., Mendoza Quevedo, J., Bacic, G., Karlovic, D., Krsul, D., Zelic, M., Luksic, I., Mamic, M., Bakmaz, B., Coza, I., Dijan, E., Katusic, Z., Mihanovic, J., Rakvin, I., Frantzeskou, K., Gouvas, N., Kokkinos, G., Papatheodorou, P., Pozotou, I., Stavrinidou, O., Yiallourou, A., Martinek, L., Skrovina, M., Szubota, I., Zatecky, J., Javurkova, V., Klat, J., Avlund, T., Christensen, P., Harbjerg, J. L., Iversen, L. H., Kjaer, D. W., Kristensen, H. O., Mekhael, M., Ebbehoj, A. L., Krarup, P., Schlesinger, N., Smith, H., Abdelsamed, A., Azzam, A. Y., Salem, H., Seleim, A., Abdelmajeed, A., Abdou, M., Abosamak, N. E., AL-Sayed, M., Ashoush, F., Atta, R., Elazzazy, E., Elhoseiny, M., Elnemr, M., Elqasabi, M. S., Elsayed Hewalla, M. E., Elsherbini, I., Essam, E., Eweda, M., Ghallab, I., Hassan, E., Metwalli, M., Mourad, M., Qatora, M. S., Ragab, M., Sabry, A., Saifeldin, H., Saleh Mesbah Mohamed Elkaffas, M., Samih, A., Samir Abdelaal, A., Shehata, S., Shenit, K., Attia, D., Kamal, N., Osman, N., Abbas, A. M., Abd Elazeem, H. A. S., Abdelkarem, M. M., Alaa, S., Ali, A. K., Ayman, A., Azizeldine, M. G., Elkhayat, H., Melghazaly, S., Monib, F. A., Nageh, M. A., Saad, M. M., Salah, M., Shahine, M., Yousof, E. A., Youssef, A., Eldaly, A., Elfiky, M., Nabil, A., Amira, G., Sallam, I., Sherief, M., Abdelrahman, A., Aboulkassem, H., Ghaly, G., Hamdy, R., Morsi, A., Sherif, G., Abdeldayem, H., Abdelkader Salama, I., Balabel, M., Fayed, Y., Sherif, A. E., Bekele, D., Sarjanoja, E., Helminen, O., Huhta, H., Kauppila, J. H., Beyrne, C., Jouffret, L., Lugans, L., Marie-Macron, L., Chouillard, E., De Simone, B., Bettoni, J., Dakpe, S., Devauchelle, B., Lavagen, N., Testelin, S., Boucher, S., Breheret, R., Gueutier, A., Kahn, A., Kun-Darbois, J., Barrabe, A., Lakkis, Z., Louvrier, A., Manfredelli, S., Mathieu, P., Chebaro, A., Drubay, V., El amrani, M., Eveno, C., Lecolle, K., Legault, G., Martin, L., Piessen, G., Pruvot, F. R., Truant, S., Zerbib, P., Ballouhey, Q., Barrat, B., Laloze, J., Salle, H., Taibi, A., Usseglio, J., Bergeat, D., Merdrignac, A., Le Roy, B., Perotto, L. O., Scalabre, A., Aime, A., Ezanno, A., Malgras, B., Bouche, P., Tzedakis, S., Cotte, E., Glehen, O., Kepenekian, V., Lifante, J., Passot, G., D'Urso, A., Felli, E., Mutter, D., Pessaux, P., Seeliger, B., Bardet, J., Berry, R., Boddaert, G., Bonnet, S., Brian, E., Denet, C., Fuks, D., Gossot, D., Grigoroiu, M., Laforest, A., Levy-Zauberman, Y., Louis-Sylvestre, C., Moumen, A., Pourcher, G., Seguin-Givelet, A., Tribillon, E., Duchalais, E., Espitalier, F., Ferron, C., Malard, O., Bork, U., Distler, M., Fritzmann, J., Kirchberg, J., Praetorius, C., Riediger, C., Weitz, J., Welsch, T., Wimberger, P., Beyer, K., Kamphues, C., Lauscher, J., Loch, F. N., Schineis, C., Albertsmeier, M., Angele, M., Kappenberger, A., Niess, H., Schiergens, T., Werner, J., Becker, R., Jonescheit, J., Pergolini, I., Reim, D., Boeker, C., Hakami, I., Mall, J., Liokatis, P., Smolka, W., Nowak, K., Reinhard, T., Holzle, F., Modabber, A., Winnand, P., Knitschke, M., Kauffmann, P., Wolfer, S., Kleeff, J., Lorenz, K., Michalski, C., Ronellenfitsch, U., Schneider, R., Bertolani, E., Konigsrainer, A., Loffler, M. W., Quante, M., Steidle, C., Uberruck, L., Yurttas, C., Betz, C. S., Bewarder, J., Bottcher, A., Burg, S., Busch, C., Gosau, M., Heuer, A., Izbicki, J., Klatte, T. O., Koenig, D., Moeckelmann, N., Nitschke, C., Priemel, M., Smeets, R., Speth, U., Thole, S., Uzunoglu, F. G., Vollkommer, T., Zeller, N., Battista, M. J., Gillen, K., Hasenburg, A., Krajnak, S., Linz, V., Schwab, R., Angelou, K., Haidopoulos, D., Rodolakis, A., Antonakis, P., Bramis, K., Chardalias, L., Contis, I., Dafnios, N., Dellaportas, D., Fragulidis, G., Gklavas, A., Konstadoulakis, M., Memos, N., Papaconstantinou, I., Polydorou, A., Theodosopoulos, T., Vezakis, A., Antonopoulou, M. I., Manatakis, D. K., Tasis, N., Arkadopoulos, N., Danias, N., Economopoulou, P., Kokoropoulos, P., Larentzakis, A., Michalopoulos, N., Selmani, J., Sidiropoulos, T., Tsaousis, V., Vassiliu, P., Bouchagier, K., Klimopoulos, S., Paspaliari, D., Stylianidis, G., Baxevanidou, K., Bouliaris, K., Chatzikomnitsa, P., Efthimiou, M., Giaglaras, A., Kalfountzos, C., Koukoulis, G., Ntziovara, A. 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V., Cosimelli, M., Folli, S., Gennaro, M., Giannini, L., Gronchi, A., Guaglio, M., Macchi, A., Martinelli, F., Mazzaferro, V., Mosca, A., Pasquali, S., Piazza, C., Raspagliesi, F., Rolli, L., Salvioni, R., Sarpietro, G., Sarre, C., Sorrentino, L., Agnes, A., Alfieri, S., Belia, F., Biondi, A., Cozza, V., D'Amore, A., D'Ugo, D., De Simone, V., Fagotti, A., Gasparini, G., Gordini, L., Litta, F., Lombardi, C. P., Lorenzon, L., Marra, A. A., Marzi, F., Moro, A., Parello, A., Perrone, E., Persiani, R., Ratto, C., Rosa, F., Saponaro, G., Scambia, G., Scrima, O., Sganga, G., Tudisco, R., Belli, A., Granata, V., Izzo, F., Palaia, R., Patrone, R., Carrano, F. M., Carvello, M. M., De Virgilio, A., Di Candido, F., Ferreli, F., Gaino, F., Mercante, G., Rossi, V., Spinelli, A., Spriano, G., Donati, D. M., Frisoni, T., Palmerini, E., Aprile, A., Barra, F., Batistotti, P., Ferrero, S., Fregatti, P., Scabini, S., Sparavigna, M., Asti, E., Bernardi, D., Bonavina, L., Lovece, A., Adamoli, L., Ansarin, M., Cenciarelli, S., Chu, F., De Berardinis, R., Fumagalli Romario, U., Mastrilli, F., Pietrobon, G., Tagliabue, M., Badellino, E., Ferrero, A., Massobrio, R., De Manzoni Garberini, A., Federico, P., Maida, P., Marra, E., Marte, G., Petrillo, A., Tammaro, T., Tufo, A., Berselli, M., Borroni, G., Cocozza, E., Conti, L., Desio, M., Livraghi, L., Quintodei, V., Rizzi, A., Zullo, A., Baldi, C., Corbellini, C., Sampietro, G. M., Cellerino, P., Baldini, E., Capelli, P., Isolani, S. M., Ribolla, M., Bondurri, A., Colombo, F., Ferrario, L., Guerci, C., Maffioli, A., Armao, T., Ballabio, M., Bisagni, P., Gagliano, A., Longhi, M., Madonini, M., Pizzini, P., Baietti, A. M., Biasini, M., Maremonti, P., Neri, F., Prucher, G. M., Ricci, S., Ruggiero, F., Zarabini, A. G., Barmasse, R., Mochet, S., Usai, A., Incollingo, P., Mancini, S., Marino Cosentino, L., Sagnotta, A., Fruscio, R., Grassi, T., Nespoli, L. C., Tamini, N., Anastasi, A., Bartalucci, B., Bellacci, A., Canonico, G., Capezzuoli, L., Di Martino, C., Ipponi, P., Linari, C., Montelatici, M., Nelli, T., Spagni, G., Tirloni, L., Vitali, A., Abate, E., Casati, M., Casiraghi, T., Laface, L., Schiavo, M., Arminio, A., Cotoia, A., Lizzi, V., Vovola, F., Vergari, R., D'Ugo, S., Depalma, N., Spampinato, M. G., Bartolucci, P., Brachini, G., Bruzzaniti, P., Chiappini, A., Chiarella, V., Ciccarone, F., Cicerchia, P. M., Cirillo, B., De Toma, G., Di bartolomeo, A., Fiori, E., Fonsi, G. B., Franco, G., Frati, A., Giugliano, M., Iannone, I., La Torre, F., Lapolla, P., Leonardo, C., Marruzzo, G., Meneghini, S., Mingoli, A., Ribuffo, D., Salvati, M., Santoro, A., Sapienza, P., Scafa, A. K., Simonelli, L., Zambon, M., Capolupo, G. T., Carannante, F., Caricato, M., Masciana, G., Mazzotta, E., Gattolin, A., Migliore, M., Rimonda, R., Sasia, D., Travaglio, E., Cervellera, M., Gori, A., Sartarelli, L., Tonini, V., Giacometti, M., Zonta, S., Chessa, A., Fiorini, A., Norcini, C., Colletti, G., Confalonieri, M., Costanzi, A., Frattaruolo, C., Mari, G., Monteleone, M., Bandiera, A., Bocciolone, L., Bonavina, G., Candiani, M., Candotti, G., De Nardi, P., Gagliardi, F., Medone, M., Mortini, P., Negri, G., Parise, P., Piloni, M., Sileri, P., Vignali, A., Belvedere, A., Bernante, P., Bertoglio, P., Boussedra, S., Brunocilla, E., Cipriani, R., Cisternino, G., De Crescenzo, E., De Iaco, P., Dondi, G., Frio, F., Jovine, E., Mineo Bianchi, F., Neri, J., Parlanti, D., Perrone, A. M., Pezzuto, A. P., Pignatti, M., Pinto, V., Poggioli, G., Ravaioli, M., Rottoli, M., Schiavina, R., Serenari, M., Serra, M., Solli, P., Taffurelli, M., Tanzanu, M., Tesei, M., Violante, T., Zanotti, S., Borghi, F., Cianflocca, D., Di Maria Grimaldi, S., Gelarda, E., Geretto, P., Giraudo, G., Giuffrida, M. C., Marano, A., Palagi, S., Pellegrino, L., Peluso, C., Testa, V., Agresta, F., Prando, D., Zese, M., Aquila, F., Gambacciani, C., Lippa, L., Pieri, F., Santonocito, O. S., Armatura, G., Bertelli, G., Frena, A., Marinello, P., Notte, F., Patauner, S., Scotton, G., Fulginiti, S. F., Gallo, G., Sammarco, G., Vescio, G., Balercia, P., Catarzi, L., Consorti, G., Di Marzo, F., Fontana, T., Daiko, H., Ishikawa, M., Ishiyama, K., Iwata, S., Kanematsu, K., Kanemitsu, Y., Kato, T., Kawai, A., Kobayashi, E., Kobayashi Kato, M., Moritani, K., Nakatani, F., Oguma, J., Tanase, Y., Uno, M., Al Abdallah, M., Ayasra, F., Ayasra, Y., Qasem, A., Abu Za'nouneh, F. 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C., Tang, C. Y., Teoh, L. Y., Wong, W. J., Yahaya, A. S., Alvarez, M. R., Arrangoiz, R., Cordera, F., De La Rosa Abaroa, M. A., Gomez-Pedraza, A., Hernandez, R., Maffuz-Aziz, A., Posada, J. A., Becerra Garcia, F. C., Alfaro-Goldaracena, A., Buerba, G. A., Castillejos-Molina, R. A., Chan, C., Dominguez-Rosado, I., Medina-Franco, H., Mercado, M. A., Oropeza-Aguilar, M., Pena Gomez Portugal, E., Posadas-Trujillo, O. E., Rodriguez-Covarrubias, F., Salgado-Nesme, N., Vilatoba, M., Arkha, Y., Bechri, H., El Ouahabi, A., Oudrhiri, M. Y., Derkaoui hassani, F., El Abbadi, N., Amrani, L., Belkhadir, Z. H., Benkabbou, A., Chakib, O., El Ahmadi, B., El Bouazizi, Y., Essangri, H., Ghannam, A., Majbar, A. M., Mohsine, R., Souadka, A., Hompes, R., Meima-Van Praag, E. M., Pronk, A. J. M., Sharabiany, S., Grotenhuis, B., Hartveld, L., Reijers, S., Van Houdt, W., Baaij, J., Bolster-Van Eenennaam, M., De Graaff, M., Sloothaak, D., Van Duijvendijk, P., Posma-Bouman, L., Derksen, T., Franken, J., Oosterling, S., De Bree, R., Konsten, J., Van Heinsbergen, M., Fidelis, L., Sholadoye, T. T., Tolani, M. A., Olaogun, J., Egbuchulem, I. K., Lawal, T. A., Ogundoyin, O., Olulana, D. I., Abdur-Rahman, L., Adeyeye, A., Aremu, I., Bello, J., Olasehinde, O., Popoola, A., Massoud, J., Massoud, R., Sorour, T. M., Jamal, A., Kerawala, A. A., Memon, A. S., Nafees Ahmed, R., Rai, L., Ayub, B., Hassan, N., Martins, R. S., Ramesh, P., Sayyed, R., Butt, U., Kashif, M., Khan, W. H., Qureshi, A., Umar, M., Waris Farooka, M., Wasim, T., Ayubi, A., Rashid, I., Waqar, S. H., Falcon, G. M., Robles, R., Jocson, R., Teh, C., Major, P., Bobinski, M., Kotarski, J., Rasoul-Pelinska, K., Azevedo, C., Machado, D., Mendes, F., De Sousa, X., Fernandes, U., Ferreira, C., Guidi, G., Leal, C., Marcal, A., Marques, R., Martins, D., Melo, A., Tenreiro, N., Vaz Pereira, R., Vieira, B., Almeida, J. I., Correia de Sa, T., Costa, M. J. M. A., Fernandes, V., Ferraz, I., Gil, C. G., Lima Da Silva, C., Lopes, L., Machado, N., Marialva, J., Nunes Coelho, M., Pedro, J., Pereira, C., Reis, R., Ribeiro, A., Santos, R., Saraiva, P., Silva, R., Tavares, F., Teixeira, M., Almeida, A. C., Amaral, M. J., Andrade, R., Athayde Nemesio, R., Breda, D., Camacho, C., Canhoto, C., Colino, M., Correia, S., De Barros, J., De Oliveira Lopez, A. L., Duque, M., Garrido, S., Guerreiro, P., Guimaraes, A., Lazaro, A., Lopes, C., Nogueira, O., Oliveira, A., Oliveira, J. M., Rodrigues, M., Ruivo, A., Santos, E., Silva, M., Simoes, J., Valente Da Costa, A., Almeida, A., Cavaleiro, S., Devezas, V., Faria, C. S., Jacome, F., Magalhaes Maia, M., Nogueiro, J., Pereira, A., Pereira-Neves, A., Pina-Vaz, T., Santos-Sousa, H., Silveira, H., Vaz, S., Vieira, P., Gomes Da Costa, A., Lobo Antunes, I., Pinto, J., Tojal, A., Cardoso, N., Cardoso, P., Domingues, J. C., Henriques, P., Manso, M. I., Martins Dos Santos, G., Morais, H., Pereira, R., Revez, T., Ribeiro, R., Ribeiro, V. I., Sousa, S., Teixeira, J., Amorim, E., Baptista, V. H., Cunha, M. F., Dias, B., Fazenda, A., Melo Neves, J. P., Policarpo, F., Sampaio Da Novoa Gomes Miguel, I. I., Veiga, D., Andrade, A. K., Bandovas, J. P., Borges, N., Branquinho, A., Chumbinho, B., Correia, J., Fidalgo, H., Figueiredo De Barros, I., Frade, S., Gomes, J., Maciel, J., Pina, S., Rodrigues, A., Silva, N., Silveira Nunes, I., Sousa, R., Ascensao, J., Azevedo, P., Costeira, B., Cunha, C., Garrido, R., Gomes, H., Lourenco, I., Mendinhos, G., Miranda, P., Nobre Pinto, A., Peralta Ferreira, M., Ribeiro, J., Rio Rodrigues, L., Sousa Fernandes, M., Azevedo, J., Galvao, D., Soares, A. C., Vieira, A., Patricio, B., Santos, P. M. D. D., Vieira Paiva Lopes, A. C., Cunha, R., Faustino, A., Freitas, A., Martins, A. B., Mendes, J. R., Parreira, R., Rosa, J., Teves, M., Abreu Da Silva, A., Claro, M., Costa Santos, D., Deus, A. C., Grilo, J. V., Borges, F., Corte Real, J., Henriques, S., Lima, M. J., Matos Costa, P., Brito da Silva, F., Caiado, A., Fonseca, F., Angelo, M., Baiao, J. M., Martins Jordao, D., Vieira Caroco, T., Messias, J., Millan, A., Salgado, I., Baia, C., Canotilho, R., Correia, A. M., Ferreira Pinto, A. 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V., Garmanova, T., Kazachenko, E., Markaryan, D., Rodimov, S., Tsarkov, P., Tulina, I., Litvina, Y., Provozina, A., Agapov, M., Galliamov, E., Kakotkin, V., Kubyshkin, V., Alshahrani, M., Alsharif, F., Eskander, M., Al Raddadi, R., Majrashi, S., Mashat, A., Akeel, N., Alharthi, M., Aljiffry, M., Basendowah, M., Farsi, A., Ghunaim, M., Khoja, A., Maghrabi, A., Malibary, N., Nassif, M., Nawawi, A., Saleem, A., Samkari, A., Trabulsi, N., Al Awwad, S., Alghamdi, M., Alnumani, T., Nasser, M., Said bayazeed, A., Alhefdhi, A., Almalik, O., Alomair, A., Alotaibi, N., Alresaini, F., Alsalamah, R., Alsobhi, S., Mahasin, Z., Othman, E., Velagapudi, S., Ghedan, S., Alharthi, R., Awad, S., Sharara, M., Abdelrahman, S., Althobaiti, W., Al Habes, H., Alamri, A., Alkarak, S., Alqannas, M., Alyami, M., Alzamanan, M., Cortes Guiral, D., Elawad, A., Alaamer, O., Alriyees, L., Alselaim, N., Abdulkareem, A., Ajlan, A., Akkour, K., Al-Habib, A., Al-Khayal, K., Alatar, A., Alburakan, A., Alhalal, H., Alhassan, B., Alhassan, N., Alobeed, O., Alsaif, A., Alsaif, F., Alshammari, S., Alshaygy, I., Barry, M., Bin Nasser, A., Bin Traiki, T., Bokhari, A., Elwatidy, S., Helmi, H., Madkhali, A., Nouh, T., Rabah, P. D., Zubaidi, A., Paunovic, I., Slijepcevic, N., Aleksic, L., Antic, A., Barisic, G., Ceranic, M., Galun, D., Grubac, Z., Jelenkovic, J., Kecmanovic, D., Kmezic, S., Knezevic, D., Krivokapic, Z., Latincic, S., Markovic, V., Matic, S., Miladinov, M., Pavlov, M., Pejovic, I., Radenkovic, D., Tadic, B., Vasljevic, J., Velickovic, D., Zivanovic, M., Perovic, M., Srbinovic, L., Andrijasevic, S., Bozanovic, T., Cerovic Popovic, R., Dokic, M., Janjic, T., Jeremic, K., Kadija, S., Ladjevic Likic, I., Mirkovic, L., Pantovic, S., Pilic, I., Radojevic, M., Stefanovic, A., Vidakovic, S., Vilendecic, Z., Antic, S., Dunderovic, D., Jelovac, D., Jezdic, Z., Konstantinovic, V., Kotlar, B., Kuzmanovic, C., Lazic, M., Petrovic, M., Popovic, F., Pucar, A., Romic, M., Sumrak, S., Vujanac, V., Bascarevic, V., Bogdanovic, I., Grujicic, D., Ilic, R., Milicevic, M., Milisavljevic, F., Miljkovic, A., Paunovic, A., Scepanovic, V., Stanimirovic, A., Todorovic, M., Jotic, A., Milovanovic, J., Trivic, A., Bumbasirevic, U., Dzamic, Z., Kajmakovic, B., Prijovic, N., Zivkovic, M., Buta, M., Cvetkovic, A., Djurisic, I., Gacic, S., Goran, M., Inic, Z., Jeftic, N., Jevric, M., Jokic, V., Markovic, I., Milanovic, M., Nikolic, S., Pejnovic, L., Savkovic, N., Spurnic, I., Stevic, D., Stojiljkovic, D., Vucic, N., Zegarac, M., Karamarkovic, A., Kenic, M., Kovacevic, B., Krdzic, I., Milutinovic, V., Lieske, B., Galis, B., Simko, K., Almgla, N., Bernon, M., Boutall, A., Cairncross, L., Herman, A., Hilton, T., Jonas, E., Kloppers, C., Malherbe, F., Mugla, W., Nel, D., Rayamajhi, S., Van Wyngaard, T., Vogel, J., Castano-Leon, A. M., Delgado Fernandez, J., Eiriz Fernandez, C., Espino Segura-Illa, M., Esteban Sinovas, O., Garcia Perez, D., Gomez, P., Jimenez-Roldan, L., Lagares, A., Moreno-Gomez, L., Paredes, I., Perez Nunez, A., Sanchez Aniceto, G., Santas, M., Fernandez Rodriguez, P., Paniagua Garcia Senorans, M., Sanchez-Santos, R., Vigorita, V., Acrich, E., Baena Sanfeliu, E., Barrios, O., Golda, T., Santanach, C., Serrano-Navidad, M., Sorribas Grifell, M., Vives, R. V., Escola, D., Jimenez, A., Cayetano Paniagua, L., Gomez Fernandez, L., Artigues, E., Bernal-Sprekelsen, J. C., Catala Bauset, J. C., Collera, P., Diaz Del Gobbo, R., Farre Font, R., Flores Clotet, R., Gomez Diaz, C. J., Guardia, N., Guariglia, C. A., Osorio, A., Sanchez Jimenez, R., Sanchon, L., Soto Montesinos, C., Albi Martin, B., Garcia Villayzan, J. E., Alonso-Lamberti, L., Assaf, M., Baeza Pintado, N., Carabias, A., Garcia-Quijada, J., Huertas Fernandez, M. A., Jimenez Miramon, J., Jimenez, V., Jover, J. M., Landeo Aguero, S. A., Leon, R., Martin Salamanca, M. B., Perez Simon, V., Ponce, S., Rodriguez, J. L., Salazar, A., Valle Rubio, A., Aguado, H., Aldecoa Ansorregui, I., Bravo Infante, R., De Lacy, F. B., Di Somma, A., Diaz-Feijoo, B., Ensenat Nora, J., Fabregas, N., Ferres, A., Gil Ibanez, B., Gonzalez Sanchez, J. J., Gracia, I., Hoyos Castro, J. A., Lacy, A. M., Langdon, C., Momblan, D., Morales, X., Oleaga, L., Otero, A., Pedrosa, L., Poblete Carrizo, J., Reyes Figueroa, L. A., Roldan Ramos, P., Rumia-Arboix, J., Tercero-Uribe, A. I., Topczewski, T. E., Torales, J., Torne, A., Torne, R., Turrado-Rodriguez, V., Valero, R., Valverde, S., Anula, R., Cano-Valderrama, O., Del Campo Martin, M., Diez-Valladares, L., Dominguez, I., Dziakova, J., Garcia Alonso, M., Garcia Romero, E., Gomez Latorre, L., Muguerza, J. M., Pizarro, M. J., Saez Carlin, P., Sanchez Del Pueblo, C., Sanchez-Pernaute, A., Sanz Ortega, G., Sanz-Lopez, R., Torres, A., Garces-Albir, M., Lopez, F., Martin-Arevalo, J., Moro-Valdezate, D., Pla-Marti, V., Beltran De Heredia, J., De Andres Asenjo, B., Gomez Sanz, T., Jezieniecki, C., Nunez Del Barrio, H., Ortiz De Solorzano Aurusa, F. J., Romero De Diego, A., Ruiz Soriano, M., Trujillo Diaz, J., Vazquez Fernandez, A., Lora-Cumplido, P., Sosa, M. V., Gonzalez-Gonzalez, E., Minaya Bravo, A. M., Alonso de la Fuente, N., Cazador Labat, M., Cecchini, L., Espinosa, C. A., Jimenez Toscano, M., Lopez Campillo, A., Mancebo, G., Martorell, P., Munarriz, M., Grau-Talens, E. J., Martin-Perez, B., Benavides Buleje, J. A., Carrasco Prats, M., Fernandez, P. V., Fernandez-Lopez, A., Garcia Escudero, D., Garcia Porcel, V. J., Garcia Soria, V., Gimenez Frances, C., Gonzalez Valverde, F. M., Gurrea, E., Lopez-Morales, P., Marco Garrido, A., Martinez Alonso, J. A., Medina, E., Munoz Camarena, J. M., Parra Banos, P. A., Pena Ros, E., Ramirez Faraco, M., Ruiz-Marin, M., Sanchez Rodriguez, C., Valero Soriano, M., Estaire Gomez, M., Fernandez Camunas, A., Garcia Santos, E. P., Jimenez Higuera, E., Martinez-Pinedo, C., Munoz-Atienza, V., Padilla-Valverde, D., Picon Rodriguez, R., Redondo Calvo, F. J., Sanchez-Garcia, S., Sanchez-Pelaez, D., Colombari, R. C., Del valle, E., Fernandez, M., Lozano Lominchar, P., Rey Valcarcel, C., Steiner, M. A., Tudela, M., Zorrilla Ortuzar, J., Alcaide Matas, F., Garcia Perez, J. M., Troncoso Pereira, P., Mora-Guzman, I., Abellan, M., Achalandabaso Boira, M., Jorba, R., Memba Ikuga, R., Olona, C., Sales Mallafre, R., Cavalle Busquets, P., Gavalda Pellice, M. G. P., Salinas Pena, J., Aragon Achig, E. J., Barbier, L., Caja Vivancos, P., Gainza, A., Garcia Gutierrez, J. J., Mallabiabarrena Ormaechea, G., Marin, H., Martin Playa, P., Melchor Corcostegui, I., Prieto Calvo, M., Rodriguez Fraga, A., Villalabeitia Ateca, I., De Andres Olabarria, U., Duran Ballesteros, M., Fernandez Pablos, F. J., Ibanez-Aguirre, F. J., Sanz Larrainzar, A., Ugarte-Sierra, B., De La Hoz Rodriguez, A., Di Martino, M., Garcia Septiem, J., Martin-Perez, E., Munoz De Nova, J. L., Calvo Espino, P., Guillamot Ruano, P., Colao Garcia, L., Diaz Perez, D., Esteban Agusti, E., Galindo Jara, P., Gutierrez Samaniego, M., Hernandez Bartolome, M. A., Serrano Gonzalez, J., Alonso Poza, A., Dieguez, B., Garcia-Conde, M., Hernandez-Garcia, M., Losada, M., Chiesa-Estomba, C. M., Gonzalez Garcia, J. A., Larruscain, E., Sistiaga-Suarez, J. A., Alvarez, E., Chavarrias, N., Frias, L., Garcia Pineda, V., Gegundez Simon, A., Gortazar, S., Gracia, M., Guevara, J., Hernandez Gutierrez, A., Loayza, A., Maria Dolores, D. T., Marti, C., Melendez, M., Moreno-Palacios, E., Perez, Y., Prieto Nieto, M. I., Ramos-Martin, P., Rubio-Perez, I., Saavedra, J., Sanchez-Mendez, J. I., Siegrist Ridruejo, J., Urbieta, A., Zapardiel, I., Cantalejo diaz, M., De Miguel Ardevines, M. D. C., Duque-Mallen, V., Gascon Ferrer, I., Gonzalez-Nicolas Trebol, M. T., Gracia-Roche, C., Herrero Lopez, M., Jariod Ferrer, U. M., Lanzon, A., Martinez German, A., Matute, M., Redondo, C., Sanchez Fuentes, N., Sanchez-Rubio, M., Santero-Ramirez, M. S., Saudi, S., Simon Sanz, M. V., Uson-Bouthelier, T., Blazquez Martin, A., Diez Alonso, M., Garcia Rico, E., Garcia-Loarte Gomez, E., Garcia-Moreno Nisa, F., Gutierrez Calvo, A., Hernandez, P., Lasa, I., Mendoza-Moreno, F., Morales Palacios, N., Ovejero Merino, E., Vera Mansilla, C., Acebes Garcia, F., Bailon, M., Bueno Canones, A. D., Choolani Bhojwani, E., Marcos-Santos, P., Miguel, T., Pacheco Sanchez, D., Perez-Saborido, B., Sanchez Gonzalez, J., Tejero-Pintor, F. J., Alconchel, F., Conesa, A., Gil Martinez, J., Gutierrez Fernandez, A. I., Lopez Abad, A., Nicolas-Lopez, T., Ramirez Romero, P., Roca Calvo, M. J., Rodrigues, K., Ruiz Manzanera, J. J., Soriano, A. I., Cano, A., Capitan-Morales, L., Cintas Catena, J., Gomez-Rosado, J., Oliva Mompean, F., Perez Sanchez, M. A., Rio Lafuente, F. D., Torres Arcos, C., Valdes-Hernandez, J., Cholewa, H., Domingo, S., Frasson, M., Lago, V., Marina Martin, T., Martinez Chicote, C., Sancho-Muriel, J., Landaluce-Olavarria, A., Lecumberri, D., Abad Gurumeta, A., Abad-Motos, A., Martinez-Hurtado, E., Ripolles-Melchor, J., Ruiz Escobar, A., Cuadrado-Garcia, A., Garcia-Sancho Tellez, L., Heras Aznar, J., Mate, P., Ortega Vazquez, I., Picardo, A. L., Rojo Lopez, J. A., Sanchez Cabezudo Noguera, F., Serralta De Colsa, D., Anchuelo Latorre, J., Cagigas Fernandez, C., Caina Ruiz, R., Gomez Ruiz, M., Hernanz, F., Jimeno Fraile, J., Martinez-Perez, P., Poch, C., Santarrufina Martinez, S., Valbuena Jabares, V., Moliner-Sanchez, C., Pingarron-Martin, L., Rey-Biel, J., Ruiz Martin, I., Blas Laina, J. L., Cros, B., Escartin, J., Garcia Egea, J., Nogues, A., Talal El-Abur, I., Yanez, C., Cagigal Ortega, E. P., Cervera, I., Diaz Pena, P., Elena, G. D. C. R., Enjuto, D., Fernandez Bernabe, P., Garces Garcia, R., Gonzalez, J., Hernandez, I., Herrera-Merino, N., Marqueta De Salas, M., Martinez Pascual, P., Perez Gonzalez, M., Ramos Bonilla, A., Rodriguez Gomez, L., Bescos, C., Blanco-Colino, R., Brana, I., Caimari, B., De Pablo Garcia-Cuenca, A., Duran-Valles, F., Espin-Basany, E., Giralt Lopez De Sagredo, J., Pamias, J., Pellino, G., Prat, N., Pujol Pina, R., Saez Barba, M., Arulanantham, A., Bandara, G. B. K., Jayarajah, U., Ravindrakumar, S., Rodrigo, V. S., Srishankar, S., Ali Karar, A. A., Elbe, P., Lindqvist, E. K., Taflin, H., Alga, A., Heinius, G., Nordberg, M., Pieniowski, E., Gkekas, I., Lofgren, N., Rutegard, M., Sund, M., Arigoni, M., Bernasconi, M., Christoforidis, D., Di Giuseppe, M., La Regina, D., Mongelli, F., Chevallay, M., Dwidar, O., Gialamas, E., Sauvain, M., Klenke, F., Kollar, A., Kurze, C., Adamina, M., Bachler, T., Crugnale, A. S., Giardini, M., Guglielmetti, L., Peros, G., Solimene, F., Aghayeva, A., Hamzaoglu, I., Sahin, I., Akaydin, E., Aliyeva, Z., Aytac, E., Baca, B., Dulgeroglu, O., Ozben, V., Ozmen, B. B., Uras, C., Arikan, A. E., Bilgin, I. A., Bozkirli, B., Ceyhan, G. O., Kara, H., Karahasanoglu, T., Celik, H., Meydanli, M. M., Akilli, H., Ayhan, A., Kuscu, E., Onan, M. A., Akgor, U., Dincer, H. A., Erol, T., Gultekin, M., Orhan, N., Ozgul, N., Salman, M. C., Soyak, B., Alhamed, A., Ergun, S., Ozcelik, M. F., Sanli, A. N., Uludag, S. S., Velidedeoglu, M., Zengin, A. K., Bozkurt, M. A., Kara, Y., Kocatas, A., Cimenoglu, B., Demirhan, R., Saracoglu, K., Azamat, I. F., Balik, E., Bugra, D., Giray, B., Kulle, C. B., Taskiran, C., Vatansever, D., Gozal, K., Guler, S. A., Koken, H., Tatar, O. C., Utkan, N. Z., Yildirim, A., Yuksel, E., Akin, E., Altintoprak, F., Bayhan, Z., Cakmak, G., Capoglu, R., Celebi, F., Demir, H., Dikicier, E., Firat, N., Gonullu, E., Kamburoglu, M. B., Kocer, B., Kucuk, I. F., Mantoglu, B., Colak, E., Kucuk, G. O., Uyanik, M. S., Goksoy, B., Bozkurt, E., Citgez, B., Mihmanli, M., Tanal, M., Yetkin, G., Akalin, M., Arican, C., Avci, E. K., Aydin, C., Demirli Atici, S., Emiroglu, M., Kaya, T., Kebabci, E., Kilinc, G., Kirmizi, Y., Ogucu, H., Salimoglu, S., Sert, I., Tugmen, C., Tuncer, K., Uslu, G., Yesilyurt, D., Karaman, E., Kolusari, A., Yildiz, A., Benson, O., Lule, H., Agilinko, J., Ahmeidat, A., Barabasz, M., Bekheit, M., Cheung, L. K., Colloc, T., Cymes, W., Elhusseini, M., Gradinariu, G., Hannah, A., Kamera, B. S., Mignot, G., Shaikh, S., Sharma, P., Abu-Nayla, I., Agrawal, A., Al-Mohammad, A., Ali, S., Ashcroft, J., Azizi, A., Baker, O., Balakrishnan, A., Byrne, M., Colquhoun, A., Cotter, A., Coughlin, P., Davies, R. J., Durrani, A., Elshaer, M., Fordington, S., Forouhi, P., Georgiades, F., Grimes, H., Habeeb, A., Hudson, V., Hutchinson, P., Irune, E., Jah, A., Khan, D. Z., Kyriacou, H., Lamb, B., Liau, S., Luke, L., Mahmoud, R., Mannion, R., Masterson, L., Mitrofan, C. G., Mohan, M., Morris, A., Murphy, S., O'Neill, R., Price, S., Pushpa-Rajah, J., Raby-Smith, W., Ramzi, J., Rooney, S., Santarius, T., Singh, A., Tan, X. S., Townson, A., Tweedle, E., Walker, C., Waseem, S., Yordanov, S., Jones, T., Kattakayam, A., Loh, C., Lunevicius, R., Pringle, S., Schache, A., Sheel, A., Rossborough, C., Angelou, D., Choynowski, M., Mcaree, B., Mccanny, A., Neely, D., Tutoveanu, G., Ahad, S., De La Cruz Monroy, M. F. I., Mosley, F., Oktseloglou, V., Alanbuki, A., Patel, M., Shabana, A., Perera, E., Raveendran, D., Ravi-Shankar, K., Thiruchelvam, J., Arrowsmith, L., Campbell, W., Grove, T., Kontovounisios, C., Warren, O., Rolland, P., Aggarwal, A., Brown, S., Jelley, C., Neal, N., Clifford, R., Eardley, N., Krishnan, E., Manu, N., Martin, E., Roy Mahapatra, S., Serevina, O. L., Smith, C., Vimalachandran, D., Bordenave, M., Houston, R., Putnam, G., Robson, A., Tustin, H., Emslie, K., Labib, P. L., Marchbank, A., Miller, D., Minto, G., Natale, J., Nwinee, H., Panahi, P., Rogers, L., Abubakar, A., Akhter Rahman, M. M., Ko, K. Y. K., O'Brien, H., Sasapu, K., Woodun, H., Inglis, R., Ng, H. J., De Gea Rico, A., Ghazali, N., Lambert, J., Markose, G., Math, S., Sarantitis, I., Shrestha, D., Sultana, A., Taggarsi, M., Timbrell, S., Vaz, O. P., Vitone, L., Day, A., Dent, H., Fahim, M., Waheed, S., Hunt, A., Laskar, N., Gupta, A., Steinke, J., Thrumurthy, S., Massie, E., Mcgivern, K., Rutherford, D., Wilson, M., Hardie, J., Kazzaz, S., Handa, S., Kaushal, M., Kler, A., Patel, P., Redfern, J., Tezas, S., Aawsaj, Y., Amonkar, S., Blackwell, L., Blake, D., Carter, J., Emerson, H., Fisher, A., Katory, M., Korompelis, P., Mccormick, W., Mustafa, A., Pearce, L., Ratnavelu, N., Reehal, R., Kretzmer, L., Lalou, L., Manku, B., Parwaiz, I., Stafford, J., Abdelkarim, M., Asqalan, A., Gala, T., Ibrahim, S., Maw, A., Mithany, R., Morgan, R., Sundaram Venkatesan, G., Ang, K., Caruana, E. J., Chowdhry, M. F., Mohammad, A., Nakas, A., Rathinam, S., Boal, M., Brown, O., Dwerryhouse, S., Higgs, S., Vallance, A., Boyd, E., Irvine, V., Kirk, A., Bakolas, G., Boulton, A., Chandock, A., Khan, T., Kumar, M., Agoston, P., Bille, A., Challacombe, B., Fraser, S., Harrison-Phipps, K., King, J., Mehra, G., Mills, L., Najdy, M., Nath, R., Okiror, L., Pilling, J., Rizzo, V., Routledge, T., Sayasneh, A., Stroman, L., Wali, A., Fehervari, M., Fotopoulou, C., Habib, N., Hamrang-Yousefi, S., Jawad, Z., Jiao, L., Pai, M., Ploski, J., Rajagopal, P., Saso, S., Sodergren, M., Spalding, D., Laws, S., Hardie, C., Mcnaught, C., Alam, R., Budacan, A., Cahill, J., Kalkat, M., Karandikar, S., Kenyon, L., Naumann, D., Patel, A., Ayorinde, J., Chase, T., Cuming, T., Ghanbari, A., Humphreys, L., Tayeh, S., Aboelkassem Ibrahim, A., Bichoo, R., Cao, H., Chai, A. K. W., Choudhury, J., Evans, C., Fitzjohn, H., Ikram, H., Langstroth, M., Loubani, M., Mcmillan, A., Nazir, S., Qadri, S. S. A., Robinson, A., Ross, E., Sehgal, T., Wilkins, A., Dixon, J., Dunning, J., Freystaetter, K., Jha, M., Lester, S., Madhavan, A., Thulasiraman, S. V., Viswanath, Y., Curl-Roper, T., Delimpalta, C., Liao, C. C. L., Velchuru, V., Westwood, E., Belcher, E., Bond-Smith, G., Chidambaram, S., Di Chiara, F., Fasanmade, K., Fraser, L., Fu, H., Ganau, M., Gore, S., Graystone, J., Jeyaretna, D., Khatkar, H., Lami, M., Maher, M., Mastoridis, S., Mihai, R., Piper, R., Prabhu, S., Risk, O. B. F., Selbong, U., Shah, K., Smillie, R., Soleymani majd, H., Sravanam, S., Stavroulias, D., Tebala, G. D., Vatish, M., Verberne, C., Wallwork, K., Winter, S., Bhatti, M. I., Boyd-Carson, H., Elsey, E., Gemmill, E., Herrod, P., Jibreel, M., Lenzi, E., Saafan, T., Sapre, D., Sian, T., Watson, N., Athanasiou, A., Bourke, G., Bradshaw, L., Brunelli, A., Burke, J., Coe, P., Costigan, F., Elkadi, H., Johnstone, J., Kanatas, A., Kantola, V., Kaufmann, A., Laios, A., Lam, S., Macinnes, E., Munot, S., Nahm, C., Otify, M., Pompili, C., Smith, I., Theophilou, G., Toogood, G., Wade, R., Ward, D., West, C., Annamalai, S., Ashmore, C., Boddy, A., Hossain, T., Kourdouli, A., Gvaramadze, A., Jibril, A., Prusty, L., Thekkinkattil, D., Harky, A., Shackcloth, M., Askari, A., Cirocchi, N., Kudchadkar, S., Patel, K., Sagar, J., Shaw, S., Talwar, R., Abdalla, M., Edmondson, R., Ismail, O., Jones, D., Newton, K., Stylianides, N., Aderombi, A., Andaleeb, U., Bajomo, O., Beatson, K., Garrett, W., Mehmood, M., Ng, V., Al-Habsi, R., Divya, G. 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D, Geddes, A, Mccaul, J, Mcmahon, J, H Khan, A, Khan, F, Mansuri, A, Mukherjee, S, Sarigul, M, Singh, S, L Tan, K, Woodham, A, Adiamah, A, Brewer, H, Chowdhury, A, Evans, J, Humes, D, Jackman, J, Koh, A, Lewis-Lloyd, C, Oyende, O, Reilly, J, Worku, D, Cool, P, Cribb, G, Shepherd, K, Bisset, C, Moug, S, Elson, N, Faulkner, G, Saleh, P, Underwood, C, Brixton, G, Findlay, L, Klatte, T, Majkowska, A, Manson, J, Potter, R, Bhalla, A, Chia, Z, Daliya, P, Goyal, A, Grimley, E, Hamad, A, Kumar, A, L Malcolm, F, Theophilidou, E, Bowden, J, Campain, N, Daniels, I, Fowler, G, John, J, Massey, L, Mcdermott, F, Mcgrath, J, Mclennan, A, Ng, M, Pascoe, J, Rajaretnam, N, Bulathsinhala, S, Davidson, B, Fusai, G, Hidalgo Salinas, C, Machairas, N, Pissanou, T, M Pollok, J, A Raptis, D, Soggiu, F, Tzerbinis, H, E Xyda, S, Beamish, A, Davies, E, Foulkes, R, Magowan, D, Nassa, H, Ooi, R, Price, C, Smith, L, Solari, F, Tang, A, Williams, G, Al-Tamimi, Y, Bacon, A, Beasley, N, Chew, D, Crank, M, Ilenkovan, N, Macdonald, M, Narice, B, Rominiyi, O, Thompson, A, Varley, I, Drake, T, Harrison, E, Linder, G, Mayes, J, Mcgregor, R, Skipworth, R, Zamvar, V, Hawkin, P, Raymond, T, Ryska, O, Baron, R, Dunne, D, Gahunia, S, Halloran, C, Howes, N, Mckinney, R, Mcnicol, F, Russ, J, Szatmary, P, R Tan, J, Thomas, A, Whelan, P, Anzak, A, Banerjee, A, Fuwa, O, Hughes, F, D Jayasinghe, J, Knowles, C, Kocher, H, Leal Silva, I, S Ledesma, F, Minicozzi, A, Navaratne, L, Rahman, R, Ramamoorthy, R, Sohrabi, C, Thaha, M, Thakur, B, Venn, M, Yip, V, Baumber, R, Parry, J, Evans, S, Jeys, L, Morris, G, Parry, M, Ahmadi, N, Aresu, G, M Barrett-Brown, Z, S Coonar, A, Durio Yates, H, Gearon, D, Hogan, J, King, M, Peryt, A, S Pradeep, I, Adishesh, M, Atherton, R, Baxter, K, Brocklehurst, M, Chaudhury, M, Krishnamohan, N, Mcaleer, J, Owens, G, Parkin, E, Patkar, P, Phang, I, Aladeojebi, A, Ali, M, Barmayehvar, B, Gaunt, A, Gowda, M, Halliday, E, Kitchen, M, Mansour, F, Thomas, M, Zakai, D, Abbassi-Ghadi, N, Assalaarachchi, H, Currie, A, Flavin, M, Frampton, A, Hague, M, Hammer, C, Hopper, J, Horsnell, J, Humphries, S, Kamocka, A, K Madhuri, T, Preston, S, Singh, P, Stebbing, J, Tailor, A, Walker, D, Aljanadi, F, Jones, M, Mhandu, P, O'Donnell, C, Turkington, R, Al-Ishaq, Z, Bhasin, S, S Bodla, A, Burahee, A, Crichton, A, Fossett, R, Pigadas, N, Pickford, S, Rahman, E, Snee, D, Vidya, R, Yassin, N, Fountain, D, T Hasan, M, Karabatsou, K, Laurente, R, Pathmanaban, O, Al-Mukhtar, A, Edwards, J, Giblin, A, Kelty, C, Lee, M, Lye, G, Newman, T, Sharkey, A, Steele, C, Sureshkumar Shah, N, Whitehall, E, Athwal, R, Baker, A, Jones, L, Konstantinou, C, Ramcharan, S, Vatish, J, Wilkin, R, Ethunandan, M, K Sekhon, G, Shields, H, Singh, R, Wensley, F, Lawday, S, Lyons, A, Abbott, T, Anwar, S, Ghufoor, K, Chung, E, Hagger, R, Hainsworth, A, Karim, A, Owen, H, Ramwell, A, Williams, K, Baker, C, Davies, A, Gossage, J, Kelly, M, Knight, W, Hall, J, Harris, G, James, G, Kang, C, J Lin, D, D Rajgor, A, Royle, T, Scurrah, R, Steel, B, J Watson, L, Choi, D, Hutchison, R, Jain, A, Luoma, V, Marcus, H, May, R, Menon, A, Pramodana, B, Webber, L, A Aneke, I, Asaad, P, Brown, B, Collis, J, Duff, S, Khan, A, Moura, F, Wadham, B, Warburton, H, Elmoslemany, T, Jenkinson, M, Millward, C, Zakaria, R, Mccluney, S, Parmar, C, Shah, S, Allison, J, S Babar, M, Collard, B, Goodrum, S, Lau, K, Scott, R, Thomas, E, Whitmore, H, Balasubramaniam, D, Jayasankar, B, Kapoor, S, Ramachandran, A, Elhamshary, A, Imam, Smb, Kapriniotis, K, Kasivisvanathan, V, Lindsay, J, Rakhshani-Moghadam, S, Beech, N, Chand, M, Green, L, Kalavrezos, N, Kiconco, H, Mcewen, R, Schilling, C, Sinha, D, Pereca, J, Chopra, S, Egbeare, D, Thomas, R, Combellack, T, Jones, Sef, Kornaszewska, M, Mohammed, M, Sharma, A, Tahhan, G, Valtzoglou, V, Williams, J, Eskander, P, Gash, K, Gourbault, L, Hanna, M, Maccabe, T, Newton, C, Olivier, J, Rozwadowski, S, Teh, E, West, D, Al-Omishy, H, Baig, M, Bates, H, Di Taranto, G, Dickson, K, Dunne, N, Gill, C, Howe, D, Jeevan, D, Khajuria, A, Martin-Ucar AMcEvoy, K, Naredla, P, Robertson, S, Sait, M, R Sarma, D, Shanbhag, S, Shortland, T, Simmonds, S, Skillman, J, Tewari, N, Walton, G, A Akhtar, M, Brunt, A, Mcintyre, J, Milne, K, M Rashid, M, Sgro, A, E Stewart, K, Turnbull, A, Aguilar Gonzalez, M, Talukder, S, Boyle, C, Fernando, D, Gallagher, K, Laird, A, Tham, D, Bath, M, Patki, P, Tanabalan, C, Arif, T, Magee, C, Nambirajan, T, Powell, S, Vinayagam, R, Flindall, I, Hanson, A, Mahendran, V, Green, S, Lim, M, Macdonald, L, Miu, V, Onos, L, Sheridan, K, Young, R, Alam, F, Griffiths, O, Houlden, C, Jones, R, S Kolli, V, K Lala, A, Leeson, S, Peevor, R, Seymour, Z, Chen, L, Henderson, E, Loehrer, A, Brown, K, Fleming, D, Heron, C, Hill, C, Kay, H, Leede, E, Mcelhinney, K, Olson, K, C Osterberg, E, Riley, C, Srikanth, P, Thornhill, M, Blazer, D, Dilalla, G, S Hwang, E, Lee, W, Lidsky, M, Plichta, J, Rosenberger, L, Scheri, R, Turnage, K, Visgauss, J, Zani, S, Farma, J, Clark, J, Kwon, D, Etchill, E, E Gabre-Kidan AJenny, H, Kent, A, Ladd, M, Long, C, Malapati, H, Margalit, A, Rapaport, S, Rose, J, Stevens, K, Tsai, L, Vervoort, D, Yesantharao, P, Dehal, A, Klaristenfeld, D, Huynh, K, Brown, L, Ganly, I, Mullinax, J, Gusani, N, Hazelton, J, Maines, J, S Oh, J, Ssentongo, A, Ssentongo, P, Azam, M, Choudhry, A, Marx, W, Fleming, J, Fuson, A, Gigliotti, J, Ovaitt, A, Ying, Y, K Abel, M, Andaya, V, Bigay, K, A Boeck, M, Chern, H, Corvera, C, El-Sayed, I, Glencer, A, Ha, P, Hamilton, Bc, Heaton, C, Hirose, K, M Jablons, D, Kirkwood, K, Z Kornblith, L, R Kratz, J, Lee, R, N Miller, P, Nakakura, E, Nunez-Garcia, B, O'Donnell, R, Ozgediz, D, Park, P, Robinson, B, Sarin, A, Sheu, B, Varma, M, Wai, K, Wustrack, R, J Xu, M, Beswick, D, Goddard, J, Manor, J, Song, J, Fullmer, T, Gaskill, C, Gross, N, Kiong, K, L Roland, C, N Zafar, S, Abdallah, M, Abouassi, A, Almasri, M, Kulkarni, G, Marwan, H, Mehdi, M, Aoun, S, S Ban, V, H Batjer, H, Caruso, J, Abbott, D, Acher, A, Aiken, T, Barrett, J, Foley, E, Schwartz, P, Hawkins, A, Maiga, A, Laufer, J, Scasso, S, Surgery, Graduate School, Glasbey, J, Nepogodiev, D, Simoes, J, Omar, O, Li, E, Abou Chaar, M, Chaudhry, D, Videria, J, Gujjuri, R, Kaafarani, H, Minaya-Bravo, A, Mckay, S, Roberts, K, Miguel-Mendez, C, Smart, N, Stewart, G, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), COVIDSurg Collaborative, Kolias, Angelos [0000-0003-3992-0587], Stewart, Grant [0000-0003-3188-9140], Apollo - University of Cambridge Repository, Glasbey JC, Nepogodiev D, Simoes JFF, Omar O, Li E, Venn ML, Pgdme, Abou Chaar MK, Capizzi V, Chaudhry D, Desai A, Edwards JG, Evans JP, Fiore M, Videria JF, Ford SJ, Ganly I, Griffiths EA, Gujjuri RR, Kolias AG, Kaafarani HMA, Minaya-Bravo A, McKay SC, Mohan HM, Roberts KJ, San Miguel-Méndez C, Pockney P, Shaw R, Smart NJ, Stewart GD, Sundar Mrcog S, Vidya R, Bhangu AA, COVIDSurg Collaborative, Palmerini Emanuela, Frisoni Tommaso, Donati Davide, A Belvedere, P Bernante, P Bertoglio, S Boussedra, E Brunocilla, R Cipriani, G Cisternino, E De Crescenzo, P De Iaco, G Dondi, F Frio, E Jovine, F Mineo Bianchi, J Neri, D Parlanti, A M Perrone, A P Pezzuto, M Pignatti, V Pinto, G Poggioli, M Ravaioli, M Rottoli, R Schiavina, M Serenari, M Serra, P Solli, M Taffurelli, M Tanzanu, M Tesei, T Violante, S Zanotti, V Tonini, M Cervellera, A Gori, L Sartarelli, Glasbey, James C, Simoes, Joana F F, Venn, Mary L, Pgdme, null, Abou Chaar, Mohammad K, Edwards, Jonathan G, Evans, Jonathan P, Videria, Jose Flavio, Ford, Samuel J, Griffiths, Ewen A, Gujjuri, Rohan R, Kolias, Angelos G, Kaafarani, Haytham M A, McKay, Siobhan C, Mohan, Helen M, Roberts, Keith J, Smart, Neil J, Stewart, Grant D, Sundar Mrcog, Sudha, and Bhangu, Aneel A, Toia, F
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Male ,Cancer Research ,Outcome Assessment ,International Cooperation ,Settore MED/18 - CHIRURGIA GENERALE ,Settore MED/19 - Chirurgia Plastica ,030230 surgery ,Aged ,Aged, 80 and over ,COVID-19 ,Cohort Studies ,Critical Care ,Elective Surgical Procedures ,Epidemics ,Female ,Humans ,Logistic Models ,Middle Aged ,Neoplasms ,Outcome Assessment, Health Care ,Postoperative Complications ,SARS-CoV-2 ,0302 clinical medicine ,Operating theater ,cohort studies ,Health care ,middle aged ,80 and over ,Medicine ,Lung ,Cancer ,COVID-19/epidemiology ,OUTCOMES ,Manchester Cancer Research Centre ,Pulmonary Complication ,ORIGINAL REPORTS ,aged ,Oncology ,030220 oncology & carcinogenesis ,Pneumonia & Influenza ,Patient Safety ,Elective Surgical Procedure ,Life Sciences & Biomedicine ,6.4 Surgery ,Cohort study ,Human ,medicine.medical_specialty ,elective surgical procedures/methods ,Logistic Model ,Health Care ,Clinical Sciences ,Oncology and Carcinogenesis ,Epidemic ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,cancer surgery ,SARS-CoV-2 pandemic ,epidemics ,COVIDSurg Collaborative ,NO ,outcome assessment, health care/methods ,03 medical and health sciences ,male ,Settore MED/28 - Malattie Odontostomatologiche ,Clinical Research ,1112 Oncology and Carcinogenesis ,Oncology & Carcinogenesis ,Elective surgery ,Elective Cancer Surgery in SARS-CoV-2, Elective Cancer Surgery in COVID-19, covid 19, sars-cov-2 ,Science & Technology ,business.industry ,Prevention ,ResearchInstitutes_Networks_Beacons/mcrc ,Evaluation of treatments and therapeutic interventions ,1103 Clinical Sciences ,Pneumonia ,Odds ratio ,medicine.disease ,Good Health and Well Being ,neoplasms/surgery ,critical care/methods ,Emergency medicine ,postoperative complications/prevention & control ,Neoplasm ,Postoperative Complication ,Cohort Studie ,business ,aged, 80 and over ,SARS-CoV-2/physiology ,logistic models - Abstract
PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks. Copyright © 2020 American Society of Clinical Oncology. All rights reserved. Bowel and Cancer Research; Sarcoma UK; Yorkshire Cancer Research; European Society of Coloproctology; National Institute for Health Research: 16.136.79; Bowel Disease Research Foundation; Urology Foundation Supported by a National Institute for Health Research (NIHR) Global Health Research Unit grant (NIHR 16.136.79) using UK aid from the UK government to support global health research, Association of Coloproctology of Great Britain and Ireland, Bowel & Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research. The funders had no role in the study design; data collection, analysis, and interpretation; or writing of this report. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, or UK Department of Health and Social Care.
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- 2021
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5. Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications
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Body, J.-J.; Department of Medicine, CHU Brugmann, Universite Libre de Bruxelles, Brussels, Belgium, Bergmann, P.; Department of Radioisotopes, CHU Brugmann, Universite Libre de Bruxelles, Brussels, Belgium, Boonen, S.; Center for Metabolic Bone Diseases, Katholieke University Leuven, Leuven, Belgium, Devogelaer, J.-P.; Department of Rheumatology, Saint Luc University Hospital, Universite Catholique de Louvain, Brussels, Belgium, Gielen, E.; Gerontology and Geriatrics Section, Department of Experimental Medicine, K.U. Leuven, Leuven, Belgium, Goemaere, S.; Department of Rheumatology and Endocrinology, State University of Gent, Gent, Belgium, Kaufman, J.-M.; Department of Endocrinology, State University of Gent, Gent, Belgium, Rozenberg, S.; Department of Gynaecology–Obstetrics, Universite Libre de Bruxelles, Brussels, Belgium, Reginster, J.-Y.; Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium, Body, J.-J.; Department of Medicine, CHU Brugmann, Universite Libre de Bruxelles, Brussels, Belgium, Bergmann, P.; Department of Radioisotopes, CHU Brugmann, Universite Libre de Bruxelles, Brussels, Belgium, Boonen, S.; Center for Metabolic Bone Diseases, Katholieke University Leuven, Leuven, Belgium, Devogelaer, J.-P.; Department of Rheumatology, Saint Luc University Hospital, Universite Catholique de Louvain, Brussels, Belgium, Gielen, E.; Gerontology and Geriatrics Section, Department of Experimental Medicine, K.U. Leuven, Leuven, Belgium, Goemaere, S.; Department of Rheumatology and Endocrinology, State University of Gent, Gent, Belgium, Kaufman, J.-M.; Department of Endocrinology, State University of Gent, Gent, Belgium, Rozenberg, S.; Department of Gynaecology–Obstetrics, Universite Libre de Bruxelles, Brussels, Belgium, and Reginster, J.-Y.; Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium
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- 2013
6. Pamiparib Combined With Surufatinib for the Neoadjuvant Treatment of Unresectable Ovarian Cancer
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Bai-Rong Xia, Chairman of Department of Gynaecology Surgery
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- 2024
7. Randomized Comparison of Mindfulness Versus Group Support for Treatment of Low Sexual Desire in Women (DESIRE)
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Lori Brotto, Professor, UBC Department of Gynaecology
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- 2024
8. An Exploratory Clinical Study of Statins for Improving Chemotherapy and Maintenance in Patients With Ovarian Cancer
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Bai-Rong Xia, Chairman of Department of Gynaecology Surgery
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- 2024
9. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
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[ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, Rantala, Johanna, [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, and Rantala, Johanna
- Abstract
To access publisher's full text version of this article click on the hyperlink below, The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.
10. 'Sweet Expectation and Positive Thinking' the Use of the Mandala in the Induction of Labor (Mandala)
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Bianca Masturzo, Head of Department of Gynaecology and Obstetrics
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- 2024
11. Vacuum Delivery in All-fours Position vs Traditional Position (VaDe-4)
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Bianca Masturzo, Head of Department of Gynaecology and Obstetrics
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- 2022
12. The development of clinical guidelines in China : insights from a national survey
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Song, Yang, Li, Jing, Chen, Yaolong, Guo, Ruixia, Alonso-Coello, Pablo, Zhang, Yuan, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Song Y] Department of Gynaecology, First Afliated Hospital of Zhengzhou Uni versity, Zhengzhou, China. Iberoamerican Cochrane Centre – Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. [Li J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Chen Y] Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China. WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China. [Guo R] Department of Gynaecology, First Afliated Hospital of Zhengzhou Uni versity, Zhengzhou, China. [Alonso-Coello P] Iberoamerican Cochrane Centre – Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBER ESP), Madrid, Spain. [Zhang Y] Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Canada, and Vall d'Hebron Barcelona Hospital Campus
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Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Medicina clínica ,Practice guideline ,China ,Evidence-Based Medicine ,profesiones sanitarias::profesiones sanitarias::medicina::medicina clínica::medicina basada en datos científicos [DISCIPLINAS Y OCUPACIONES] ,Research ,Health Policy ,técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Evidence-based practice ,Enquestes ,Humans ,administración de los servicios de salud::gestión de la atención al paciente::prestación sanitaria [ATENCIÓN DE SALUD] ,Public aspects of medicine ,RA1-1270 ,Surveys and questionnaires ,Delivery of Health Care ,Assistència sanitària - Utilització ,Health Occupations::Health Occupations::Medicine::Clinical Medicine::Evidence-Based Medicine [DISCIPLINES AND OCCUPATIONS] ,Health Services Administration::Patient Care Management::Delivery of Health Care [HEALTH CARE] - Abstract
Background Previous research suggests that the quality of clinical guidelines (CGs) in China is suboptimal. However, little is known about the methodology that CGs follow. We conducted a national survey of methods used by Chinese CG developers for CG development, adaptation, and updating. Methods We used a previously piloted questionnaire based on methodologies of CG development, adaptation, and updating, which was distributed during September–November 2020 to 114 organizations identified from published Chinese CGs (searched 2017–2020), recommended by Chinese CG developers, and recommended by clinical discipline experts. Results We collected 48 completed questionnaires (42.1% response). Most organizations developed CGs based on scientific evidence (89.6%), existing CGs (75%), or expert experience and opinion (64.6%). Only a few organizations had a specific CG development division (6.3%), a CG monitoring plan (on clinicians 33.3%; on patients 18.8%), funding (33.3%), or a conflict-of-interest (COI) management policy (23.4%). Thirty (62.5%) organizations reported using a CG development methodology handbook, from international organizations (14/30, 46.7%), methodology or evaluation resources (3/30, 10.0%), expert experience and opinion (3/30, 10.0%), or in-house handbooks (3/30, 10.0%). One organization followed a published adaptation methodology. Thirty-eight organizations (88.4%) reported de novo CG development: 21 (55.3%) formed a CG working group, and 29 (76.3%) evaluated the quality of evidence (21 [72.4%] using a methodological tool). Nineteen organizations (52.8%) reported CG adaptation: three (31.6%) had an adaptation working group, and 12 (63.2%) evaluated the quality of source CGs (2 (16.7%) using the AGREE II instrument). Thirty-three organizations (68.8%) updated their CGs, seven (17.5%) using a formal updating process. Conclusions Our study describes how CGs are developed in a middle-income country like China. To ensure better healthcare, there is still an important need for improvement in the development, adaptation, and updating of CG in China.
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- 2021
13. Effectiveness of Liquid Crystal Contact Thermography in Detecting Pathological Changes in Female Breasts
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National Center for Research and Development, Poland, Braster S.A., Bioscience, S.A., and Pawel Basta, Ass. Prof. Department of Gynaecology and Oncology Jagiellonian University, Medical College
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- 2018
14. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
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Mavaddat, N., Antoniou, A.C., Mooij, T.M., Hooning, M.J., Heemskerk-Gerritsen, B.A., Nogues, C., Laborde, L., Breysse, E., Stoppa-Lyonnet, D., Gauthier-Villars, M., Buecher, B., Caron, O., Fourme-Mouret, E., Fricker, J.P., Lasset, C., Bonadona, V., Berthet, P., Faivre, L., Luporsi, E., Mari, V., Gladieff, L., Gesta, P., Sobol, H., Eisinger, F., Longy, M., Dugast, C., Colas, C., Coupier, I., Pujol, P., Corsini, C., Lortholary, A., Vennin, P., Adenis, C., Nguyen, T.D., Delnatte, C., Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Bignon, Y.J., Demange, L., Penet, C., Dreyfus, H., Cohen-Haguenauer, O., Venat-Bouvet, L., Leroux, D., Zattara-Cannoni, H., Fert-Ferrer, S., Bera, O., Ellis, S., Barrowdale, D., Frost, D., Evans, D.G., Izatt, L., Adlard, J., Eeles, R., Brewer, C., Tischkowitz, M., Henderson, A., Cook, J., Eccles, D., Hogervorst, F.B.L., Collee, J.M., Asperen, C.J. van, Mensenkamp, A.R., Ausems, M.G.E.M., Meijers-Heijboer, H.E.J., Engelen, K. van, Blok, M.J., Oosterwijk, J.C., Verloop, J., Broek, E. van den, Mourits, M.J.E., Koppert, L.B., Hopper, J.L., John, E.M., Chung, W.K., Andrulis, I.L., Daly, M.B., Buys, S.S., Benitez, J., Caldes, T., Jakubowska, A., Simard, J., Singer, C.F., Tan, Y., Olah, E., Navratilova, M., Foretova, L., Gerdes, A.M., Roos-Blom, M.J., Leeuwen, F.E. van, Arver, B., Olsson, H., Schmutzler, R.K., Engel, C., Kast, K., Phillips, K.A., Terry, M.B., Milne, R.L., Goldgar, D.E., Rookus, M.A., Andrieu, N., Easton, D.F., GENEPSO, EMBRACE, HEBON, kConFab Investigators, IBCCS, kConFab, BCFR, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Erasmus MC Cancer Institute, Rotterdam, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Catherine-de-Sienne [Nantes] (CCS), Manchester University NHS Foundation Trust (MFT), Guy's & St Thomas' NHS Foundation Trust, Chapel Allerton Hospital, University of Leeds, Royal Marsden NHS Foundation Trust, Royal Devon & Exeter Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Wessex clinical genetics service, Vrije Universiteit Amsterdam [Amsterdam] (VU), University Medical Center Groningen [Groningen] (UMCG), Department of Medical Genetics, University Medical Center [Utrecht], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Department of Epidemiology, Cancer Prevention Institute of California, Columbia University [New York], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Division of Population Science, Fox Chase Cancer Center, Department of Internal Medicine, Huntsman Cancer Institute, Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Medizinische Universität Wien = Medical University of Vienna, National Institute of Oncology, Masaryk Memorial Cancer Institute (MMCI), Masaryk University [Brno] (MUNI), Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, The Netherlands Cancer Institute [Amsterdam, The Netherlands], Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Dept of Haematology and Medical Oncology, Peter MacCallum Cancer Center, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Cancer Epidemiology Centre, Cancer Council Victoria, International Agency for Cancer Research (IACR), Netherlands Cancer Institute, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Andrieu, Nadine, Human genetics, Epidemiology and Data Science, Mavaddat, Nasim [0000-0003-0307-055X], Eeles, Ros [0000-0002-3698-6241], Engel, Christoph [0000-0002-7247-282X], Apollo - University of Cambridge Repository, Pomeranian Medical University-International Hereditary Cancer Centre, Masaryk Memorial Cancer Institute (RECAMO), Columbia Mailman School of Public Health-Columbia University [New York], Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Antoniou, Antonis [0000-0001-9223-3116], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Medical Oncology, Surgery, Cancer Research UK (Reino Unido), NIH - National Cancer Institute (NCI) (Estados Unidos), United States Department of Health and Human Services, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea. European Research Council (ERC), Norwegian EEA Financial Mechanism, Hungarian Scientific Research Fund (Hungría), Ministry of Education, Youth and Sports (República Checa), MH CZ -DRO (MMCI), National Health and Medical Research Council (Australia), Australian National Breast Cancer Foundation, Cancer Australia, ERA-NET TRANSAN JTC 2012 Cancer, Transcan grant, Biotechnology and Biological Sciences Research Council (Reino Unido), Pink Ribbons Project, Netherlands Organisation of Scientific Research, Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Deutsche Krebshilfe, National Institute for Health Research (Reino Unido), Unión Europea. Comisión Europea. 7 Programa Marco, Ministry of Economic Development, Innovation and Export Trade-grant, Canadian Institutes of Health Research, Cancer Research UK, NIH National Cancer Institute (NCI), United States Department of Health & Human Services National Institutes of Health (NIH) - USA, Ministerio de Economia y Competividad (MINECO), European Research Council (ERC), Hungarian Research Grants, MEYS -NPS I, National Health and Medical Research Council of Australia, BBMRI grant, Pink Ribbon grants, Netherlands Organisation of Scientific Research grant, KWF Kankerbestrijding, Instituto de Salud Carlos III - ISCIII, National Institute for Health Research (NIHR), European Union Seventh Framework Program (2007-2013), Canadian Institutes of Health Research (CIHR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), United States of Department of Health & Human Services, European Research Council, APH - Quality of Care, APH - Methodology, Graduate School, ARD - Amsterdam Reproduction and Development, RS: GROW - R4 - Reproductive and Perinatal Medicine, and MUMC+: DA KG Lab Centraal Lab (9)
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endocrine system diseases ,SURGERY ,[SDV]Life Sciences [q-bio] ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Cohort Studies ,0302 clinical medicine ,BRCA2 Mutation ,Breast cancer ,Surgical oncology ,Prospective Studies ,Prospective cohort study ,skin and connective tissue diseases ,Salpingo-oophorectomy/methods ,0303 health sciences ,Natural menopause ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Obstetrics ,BRCA1 Protein ,Breast Neoplasms/epidemiology ,Incidence (epidemiology) ,Incidence ,WOMEN ,ASSOCIATION ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,OVARIAN ,BRCA2 Protein/genetics ,3. Good health ,Menopause ,Risk-reducing salpingo-oophorectomy ,[SDV] Life Sciences [q-bio] ,030220 oncology & carcinogenesis ,SURVIVAL ,Female ,Research Article ,Cohort study ,Adult ,medicine.medical_specialty ,Salpingo-oophorectomy ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,lcsh:RC254-282 ,03 medical and health sciences ,breast cancer ,SDG 3 - Good Health and Well-being ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,medicine ,Humans ,METAANALYSIS ,030304 developmental biology ,BRCA2 Protein ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,business.industry ,CONSORTIUM ,risk-reducing salpingo-oophorectomy ,International Agencies ,medicine.disease ,BRCA1 ,BRCA2 ,KCONFAB ,REDUCTION ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,LINK ,Mutation ,BRCA1 Protein/genetics ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Risk Reduction Behavior - Abstract
The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO. The BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the BCFR. CNIO was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare Diseases (CIBERER). CNIO was also partially supported by FISPI16/00440. INHERIT was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program-grant #CRN-87521-and the Ministry of Economic Development, Innovation and Export Trade-grant #PSR-SIIRI-701. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministere de l'Economie, de la Science et de l' Innovation du Quebec through Genome Quebec, and The Quebec Breast Cancer Foundation. Jacques Simard is a Chairholder of the Canada Research Chair in Oncogenetics. EMBRACE is supported by the Cancer Research UK grants C1287/A23382 and C1287/A16563. D. Gareth Evans is supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by the Cancer Research UK grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Antonis C. Antoniou is funded by Cancer Research UK grants C12292/A20861 and C12292/A11174. MT is funded by the European Union Seventh Framework Program (2007-2013)/European Research Council (310018). The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 110837, Rita K. Schmutzler). The national French cohort, GENEPSO, had been supported by a grant from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by a grant from INCa as part of the European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, no. 2014-008). HCSC was supported by CIBERONC 161200301 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46, and the Transcan grant JTC 2012 Cancer 12-054. The IHCC was supported by Grant PBZ_ KBN_122/P05/2004 and ERA-NET TRANSAN JTC 2012 Cancer 12-054 (ERA-NET-TRANSCAN/07/2014). This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195); the Australian National Breast Cancer Foundation (IF 17); the National Health and Medical Research Council (454508, 288704, 145684); the National Institute of Health U.S.A. (1RO1CA159868); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation fellow. MODSQUAD-Czech Republic, Brno, was supported by MH CZ -DRO (MMCI, 00209805) and by MEYS -NPS I -LO1413 to LF and MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228, and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society. The funders had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. Sí
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- 2020
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15. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
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Luigi Mori, Sara González, Elia Grau, Dieter Niederacher, Alexandra C. Kölbl, Ares Solanes, Cassandra B. Nichols, Marine Guillaud-Bataille, Ulrike Schoenwiese, Katherine L. Nathanson, Alfons Meindl, Ellen Honisch, Hans Ehrencrona, Ute Enders, Anke Waha, Trinidad Caldés, Inge Søkilde Pedersen, Ana Blanco, Emma Tudini, Conxi Lázaro, Paolo Radice, Torben A Kruse, María Concepción Alonso-Cerezo, Chantal Farra, Shan Wang-Gohrke, Wilko Weichert, Heli Nevanlinna, Setareh Moghadasi, Bernd Auber, Carla Bruzzone, Aliana Guerrieri-Gonzaga, Sabine Grill, Raymonda Varon, Nicolas Derive, Ana Vega, Nicolai Maass, Åke Borg, Cora M. Aalfs, Nadia Naldi, Silvia Iglesias, Kai Ren Ong, Encarna B. Gomez Garcia, Karl Hackmann, Emma R. Woodward, Norbert Arnold, David E. Goldgar, Bernard Peissel, Karolin Bucksch, Berardino Porfirio, Françoise Révillion, Angel Izquierdo, Isabell Witzel, Sebastian Wagner, Silke Zachariae, Elisa Alducci, Mads Thomassen, Jesús del Valle, Valentina Zampiga, Kerstin Rhiem, Lidia Moserle, Edenir Inêz Palmero, Maaike P.G. Vreeswijk, Christoph Mundhenke, Laura Papi, Alejandro Moles-Fernández, Paula Rofes, Ulrike Faust, Andrea Gehrig, Sandrine M. Caputo, Logan C. Walker, Fiona Lalloo, Ute Felbor, Joan Brunet, Henriette Roed Nielsen, Sean V. Tavtigian, Beatrice Bortesi, Thomas Hansen, Maria Grazia Tibiletti, Estela Carrasco, Lisa Wiesmüller, Viviana Gismondi, Sophie Krieger, Pedro Pérez-Segura, Esther Pohl-Rescigno, Emanuela Lucci-Cordisco, Barbara Wappenschmidt, Rui Manuel Reis, Gabriele Lorenzo Capone, Ileana Carnevali, Christi J. van Asperen, KCon Fab Investigators, Jochen Seggewiß, Rhiannon J. Walters, Irmgard Debatin, Susan M. Domchek, Marco Montagna, Francesca Gensini, Kristiina Aittomäki, Véronique Dutrannoy, Arcangela De Nicolo, Giulia Cagnoli, Elisa J. Cops, Henrique de Campos Reis Galvão, Giulia Cini, Barbara Riboli, Eva Tornero, Paul A. James, Judith Balmaña, Anne-Marie Gerdes, Heide Hellebrand, Miriam Fine, Mathias Stiller, Aldo Germani, Diana Eccles, Britta Blümcke, Dominique Stoppa-Lyonnet, Elena Leinert, Alexandra Lewis, Daniela Rivera, Verena Hübbel, Fergus J. Couch, Gunnar Schmidt, Katharina Keupp, Bernhard H. F. Weber, Tilman Heinrich, Mariarosaria Calvello, Michael Dean, Udo Jeschke, Vanessa Lattimore, Linda A.M. Janssen, Siranoush Manoukian, Eva Gross, Kelly J. Sullivan, Doris Steinemann, Susanne Ledig, Alessandra Viel, Christoph Engel, Ana Sánchez de Abajo, Nina Ditsch, Sandra Bonache, Maria A. Caligo, Katharina Pfeifer, Thomas Haaf, Christian Sutter, Eric Hahnen, Laura Matricardi, Marc Tischkowitz, Alex Teulé, Katherine M. Tucker, Jutta Giesecke, Silvia Tognazzo, Gemma Montalban, Carolina Gómez, Anders Kvist, Joanna Lim, Alison H. Trainer, Rachel Susman, Judit Horvath, Amanda B. Spurdle, Mirjam Larsen, Therese Törngren, Mónica Salinas, Nicholas Pachter, Rachel Austin, Nicola K. Poplawski, C Zeder-Göß, Juliane Ramser, Julia Ritter, Anne Sophie Vesper, Paola Concolino, D. Gareth Evans, Clemens R. Müller, Matilde Navarro, Sara Torres-Esquius, Claus R. Bartram, Laura Cortesi, Jacopo Azzollini, Marion Harris, Edward M. Clarke, Marion Kiechle, Lídia Feliubadaló, Almuth Caliebe, Karen N. Herold, Charlotte Kvist Lautrup, Anne S. Quante, Gardenia Vargas-Parra, Michael T. Parsons, Pietro Cavalli, Hongyan Li, Rodrigo Augusto Depieri Michelli, Irene Feroce, Achim Wöckel, Kerstin Wieland, Silke Kaulfuß, Soo Hwang Teo, Angela Velasco, Capucine Delnatte, Marta Pineda, Marion van Mackelenbergh, Eva Montes, Angela Toss, Rita K. Schmutzler, William D. Foulkes, Alvaro N.A. Monteiro, Jan Hauke, Monica Marabelli, Miguel de la Hoya, Sara Gutiérrez-Enríquez, Esther Darder, Simona Agata, Amanda E. Toland, Bernardo Bonanni, Liliana Varesco, Orland Diez, Andreas Rump, Virginie Caux-Moncoutier, Gaetana Gambino, Markus Loeffler, Claude Houdayer, Elena Barbieri, Adrià López-Fernández, et. al., Universidade do Minho, QIMR Berghofer Medical Research Institute, Chinese Academy of Geological Sciences [Beijing] (CAGS), Ministry of Land and Resources (MLR), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Programa de Càncer Hereditari, Unitat de Diagnòstic Molecular, Laboratori de Recerca Translacional, Institut Català d'Oncologia-IDIBELL, Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Helsinki University Central Hospital, University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), Università degli Studi di Milano [Milano] (UNIMI), Medical Oncology Department, Vall d'Hebron University Hospital [Barcelona], Institute of Human Genetics, Universität Heidelberg [Heidelberg], Fundación Pública Galega de Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica-USC, CIBER-ER, Division of Cancer Prevention and Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Genetic Counseling and Hereditary Cancer Programme, Catalan Institute of Oncology, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Institut Curie [Paris], Programa de Consell Genètic en Càncer, Institut Català d'Oncologia, Girona-IdIBGi, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Centre René Gauducheau, CRLCC René Gauducheau, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Ludwig-Maximilians-Universität München (LMU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetics, University of Southampton, Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Department of Genomic Medicine, University of Manchester [Manchester], Department of Medical Genetics, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU)-Centre of Familial Breast and Ovarian Cancer, Obstetrics and Gynaecology, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institüt für Humangenetik [Würzburg], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Institute of Chemistry [Budapest], Faculty of Sciences [Budapest], Eötvös Loránd University (ELTE)-Eötvös Loránd University (ELTE), Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), I. Frauenklinik, Klinikum der Ludwig-Maximilians-Universitaet, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Department of Oncology, Lund University [Lund]-Clinical Sciences, Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Institute for Medical Informatics, Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, University Medical Center Kiel, Department of Obstetrics and Gynecology, University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Medical Genetics Unit, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Biochemistry, Section of Molecular Diagnostics, Laboratoire d'Oncologie Moléculaire Humaine, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Institute of Cell and Molecular Pathology, Medizinische Hochschule Hannover (MHH), University of California [Santa Cruz] (UCSC), University of California, Heidelberg University Hospital [Heidelberg], International Agency for Cancer Research (IACR), Programa de Consejo Genético en Cáncer, Instituto Catalán de Oncología-IDIBELL, L'Hospitalet, Programa de Diagnòstic Molecular de Càncer Hereditari, Laboratori de Recerca Translacional, Institut Català d'Oncologia-IDIBELL, Hospital Duran i Reynals, Hospitalet de Llobregat, Unit of Hereditary Cancers, Istituto Nazionale per la Ricerca sul Cancro, CIBER de Enfermedades Raras (CIBERER), Unit of Experimental Oncology 1, Centro di Riferimento Oncologico, University of Otago [Dunedin, Nouvelle-Zélande], Institute of Pathology, Department of Gynecology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), King‘s College London, Molecular Diagnostic Unit, IDIBELL-Catalan Institute of Oncology, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Division of Molecular Gynaeco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center University of Cologne, Medicum, Research Programs Unit, Genome-Scale Biology (GSB) Research Program, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, HUS Gynecology and Obstetrics, University Management, University of Helsinki, Università degli Studi di Milano = University of Milan (UNIMI), Universität Heidelberg [Heidelberg] = Heidelberg University, Department of Genetics and Pathology, Uppsala University, Julius-Maximilians-Universität Würzburg (JMU)-Centre of Familial Breast and Ovarian Cancer, Julius-Maximilians-Universität Würzburg (JMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Firenze = University of Florence (UniFI), Université de Lille-UNICANCER-Université de Lille-UNICANCER, University of California [Santa Cruz] (UC Santa Cruz), University of California (UC), Universität Leipzig, University of Cologne, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), and Klinische Genetica
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Male ,Multifactorial Inheritance ,BRCA1 ,BRCA2 ,classification ,clinical ,multifactorial ,quantitative ,uncertain significance ,variant ,Alternative Splicing ,BRCA1 Protein ,BRCA2 Protein ,Computational Biology ,Early Detection of Cancer ,Female ,Genetic Predisposition to Disease ,Humans ,Likelihood Functions ,Neoplasms ,Mutation, Missense ,Medicina Básica [Ciências Médicas] ,Settore MED/03 - GENETICA MEDICA ,GUIDELINES ,Genetic analysis ,CLINGEN ,SEQUENCE VARIANTS ,Missense mutation ,FUNCTIONAL ASSAYS ,Genetics (clinical) ,BRCA1, BRCA2, quantitative, clinical, classification, multifactorial, variant, uncertain significance ,0303 health sciences ,education.field_of_study ,030305 genetics & heredity ,1184 Genetics, developmental biology, physiology ,SPLICING ANALYSIS ,OVARIAN ,BRCA2 Protein/genetics ,3. Good health ,ddc ,Mutation (genetic algorithm) ,Ciências Médicas::Medicina Básica ,Medical genetics ,Special Articles ,medicine.medical_specialty ,Posterior probability ,Population ,Computational biology ,Biology ,INTEGRATED EVALUATION ,03 medical and health sciences ,Special Article ,medicine ,Genetics ,BREAST-CANCER ,Genetic variability ,ddc:610 ,education ,030304 developmental biology ,Tumors ,Science & Technology ,Proteins ,Computational Biology/methods ,RISKS ,Mutation ,BRCA1 Protein/genetics ,3111 Biomedicine ,Missense ,Proteïnes ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Genètica ,Neoplasms/diagnosis - Abstract
The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification., Ohio State University Comprehensive Cancer Center Barretos Cancer Hospital. Grant Number: FINEP ‐ CT‐INFRA (02/2010) Breast Cancer Foundation of New Zealand Canadian Institutes of Health Research. Grant Number: PSR‐SIIRI‐701 Cancer Research UK. Grant Numbers: C8197/A16565, C5047/A8384, C1281/A12014, C12292/A11174, C1287/A10710, C1287/A10118, C1287/A16563, C5047/A10692, C5047/A15007 Department of Defence, USA. Grant Number: W81XWH‐10‐1‐0341 Helsinki University Hospital Research fund Scientific Foundation Asociación Española Contra el Cáncer Leiden University Medical Centre. Grant Number: Grant 30.925 Generalitat de Catalunya. Grant Numbers: PERIS_MedPerCan, URDCat, 2017SGR1282, 2017SGR496 Royal Society of New Zealand Cancer Council Victoria Netherlands Organization for Scientific Research (NWO). Grant Number: Grant 017.008.022 Breast Cancer Research Foundation Cancer Foundation of Western Australia EU H2020. Grant Number: 634935 Fundación Mutua Madrileña Seventh Framework Programme. Grant Numbers: 634935, 223175, 633784 Cancer Council South Australia Government of Galicia. Grant Number: Consolidation and structuring program: IN607B Cancer Council Tasmania Italian Association of Cancer Research. Grant Number: 15547 Queensland Cancer Fund AstraZeneca National Institute of Health (USA). Grant Numbers: 1U19 CA148065‐01, CA128978, CA192393, 1U19 CA148537, P50 CA1162091, CA116167, 1U19 CA148112 Newcastle University Dutch Cancer Society KWF. Grant Numbers: KWF/Pink Ribbon‐11704, UL2012‐5649 National Institute for Health Research. Grant Number: Manchester Biomedical Research centre (IS‐BRC‐1215 National Council of Technological and Scientific Development (CNPq) Instituto de Salud Carlos III. Grant Numbers: FIS PI15/00355, FIS PI13/01711, CIBERONC, FIS PI16/01218, PI16/00563 French National Institute of Cancer National Breast Cancer Foundation National Health and Medical Research Council. Grant Numbers: ID1061778, ID1104808 Carlos III National Health Centro de Investigación Biomédica en Red de Enferemdades Raras. Grant Number: ACCI 2016: ER17P1AC7112/2018 Cancer Council NSW Deutsche Krebshilfe. Grant Numbers: (#110837, #70111850 Fondazione Pisa. Grant Number: Grant “Clinical characterization of BRCA 1/2 Mis
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- 2019
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16. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
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Figlioli, G., Bogliolo, M., Catucci, I., Caleca, L., Lasheras, S. V., Pujol, R., Kiiski, J. I., Muranen, T. A., Barnes, D. R., Dennis, J., Michailidou, K., Bolla, M. K., Leslie, G., Aalfs, C. M., Balleine, R., Baxter, R., Braye, S., Carpenter, J., Dahlstrom, J., Forbes, J., Lee, C. S., Marsh, D., Morey, A., Pathmanathan, N., Scott, R., Simpson, P., Spigelman, A., Wilcken, N., Yip, D., Zeps, N., Adank, M. A., Adlard, J., Agata, S., Cadoo, K., Agnarsson, B. A., Ahearn, T., Aittomaki, K., Ambrosone, C. B., Andrews, L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Arnold, N., Aronson, K. J., Arun, B. K., Asseryanis, E., Auber, B., Auvinen, P., Azzollini, J., Balmana, J., Barkardottir, R. B., Barrowdale, D., Barwell, J., Beane Freeman, L. E., Beauparlant, C. J., Beckmann, M. W., Behrens, S., Benitez, J., Berger, R., Bermisheva, M., Blanco, A. M., Blomqvist, C., Bogdanova, N. V., Bojesen, A., Bojesen, S. E., Bonanni, B., Borg, A., Brady, A. F., Brauch, H., Brenner, H., Bruning, T., Burwinkel, B., Buys, S. S., Caldes, T., Caliebe, A., Caligo, M. A., Campa, D., Campbell, I. G., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Claes, K. B. M., Clarke, C. L., Collavoli, A., Conner, T. A., Cox, D. G., Cybulski, C., Czene, K., Daly, M. B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y. C., Dite, G. S., Ditsch, N., Domchek, S. M., Dorfling, C. M., dos-Santos-Silva, I., Durda, K., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Ellberg, C., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J., Flyger, H., Foulkes, W. D., Friebel, T. M., Friedman, E., Gabrielson, M., Gaddam, P., Gago-Dominguez, M., Gao, C., Gapstur, S. M., Garber, J., Garcia-Closas, M., Garcia-Saenz, J. A., Gaudet, M. M., Gayther, S. A., Belotti, M., Bertrand, O., Birot, A. -M., Buecher, B., Caputo, S., Dupre, A., Fourme, E., Gauthier-Villars, M., Golmard, L., Le Mentec, M., Moncoutier, V., de Pauw, A., Saule, C., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Bressac-de-Paillerets, B., Caron, O., Guillaud-Bataille, M., Bignon, Y. -J., Uhrhammer, N., Bonadona, V., Lasset, C., Berthet, P., Castera, L., Vaur, D., Bourdon, V., Nogues, C., Noguchi, T., Popovici, C., Remenieras, A., Sobol, H., Coupier, I., Pujol, P., Adenis, C., Dumont, A., Revillion, F., Muller, D., Barouk-Simonet, E., Bonnet, F., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Guimbaud, R., Feillel, V., Toulas, C., Dreyfus, H., Leroux, C. D., Peysselon, M., Rebischung, C., Legrand, C., Baurand, A., Bertolone, G., Coron, F., Faivre, L., Jacquot, C., Lizard, S., Kientz, C., Lebrun, M., Prieur, F., Fert-Ferrer, S., Mari, V., Venat-Bouvet, L., Bezieau, S., Delnatte, C., Mortemousque, I., Colas, C., Coulet, F., Soubrier, F., Warcoin, M., Bronner, M., Sokolowska, J., Collonge-Rame, M. -A., Damette, A., Gesta, P., Lallaoui, H., Chiesa, J., Molina-Gomes, D., Ingster, O., Manouvrier-Hanu, S., Lejeune, S., Giles, G. G., Glendon, G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Guenel, P., Gutierrez-Barrera, A. M., Haeberle, L., Haiman, C. A., Hakansson, N., Hall, P., Hamann, U., Harrington, P. A., Hein, A., Heyworth, J., Hillemanns, P., Hollestelle, A., Hopper, J. L., Hosgood, H. D., Howell, A., Hu, C., Hulick, P. J., Hunter, D. J., Imyanitov, E. N., Aghmesheh, M., Greening, S., Amor, D., Gattas, M., Botes, L., Buckley, M., Friedlander, M., Koehler, J., Meiser, B., Saleh, M., Salisbury, E., Trainer, A., Tucker, K., Antill, Y., Dobrovic, A., Fellows, A., Fox, S., Harris, M., Nightingale, S., Phillips, K., Sambrook, J., Thorne, H., Armitage, S., Arnold, L., Kefford, R., Kirk, J., Rickard, E., Bastick, P., Beesley, J., Hayward, N., Spurdle, A., Walker, L., Beilby, J., Saunders, C., Bennett, I., Blackburn, A., Bogwitz, M., Gaff, C., Lindeman, G., Pachter, N., Scott, C., Sexton, A., Visvader, J., Taylor, J., Winship, I., Brennan, M., Brown, M., French, J., Edwards, S., Burgess, M., Burke, J., Patterson, B., Butow, P., Culling, B., Caldon, L., Callen, D., Chauhan, D., Eisenbruch, M., Heiniger, L., Chauhan, M., Christian, A., Dixon, J., Kidd, A., Cohen, P., Colley, A., Fenton, G., Crook, A., Dickson, R., Field, M., Cui, J., Cummings, M., Dawson, S. -J., Defazio, A., Delatycki, M., Dudding, T., Edkins, T., Farshid, G., Flanagan, J., Fong, P., Forrest, L., Gallego-Ortega, D., George, P., Gill, G., Kollias, J., Haan, E., Hart, S., Jenkins, M., Hunt, C., Lakhani, S., Lipton, L., Lobb, L., Mann, G., Mclachlan, S. A., O'Connell, S., O'Sullivan, S., Pieper, E., Robinson, B., Saunus, J., Scott, E., Shelling, A., Williams, R., Young, M. A., Isaacs, C., Jakimovska, M., Jakubowska, A., James, P., Janavicius, R., Janni, W., John, E. M., Jones, M. E., Jung, A., Kaaks, R., Karlan, B. Y., Khusnutdinova, E., Kitahara, C. M., Konstantopoulou, I., Koutros, S., Kraft, P., Lambrechts, D., Lazaro, C., Le Marchand, L., Lester, J., Lesueur, F., Lilyquist, J., Loud, J. T., K. H., Lu, Luben, R. N., Lubinski, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martens, J. W. M., Maurer, T., Mavroudis, D., Mebirouk, N., Meindl, A., Menon, U., Miller, A., Montagna, M., Nathanson, K. L., Neuhausen, S. L., Newman, W. G., Nguyen-Dumont, T., Nielsen, F. C., Nielsen, S., Nikitina-Zake, L., Offit, K., Olah, E., Olopade, O. I., Olshan, A. F., Olson, J. E., Olsson, H., Osorio, A., Ottini, L., Peissel, B., Peixoto, A., Peto, J., Plaseska-Karanfilska, D., Pocza, T., Presneau, N., Pujana, M. A., Punie, K., Rack, B., Rantala, J., Rashid, M. U., Rau-Murthy, R., Rennert, G., Lejbkowicz, F., Rhenius, V., Romero, A., Rookus, M. A., Ross, E. A., Rossing, M., Rudaitis, V., Ruebner, M., Saloustros, E., Sanden, K., Santamarina, M., Scheuner, M. T., Schmutzler, R. K., Schneider, M., Senter, L., Shah, M., Sharma, P., Shu, X. -O., Simard, J., Singer, C. F., Sohn, C., Soucy, P., Southey, M. C., Spinelli, J. J., Steele, L., Stoppa-Lyonnet, D., Tapper, W. J., Teixeira, M. R., Terry, M. B., Thomassen, M., Thompson, J., Thull, D. L., Tischkowitz, M., Tollenaar, R. A. E. M., Torres, D., Troester, M. A., Truong, T., Tung, N., Untch, M., Vachon, C. M., van Rensburg, E. J., van Veen, E. M., Vega, A., Viel, A., Wappenschmidt, B., Weitzel, J. N., Wendt, C., Wieme, G., Wolk, A., Yang, X. R., Zheng, W., Ziogas, A., Zorn, K. K., Dunning, A. M., Lush, M., Wang, Q., Mcguffog, L., Parsons, M. T., Pharoah, P. D. P., Fostira, F., Toland, A. E., Andrulis, I. L., Ramus, S. J., Swerdlow, A. J., Greene, M. H., Chung, W. K., Milne, R. L., Chenevix-Trench, G., Dork, T., Schmidt, M. K., Easton, D. F., Radice, P., Hahnen, E., Antoniou, A. C., Couch, F. J., Nevanlinna, H., Surralles, J., Peterlongo, P., Caleca, Laura [0000-0002-3381-7493], Muranen, Taru A. [0000-0002-5895-1808], Dennis, Joe [0000-0003-4591-1214], Adlard, Julian [0000-0002-1693-0435], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Devilee, Peter [0000-0002-8023-2009], Foulkes, William D. [0000-0001-7427-4651], Isaacs, Claudine [0000-0002-9646-1260], Jakimovska, Milena [0000-0002-1506-0669], Konstantopoulou, Irene [0000-0002-0470-0309], Lesueur, Fabienne [0000-0001-7404-4549], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Peto, Julian [0000-0002-1685-8912], Punie, Kevin [0000-0002-1162-7963], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Viel, Alessandra [0000-0003-2804-0840], Wieme, Greet [0000-0003-2718-5300], Zheng, Wei [0000-0003-1226-070X], Ziogas, Argyrios [0000-0003-4529-3727], Greene, Mark H. [0000-0003-1852-9239], Nevanlinna, Heli [0000-0002-0916-2976], Peterlongo, Paolo [0000-0001-6951-6855], Apollo - University of Cambridge Repository, Medical Oncology, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Yorkshire Regional Genetics Service, Department of Pathology, University Hospital and University of Iceland School of Medicine, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Università degli Studi di Milano [Milano] (UNIMI), Medical Oncology Department, Vall d'Hebron University Hospital [Barcelona], University of Iceland [Reykjavik]-Landspitali - University Hospital, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Leicestershire Clinical Genetics Service, University Hospitals Leicester, Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Chaim Sheba Medical Center, Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Department of Oncology, Department of Obstetrics and Gynaecology (MHH), Hannover Medical School [Hannover] (MHH), Division of Cancer Prevention and Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, North West Thames Regional Genetics, Northwick Park Hospital, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Division of Clinical Epidemiology and Aging Research, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Molecular Epidemiology Research Group, Department of Internal Medicine, Huntsman Cancer Institute, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Cancer Epidemiology, Division of Cancer Epidemiology, Division of Cancer Epidemiology and Genetics, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Division of Population Science, Fox Chase Cancer Center, Department of Human Genetics & Department of Pathology, Leiden University Medical Center (LUMC), Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Obstetrics and Gynecology [Munich, Germany], University-Hospital Munich-Großhadern [München]-Ludwig Maximilian University [Munich] (LMU), Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Wessex clinical genetics service, Lund University Hospital, Department of Genomic Medicine, University of Manchester [Manchester], Department of Breast Surgery, Herlev and Gentofte Hospital, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, National Institutes of Health [Bethesda] (NIH), Epidemiology Research Program, American Cancer Society, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), University of Melbourne, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], International Agency for Cancer Research (IACR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Molecular Genetics of Breast Cancer, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Department of Medical Oncology, Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, The Christie, Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion, Vilnius University [Vilnius]-Hospital Santariskiu Clinics, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of Epidemiology, Cancer Prevention Institute of California, Unit of Nutrition and Cancer, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Institute of Biochemistry and Genetics [Bashkortostan Republic, Russia], Russian Academy of Sciences / Ufa Scientific Centre [Bashkortostan Republic, Russia]], National Center for Scientific Research 'Demokritos' (NCSR), Harvard School of Public Health, Laboratory for translational genetics Leuven, Genetic Counseling and Hereditary Cancer Programme, Catalan Institute of Oncology, University of Hawai‘i [Mānoa] (UHM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Genetics Branch, Strangeways Research Laboratory, Unit of Medical Genetics, Fondazione IRCCS INT, Department of Gynaecology and Obstetrics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Women's Health [London], University College London Hospitals (UCLH), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Medicine, Medical Genetics, Abramson Cancer Center-Perelman School of Medicine, Department of Population Sciences, Beckman Research Institute of City of Hope, Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, University of Chicago, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Genetics Group, Spanish National Cancer Research Centre, Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Genetics, Portuguese Oncology Institute, Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), University of Munich, Karolinska University Hospital [Stockholm], Umm Al-Qura University, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Netherlands Cancer Institute, IT University of Copenhagen (ITU), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Queen's University [Belfast] (QUB), Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University School of Medicine [Nashville], Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Odense University Hospital, Instituto de Genética Humana, Pontificia Universidad Javeriana (PUJ), HELIOS Hospital Berlin-Buch, Cancer Genetics Laboratory, University of Pretoria [South Africa], Genomic Medicine Group, Universidade de Santiago de Compostela [Spain] (USC ), Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of Science and Technology Beijing [Beijing] (USTB), University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Université de Pau et des Pays de l'Adour (UPPA), Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, The institute of cancer research [London], Department of Medical Genetics, Mayo Clinic, Cancer Epidemiology Centre, Cancer Council Victoria, Queensland Institute of Medical Research, Cancer Research U.K. Genetic Epidemiology Unit, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Department of Laboratory Medicine and Pathology, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine-Fondazione IRCCS Istituto Nazionale Tumori (INT), Muranen, Taru A [0000-0002-5895-1808], Foulkes, William D [0000-0001-7427-4651], Greene, Mark H [0000-0003-1852-9239], Institut Català de la Salut, [Figlioli G, Catucci I] IFOM - the FIRC Institute for Molecular Oncology, Genome Diagnostics Program, Milan, Italy. [Bogliolo M, Pujol R] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. Institute of Biomedical Research, Sant Pau Hospital, Barcelona, Spain. [Caleca L] Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy. [Lasheras SV] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Genètica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Hospital Universitari Vall d'Hebron, University of Iceland [Reykjavik], Università degli Studi di Milano = University of Milan (UNIMI), Universiteit Leiden-Universiteit Leiden, University of Pennsylvania-University of Pennsylvania, University of Pennsylvania, Georgetown University [Washington] (GU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universität Heidelberg [Heidelberg] = Heidelberg University, European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Human Genetics, Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona, Universitat Autònoma de Barcelona [Barcelona] (UAB), Università degli studi di Milano [Milano], University Hospitals of Leicester, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biology, University of Pisa, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pomeranian Medical University-International Hereditary Cancer Centre, McGill University, University of Kansas Medical Center [Lawrence], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncology-University of Cambridge [UK] (CAM), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Università degli Studi di Roma 'La Sapienza' [Rome], IT University of Copenhagen, Laval University [Québec], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pontificia Universidad Javeriana, University of Santiago de Compostela, Læknadeild (HÍ), Faculty of Medicine (UI), Biomedical Center (UI), Lífvísindasetur (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), MINES ParisTech - École nationale supérieure des mines de Paris, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Universidade do Porto, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea, Against Breast Cancer, Cancer Research UK (Reino Unido), Unión Europea. Comisión Europea. H2020, Cancer UK Grant, Canadian Institutes of Health Research, Ministère de Économie, de la science et de innovation (Canadá), NIH - National Cancer Institute (NCI) (Estados Unidos), Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Xunta de Galicia (España), Canadian Cancer Society, California Breast Cancer Research Program, California Department of Public Health, Medical Research Council (Reino Unido), Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases), Federal Ministry of Education & Research (Alemania), German Cancer Aid, Helsinki University Central Hospital Research Fund, Finlands Akademi (Finlandia), Deutsche Forschungsgemeinschaft (Alemania), Russian Foundation for Basic Research, Ministry of Science and Higher Education (Rusia), National Health and Medical Research Council (Australia), Biobanking and BioMolecular resources Research Infrastructure (Países Bajos), Estée Lauder Companies’ Breast Cancer Campaign, Swedish Research Council, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Lon V. Smith Foundation, Research Coincil of Lithuania, Italian Association for Cancer Research, University of Kansas. Cancer Center (Estados Unidos), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), French National Cancer Institute, Netherlands Organisation for Health Research and Development, Pink Ribbons Project, United States of Department of Health & Human Services, HUS Gynecology and Obstetrics, Clinicum, University of Helsinki, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, University Management, HUS Comprehensive Cancer Center, Biosciences, Helsinki University Hospital, and Lietuvos Mokslo Taryba (Lituania)
- Subjects
0301 basic medicine ,Gene mutation ,Càncer - Aspectes genètics ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Mama - Càncer ,Fanconi anemia ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Brjóstakrabbamein ,Medicine and Health Sciences ,Pharmacology (medical) ,FANCM ,631/208/68 ,skin and connective tissue diseases ,Cancer genetics ,Triple-negative breast cancer ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Manchester Cancer Research Centre ,Otros calificadores::Otros calificadores::/genética [Otros calificadores] ,article ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES] ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Life Sciences & Biomedicine ,3122 Cancers ,ABCTB Investigators ,lcsh:RC254-282 ,KConFab ,Olaparib ,Càncer de mama ,GEMO Study Collaborators ,03 medical and health sciences ,breast cancer ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,SDG 3 - Good Health and Well-being ,631/67/68 ,medicine ,Other subheadings::Other subheadings::/genetics [Other subheadings] ,Erfðafræði ,Radiology, Nuclear Medicine and imaging ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,ddc:610 ,Risk factor ,CHEK2 ,Krabbamein ,Cancer och onkologi ,FancM ,Science & Technology ,cancer ,MUTATIONS ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Biology and Life Sciences ,nutritional and metabolic diseases ,cancer genetics ,medicine.disease ,GENE ,Expressió gènica ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES] ,030104 developmental biology ,chemistry ,692/4028/67/68 ,Cancer and Oncology ,FANCONI-ANEMIA ,Cancer research ,gene expression ,C.5791C-GREATER-THAN-T ,business - Abstract
Publisher's version (útgefin grein), Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors., Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the “Fondo Europeo de Desarrollo Regional, una manera de hacer Europa” (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. BCAC: we thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Tu Nguyen-Dumont is a National Breast Cancer Foundation (Australia) Career Development Fellow. ABCS thanks the Blood bank Sanquin, The Netherlands. Samples are made available to researchers on a non-exclusive basis. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. Hedy Rennert, Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Muñoz Garzón, Alejandro Novo Domínguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Peña Fernández, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), José Antúnez, Máximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigación Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquín González-Carreró and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. Investigators from the CPS-II cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Kröber and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nüchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Heidi Toiminen, Kristiina Aittomäki, Irja Erkkilä and Outi Malkavaara. HMBCS thanks Peter Hillemanns, Hans Christiansen and Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myöhänen, Helena Kemiläinen. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB “Georgi D. Efremov), Katerina Kubelka, Mitko Karadjozov (Adzibadem-Sistina” Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika” Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group) thanks Daniela Zaffaroni, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines and Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thanks study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander and Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CIMBA: we are grateful to all the families and clinicians who contribute to the studies; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Griškevičius; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), thanks in particular: Giulia Cagnoli, Roberta Villa, Irene Feroce, Mariarosaria Calvello, Riccardo Dolcetti, Giuseppe Giannini, Laura Papi, Gabriele Lorenzo Capone, Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato, Isabella Marchi, Elena Bandieri, Antonio Russo, Daniele Calistri and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. FPGMX: members of the Cancer Genetics group (IDIS): Ana Blanco, Miguel Aguado, Uxía Esperón and Belinda Rodríguez. We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Diana Torres, Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Mélanie Léoné, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valérie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study. Drs.Sofia Khan, Irja Erkkilä and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C.M. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): A.W. van den Belt-Dusebout. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Overbeek; the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Aniko Bozsik, Zoltan Matrai, Miklos Kasler, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clinicians and patients for their contributions to this study; HVH (University Hospital Vall d’Hebron) the authors acknowledge the Oncogenetics Group (VHIO) and the High Risk and Cancer Prevention Unit of the University Hospital Vall d’Hebron, Miguel Servet Progam (CP10/00617), and the Cellex Foundation for providing research facilities and equipment; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab investigators, research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O’Conor; Christina Selkirk; Helena Jernström, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna Öfverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellström Pigg, Richard Rosenquist; from Linköping University Hospital: Marie Stenmark-Askmalm, Sigrun Liedgren; Cecilia Zvocec, Qun Niu; Joyce Seldon and Lorna Kwan; Dr. Robert Nussbaum, Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad and Salina Chan; Carole Pye, Patricia Harrington and Eva Wozniak. OSUCCG thanks Kevin Sweet, Caroline Craven, Julia Cooper, Michelle O’Conor and Amber Aeilts. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union’s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l’Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BCINIS study was funded by the BCRF (The Breast Cancer Research Foundation, USA). The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l’Alimentation, de l’Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the German Research Foundation (Do 761/10-1). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. E.K was supported by the program for support the bioresource collections №007-030164/2 and study was performed as part of the assignment of the Ministry of Science and Higher Education of Russian Federation (№АААА-А16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. LMBC is supported by the ‘Stichting tegen Kanker’. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov” and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council [grant 2017-00644 for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER)]. The SZBCS is financially supported under the program of Minister of Science and Higher Education “Regional Initiative of Excellence” in years 2019-2022, Grant No 002/RID/2018/19. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. CIMBA CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015 and Nr. P-MIP-19-164. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Funds from Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’) to S. Manoukian. UNIROMA1: Italian Association for Cancer Research (AIRC; grant no. 21389) to L. Ottini. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: NIH/NCI grant P30-CA006927. The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. Ana Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program, the French National Institute of Cancer (INCa) (grants AOR 01 082, 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015) and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). GEORGETOWN: the Survey, Recruitment and Biospecimen Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008) and the Fisher Center for Hereditary Cancer and Clinical Genomics Research. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. HVH (University Hospital Vall d’Hebron) This work was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds: FIS PI12/02585 and PI15/00355. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, P18/01029, and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338, 2017SGR449, and PERIS Project MedPerCan), and CERCA program. IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5 × 1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-45012). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: was funded by the Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Researc h UK. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.
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- 2019
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17. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations
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Douglas F. Easton, T.M. Mooij, Christian F. Singer, Lenka Foretova, Matti A. Rookus, Karin Kast, Kai-ren Ong, Louise Izatt, Jessica Moretta-Serra, Margreet G. E. M. Ausems, Diana Eccles, Patrick J. Morrison, Jan C. Oosterwijk, Mary B. Daly, Alex Henderson, Rita K. Schmutzler, Ana Osorio, Charlotte J. Dommering, Anne-Marie Gerdes, Marie Navratilova, Ibccs, Carole Brewer, Mieke Kriege, Mary Beth Terry, Christoph Engel, D. Gareth Evans, Edith Olah, Jackie Cook, David E. Goldgar, Anna Jakubowska, Antonis C. Antoniou, Jacques Simard, Laurence Gladieff, Catherine Noguès, Esther M. John, Brita Arver, Håkan Olsson, Jasmine A. McDonald, Irene L. Andrulis, Nadine Andrieu, Munaza Ahmed, Yen Y. Tan, Yuyan Liao, Embrace, Genepso, Bcfr, Hebon, kConFab, Trinidad Caldés, Véronique Mari, Roger L. Milne, Michael Friedlander, Elisabeth Luporsi, John L. Hopper, Marie-José Roos-Blom, Flora E. van Leeuwen, Sue-Anne McLachlan, Saundra S. Buys, Debra Frost, Daniel Barrowdale, Bruno Buecher, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Service de Génétique Oncologique, Institut Curie [Paris], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Claudius Regaud, Centre Alexis Vautrin (CAV), Newcastle Upon Tyne Hospitals NHS Trust, Department of Clinical Genetics, Royal Devon & Exeter Hospital, St Mary's Hospital, Wessex Clinical Genetics Service, Princess Anne Hospital, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Northern Ireland Regional Genetics Centre, Belfast City Hospital, Department of Clinical Genetics and Human Genetics, VU University Medical Center [Amsterdam], Department of Genetics, Department of Medical Genetics, University Medical Center [Utrecht], Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Internal Medicine, Huntsman Cancer Institute, Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Epidemiology, Cancer Prevention Institute of California, Division of Population Science, Fox Chase Cancer Center, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Human Genetics Group, Spanish National Cancer Research Centre, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, National Institute of Oncology, Masaryk University [Brno] (MUNI), Odense University Hospital, Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Departments of Epidemiology and Molecular Pathology, The Netherlands Cancer Institute, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Cancer Epidemiology Centre, Cancer Council Victoria, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Netherlands Cancer Institute, Innovation et Développement dans l'Agriculture et l'Alimentation (UMR Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195), the Australian National Breast Cancer Foundation (IF 17), the National Health and Medical Research Council (454508, 288704, 145684), the US National Institute of Health (1RO1CA159868), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. MODSQUAD Czech Republic, Brno was supported by MH CZ—DRO (MMCI, 00209805) and by MEYS—NPS I - LO1413 to LF, MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research grants KTIA-OTKA CK80745 and NKFI OTKA K-112228 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. € Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society., European Project: 294576,EC:FP7:ERC,ERC-2011-ADG_20110310,RISK FACTORS CANCER(2012), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), MUMC+: DA KG Lab Centraal Lab (9), Universität Leipzig [Leipzig], Institut Curie, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, CRLCC Institut Claudius Regaud, Sheffield Children's Hospital, Birmingham Women's Hospital Healthcare NHS Trust, Pomeranian Medical University-International Hereditary Cancer Centre, Laval University [Québec], Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Innovation et Développement dans l'Agriculture et l'Agro-alimentaire (Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre national d'études agronomiques des régions chaudes (CNEARC)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Andrieu, Nadine, Genetic and environmental risk factors for common malignant tumours especially breast cancer and melanoma. - RISK FACTORS CANCER - - EC:FP7:ERC2012-04-01 - 2017-03-31 - 294576 - VALID, Medical Oncology, Pathology, Radiology & Nuclear Medicine, Columbia Mailman School of Public Health-Columbia University [New York], Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Targeted Gynaecologic Oncology (TARGON), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,INDUCED-ABORTION ,endocrine system diseases ,BIRTH ,[SDV]Life Sciences [q-bio] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,SUSCEPTIBILITY ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,SDG 3 - Good Health and Well-being ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Medicine ,COHORT ,Prospective cohort study ,skin and connective tissue diseases ,REPRODUCTIVE FACTORS ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,PARITY ,business.industry ,Proportional hazards model ,Obstetrics ,Hazard ratio ,Retrospective cohort study ,medicine.disease ,CARRIERS ,OVARIAN ,Confidence interval ,[SDV] Life Sciences [q-bio] ,KCONFAB ,030104 developmental biology ,Oncology ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,030220 oncology & carcinogenesis ,Cohort ,COLLABORATIVE REANALYSIS ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Breast feeding - Abstract
Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
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- 2018
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18. The Safety and Effectiveness of Jobelyn in Pre-operative Management of Anaemia in Gynaecological Patients
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Health Forever Product Limited. Lagos, Nigeria and Dr. A. Tayo, CONSULTANT IN THE DEPARTMENT OF GYNAECOLOGY AND OBSTETRICS, LASUTH
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- 2016
19. The rates of vaginal births after cesarean section have increased during the last decades: a nationwide register-based cohort study in Finland
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Matias Vaajala, Rasmus Liukkonen, Ville Ponkilainen, Maiju Kekki, Ville M. Mattila, Ilari Kuitunen, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, and Department of Musculoskeletal Diseases
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3123 Gynaecology and paediatrics ,Obstetrics and Gynecology ,General Medicine ,3126 Surgery, anesthesiology, intensive care, radiology - Abstract
Purpose Epidemiological studies assessing the effects of previous cesarean section (CS) on subsequent delivery mode using large nationwide study populations. This study aims to calculate the incidence rates of trial of labors after cesarean section (TOLACs) and evaluate the annual rates of vaginal births after cesarean section (VBAC) during the last decades in Finland. Methods Data from the National Medical Birth Register (MBR) were used to evaluate incidence rates of VABC in the Finnish population (1998–2018). All nulliparous women having their first and second pregnancy during our study period, and with the mode of delivery identified in both of these pregnancies were included in this study. Absolute annual numbers and incidence rates for TOLACs, elective CS, and VBAC were calculated. Results The absolute number of TOLACs had an increasing trend during our study period, increasing up to 2118 TOLACs in 2016. The incidence rates for elective CS after the first CS had a decreasing trend, decreasing from 45% in 1999, to 28% in 2018. The absolute number of VBACs had an increasing trend during our study period, peaking in 2016 (1466 VBACs). The rates for VBAC remained relatively constant, ranging between 38 and 52%, but a slightly increasing trend at the end of the study period was seen. Conclusion Despite the increasing annual total number of deliveries with CS in the first pregnancy, the absolute numbers and rates for VBACs have increased towards the end of the study period in Finland. The epidemiology of TOLACs and VBACs should be better studied around the world, as with the rapidly increasing rate of CSs, these events are becoming more common challenges in health care.
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- 2023
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20. Birth rate among women with fear of childbirth: a nationwide register-based cohort study in Finland
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Matias Vaajala, Rasmus Liukkonen, Ville Ponkilainen, Ville M. Mattila, Maiju Kekki, Ilari Kuitunen, Tampere University, Clinical Medicine, Department of Musculoskeletal Diseases, and Department of Gynaecology and Obstetrics
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3123 Gynaecology and paediatrics ,Epidemiology - Abstract
PURPOSE: The association between fear of childbirth (FOC) and subsequent birth rate is not well studied. The aim of this study is to evaluate the birth rate, and risk for second pregnancy ending in delivery among women with FOC compared to women without FOC in their first pregnancy. METHODS: Data from the National Medical Birth Register were used to evaluate the birth rate after the first pregnancy in women with FOC. Cox regression model was used to evaluate the risk for the second pregnancy ending in delivery in women with FOC compared to reference individuals without FOC. The results were interpreted with adjusted hazard ratios (aHRs) and 95% confidence intervals (CI). RESULTS: In total, 375,619 women were included in this study. Of these, 9660 (2.6%) had FOC in the first pregnancy (exposed group), and 365,959 (97.4%) had no FOC (non-exposed group). In the exposed group, 3600 (37.3%) women had second pregnancy ending in delivery during the study period, and 206,347 (56.4%) had the second pregnancy ending in delivery in the non-exposed group. The risk for the second pregnancy ending in delivery was lower among women with FOC (aHR 0.61, CI 0.59-0.63). CONCLUSIONS: FOC complicates pregnancy and delivery and is strongly associated with lower likelihood to get pregnant again. Therefore, more research should be focused on the optimal prevention of FOC using a standardized procedure of care and treatment for women with FOC. publishedVersion
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- 2023
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21. Trends in the epidemiology of fear of childbirth and association with intended mode of delivery: A nationwide register‐based cohort study in Finland
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Matias Vaajala, Rasmus Liukkonen, Ilari Kuitunen, Ville Ponkilainen, Ville M. Mattila, Maiju Kekki, Tampere University, Clinical Medicine, Department of Musculoskeletal Diseases, and Department of Gynaecology and Obstetrics
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3123 Gynaecology and paediatrics ,Obstetrics and Gynecology ,General Medicine ,3121 Internal medicine - Abstract
Introduction: Fear of childbirth (FOC) is a common obstetrical challenge that affects the health of women. The epidemiology of FOC has not been studied in Finland for the last decade. The aim of this study was to analyze the epidemiology and risk factors for FOC and to evaluate the association between FOC and the rate of elective cesarean section (CS) as an intended mode of delivery. Material and methods: Data from the National Medical Birth Register were used to evaluate the epidemiology of FOC and to determine the main risk factors for FOC in Finland between 2004 and 2018. Nulliparous and multiparous women were analyzed separately. Logistic regression model was used to determine the main risk factors for FOC. Multivariable logistic regression model was used to assess the intended mode of delivery in those pregnancies with diagnosed maternal FOC. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) were calculated. Results: A total of 1 million pregnancies were included. The annual rate of pregnancies with maternal FOC increased from 1.5% (CI: 1.4–1.6) in 2004 to 9.1% (CI: 8.7–9.3) in 2018 for all women. For nulliparous women, the rate increased from 1.1% (CI: 1.0–1.3) in 2004 to 7.1% (CI: 6.7–7.5) in 2018, and from 1.8% (CI: 1.7–2.0) in 2004 to 10.3% (10.0–10.7) in 2018 for multiparous women. The strongest risk factors for maternal FOC were higher maternal age and gestational diabetes. For multiparous women, the strongest risk factors were gestational diabetes and previous CS. The total odds for elective CS were notably higher among women with FOC (aOR 8.63, CI: 8.39–8.88). Conclusions: The incidence of maternal FOC rose six-fold during our study period. However, the numbers of elective CS among women with this diagnosis, which had earlier risen in parallel, leveled off in 2014. publishedVersion
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- 2023
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22. Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
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Jouko Nurkkala, Anni Kauko, null FinnGen, Hannele Laivuori, Tanja Saarela, Jaakko S. Tyrmi, Felix Vaura, Susan Cheng, Natalie A. Bello, Jenni Aittokallio, Teemu Niiranen, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, HUS Gynecology and Obstetrics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Department of Medical and Clinical Genetics, Clinicum, and Helsinki Institute of Life Science HiLIFE
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Physiology ,Preeclampsia ,3121 Internal medicine ,Risk factors ,Pregnancy-induced ,3123 Gynaecology and paediatrics ,3121 General medicine, internal medicine and other clinical medicine ,Hypertension ,Blood pressure ,Genetics ,Internal Medicine ,Polymorphism ,Single nucleotide ,Cardiology and Cardiovascular Medicine - Abstract
Background:Preexisting hypertension increases risk for preeclampsia. We examined whether a generic blood pressure polygenic risk score (BP-PRS), compared with a preeclampsia-specific polygenic risk score (PE-PRS), could better predict hypertensive disorders of pregnancy.Methods:Our study sample included 141 298 genotyped FinnGen study participants with at least one childbirth and followed from 1969 to 2021. We calculated PRSs for SBP and preeclampsia using summary statistics for greater than 1.1 million single nucleotide polymorphisms.Results:We observed 8488 cases of gestational hypertension (GHT) and 6643 cases of preeclampsia. BP-PRS was associated with GHT [multivariable-adjusted hazard ratio for 1SD increase in PRS (hazard ratio 1.38; 95% CI 1.35-1.41)] and preeclampsia (1.26, 1.23-1.29), respectively. The PE-PRS was also associated with GHT (1.16; 1.14-1.19) and preeclampsia (1.21, 1.18-1.24), but with statistically more modest magnitudes of effect (P = 0.01). The model c-statistic for preeclampsia improved when PE-PRS was added to clinical risk factors (P = 4.6 × 10-15). Additional increment in the c-statistic was observed when BP-PRS was added to a model already including both clinical risk factors and PE-PRS (P = 1.1 × 10-14).Conclusion:BP-PRS is strongly associated with hypertensive disorders of pregnancy. Our current observations suggest that the BP-PRS could capture the genetic architecture of preeclampsia better than the current PE-PRSs. These findings also emphasize the common pathways in the development of all BP disorders. The clinical utility of a BP-PRS for preeclampsia prediction warrants further investigation. publishedVersion
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- 2022
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23. Combined genetic and splicing analysis of BRCA1 c.[594-2A > C; 641A > G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms
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Barbara Wappenschmidt, Fergus J. Couch, Norbert Arnold, Claude Houdayer, Manjeet K. Bolla, Omar Soukarieh, Sean V. Tavtigian, Irene L. Andrulis, Alexandra Becker, Alexandra Martins, Qin Wang, Sara Margolin, Paolo Radice, Janet E. Olson, Mitul Shah, Juul T. Wijnen, Amanda B. Spurdle, Nichola Johnson, Carole Brewer, Harald Surowy, Graham G. Giles, Ana Blanco, Kamila Czene, Thomas Hansen, Wendy S. Rubinstein, Anja Rudolph, Christian F. Singer, Antonis C. Antoniou, Douglas F. Easton, Fiona M. Blows, Michael T. Parsons, kConFab Investigators, Annika Lindblom, Nicola K. Poplawski, Melissa C. Southey, Emily Hallberg, Vanessa Lattimore, Yvette van Ierland, Logan C. Walker, Joe Dennis, Gord Glendon, Ana Vega, Diether Niederacher, Laurent Castera, David E. Goldgar, Ulrike Faust, Roger L. Milne, Marta Santamariña, Lesley McGuffog, Jan Hauke, Christi J. van Asperen, Michela Raponi, Irene López-Perolio, Diana Baralle, Tina Pesaran, Huong Meeks, Peter J. Hulick, Miguel de la Hoya, Philip Whiley, Raquel Behar, Jenny Chang-Claude, Elizabeth C. Chao, Henrik Flyger, Doris Steinemann, Pham Phuong Mai, Stig E. Bojesen, Maaike P.G. Vreeswijk, Sandrine M. Caputo, Jan Sullivan, Julian Peto, Barbara Burwinkel, Laura Galastri, Per Hall, Kyriaki Michailidou, Bernd Dworniczak, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Fundación Pública Galega Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica--USC, CIBER de Enfermedades Raras (CIBERER), Division of Genetics and Population Health, Queensland Institute of Medical Research, Genetics, University of Southampton, University of Otago [Dunedin, Nouvelle-Zélande], Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, Human Genetics Division [Southampton], Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Institut Laue-Langevin (ILL), University of Melbourne, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Institute of Cell and Molecular Pathology, Medizinische Hochschule Hannover (MHH), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), DIEP/DSV (DIEP/DSV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Ambry Genetics [Aliso Viejo, CA, USA], Department of Clinical Genetics, Royal Devon & Exeter Hospital, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Metabolic Unit, Dept Clinical Chemistry, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), Molecular Epidemiology Research Group, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Breast Surgery, Herlev and Gentofte Hospital, Karolinska University Hospital [Stockholm], Division of Cancer Epidemiology, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Cancer Epidemiology Centre, Cancer Council Victoria, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Science and Technology Beijing [Beijing] (USTB), Strangeways Research Laboratory, University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Cancer Research U.K. Genetic Epidemiology Unit, Department of Laboratory Medicine and Pathology, Mayo Clinic, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, Center for Human and Clinical Genetics, Université de Pau et des Pays de l'Adour (UPPA), International Agency for Cancer Research (IACR), ILL, Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Antoniou, Antonis [0000-0001-9223-3116], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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0301 basic medicine ,Adult ,RNA Splicing ,[SDV]Life Sciences [q-bio] ,DNA Mutational Analysis ,Breast Neoplasms ,Biology ,03 medical and health sciences ,Exon ,Genetics ,Humans ,Allele ,Molecular Biology ,Gene ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,Aged ,Ovarian Neoplasms ,Messenger RNA ,BRCA1 Protein ,Tumor Suppressor Proteins ,Alternative splicing ,RNA ,General Medicine ,Articles ,Exons ,Middle Aged ,Splicing regulatory element ,3. Good health ,Gene Expression Regulation, Neoplastic ,Alternative Splicing ,030104 developmental biology ,RNA splicing ,Mutation ,Female ,RNA Splice Sites - Abstract
A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A>C (IVS9-2A>C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-scale genetic and clinical resources from the ENIGMA, CIMBA and BCAC consortia to assess pathogenicity of c.594-2A>C. The combined odds for causality considering case-control, segregation, and breast tumor pathology information was 3.23x10-8. Our data indicate that c.594-2A>C is always in cis with c.641A>G.The spliceogenic effect of c.[594-2A>C;641A>G] was characterized using RNA analysis of human samples and splicing minigenes. As expected, c.[594-2A>C; 641A>G] caused exon 10 skipping, albeit not due to c.594-2A>C impairing the acceptor site but rather by c.641A>G modifying exon 10 splicing regulatory element(s). Multiple blood-based RNA assays indicated that the variant allele did not produce detectable levels of full-length transcripts, with a per allele BRCA1 expression profile comprised of ?70-80% truncating transcripts, and ?20-30% of in-frame ?9,10 transcripts predicted to encode a BRCA1 protein with tumor suppression function.We confirm that BRCA1c.[594-2A>C;641A>G] should not be considered a high-risk pathogenic variant. Importantly, results from our detailed mRNA analysis suggest that BRCA-associated cancer risk is likely not markedly increased for individuals who carry a truncating variant in BRCA1 exons 9 or 10, or any other BRCA1 allele that permits 20-30% of tumor suppressor function. More generally, our findings highlight the importance of assessing naturally occurring alternative splicing for clinical evaluation of variants in disease-causing genes.
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- 2016
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24. Sexual Activity and Dyspareunia After Pelvic Organ Prolapse Surgery: A 5-Year Nationwide Follow-up Study
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Wihersaari, Olga, Karjalainen, Päivi, Tolppanen, Anna Maija, Mattsson, Nina, Nieminen, Kari, Jalkanen, Jyrki, Tampere University, Clinical Medicine, and Department of Gynaecology and Obstetrics
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3123 Gynaecology and paediatrics ,Urology ,3121 Internal medicine - Abstract
Background: Even though surgery generally improves sexual function and alleviates dyspareunia related to pelvic organ prolapse (POP), knowledge of the long-term effects is scarce. Objective: To describe changes in sexual activity and dyspareunia rates after POP surgery and to identify potential risk factors for the occurrence of dyspareunia. Design, setting, and participants: This was a prospective longitudinal cohort study of women aged over 18 yr undergoing POP surgery in Finland during 2015. Out of 3515 participants, sexual activity and dyspareunia data were available at baseline, 6 mo, 2 yr, and 5 yr for 79%, 68%, 63%, and 57%, respectively. Intervention: Native tissue, transvaginal mesh, and abdominal mesh repair. Outcome measurements and statistical analysis: Rates of sexual activity and dyspareunia were assessed using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) at baseline and at 6 mo, 2 yr, and 5 yr after surgery. As a secondary outcome, risk factors for overall, persisting, and de novo dyspareunia were assessed using logistic regression models. Results and limitations: The proportion of sexually active women increased from 40.7% to 43% after surgery. Preoperative dyspareunia resolved in >50% of cases during the first 6 mo, irrespective of the surgical approach. De novo dyspareunia rates were low at all time points (1.9–3.1%). Several potential risk factors associated with preoperative and postoperative dyspareunia were identified: younger age, lower preoperative body mass index, lower prolapse stage at baseline, either pelvic pain or dyspareunia at baseline, prior surgery (stress urinary incontinence surgery, posterior colporrhaphy, POP surgery, hysterectomy), and posterior repair. Conclusions: Dyspareunia is significantly reduced after POP repair irrespective of the surgical approach. However, multiple factors seem to be associated with persisting and de novo symptoms, which should be considered in preoperative counseling. Patient summary: Our 5-year follow-up study demonstrates that surgery to repair pelvic organ prolapse (POP) in women improves sexual activity and reduces painful intercourse. Multiple factors, such as preoperative pain, previous POP surgery, and prolapse stage, may be associated with painful intercourse after surgery. publishedVersion
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- 2022
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25. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
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Lawrenson, Kate, Kar, Siddhartha, McCue, Karen, Kuchenbaeker, Karoline, Michailidou, Kyriaki, Tyrer, Jonathan, Beesley, Jonathan, Ramus, Susan J., Li, Qiyuan, Delgado, Melissa K., Lee, Janet M., Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K., Arver, Brita, Bandera, Elisa V., Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Benitez, Javier, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Børresen-Dale, Anne Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Bruinsma, Fiona, Brunet, Joan, Buhari, Shaik Ahmad, Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Canniotto, Rikki, Chang-Claude, Jenny, Chiquette, Jocelyne, Choi, Ji Yeob, Claes, Kathleen B M, Cook, Linda S., Cox, Angela, Cramer, Daniel W., Cross, Simon S., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, Dennis, Joe, Devilee, Peter, Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Dumont, Martine, Ehrencrona, Hans, Ejlertsen, Bent, Ellis, Steve, Engel, Christoph, Lee, Eunjung, Evans, D. Gareth, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fridley, Brooke L., Friedman, Eitan, Frost, Debra, Gambino, Gaetana, Ganz, Patricia A., Garber, Judy, García-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Ghoussaini, Maya, Giles, Graham G., Glasspool, Rosalind, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Goode, Ellen L., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Heitz, Florian, Herzog, Josef, Høgdall, Estrid, Høgdall, Claus K., Hogervorst, Frans B L, Hollestelle, Antoinette, Hopper, John L., Hulick, Peter J., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jensen, Allan, John, Esther M., Johnson, Nichola, Kabisch, Maria, Kang, Daehee, Kapuscinski, Miroslav, Karlan, Beth Y., Khan, Sofia, Kiemeney, Lambertus A., Kjaer, Susanne Kruger, Knight, Julia A., Konstantopoulou, Irene, Kosma, Veli Matti, Kristensen, Vessela, Kupryjanczyk, Jolanta, Kwong, Ava, De La Hoya, Miguel, Laitman, Yael, Lambrechts, Diether, Le, Nhu, De Leeneer, Kim, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Lindblom, Annika, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer T., Lu, Karen, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Le Marchand, Loic, Margolin, Sara, Marme, Frederik, Massuger, Leon F A G, Matsuo, Keitaro, Mazoyer, Sylvie, McGuffog, Lesley, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Milne, Roger L., Montagna, Marco, Moysich, Kirsten B., Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Nord, Silje, Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olswold, Curtis, O'Malley, David, Orlow, Irene, Orr, Nick, Osorio, Ana, Park, Sue Kyung, Pearce, Celeste L., Pejovic, Tanja, Peterlongo, Paolo, Pfeiler, Georg, Phelan, Catherine M., Poole, Elizabeth M., Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Rhenius, Valerie, Rhiem, Kerstin, Risch, Harvey A., Rodriguez, Gus, Rossing, Mary Anne, Rudolph, Anja, Salvesen, Helga B., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Sellers, Thomas A., Seynaeve, Caroline, Shah, Mitul, Shen, Chen Yang, Shu, Xiao Ou, Sieh, Weiva, Singer, Christian F., Sinilnikova, Olga M., Slager, Susan, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stenmark-Askmalm, Marie, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia, Toland, Amanda Ewart, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tseng, Chiu Chen, Tung, Nadine, Tworoger, Shelley S., Vachon, Celine, Van Den Ouweland, Ans M W, Van Doorn, Helena C., Van Rensburg, Elizabeth J., Van't Veer, Laura J., Vanderstichele, Adriaan, Vergote, Ignace, Vijai, Joseph, Wang, Qin, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wu, Anna H., Yannoukakos, Drakoulis, Yoon, Sook Yee, Yu, Jyh Cherng, Zheng, Wei, Zheng, Ying, Khanna, Kum Kum, Simard, Jacques, Monteiro, Alvaro N., French, Juliet D., Couch, Fergus J., Freedman, Matthew L., Easton, Douglas F., Dunning, Alison M., Pharoah, Paul D., Edwards, Stacey L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Gayther, Simon A., Bowtell, David, DeFazio, Anna, Webb, Penny, Collonge-Rame, Marie Agnès, Damette, Alexandre, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Ferrer, Sandra Fert, Bignon, Yves Jean, Uhrhammer, Nancy, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine, Peysselon, Magalie, Peyrat, Jean Philippe, Fournier, Joëlle, Révillion, Françoise, Adenis, Claude, Vénat-Bouvet, Laurence, Léone, Mélanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Verny-Pierre, Carole, Lasset, Christine, Bonadona, Valérie, Barjhoux, Laure, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Coupier, Isabelle, Pujol, Pascal, Sokolowska, Johanna, Bronner, Myriam, Delnatte, Capucine, Bézieau, Stéphane, Mari, Véronique, Gauthier-Villars, Marion, Buecher, Bruno, Rouleau, Etienne, Golmard, Lisa, Moncoutier, Virginie, Belotti, Muriel, De Pauw, Antoine, Elan, Camille, Fourme, Emmanuelle, Birot, Anne Marie, Saule, Claire, Laurent, Maïté, Houdayer, Claude, Lesueur, Fabienne, Mebirouk, Noura, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Muller, Danièle, Fricker, Jean Pierre, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Mortemousque, Isabelle, Bressac-De-Paillerets, Brigitte, Caron, Olivier, Guillaud-Bataille, Marine, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brady, Angela, Barwell, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Cook, Jackie, Snape, Katie, Murray, Alex, McCann, Emma, Rookus, M. A., Van Leeuwen, F. E., Van Der Kolk, L. E., Schmidt, M. K., Russell, N. S., De Lange, J. L., Wijnands, R., Collée, J. M., Hooning, M. J., Seynaeve, C., Van Deurzen, C. H M, Obdeijn, I. M., Van Asperen, C. J., Tollenaar, R. A E M, Van Cronenburg, T. C T E F, Kets, C. M., Ausems, M. G E M, Van Der Pol, C. C., Van Os, T. A M, Waisfisz, Q., Meijers-Heijboer, H. E J, Gómez-Garcia, E. B., Oosterwijk, J. C., Mourits, M. J., De Bock, G. H., Vasen, H. F., Siesling, S., Verloop, J., Overbeek, L. I H, Fox, Stephen, Kirk, Judy, Lindeman, Geoff, Price, Melanie, NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Dutch Cancer Society (Holanda), Breast Cancer Research Trust, Instituto de Salud Carlos III, Lon V. Smith Foundation, Federal Ministry of Education & Research (Alemania), Finlands Akademi (Finlandia), United States Army Medical Research and Development Command, California Breast Cancer Research Program, German Cancer Aid, Canadian Institutes of Health Research, Ministère de Économie, Innovation et Exportation (Canadá), Ministry of Higher Education (Malasia), National Medical Research Council (Singapur), University of Oulu (Finlandia), Yorkshire Cancer Research, Hellenic Cooperative Oncology Group, California Cancer Research Program, Danish Cancer Society, Ministry of Science and Higher Education (Polonia), Asociación Española Contra el Cáncer, University of Kansas. Cancer Center (Estados Unidos), Hungarian Research Grants, Norwegian EEA Financial Mechanism, Canadian Breast Cancer Network, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Congressionally Directed Medical Research Programs (Estados Unidos), NRG Oncology National (Estados Unidos), Unión Europea. Comisión Europea. 7 Programa Marco, Medical Oncology, Obstetrics & Gynecology, Clinical Genetics, 1 Department of Preventive Medicine, Keck School of MediCenter, Kansas City, Kansas 66160, USA. 90 Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer 52621, Israel. 91 Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, Pisa 56126, Italy. 92 UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, California 90024, USA. 93 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 94 Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK. 95Women’s Cancer, UCL EGA Institute for Women’s Health, London WC1E 6AU, UK. 96 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. 97 Cancer Research UK Clinical Trials Unit, The BeatsonWest of Scotland Cancer Centre, Glasgow G12 0YN, UK. 98 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. 99 Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Que´bec H3A 1A1, Canada. 100 Department of Medicine, McGill University, Montreal, Que´bec H3A 1A1, Canada. 101 Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. 102 Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55902, USA. 103 Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 104Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 105 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA. 106 Department of Genetics and Pathology, Pomeranian Medical University, 70-204 Szczecin, Poland. 107 Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, 94805 Villejuif, France. 108 University Paris- Sud, 91405 Villejuif, France. 109 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 110 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark. 111 Department of Oncology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK. 112 Saw Swee Hock School of Public Health, National University of Singapore Singapore 119077, Singapore. 113 Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, 50603 Kuala Lumpur, Malaysia. 114 Cancer Research Initiatives Foundation, Subang Jaya, 47500 Selangor, Malaysia. 115 Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136 Essen, Germany. 116 Department of Gynecology and Gynecologic Oncology, Dr Horst Schmidt Kliniken Wiesbaden, 65199 Wiesbaden, Germany. 117 Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte California 91010, USA. 118 Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, 2730 Copenhagen, Denmark. 119 Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark. 120 Department of Gynecology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark. 121 Family Cancer Clinic, Netherlands Cancer Institute, 1006 Amsterdam, The Netherlands. 122 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 Rotterdam, The Netherlands. 123 Center for Medical Genetics, NorthShore University Health System, Evanston, Illinois 60201, USA. 124 N.N. Petrov Institute of Oncology, St Petersburg 197758, Russia. 125 Lombardi Comprehensive Cancer Center, Georgetown University, Washington District of Columbia 20057, USA. 126 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi 464-8681, Japan. 127 State Research Institute Centre for Innovative Medicine, LT-01102 Vilnius, Lithuania. 128 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California 94538, USA. 129 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 08826, Korea. 130 Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria 3010, Australia. 131Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 132 Radboud University Medical Centre, Radboud Institute for Health Sciences, 6500 Nijmegen, The Netherlands. 133 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. 134 Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. 135 Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, 70210 Kuopio, Finland. 136 Cancer Center, Kuopio University Hospital, 70210 Kuopio, Finland. 137 Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland. 138 Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, 1478 Oslo, Norway. 139 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China. 140 Department of Surgery, The University of Hong Kong, Hong Kong, China. 141Vesalius Research Center, VIB, 3000 Leuven, Belgium. 142 Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, Belgium. 143 Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 144 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry CV4 7AL, UK. 145 Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 146 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), 20133 Milan, Italy. 147 University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA. 148 Department of Oncology - Pathology, Karolinska Institutet, SE- 171 77 Stockholm, Sweden. 149 National Center for Tumour Diseases, University of Heidelberg, 69117 Heidelberg, Germany. 150 Department of Gynaecology, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 151 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka 812-8582, Japan. 152 Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria 3004, Australia. 153 Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow G61 1BD, UK. 154 Division of Gynaecology and Obstetrics, Technische Universita¨t Mu¨nchen, 81675 Munich, Germany. 155 Department of Human Genetics, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 156 Immunology and Molecular Oncology Unit, Instituto Oncologico Veneto IOV, IRCCS, 35128 Padua, Italy. 157 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 158 Institute of Population Health, University of Manchester, Manchester M13 9PL, UK. 159 Laboratory Medicine Program, University Health Network, Toronto, Ontario M5G 1L7, Canada. 160 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada. 161 The University of Texas School of Public Health, Houston, Texas 77030, USA. 162 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA. 163 Department of Medicine and Genetics, University of California, San Francisco, California 94143, USA. 164 Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 165 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 166 Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary. 167 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA. 168 The Ohio State University and the James Cancer Center, Columbus, Ohio 43210, USA. 169 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York 10017, USA. 170 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28019 Madrid, Spain. 171 Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain. 172 Department of Surgery, Seoul National University College of Medicine, Seoul, 03080 Korea. 173 Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, USA. 174 Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. 175 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, 16 20139 Milan, Italy. 176 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria. 177 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida 33606, USA. 178 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 179 Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts 02115, USA. 180 Laboratory of Cancer Genetics and Tumour Biology, Northern Finland Laboratory Centre NordLab, FI-90014 Oulu, Finland. 181 Laboratory of Cancer Genetics and Tumour Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland. 182 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT),cine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA. 2 Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 3 QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia. 4 Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 5 Medical College, Xiamen University, Xiamen 361102, China. 6 Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 7 Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki 00029 HUS, Finland. 8 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario Canada, M5G 1X5. 9 Department of Molecular Genetics, University of Toronto, Toronto, OntarioCanada, M5S 1A8. 10 Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, California 92697, USA. 11 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany. 12 University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 13 Department of Oncology, Karolinska University Hospital, Stockholm 171 77, Sweden. 14 Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA. 15 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan 20141, Italy. 16 Department of Pathology, Landspitali University Hospital and BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik 600169- 2039, Iceland. 17 University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen 91054, Germany. 18 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid E-28029, Spain. 19 Centro de Investigacio´n en Red de Enfermedades Raras, Valencia 28029, Spain. 20 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710, USA. 21 Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 22 Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway. 23 Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway. 24 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland. 25 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. 26 International Epidemiology Institute, Rockville, Maryland 20850, USA. 27 Gynaecology Research Unit, Hannover Medical School, Hannover D-30625, Germany. 28 Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark. 29 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. 30 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 31 Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 32 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo N-0310, Norway. 33 K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo N-0310, Norway. 34 Dr Margarete Fischer- Bosch-Institute of Clinical Pharmacology, Stuttgart D-70376, Germany. 35 University of Tu¨bingen, Tu¨bingen 72074, Germany. 36 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 37 International Agency for Research on Cancer, Lyon 69008, France. 38 Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 39 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. 40 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d’Investigacio´ Biome`dica de Girona), Catalan Institute of Oncology, Girona 08908, Spain. 41 Department of Surgery, National University Health System, Singapore 119077, Singapore. 42 Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 43 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg 69120, Germany. 44 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki 00029 HUS, Finland. 45 Department of Pathology, Helsinki University Central Hospital, Helsinki 00029, Finland. 46 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. 47 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigacio´n Sanitaria del Hospital Clı ´nico San Carlos), Madrid 28040, Spain. 48 Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia. 49 Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo 14263, New York, USA. 50 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 51 University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany. 52 Unite´ de recherche en sante´ des populations, Centre des maladies du sein Descheˆnes-Fabia, Centre de recherche FRSQ du Centre hospitalier affilie´ universitaire de Que´bec, Que´bec City, Que´bec Canada, G1J 1Z4. 53 Cancer Research Institute, Seoul National University, Seoul 08826, Korea. 54 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. 55 Center for Medical Genetics, Ghent University, Ghent 9000, Belgium. 56 Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA. 57 Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield S10 2TN, UK. 58 Harvard HT Chan School of Public Health, Boston, Massachusetts 02115, USA. 59 Obstetrics and Gynecology Epidemiology Center, Brigham andWomen’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 60 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK. 61 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-115, Poland. 62 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE-171 77, Sweden. 63 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. 64 INSERM U1052, CNRS UMR5286, Universite´ Lyon, Centre de Recherche en Cance´rologie de Lyon, Lyon 69373, France. 65 Department of Pathology and Laboratory Diagnostics the Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology,Warsaw 44-101, Poland. 66 Department of Pathology, Leiden University Medical Center, Leiden 2333, The Netherlands. 67 Department of Human Genetics, Leiden University Medical Center, Leiden 2333, The Netherlands. 68 Oncogenetics Group, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO) and Universitat Auto`noma de Barcelona, Barcelona, 186 Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, 50931 Cologne, Germany. 187Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut 06510, USA. 188Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois 60201, USA. 189 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. 190Department of Epidemiology, University of Washington, Seattle, Washington 98109, USA. 191National Cancer Institute, Bangkok 10400, Thailand. 192 Research Oncology, Guy’s Hospital, King’s College London, London SE1 9RT, UK. 193Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. 194 Cancer Control and Population Sciences, Duke Cancer Institute, Durham, North Carolina 27710, USA. 195Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands. 196Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, 50676 Cologne, Germany. 197 Center for Integrated Oncology, University Hospital of Cologne, 50676 Cologne, Germany. 198 Center for Molecular Medicine, University Hospital of Cologne, 50676 Cologne, Germany. 199 Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, 50676 Cologne, Germany. 200 Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. 201 School of Public Health, China Medical University, Taichung 404, Taiwan. 202Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford California 94305, USA. 203 Unite´ Mixte de Ge´ne´tique Constitutionnelle des Cancers Fre´quents, Hospices Civils de Lyon – Centre Le´on Be´rard, Lyon 69008, France. 204 INSERM U1052, CNRS UMR5286, Universite´ Lyon 1, Centre de Recherche en Cance´rologie de Lyon, Lyon 69003, France. 205Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia. 206Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linko¨ping University, 581 83 Linko¨ping, Sweden. 207 Institut Curie, Department of Tumour Biology, Paris, France, Institut Curie, INSERM U830, 75248 Paris, France. 208Universite´ Paris Descartes, Sorbonne Paris Cite´, 75270 Paris, France. 209 Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany. 210Department of Genetics, Portuguese Oncology Institute, Porto 4200-072, Portugal. 211 Biomedical Sciences Institute (ICBAS), Porto University, Porto 4099-002, Portugal. 212Department of Epidemiology, Mailman School of Public Health, Columbia University, New York 10027, USA. 213Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark. 214UO Anatomia Patologica, Ospedale di Circolo-Universita` dell’Insubria, 21100 Varese, Italy. 215 Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia. 216 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), 64 - 35128 Padua, Italy. 217Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA. 218Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK. 219 Institute of Human Genetics, Pontificia Universidad Javeriana, Cra. 7 #40-62 Bogota, Colombia. 220Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. 221Department of Clinical Genetics, Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands. 222Department of Gynecology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 CE Rotterdam, The Netherlands. 223Division of Gynecological Oncology, Department of Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 224University Hospital Ulm, 89069 Ulm, Germany. 225Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda Maryland 20892, USA. 226 Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 227 Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research ‘Demokritos’, Athens 153 10, Greece. 228 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, 47500 Subang Jaya, Malaysia. 229 University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Malaysia. 230Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114 Taiwan. 231 Shanghai Center for Disease Control and Prevention, Shanghai, China. 232 Cancer Epidemiology Program, Division of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. 233Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. 234 Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. 235 Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia. 236 Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK. 237 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia. 238 Department of Gynaecological Oncology, Westmead Institute for Cancer Research, Westmead Hospital Westmead, New South Wales 2145, Australia., Tyrer, Jonathan [0000-0003-3724-4757], Dennis, Joe [0000-0003-4591-1214], Rhenius, Valerie [0000-0003-4215-3235], Song, Honglin [0000-0001-5076-7371], Wang, Jean [0000-0002-9139-0627], Easton, Douglas [0000-0003-2444-3247], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Quality of care, Anesthesiology, Human genetics, CCA - Cancer biology, and VU University medical center
- Subjects
endocrine system diseases ,Messenger ,IDENTIFIES 3 ,MODIFIERS ,Brjóstakrabbamein ,BRCA2 MUTATION CARRIERS ,Medicine and Health Sciences ,GWAS ,INVESTIGATORS ,African Continental Ancestry Group ,Asian Continental Ancestry Group ,Breast Neoplasms ,Chromosomes, Human, Pair 19 ,Female ,Genome-Wide Association Study ,Genotype ,Humans ,Ovarian Neoplasms ,RNA, Messenger ,Alleles ,Genetic Predisposition to Disease ,Polymorphism, Single Nucleotide ,skin and connective tissue diseases ,COMMON VARIANTS ,EPITHELIAL-CELLS ,Single Nucleotide ,female genital diseases and pregnancy complications ,NAF12 ,Medical Genetics ,Human ,endocrine system ,Science ,Chromosomes, Human, Pair 19/genetics ,Black People ,Breast Neoplasms/genetics ,Chromosomes ,Article ,Ovarian Neoplasms/genetics ,SDG 3 - Good Health and Well-being ,Asian People ,REVEALS ,Polymorphism ,GENOME-WIDE ASSOCIATION ,Krabbamein ,Medicinsk genetik ,Cancer och onkologi ,Pair 19 ,Arfgengi ,GENE ,Eggjastokkar ,Cancer and Oncology ,RNA ,BRCA1 Protein/genetics - Abstract
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P, A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.
- Published
- 2016
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26. Long-Term Efficacy and Tolerability of Flutamide Combined with Oral Contraception in Moderate to Severe Hirsutism: A 12-Month, Double-Blind, Parallel Clinical Trial
- Author
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A. Millet, E. Torres, F. Escobar-Jiménez, E. López, Joaquim Calaf, Fortuny A, Juan José Espinós, Justo Callejo, J. Alcañiz, O. Vidal, Spanish Working Group for Hirsutism, [Calaf, J, Espinos, JJ] Department of Gynaecology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [López, E] Department of Gynaecology, Hospital Virgen de la Arrixaca, Murcia, Spain. [Millet, A] Department of Gynaecology, Hospital Clínico Universitario de Valencia, Valencia, Spain. [Alcaniz, J] Department of Endocrinology), Clínica Puerta de Hierro,28035 Madrid, Spain. [Fortuny, A] Department of Gynaecology, Hospital Clıinic i Provincial de Barcelona, 08036 Barcelona,Spain. [Vidal, O] Department of Endocrinology, Hospital Juan Canalejo, 15006 La Coruña, Spain. [Callejo, J] Department of Gynaecology, Hospital San Joan de Déu, 08950 Barcelona, Spain. [Escobar-Jiménez,F, Torres, E] Department of Endocrinology, Hospital Clínico de Granada, Granada, Spain, and The study has been sponsored by Ipsen Pharma, S.A., Barcelona, Spain.
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Hirsutism ,Time Factors ,Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings] ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Antiandrogen ,Biochemistry ,Flutamide ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Placebos ,chemistry.chemical_compound ,Endocrinology ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Reproductive Control Agents::Contraceptive Agents::Contraceptive Agents, Female::Contraceptives, Oral::Contraceptives, Oral, Hormonal [Medical Subject Headings] ,Acné Vulgar ,Acne Vulgaris ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Placebos [Medical Subject Headings] ,Anticonceptivos Hormonales Orales ,Levonorgestrel ,Chemicals and Drugs::Organic Chemicals::Amides::Anilides::Flutamide [Medical Subject Headings] ,Adolescente ,hirsutism ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Schedule [Medical Subject Headings] ,education.field_of_study ,Adulto ,Quimioterapia Combinada ,Femenino ,Antagonistas de Andrógenos ,Polycystic ovary ,Humanos ,Treatment Outcome ,Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormone Antagonists::Androgen Antagonists [Medical Subject Headings] ,Tolerability ,Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings] ,Drug Therapy, Combination ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Oral contraceptive pill ,Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Dermatitis::Dermatitis, Seborrheic [Medical Subject Headings] ,medicine.drug_class ,Resultado del Tratamiento ,Population ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Therapy, Combination [Medical Subject Headings] ,Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Virilism::Hirsutism [Medical Subject Headings] ,Drug Administration Schedule ,Contraceptives, Oral, Hormonal ,Dermatitis Seborreica ,Double-Blind Method ,Internal medicine ,Método Doble Ciego ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,medicine ,Humans ,Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Acneiform Eruptions::Acne Vulgaris [Medical Subject Headings] ,Relación Dosis-Respuesta a Droga ,education ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,Dose-Response Relationship, Drug ,business.industry ,Esquema de Medicación ,Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Dose-Response Relationship, Drug [Medical Subject Headings] ,Biochemistry (medical) ,Androgen Antagonists ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Methods::Research Design::Double-Blind Method [Medical Subject Headings] ,medicine.disease ,Dermatitis, Seborrheic ,Flutamida ,Check Tags::Female [Medical Subject Headings] ,chemistry ,Hirsutismo ,business ,Factores de Tiempo - Abstract
Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; OBJECTIVE Our objective was to test the efficacy and tolerability of three doses of flutamide (125, 250, and 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol/levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome or idiopathic hirsutism. DESIGN We conducted a randomized, double-blind, placebo-controlled, parallel clinical trial. PATIENTS A total of 131 premenopausal women, suffering from moderate to severe hirsutism, were randomized to placebo or 125, 250, or 375 mg flutamide daily associated with a triphasic oral contraceptive pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline and at 3 (except hormone serum levels), 6, and 12 months. Side effects and biochemical, hematological, and hepatic parameters were assessed. METHODS We used three-way ANOVA (subject, dose, and visit) with Scheffé adjustment for multiple comparisons or nonparametrical Friedman test and least-squares mean (paired data) and Kruskall-Wallis test for unpaired data analyses. We used chi(2) or Fisher's test for categorical data. RESULTS A total of 119 patients were included in the intention-to-treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne, and seborrhea scores after 12 months compared with placebo without differences among dose levels. Similar related side effects were observed with placebo and 125 mg flutamide (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared with placebo. CONCLUSIONS Flutamide at 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism. Yes
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27. Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children
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Polina Girchenko, Marius Lahti-Pulkkinen, Jari Lipsanen, Kati Heinonen, Jari Lahti, Ville Rantalainen, Esa Hämäläinen, Hannele Laivuori, Pia M. Villa, Eero Kajantie, Katri Räikkönen, Department of Psychology and Logopedics, Developmental Psychology Research Group, Teachers' Academy, Medicum, HUSLAB, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Clinicum, HUS Gynecology and Obstetrics, Children's Hospital, Lastentautien yksikkö, HUS Children and Adolescents, Tampere University, Welfare Sciences, Clinical Medicine, and Department of Gynaecology and Obstetrics
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Risk ,Mothers ,PROFILE ,3124 Neurology and psychiatry ,Body Mass Index ,SUPPLEMENTATION ,DIET ,Cellular and Molecular Neuroscience ,INFLAMMATION ,3123 Gynaecology and paediatrics ,Pregnancy ,Humans ,OXIDATIVE STRESS ,AUTISM ,Child ,Molecular Biology ,OUTCOMES ,Mental Disorders ,3112 Neurosciences ,RISKS ,Psychiatry and Mental health ,OBESITY ,1182 Biochemistry, cell and molecular biology ,Female ,HEALTH ,3111 Biomedicine - Abstract
Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4–12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7–65.6%, and hence the predictive significance of the model, and mediated 60.8–75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolomic perturbations during pregnancy are associated with a higher risk of mental and behavioral disorders in children. These findings may allow identifying metabolomic targets for personalized interventions.
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- 2022
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28. Searching for a paternal phenotype for preeclampsia
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for FINNPEC, Jaatinen, Noora, Jääskeläinen, Tiina, Ekholm, Eeva, Laivuori, Hannele, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Department of Food and Nutrition, Pregnancy and Genes, Medicum, Department of Medical and Clinical Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, and University of Helsinki
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lifestyle ,GENETICS ,phenotype ,COMPONENTS ,Obstetrics and Gynecology ,General Medicine ,PREDISPOSITION ,DISEASE ,preeclampsia ,PREGNANCY ,risk factor ,HYPERTENSIVE DISORDERS ,RISK-FACTOR ,3123 Gynaecology and paediatrics ,ECLAMPSIA ,paternal ,pregnancy complication ,FETAL - Abstract
Introduction: Preeclampsia (PE) is a heterogeneous disorder and research to date has principally focused on maternal factors. In this study, however, we considered the associations between background factors and preeclampsia in men who fathered preeclamptic and non-preeclamptic pregnancies. Material and methods: From 2008 to 2011, participants in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort completed a questionnaire on their background information. Questionnaire data were available from 586 men who had fathered a preeclamptic pregnancy (PE fathers) and 660 control men who had fathered a non-preeclamptic pregnancy. Two different control groups were established: Group 1: healthy controls (n = 457), which consisted of fathers whose current partners were healthy women with uncomplicated pregnancies; Group 2: other controls (n = 203), which also included fathers whose current partners had other pregnancy complications. Results: The PE fathers more often reported preeclampsia in a previously fathered pregnancy (p < 0.05 for all). The PE and control fathers were similar in age, body mass index, smoking, and preexisting medical conditions. There were no differences in the socioeconomic background or health history of the PE and control fathers or their parents. Conclusions: In the FINNPEC study cohort, the occurrence of preeclampsia in a previously fathered pregnancy was more common among the men who had fathered a preeclamptic pregnancy; other paternal phenotypic and lifestyle characteristics did not play a significant role in preeclampsia susceptibility of their partners. publishedVersion
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- 2022
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29. No association in maternal serum levels of TMAO and its precursors in pre-eclampsia and in non-complicated pregnancies
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Tiina Jääskeläinen, Olli Kärkkäinen, Seppo Heinonen, Kati Hanhineva, Hannele Laivuori, Tampere University, Department of Gynaecology and Obstetrics, Clinical Medicine, Department of Food and Nutrition, Pregnancy and Genes, Medicum, Department of Medical and Clinical Genetics, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Genomics of Neurological and Neuropsychiatric Disorders, and Institute for Molecular Medicine Finland
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RISK ,MORTALITY ,OXIDE ,Obstetrics and Gynecology ,TMAO ,METABOLISM ,Preeclampsia ,Methylamines ,Pre-Eclampsia ,FISH ,Risk Factors ,Pregnancy ,CARDIOVASCULAR-DISEASE ,3123 Gynaecology and paediatrics ,Case-Control Studies ,LC -MS ,PHOSPHATIDYLCHOLINE ,Internal Medicine ,Animals ,Humans ,Female ,Biomarkers ,CARNITINE - Abstract
Only a few studies have explored the role of microbiota-dependent metabolite trimethylamine N-oxide (TMAO) in non-complicated pregnancy and in pre-eclampsia (PE). We enrolled 139 PE and 29 healthy pregnant women in a nested case control study. We hypothesized that elevated levels of circulating TMAO and its precursors choline and glycine betaine in the late second or in third trimester might contribute to the PE and are associated with the onset of the disease and clinical features such as elevated blood pressure. The association with a few available lifestyle factors (use of fish and physical activity) was also evaluated. In contrast with the previous findings, there was no difference in TMAO concentration between PE and healthy women. In addition, TMAO concentration was not associated with any of the PE related clinical features, angiogenic or inflammatory markers. In future, it is crucial to obtain longitudinal data on TMAO in both non-complicated and in PE pregnancies before we could have more detailed understanding of TMAO. publishedVersion
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- 2022
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30. Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes
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Emilia Huvinen, Jari Lahti, Miira M. Klemetti, Paula H. Bergman, Katri Räikkönen, Marju Orho-Melander, Hannele Laivuori, Saila B. Koivusalo, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, Clinicum, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, University of Helsinki, Department of Psychology and Logopedics, Department of Public Health, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, and Department of Medical and Clinical Genetics
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Lifestyle intervention ,Blood Glucose ,METFORMIN ,Endocrinology, Diabetes and Metabolism ,PROGRESSION ,VARIANTS ,3121 Internal medicine ,GLUCOSE ,Body Mass Index ,MELLITUS ,Polygenic risk score ,Pregnancy ,Risk Factors ,3123 Gynaecology and paediatrics ,SCORE ,Internal Medicine ,Humans ,Life Style ,Gestational diabetes ,POLYMORPHISMS ,Genetic risk ,Physical activity ,Prevention ,Postpartum Period ,1184 Genetics, developmental biology, physiology ,WOMEN ,Type 2 diabetes ,ASSOCIATION ,Gene-environment interaction ,Diet ,CONVERSION ,Diabetes, Gestational ,Diabetes Mellitus, Type 2 ,3121 General medicine, internal medicine and other clinical medicine ,Female - Abstract
Aims/hypothesis The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. Methods The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m2 and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. Results Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA1c) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). Conclusions/interpretation Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk. Clinical trial registration ClinicalTrials.gov identifier: NCT01698385 Graphical abstract
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31. Single-administered GnRH agonist as luteal phase support in insemination cycles: a randomized controlled trial
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Riikka Leppänen, Helena Tinkanen, Heini Huhtala, Katja Ahinko, Tampere University, Department of Gynaecology and Obstetrics, Clinical Medicine, and Health Sciences
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Triptorelin Pamoate ,Pregnancy Rate ,Endocrinology, Diabetes and Metabolism ,Obstetrics and Gynecology ,Luteal Phase ,3121 Internal medicine ,3142 Public health care science, environmental and occupational health ,Insemination ,Gonadotropin-Releasing Hormone ,Endocrinology ,Ovulation Induction ,Pregnancy ,Letrozole ,Humans ,Female ,Prospective Studies - Abstract
Objective: To find out whether a single-administered GnRH agonist improves the live birth rate in real-life patients undergoing intrauterine insemination (IUI) cycles. Study Design: A prospective, randomized controlled trial in a public single tertiary center in Tampere University Hospital, Finland. Altogether 251 IUI cycles in 163 patients were randomized to triptorelin and a control group between January 2017 and April 2019. In the triptorelin group, the participants had a single administration of a subcutaneous GnRH agonist triptorelin 0.1 mg at the time of implantation. In the control group, there was no luteal phase support. The primary outcome measure was the live birth rate (LBR). The secondary outcome measures were clinical pregnancy rate (CPR) and miscarriage rate. Results: Overall, the live birth rate was lower in the triptorelin group compared to the control group (7.9 vs. 12.1%; p =.297). The clinical pregnancy rates were 12.6 and 13.7%, respectively. There were 2.4% miscarriages in the triptorelin group and no miscarriages in the control group. Ovarian stimulation with letrozole was associated with lower LBR among the triptorelin group, in comparison to the control group (0 vs. 14.7%, p =.020). In contrast, when gonadotrophin was added to the letrozole, LBR was almost doubled compared to the control group (15.9 vs. 8.3%, p =.341). Conclusion: A single administration of GnRH agonist in the luteal phase does not improve LBR in IUI cycles. acceptedVersion
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- 2022
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32. Impact of obesity on uterine contractile activity during labour: A blinded analysis of a randomised controlled trial cohort
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Tuija Hautakangas, Jukka Uotila, Joel Kontiainen, Heini Huhtala, Outi Palomäki, Tampere University, Department of Gynaecology and Obstetrics, Clinical Medicine, and Health Sciences
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Cohort Studies ,Labor, Obstetric ,3123 Gynaecology and paediatrics ,Pregnancy ,Oxytocics ,Humans ,Obstetrics and Gynecology ,Female ,Labor, Induced ,Obesity ,Oxytocin - Abstract
To investigate the impact of severe obesity (body mass index [BMI] ≥35 kg/mExploratory, blinded analysis of a randomised controlled trial cohort.Two labour wards, one in a university tertiary hospital and one in a central hospital.In all, 686 parturients with singleton pregnancies, gestational age ≥37 weeks, fetus in cephalic presentation, and intrauterine tocodynamometry during labour. [Correction added on 6 June 2022, after first online publication: the number of parturients has been corrected to 686.] METHODS: Uterine contractile activity was assessed as intrauterine pressure, frequency of contractions and basal tonus of uterine muscle. The use of oxytocin and cervical dilatation were recorded simultaneously.Primary outcome: uterine contractile activity.use of oxytocin, labour outcomes.Obese parturients reached intrauterine pressure ≥200 Montevideo units (MVU) during the first stage of labour more often than leaner parturients; 62% vs 49%; odds ratio [OR] 1.67 (95% CI 1.05-2.67) and had higher basal tone of uterine muscle. However, obese parturients without previous vaginal delivery were not able to reach the active stage of labour as often as leaner ones, and their vaginal delivery success rate was lower. If a parturient had had previous vaginal delivery, obesity did not influence uterine activity, nor was there a risk of caesarean section. Doses and total consumption of oxytocin did not differ between BMI groups.Obese nulliparas have stronger uterine contractile activity than leaner ones, but they more often fail to reach the active phase of labour and their vaginal delivery success rate is lower.Despite higher strength of uterine contractions among obese parturients, they reach the active stage of labour less often than leaner ones.
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- 2022
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33. Use of labor analgesia in trials of labor after previous cesarean section : A nationwide register-based analysis in Finland
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Matias Vaajala, Maiju Kekki, Ville M. Mattila, Ilari Kuitunen, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, and Department of Musculoskeletal Diseases
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Reproductive Medicine ,Obstetrics and Gynecology ,3121 Internal medicine - Abstract
Objectives: The literature concerning the overall use of labor analgesia among women with trials of labor after cesarean section (TOLAC) is lacking. The primary aim of this study is to report the rate of different labor analgesia methods among women with TOLAC. The secondary aim was to compare the use of labor analgesia between women with the first TOLAC and control group consisting of nulliparous women. Study design. Data from the National Medical Birth Register was used to evaluate the usage of labor analgesia in TOLACs. The use of labor analgesia in the first TOLAC is compared to the pregnancies of nulliparous women. The analgesia methods were stratified into neuraxial analgesia, pudendal, paracervical, nitrous oxide, other medical, other non-medical, and no analgesia. These are analyzed as categorized dichotomy (yes or no) variables. Results: A total of 38 596 TOLACs as second pregnancy of the mother was found during our study period. The control group consisted of a total of 327 464 pregnancies of nulliparous women. Epidural analgesia (61.6% vs 67.1%), nitrous oxide (56.1% vs 62.0%), and non-medical analgesia (30.1% vs 35.0%) were less consumed among women with TOLAC. The rate of spinal analgesia was higher among women with TOLAC (10.1% vs 7.6%) when compared to the control group. However, when only vaginal deliveries were included, the rate of labor analgesia increased especially in the TOLAC group. Conclusions: The main finding of this study is that women with TOLAC had a generally lower rate of labor analgesia. However, the rate of spinal analgesia was higher among women with TOLAC when compared to the control group, however. The results of this study inform midwives, obstetricians, and anesthesiologists on current practices and how to improve the analgetic treatment in TOLAC. publishedVersion
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- 2023
34. Delivery mode and fetal outcome in attempted vaginal deliveries after previous cesarean section: a nationwide register-based cohort study in Finland
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Matias Vaajala, Rasmus Liukkonen, Ville Ponkilainen, Maiju Kekki, Ville M. Mattila, Ilari Kuitunen, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, and Department of Musculoskeletal Diseases
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3123 Gynaecology and paediatrics ,Pediatrics, Perinatology and Child Health ,Obstetrics and Gynecology - Abstract
Purpose: Even though the risks and advantages of repeat Cesarean sections (CSs) and vaginal births after cesarean section (VBACs) are well studied, there is a scarcity of information on the effects of previous CS on maternal and fetal outcomes during subsequent deliveries. The aim of this study is to evaluate delivery mode and fetal outcomes in a trial of labor after cesarean section (TOLAC). Methods: In this nationwide retrospective cohort study, data from the National Medical Birth Register (MBR) were used to evaluate the outcomes of TOLACs. TOLACs were compared to the outcomes of the trial of labor after previous successful vaginal delivery. A multivariable logistic regression model was used to assess the primary outcomes (delivery mode, neonatal intensive care unit, and perinatal/neonatal mortality). Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were used for comparison. Results: A total of 29 352 (77.0%) women attempted vaginal delivery in the TOLAC group. In the control group, 169 377 (97.2%) women attempted vaginal delivery. The adjusted odds for urgent CS (aOR 13.05, CI 12.59–13.65) and emergency CS (aOR 3.65, CI 3.26–4.08) were notably higher in the TOLAC group when compared to the control group. The odds for neonatal intensive care unit treatment (aOR 2.05, CI 1.98–2.14), perinatal mortality (aOR 2.15, CI 1.79–2.57), and neonatal mortality (aOR 1.75, CI 1.20–2.49) were higher in the TOLAC group. Conclusions: The odds for emergency CS were higher among women who underwent TOLAC. The odds for neonatal intensive care and perinatal mortality were also higher, and further research is needed to identify those expecting women who are better suited for TOLAC to minimize the risk for a neonate. The results of this study should be acknowledged by the mother and the clinician when considering the possibility of vaginal births after cesarean section. publishedVersion
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- 2023
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35. Multifetal gestations after traumatic brain injury: a nationwide register-based cohort study in Finland
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Vaajala, Matias, Liukkonen, Rasmus, Kuitunen, Ilari, Ponkilainen, Ville, Kekki, Maiju, Mattila, Ville M., Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, and Department of Musculoskeletal Diseases
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3123 Gynaecology and paediatrics ,Obstetrics and Gynecology ,3126 Surgery, anesthesiology, intensive care, radiology - Abstract
Background There is a paucity of information regarding the association between traumatic brain injuries (TBIs) and subsequent multifetal gestations. Since TBIs are known to negatively affect the neuroendocrine system, we hypothesized that the functions of the whole reproductive system might be disturbed as a result. The aim of this study is to determine the association between previous TBIs and the risk of multifetal gestations using nationwide registers. Methods In this retrospective register-based cohort study, data from the National Medical Birth Register (MBR) were combined with data from the Care Register for Health Care. All fertile-aged women (15–49 years) who had sustained a TBI before pregnancy were included in the patient group. Women with prior fractures of the upper extremity, pelvis, and lower extremity were included in the control group. A logistic regression model was used to assess the risk for multifetal gestation after TBI. Odds ratios (ORs) and adjusted odds ratios (aOR) with 95% confidence intervals (CIs) between the groups were compared. The model was adjusted by maternal age and maternal BMI during pregnancy and previous births. The risk for multifetal gestations were evaluated during different periods following the injury (0–3 years, 3–6 years, 6–9 years, and 9 + years). Results A total of 14 153 pregnancies occurred after the mother had sustained a TBI, and 23 216 pregnancies occurred after the mother had sustained fractures of the upper extremity, pelvis, or lower extremity. Of these, 201 (1.4%) women had multifetal gestations after TBI and 331 (1.4%) women had multifetal gestations after fractures of the upper extremity, pelvis, or lower extremity. Interestingly, the total odds of multifetal gestations were not higher after TBI when compared to fractures of the upper extremity, pelvis, and lower extremity (aOR 1.04, CI 0.86–1.24). The odds were highest at 6–9 years (aOR 1.54, 1.03–2.29) and lowest at 0–3 years (aOR 0.84, CI 0.59–1.18). Conclusion The risk for multifetal gestations after TBIs was not higher than after the other traumas included in this study. Our results provide good baseline information on the effects of TBIs on the risk for multifetal gestations, but further research is required on this topic.
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36. Fear of childbirth and use of labor analgesia : A nationwide register-based analysis in Finland
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Matias Vaajala, Maiju Kekki, Ville M. Mattila, Ilari Kuitunen, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, and Department of Musculoskeletal Diseases
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3123 Gynaecology and paediatrics ,Obstetrics and Gynecology ,General Medicine ,3126 Surgery, anesthesiology, intensive care, radiology - Abstract
Objective: To calculate the rates of labor analgesia among women with fear of childbirth (FOC) in multiparous and nulliparous women, because FOC might be associated with higher rates of labor analgesia. Methods: In this retrospective register-based cohort study, data from the National Medical Birth Register was used to evaluate the usage of labor analgesia in pregnancies with FOC, when compared with those without. The analgesia methods were stratified into neuraxial analgesia, pudendal, paracervical, nitrous oxide, other medical, other non-medical, and no analgesia. Results: A total of 19 285 pregnancies with diagnosed maternal FOC were found during our study period. The control group consisted of 757 997 pregnancies without diagnosed maternal FOC. Nulliparous women with diagnosed FOC had a higher rate of epidural analgesia (70.2% vs 67.1%), spinal analgesia (12.3% vs 7.6%), and pudendal block (17.6% vs 9.6%). Multiparous women with FOC had a notably higher rate for epidural analgesia (47.0% vs 29.0%). Conclusion: The main finding in this study was that women with diagnosed FOC had a higher rate of labor analgesia. The results of this study can be used by midwives, obstetricians, and anesthesiologists to provide optimal pain relief for mothers with FOC. publishedVersion
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- 2023
37. Known risk factors of the developmental dysplasia of the hip predicting more severe clinical presentation and failure of Pavlik harness treatment
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Vilma Lankinen, Mika Helminen, Karim Bakti, Jarmo Välipakka, Hannele Laivuori, Anna Hyvärinen, HUS Children and Adolescents, HUS Gynecology and Obstetrics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Department of Medical and Clinical Genetics, Clinicum, Tampere University, Clinical Medicine, Health Sciences, Tays Research Services, and Department of Gynaecology and Obstetrics
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Risk factors ,3123 Gynaecology and paediatrics ,Pediatrics, Perinatology and Child Health ,Pavlik harness ,Ddh ,Ortolani positivity ,3126 Surgery, anesthesiology, intensive care, radiology ,Developmental dysplasia of the hip - Abstract
Purpose Developmental dysplasia of the hip (DDH) varies from mild instability of the hip to subluxation or total dislocation of the joint. Well-known risk factors of DDH include pre-natal breech position, female sex, positive family history, hip side, primiparity and the mode of delivery. Aim of the present study was to further evaluate known risk-factors of DDH, find associations with more severe dysplasia (characterized with Ortolani positivity) and find risk factors of failure of the Pavlik harness treatment. Material and methods All children with the diagnosis of DDH treated in Tampere University hospital in the years 1998–2018 were retrospectively identified for the study and the data was collected from the medical records. Teratological dislocations (n = 3) were excluded from the analysis. Total of 945 patients were included. Results Breech presentation was strongly associated with Ortolani positivity (p p = 0.291) despite the association with Ortolani positivity. Ortolani positivity (p = 0.002), positive family history (p = 0.013) and girl sex (p = 0.029) were associated with ending up for spica casting and/or operative treatment. Conclusion Breech presentation seems to increase the risk of Ortolani positive DDH. However, these infants are likely to recover with initially started Pavlik harness treatment, as it was not associated with elevated risk for undergoing more robust treatments. Positive family history and girl sex are associated with the most severe cases of developmental dysplasia of the hip, and it may predispose to the failure of the Pavlik harness treatment.
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- 2023
38. Satisfaction and dissatisfaction with pain relief and birth experience among induced and spontaneous-onset labours ending in vaginal birth: A prospective cohort study
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Mäkelä, Katja, Palomäki, Outi, Korpiharju, Heli, Helminen, Mika, Uotila, Jukka, Tampere University, Department of Gynaecology and Obstetrics, Clinical Medicine, Health Sciences, and Tays Research Services
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Reproductive Medicine ,Obstetrics and Maternal Fetal Medicine ,3123 Gynaecology and paediatrics ,Obstetrics and Gynecology ,3121 Internal medicine - Abstract
Objective: To assess pain relief and overall birth experience in induced vs. spontaneous-onset labours and to clarify variables among induced parturients determining satisfaction and dissatisfaction. Study design: A prospective study of 2042 women. 575 women with induced and 1467 with spontaneous-onset labour answered multiple questions in a questionnaire regarding the experience of birth giving. Satisfaction was numerically assessed via a visual analogue scale (VAS 0–10). Results: Induction of labour (IOL) did not worsen the average experience of pain relief, but the proportion of women dissatisfied with pain relief was slightly higher after IOL compared with spontaneous-onset labour (SOL). IOL was associated with lower satisfaction with overall birth experience compared with SOL (VAS 8.0 vs. 8.4; p < 0.001). Among IOL parturients incorrect timing of pain relief was strongly associated with dissatisfaction with pain relief, as were deficient information and induction with misoprostol. Epidural blockade was the most important factor preventing dissatisfaction with pain relief. Unsatisfactory overall experience of birth was associated with deficient pain relief, its incorrect timing or deficient information, as well as vacuum extraction as the mode of delivery. Conclusions: Induction of labour is a risk factor of dissatisfaction regarding pain relief and overall birth experience. The strongest impact on dissatisfaction among induced parturients concerning pain relief was delayed timing of effective labour analgesia. Poor pain relief, its incorrect timing and deficient information on pain relief were strong predictive factors of dissatisfaction with the overall birth experience. publishedVersion
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- 2023
39. Long-term risk of cancer among the first-degree relatives of epithelial ovarian cancer patients : A cohort study with 48 years of follow up
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Laura Kotaniemi‐Talonen, Eero Pukkala, Kristiina Aittomäki, Annika Auranen, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, and Health Sciences
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3123 Gynaecology and paediatrics ,3122 Cancers ,Obstetrics and Gynecology ,General Medicine ,3142 Public health care science, environmental and occupational health - Abstract
Introduction: The long-term risk of cancer among first-degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers. Material and methods: Using registry data, we conducted a retrospective cohort study with a total of 6501 first-degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach). Results: The overall number of cancers was not increased among the first-degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27–2.79), mostly explained by a 2.30-fold (95% CI 1.46–3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient. Conclusions: In our study cohort, we did not observe an increase in the overall cancer risk among the first-degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counselling and testing, particularly in young ovarian cancer patients and their close female relatives. publishedVersion
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- 2023
40. In vitro fertilization increases the odds of gestational diabetes: a nationwide register-based cohort study
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Matias Vaajala, Rasmus Liukkonen, Ville Ponkilainen, Ville M. Mattila, Maiju Kekki, Ilari Kuitunen, Tampere University, Clinical Medicine, Department of Musculoskeletal Diseases, and Department of Gynaecology and Obstetrics
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Endocrinology ,3123 Gynaecology and paediatrics ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,General Medicine ,3121 Internal medicine - Abstract
publishedVersion
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- 2022
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41. Quantitative urine proteomics in pregnant women for the identification of predictive biomarkers for preeclampsia
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Sakari Joenväärä, Matilda Holm, Mayank Saraswat, Rahul Agarwal, Tiialotta Tohmola, Eero Kajantie, Katri Räikkönen, Hannele Laivuori, Pia M. Villa, Esa Hämäläinen, Risto Renkonen, Tampere University, Clinical Medicine, and Department of Gynaecology and Obstetrics
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Proteomics ,Mass spectrometry ,3123 Gynaecology and paediatrics ,Medicine ,Urine ,3121 Internal medicine ,Preeclampsia ,Prediction ,Biomarkers - Abstract
Background Preeclampsia (PE) is a life-threatening disease characterized by elevated blood pressure and proteinuria. Predictive biomarkers of PE are needed, especially those predicting PE in early pregnancy. The aim of this pilot study was to identify urine proteins that could be candidates for new non-invasive markers for PE. Methods Urine samples at three time points of pregnancy (12–14, 18–20 and 26–28 weeks of gestation) were prospectively collected from high-risk women who subsequently developed PE (n = 7), high-risk women who did not develop PE (n = 6), and women without known risk factors for PE (n = 4). The samples were analyzed using mass spectrometry and we subsequently quantified 361 proteins used for further analysis. Rigorous statistical analysis with multiple methods was performed to identify biomarker candidates. Results Of the clinical risk factors analyzed, pre-pregnancy body mass index (BMIBP) was found to be the most important predictor of PE. We identified multiple proteins that correlated with BMIBP and could improve the prediction of PE in combination with BMIBP. Other statistical analyses identified six proteins that each could differentiate women who subsequently developed PE from those who did not at all three time points. Conclusions We identified multiple urine proteins that could be used to predict PE in combination with BMIBP. We also identified six proteins that are strong candidates for predicting PE already in early pregnancy.
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- 2022
42. Associations of low sex hormone-binding globulin and androgen excess in early pregnancy with fasting and post-prandial hyperglycaemia, gestational diabetes, and its severity
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Sanna Mustaniemi, Laure Morin‐Papunen, Elina Keikkala, Hanna Öhman, Heljä‐Marja Surcel, Risto Kaaja, Mika Gissler, Johan G. Eriksson, Hannele Laivuori, Eero Kajantie, Marja Vääräsmäki, Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, University of Helsinki, Helsinki University Hospital Area, HUS Gynecology and Obstetrics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Department of Medical and Clinical Genetics, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Tampere University, Clinical Medicine, and Department of Gynaecology and Obstetrics
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sexhormone‐binding globulin ,Free androgen index ,Endocrinology, Diabetes and Metabolism ,3121 Internal medicine ,pre‐pregnancy BMI ,Androgen excess ,Endocrinology ,3123 Gynaecology and paediatrics ,3121 General medicine, internal medicine and other clinical medicine ,testosterone ,Internal Medicine ,Sex hormone-binding globulin ,Testosterone ,androgen excess ,gestational diabetes ,free androgen index ,Gestational diabetes ,pre-pregnancy BMI - Abstract
Aims: We studied whether androgen excess and low sex hormone-binding globulin (SHBG) measured in early pregnancy are independently associated with fasting and post-prandial hyperglycaemia, gestational diabetes (GDM), and its severity. Materials and Methods: This nationwide case–control study included 1045 women with GDM and 963 non-diabetic pregnant controls. We measured testosterone (T) and SHBG from biobanked serum samples (mean 10.7 gestational weeks) and calculated the free androgen index (FAI). We first studied their associations with GDM and secondly with the type of hyperglycaemia (fasting, 1 and 2 h glucose concentrations during the oral glucose tolerance test), early-onset GDM (
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- 2023
43. Seroprevalence of polyomaviruses BK and JC in Finnish women and their spouses followed-up for three years
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Hanna K. Laine, Tim Waterboer, Kari Syrjänen, Seija Grenman, Karolina Louvanto, Stina Syrjänen, Tampere University, Clinical Medicine, and Department of Gynaecology and Obstetrics
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Multidisciplinary ,3123 Gynaecology and paediatrics ,3121 Internal medicine - Abstract
BK (BKPyV) and JC (JCPyV) polyomavirus infections are commonly subclinical and known infrequently to cause serious clinical diseases. Longitudinal follow-up studies regarding JCPyV and BKPyV serological outcomes are scanty. We analyzed JCPyV and BKPyV IgG-antibodies in 327 pregnant women and their 132 spouses, enrolled in the longitudinal Finnish Family HPV cohort at Turku University Hospital, Finland. Blood samples taken at baseline, and at 12-, 24-, and 36-month follow-up visits were analyzed for capsid protein VP1-antibodies using multiplex serology. Seroprevalence was constant for both BKPyV and JCPyV across the follow-up, varying between 95–99% and 59–68%, respectively, in women and between 96–97% and 66–72%, respectively, in their spouses. Seroconversion to BKPyV and JCPyV was detected in 15% and 18% of the women and in 13% and 19% of the men, respectively. Waning of BKPyV and JCPyV antibodies was infrequent, present in only 5% of the women (both viruses) and in 1.5% of the male spouses (only BKPyV). The number of lifetime sexual partners (p = 0.038) was lower among JCPyV seropositive men. To conclude, seropositivity to BKPyV and JCPyV is common among marital couples in Finland, with only slight differences between genders. In men, the sexual behavior might be associated with JCPyV seroprevalence.
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- 2023
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44. A synthesis of evidence for cancer-specific screening interventions : A Preventive Medicine Golden Jubilee Review
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Rintala, Suvi, Dahlstrom, Kristina R., Franco, Eduardo L., Louvanto, Karolina, Tampere University, Clinical Medicine, and Department of Gynaecology and Obstetrics
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3123 Gynaecology and paediatrics - Abstract
The goal of cancer screening guidelines is to inform health practitioners to practice evidence-based cancer prevention. Cancer screening aims to detect treatable precancerous lesions or early-stage disease to enable actions aimed at decreasing morbidity and mortality. Continuous assessment of the available evidence for or against screening interventions by various organizations often results in conflicting recommendations and create challenges for providers and policymakers. Here we have summarized the current cancer screening recommendations by five leading organizations in North America and Europe: the National Cancer Institute's Physician Data Query (PDQ), the U.S. Preventive Services Task Force (USPSTF), the Canadian Task Force on Preventive Health Care (CTFPHC), the Cochrane Database of Systematic Reviews (CDSR), and the UK National Screening Committee for the National Health Service (UK NSC). All organizations assess evidence based on strength, quality, and quantity, and recommendations are similar although with differences with respect to screening start and stop ages. Recommendations are consistent for colorectal cancer screening with fecal occult blood test or fecal immunochemical test, cervical cancer screening with Pap-test, HPV-test, or co-testing, and breast cancer screening with mammography. However, guidelines vary with respect to age to start and end screening and testing frequency. Tests that have proven to be inefficient or whose use is capable of causing harm are routinely recommended against. Continuous review of screening guidelines is necessary to evaluate the many promising screening tests currently under investigation. publishedVersion
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- 2023
45. The risk of developing type 2 diabetes after gestational diabetes : A registry study from Finland
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Roosa Perämäki, Mika Gissler, Meri-Maija Ollila, Janne Hukkanen, Marja Vääräsmäki, Jukka Uotila, Saara Metso, Heidi Hakkarainen, Reeta Rintamäki, Risto Kaaja, Heidi Immonen, Tampere University, Department of Gynaecology and Obstetrics, Clinical Medicine, and Department of Internal medicine
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Prediction of diabetes ,Epidemiology ,Materials Science (miscellaneous) ,Type 2 diabetes ,3121 Internal medicine ,Body mass index ,Gestational diabetes - Abstract
Aims: Women with a history of gestational diabetes (GDM) have an increased risk of developing type 2 diabetes (T2DM). We studied the risk for T2DM in women with and without GDM in relation to body mass index (BMI) and examined whether insulin treatment for GDM associates with the risk of developing T2DM. In addition, we investigated whether the risk of developing T2DM after GDM had changed in 15 years. Methods: We used data by linking four registers; Medical Birth Register, Hospital Discharge Register and Primary Care Register run by THL Finnish Institute for Health and Welfare, and Medical Reimbursement Statistics run by the Social Insurance Institution of Finland (Kela). Registry data were collected from 2005 to 2020. The follow-up started from woman's delivery in 2006-2020 and ended to the diagnosis of T2DM or December 2020. Cox proportional hazard modelling was used to estimate the effect of GDM exposure to T2DM. To assess whether the risk of developing T2DM after GDM had changed in 15 years, we compared the HR between years 2006-2008 and 2018-2020. Results: In total, 462 401 women were included in the study: 96 353 (21%) women had previous GDM. There were 5370 (1.2%) women who developed T2DM after childbirth during the follow-up. Among women with prior GDM, 3995 (4.1%) developed T2DM, while 1375 (0.4%) women without prior GDM developed T2DM during follow-up. The mean follow-up was 6.86 years (SD 4.21) for women with GDM and 9.07 years (SD 4.35) for women without GDM. The hazard ratio (HR) for developing T2DM after GDM was 18.49 (95% CI 17.39-19.67). The incidence of T2DM in women with a history of GDM began to rise almost steadily from the first year of follow-up. As BMI increased, T2DM incidence increased in both women with and without prior GDM but more in women with prior GDM. Insulin treatment had an independent association with increased risk of T2DM (HR 3.81, 95% CI 3.57-4.07). We did not observe any difference in HR between years 2006-2008 and 2018-2020. Conclusions: The relative risk for T2DM was 11-fold for women with previous GDM compared to women without previous GDM. A higher BMI and insulin treatment increased the risk of future diabetes. All measures to prevent the conversion of GDM to T2DM should be taken especially among women with overweight or obesity. publishedVersion
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- 2023
46. Factors associated with fear of childbirth in a subsequent pregnancy : a nationwide case–control analysis in Finland
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Matias Vaajala, Rasmus Liukkonen, Ilari Kuitunen, Ville Ponkilainen, Ville M. Mattila, Maiju Kekki, Tampere University, Clinical Medicine, Department of Musculoskeletal Diseases, and Department of Gynaecology and Obstetrics
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Reproductive Medicine ,3123 Gynaecology and paediatrics ,Obstetrics and Gynecology ,General Medicine ,3126 Surgery, anesthesiology, intensive care, radiology - Abstract
Background Fear of childbirth can develop due to the concerns or adverse maternal or foetal outcomes experienced in a previous pregnancy. The aim of this study was to examine the main risk factors associated with the development of fear of childbirth during subsequent pregnancies and deliveries. Methods In this case–control study, data from the National Medical Birth Register were used to evaluate the events in previous pregnancies that were potential risk factors for fear of childbirth in subsequent pregnancies. The first and second pregnancies of women registered during our study period (2004–2018) were included. The exposure variable was delivery mode, obstetric challenge or adverse neonatal outcomes during the first pregnancy. The outcome was the development of FOC during the second pregnancy. Adjusted odds ratios with 95% CIs were used for comparison. Results A total of 13 064 pregnancies were included in the case group and 195 351 in the control group. Previous emergency caesarean section was the strongest risk factor for the development of FOC in the second pregnancy (adjusted odds ratio 5.27, CIs 4.83–5.75). In addition, unplanned CS (adjusted odds ratio 3.93, CIs 3.77–4.10) and vacuum delivery (adjusted odds ratio 1.69, CIs 1.61–1.77) also increased the odds of fear of childbirth. Of the obstetric complications, third- or fourth-degree tear of the perineum was the strongest risk factor (adjusted odds ratio 2.99, CIs 2.69–3.31), followed by shoulder dystocia (adjusted odds ratio 2.82, CIs 2.16–3.62). Neonatal mortality also increased the odds for the development of FOC (adjusted odds ratio 2.17, CIs 1.77–2.64). Conclusion The main risk factors for the development of fear of childbirth in the second pregnancy were previous fear of childbirth, unplanned CS, vacuum delivery, perineal tear or shoulder dystocia. The results of this study can be used in a clinical setting to improve the prevention of fear of childbirth.
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- 2023
47. INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line
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INOVATYON study group, Colombo, N., Gadducci, A., Sehouli, J., Rulli, E., Mäenpää, J., Sessa, C., Montes, A., Ottevanger, N. B., Berger, R., Vergote, I., D'Incalci, M., Churruca Galaz, C., Chekerov, R., Nyvang, G. B., Riniker, S., Herbertson, R., Fossati, R., Barretina-Ginesta, M. P., Deryal, M., Mirza, M. R., Biagioli, E., Iglesias, M., Funari, G., Romeo, M., Tasca, G., Pardo, B., Tognon, G., Rubio-Pérez, M. J., DeCensi, A., De Giorgi, U., Zola, P., Benedetti Panici, P., Aglietta, M., Arcangeli, V., Zamagni, C., Bologna, A., Westermann, A., Heinzelmann-Schwarz, V., Tsibulak, I., Wimberger, P., Poveda, A., Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, Colombo, N, Gadducci, A, Sehouli, J, Rulli, E, Mäenpää, J, Sessa, C, Montes, A, Ottevanger, N, Berger, R, Vergote, I, D'Incalci, M, Churruca Galaz, C, Chekerov, R, Nyvang, G, Riniker, S, Herbertson, R, Fossati, R, Barretina-Ginesta, M, Deryal, M, Mirza, M, Biagioli, E, Iglesias, M, Funari, G, Romeo, M, Tasca, G, Pardo, B, Tognon, G, Rubio-Pérez, M, Decensi, A, De Giorgi, U, Zola, P, Benedetti Panici, P, Aglietta, M, Arcangeli, V, Zamagni, C, Bologna, A, Westermann, A, Heinzelmann-Schwarz, V, Tsibulak, I, Wimberger, P, and Poveda, A
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Cancer Research ,All institutes and research themes of the Radboud University Medical Center ,Oncology ,3123 Gynaecology and paediatrics ,3122 Cancers ,platinum-free interval ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] - Abstract
Background This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). Methods Patients with OC (up to two previous platinum-based lines), with a TFIp of 6–12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). Results The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94–1.35; p = 0.197). Grade 3–5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). Conclusions This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6–12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. Clinical trial registration ClinicalTrials.gov, number NCT01379989.
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- 2023
48. Previous induced abortion or miscarriage is associated with increased odds for gestational diabetes : a nationwide register-based cohort study in Finland
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Matias Vaajala, Rasmus Liukkonen, Ville Ponkilainen, Maiju Kekki, Ville M. Mattila, Ilari Kuitunen, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, and Department of Musculoskeletal Diseases
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Endocrinology ,3123 Gynaecology and paediatrics ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,General Medicine ,3121 Internal medicine - Abstract
Aims The aim of this study was to investigate the association between previous induced abortion or miscarriage and the development of gestational diabetes mellitus (GDM) using high-quality register data. Methods In this retrospective nationwide register-based cohort study, data from the national medical birth register (MBR) were used to evaluate the association between a history of miscarriage or induced abortion and GDM. We included all first pregnancies ending in delivery in which the oral glucose tolerance test was performed between 2004 and 2018. A logistic regression model was used to assess the development of GDM in the first pregnancy ending in delivery. Adjusted odds ratios (aOR) with 95% confidence intervals (Cis) were compared between groups. Results In total, 15,873 nulliparous women with a history of induced abortions, 22,337 with a history of miscarriages and 3594 with a history of both were found. The reference group consisted of 138,869 women without a history of induced abortions or miscarriages. Women with a history of induced abortions (24.7%, aOR 1.15 [CI 1.11–1.20]), a history of miscarriages (24.8%, aOR 1.14 [CI 1.10–1.18]) and a history of both (27.7% aOR 1.18 [CI 1.09–1.28]) had higher odds for the development of GDM when compared to the reference group (20.8%). The odds for GDM increased along with the increasing number of previous induced abortions and miscarriages. Conclusion Women with a history of induced abortions or miscarriages had higher odds for GDM in their first pregnancy leading to birth. Knowledge of this association will be helpful in the prevention and screening of GDM.
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- 2023
49. Traumatic brain injury during pregnancy is associated with increased rate of cesarean section : a nationwide multi-register study in Finland
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Matias Vaajala, Jeremias Tarkiainen, Rasmus Liukkonen, Ilari Kuitunen, Ville Ponkilainen, Maiju Kekki, Ville M. Mattila, Tampere University, Clinical Medicine, Department of Neurosciences and Rehabilitation, Department of Gynaecology and Obstetrics, and Department of Musculoskeletal Diseases
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Pediatrics, Perinatology and Child Health ,Obstetrics and Gynecology ,3126 Surgery, anesthesiology, intensive care, radiology ,3121 Internal medicine - Abstract
Objective: The literature on the incidence of traumatic brain injury (TBI) during pregnancy is lacking. Furthermore, only studies with small sample size have analyzed the impact of TBI during pregnancy to maternal and fetal outcomes. Thus, we aim to report the incidence of TBIs during pregnancy and study the pregnancy outcomes using nationwide high-quality registers. Methods: This nationwide retrospective register-based matched cohort study utilized two national registers. All fertile-aged (15–49 years) women with a TBI hospitalization period during pregnancy were retrieved the Care Register for Health Care. Data were then linked with the data from the National Medical Birth Register (MBR). Propensity score matching was conducted according to maternal age during pregnancy, previous cesarean section (CS), maternal smoking status, maternal body mass index, and maternal gestational diabetes. The matching was conducted using the nearest neighbor methods with a caliber width if 0.15, and with a ratio 1:3 (patients/references). Adverse maternal and fetal outcomes were compared between patient group and reference group using Chi-squared tests. Results: A total of 392 women having a TBI during pregnancy were found. The control group consisted of 722,497 women without TBI during pregnancy. Of the TBIs occurring during pregnancy, the most common types of TBIs were concussion (S06.0) (n = 359, 91.6%), diffuse traumatic brain injury (S06.2) (n = 11, 2.8%), traumatic subdural hemorrhage (n = 7, 1.8%), and unspecified intracranial injury S06.9 (n = 6, 1.5%). The incidence rates of pregnancies with a TBI have remained similar during pregnancy in Finland, peaking at 0.8 per 1000 pregnancies in 2016. The Chi-squared test showed higher rate for CS among women with TBI than for their matched references (21.4% vs. 15.5%, p = .008). Especially, women with TBI during 3rd trimester had higher rate for CS (29.0 vs. 15.0%, p = .016). Conclusions: The main findings of this study were that the incidence rates for TBI during pregnancy have remained similar during our study period (2004–2018). TBI during pregnancy, even a mild one, is associated with an increased rate for CS. Especially, TBI during the 3rd trimester was associated with high rate for CS, but the etiology behind this remains unknown. In addition, we found no evidence of difference in fetal outcomes, such as preterm birth, low birth weight, or need for intensive care unit. Future studies should focus on the indications for elective CS, and reasons for unplanned CS among women with TBI during pregnancy, as these could possibly provide important information on the effects of TBI on the course of childbirth. publishedVersion
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- 2023
50. FinnGen provides genetic insights from a well-phenotyped isolated population
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FinnGen, Kurki, Mitja I., Karjalainen, Juha, Palta, Priit, Sipilä, Timo P., Kristiansson, Kati, Donner, Kati M., Reeve, Mary P., Laivuori, Hannele, Aavikko, Mervi, Kaunisto, Mari A., Loukola, Anu, Lahtela, Elisa, Mattsson, Hannele, Laiho, Päivi, Della Briotta Parolo, Pietro, Lehisto, Arto A., Kanai, Masahiro, Mars, Nina, Rämö, Joel, Kiiskinen, Tuomo, Heyne, Henrike O., Veerapen, Kumar, Rüeger, Sina, Lemmelä, Susanna, Zhou, Wei, Ruotsalainen, Sanni, Pärn, Kalle, Hiekkalinna, Tero, Koskelainen, Sami, Paajanen, Teemu, Llorens, Vincent, Gracia-Tabuenca, Javier, Siirtola, Harri, Reis, Kadri, Elnahas, Abdelrahman G., Hiltunen, Mikko, Aalto-Setälä, Katriina, Bizaki-Vallaskangas, Argyro, Kähönen, Mika, Kosma, Veli Matti, Kurra, Venla, Mäkelä, Johanna, Mannermaa, Arto, Niemi, Mari E.K., Niemi, Marianna, Partanen, Jukka, Salminen, Aino, Schleutker, Johanna, Siltanen, Sanna, Toppila-Salmi, Sanna, Laitinen, Tarja, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, Computing Sciences, BioMediTech, Department of Clinical Physiology and Nuclear Medicine, Tays Research Services, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, Genomics of Neurological and Neuropsychiatric Disorders, Complex Disease Genetics, HUS Gynecology and Obstetrics, Department of Medical and Clinical Genetics, Medicum, HUSLAB, Bio Bank, HUS Helsinki and Uusimaa Hospital District, Faculty Common Matters (Faculty of Medicine), Centre of Excellence in Complex Disease Genetics, Research Programs Unit, and Aarno Palotie / Principal Investigator
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Multidisciplinary ,1184 Genetics, developmental biology, physiology ,3111 Biomedicine ,113 Computer and information sciences - Abstract
Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency 1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P –11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of
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- 2023
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