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236 results on '"Blok R."'

5. A statistical method for rapid determination of endurance limit based on a thermographic method

Author

Shahmirzaloo, A., Leonetti, D., Moonen, F., and Blok, R.

Abstract

The staircase method is traditionally employed to estimate the endurance limit, requiring to test of a relatively large number of specimens at several load levels to obtain a reliable dataset, making this procedure time-consuming and expensive. A rapid method, based on thermography is alternatively employed to estimate the endurance limit, intended as the fatigue strength at 1 or 2 million cycles. The procedure results in a relation between the stabilized temperature as a function of the maximum applied stress or amplitude and involves manual processing of the data to determine the endurance limit. The present paper presents a statistical model based on the Maximum Likelihood Method to estimate the endurance limit by the aforementioned thermographic method, which is automatic, and does not involve manual manipulation of the dataset., Paper 41

Published
2023
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6. UV-WATER WEATHERING DEGRADATION OF THE FLAX FIBER REINFORCED POLYMER COMPOSITES

Author

Xu, B., Hurk, B.V.D., Shahmirzaloo, A., Blok, R., and Teuffel, P.

Abstract

This study investigates the effect of weathering aging on the flax fiber reinforced polymer composites for civil engineering applications. The specimens were exposed to an accelerated weathering environment simulating the outdoor environment for up to 1500 hours. Tensile and three-point bending tests were performed to evaluate the mechanical degradation. Microscope observation was employed to check the change of fiber and matrix. All samples experienced reductions in both tensile and flexural properties with increased exposure time. However, the thickness of sample are found to affect the weathering effect, which is the increased thickness can delay the degradation of mechanical properties., Paper 33

Published
2023
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7. Comparison of proactive and conventional treatment of anastomotic leakage in rectal cancer surgery:a multicentre retrospective cohort series

Author

Talboom, K., Greijdanus, N. G., Brinkman, N., Blok, R. D., Roodbeen, S. X., Ponsioen, C. Y., Tanis, P. J., Bemelman, W. A., Cunningham, C., de Lacy, F. B., Hompes, Roel, Talboom, K., Greijdanus, N. G., Brinkman, N., Blok, R. D., Roodbeen, S. X., Ponsioen, C. Y., Tanis, P. J., Bemelman, W. A., Cunningham, C., de Lacy, F. B., and Hompes, Roel

Abstract

Purpose: Comparative studies on efficacy of treatment strategies for anastomotic leakage (AL) after low anterior resection (LAR) are almost non-existent. This study aimed to compare different proactive and conservative treatment approaches for AL after LAR. Methods: This retrospective cohort study included all patients with AL after LAR in three university hospitals. Different treatment approaches were compared, including a pairwise comparison of conventional treatment and endoscopic vacuum-assisted surgical closure (EVASC). Primary outcomes were healed and functional anastomosis rates at end of follow-up. Results: Overall, 103 patients were included, of which 59 underwent conventional treatment and 23 EVASC. Median number of reinterventions was 1 after conventional treatment, compared to 7 after EVASC (p < 0.01). Median follow-up was 39 and 25 months, respectively. Healed anastomosis rate was 61% after conventional treatment, compared to 78% after EVASC (p = 0.139). Functional anastomosis rate was higher after EVASC, compared to conventional treatment (78% vs. 54%, p = 0.045). Early initiation of EVASC in the first week after primary surgery resulted in better functional anastomosis rate compared to later initiation (100% vs. 55%, p = 0.008). Conclusion: Proactive treatment of AL consisting of EVASC resulted in improved healed and functional anastomosis rates for AL after LAR for rectal cancer, compared to conventional treatment. If EVASC was initiated within the first week after index surgery, a 100% functional anastomosis rate was achievable.

Published
2023

8. An updated evaluation of the implementation of the sigmoid take-off landmark 1 year after the official introduction in the Netherlands.

Author

Hazen, S. J. A., Sluckin, T. C., Horsthuis, K., Lambregts, D. M. J., Beets-Tan, R. G. H., Tanis, P. J., Kusters, M., Ankersmit, M., Bahadoer, R. R., Bakker, I. S., Bangert, F., Barendse, R. M., Barsom, E., Bemelman, W. A., van den Berg, K., de Bie, S. H., Blok, R. D., Boer, F. C. den, Boerma, E.-J. G., and Boogerd, L. S. F.

Subjects
RECTAL cancer, PHYSICIANS' assistants, ONLINE education, DOCTORAL students
Abstract

Purpose: The definition of rectal cancer based on the sigmoid take-off (STO) was incorporated into the Dutch guideline in 2019, and became mandatory in the national audit from December 2020. This study aimed to evaluate the use of the STO in clinical practice and the added value of online training, stratified for the period before (group A, historical cohort) and after (group B, current cohort) incorporation into the national audit. Methods: Participants, including radiologists, surgeons, surgical and radiological residents, interns, PhD students, and physician assistants, were asked to complete an online training program, consisting of questionnaires, 20 MRI cases, and a training document. Outcomes were agreement with the expert reference, inter-rater variability, and accuracy before and after the training. Results: Group A consisted of 86 participants and group B consisted of 114 participants. Familiarity with the STO was higher in group B (76% vs 88%, p = 0.027). Its use in multidisciplinary meetings was not significantly higher (50% vs 67%, p = 0.237). Agreement with the expert reference was similar for both groups before (79% vs 80%, p = 0.423) and after the training (87% vs 87%, p = 0.848). Training resulted in significant improvement for both groups in classifying tumors located around the STO (group A, 69–79%; group B, 67–79%, p < 0.001). Conclusions: The results of this study show that after the inclusion of the STO in the mandatory Dutch national audit, the STO was consequently used in only 67% of the represented hospitals. Online training has the potential to improve implementation and unambiguous assessment. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Design of Da Vinci's bridge in ice

Author

Pronk, A, primary, Blok, R, additional, van Brunschot, M, additional, van Lier, A, additional, van de Mortel, F, additional, Williams, K, additional, Arntz, M, additional, Hermens, L, additional, Koekkoek, R, additional, and van den Nieuwenhof, T, additional

Published
2016
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13. From bacteria to zooplankton: An integrative approach revealing regional spatial patterns during the spring phytoplankton bloom in the Southern Bight of the North Sea

Author

Aubert, A., Beauchard, O., de Blok, R., Artigas, F.L., Sabbe, K., Vyverman, W., Amadei Martínez, L., Deneudt, K., Louchart, A., Mortelmans, J., Rijkeboer, M., Debusschere, E., Aubert, A., Beauchard, O., de Blok, R., Artigas, F.L., Sabbe, K., Vyverman, W., Amadei Martínez, L., Deneudt, K., Louchart, A., Mortelmans, J., Rijkeboer, M., and Debusschere, E.

Abstract

Plankton comprises a large diversity of organisms, from pico- to macro-sized classes, and spans several trophic levels, whose population dynamics are characterized by a high spatio-temporal variability. Studies integrating multiple plankton groups, in respect to size classes and trophic levels, are still rare, which hampers a more thorough description and elucidation of the full complexity of plankton dynamics. Here, we present a study on the spatial variability of five in-situ monitored plankton components, ranging from bacteria to meso-zooplankton, and using a complementary set of molecular, chemical and imaging tools, with samples obtained during the phytoplankton spring bloom in the hydrodynamically complex Southern Bight of the North Sea. We hypothesized that while generally recognized spatial gradients in e.g. salinity, turbidity and nutrients will have a strong impact on plankton spatial distribution patterns, interactions within the plankton compartment but also lag effects related to preceding bloom-related events will further modulate spatial structuring of the plankton. Our study indeed revealed an overriding imprint of regional factors on plankton distribution patterns. The dominant spatial pattern mainly reflected regional differences in dissolved inorganic nutrients and particulate matter concentrations related to differences in phytoplankton bloom timing between the two main regions of freshwater influence, the Thames and the Scheldt-Rhine-Meuse. A second major pattern corresponded to the expected nearshore-offshore gradient, with increasing influence of low turbidity and low nutrient Atlantic waters in the offshore stations. Environmental forcing on specific plankton groups and inter-plankton relationships also appeared to drive plankton distribution. Although the marine plankton comprises heterogeneous functional groups, this study shows that multiple planktonic ecosystem components can be parts of common spatial gradients and that often neglected s

Published
2022

19. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Author

Fachal, L., Aschard, H., Beesley, J., Barnes, D.R., Allen, J., Kar, S., Pooley, K.A., Dennis, J., Michailidou, K., Turman, C., Soucy, P., Lemaçon, A., Lush, M., Tyrer, J.P., Ghoussaini, M., Marjaneh, M.M., Jiang, X., Agata, S., Aittomäki, K., Alonso, M.R., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arason, A., Arndt, V., Aronson, K.J., Arun, B.K., Auber, B., Auer, P.L., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Białkowska, K., Blanco, A.M., Blomqvist, C., Blot, W., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Bonanni, B., Borg, A., Bosse, K., Brauch, H., Brenner, H., Briceno, I., Brock, I.W., Brooks-Wilson, A., Brüning, T., Burwinkel, B., Buys, S.S., Cai, Q., Caldés, T., Caligo, M.A., Camp, N.J., Campbell, I., Canzian, F., Carroll, J.S., Carter, B.D., Castelao, J.E., Chiquette, J., Christiansen, H., Chung, W.K., Claes, K.B.M., Clarke, C.L., Mari, V., Berthet, P., Castera, L., Vaur, D., Lallaoui, H., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Lasset, C., Révillion, F., Vennin, P., Muller, D., Gomes, D.M., Ingster, O., Coupier, I., Pujol, P., Collonge-Rame, M.-A., Mortemousque, I., Bera, O., Rose, M., Baurand, A., Bertolone, G., Faivre, L., Dreyfus, H., Leroux, D., Venat-Bouvet, L., Bézieau, S., Delnatte, C., Chiesa, J., Gilbert-Dussardier, B., Gesta, P., Prieur, F.P., Bronner, M., Sokolowska, J., Coulet, F., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Fert-Ferrer, S., Stoppa-Lyonnet, D., Jiao, Y., Lesueur, F.L., Mebirouk, N., Barouk-Simonet, E., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Toulas, C., Reimineras, A., Sobol, H., Paillerets, B.B.-D., Cabaret, O., Caron, O., Guillaud-Bataille, M., Rouleau, E., Belotti, M., Buecher, B., Caputo, S., Colas, C., Pauw, A.D., Fourme, E., Gauthier-Villars, M., Golmard, L., Moncoutier, V., Saule, C., Donaldson, A., Murray, A., Brady, A., Brewer, C., Pottinger, C., Miller, C., Gallagher, D., Gregory, H., Cook, J., Eason, J., Adlard, J., Barwell, J., Ong, K.-R., Snape, K., Walker, L., Izatt, L., Side, L., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Ahmed, M., Morrison, P.J., Brennan, P., Eeles, R., Davidson, R., Collée, M., Cornelissen, S., Couch, F.J., Cox, A., Cross, S.S., Cybulski, C., Czene, K., Daly, M.B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y.C., Dite, G.S., Domchek, S.M., Dörk, T., dos-Santos-Silva, I., Droit, A., Dubois, S., Dumont, M., Duran, M., Durcan, L., Dwek, M., Eccles, D.M., Engel, C., Eriksson, M., Evans, D.G., Fasching, P.A., Fletcher, O., Floris, G., Flyger, H., Foretova, L., Foulkes, W.D., Friedman, E., Fritschi, L., Frost, D., Gabrielson, M., Gago-Dominguez, M., Gambino, G., Ganz, P.A., Gapstur, S.M., Garber, J., García-Sáenz, J.A., Gaudet, M.M., Georgoulias, V., Giles, G., Glendon, G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., González-Neira, A., Tibiletti, M.G., Greene, M.H., Grip, M., Gronwald, J., Grundy, A., Guénel, P., Hahnen, E., Haiman, C.A., Håkansson, N., Hall, P., Hamann, U., Harrington, P.A., Hartikainen, J.M., Hartman, M., He, W., Healey, C.S., Heemskerk-Gerritsen, B.A.M., Heyworth, J., Hillemanns, P., Hogervorst, F.B.L., Hollestelle, A., Hooning, M., Hopper, J., Howell, A., Huang, G., Hulick, P.J., Imyanitov, E.N., Sexton, A., Christian, A., Trainer, A., Spigelman, A., Fellows, A., Shelling, A., Fazio, A.D., Blackburn, A., Crook, A., Meiser, B., Patterson, B., Clarke, C., Saunders, C., Hunt, C., Scott, C., Amor, D., Marsh, D., Edkins, E., Salisbury, E., Haan, E., Neidermayr, E., Macrea, F., Farshid, G., Lindeman, G., Chenevix-Trench, G., Mann, G., Gill, G., Thorne, H., Hickie, I., Winship, I., Flanagan, J., Kollias, J., Visvader, J., Stone, J., Taylor, J., Burke, J., Saunus, J., Forbes, J., Kirk, J., French, J., Tucker, K., Wu, K., Phillips, K., Lipton, L., Andrews, L., Lobb, L., Kentwell, M., Spurdle, M., Cummings, M., Gleeson, M., Harris, M., Jenkins, M., Young, M.A., Delatycki, M., Wallis, M., Burgess, M., Price, M., Brown, M., Southey, M., Bogwitz, M., Field, M., Friedlander, M., Gattas, M., Saleh, M., Hayward, N., Pachter, N., Cohen, P., Duijf, P., James, P., Simpson, P., Fong, P., Butow, P., Williams, R., Kefford, R., Scott, R., Milne, R.L., Balleine, R., Dawson, S.–J., Lok, S., O’Connell, S., Greening, S., Nightingale, S., Edwards, S., Fox, S., McLachlan, S.-A., Lakhani, S., Antill, Y., Aalfs, C., Meijers-Heijboer, H., van Engelen, K., Gille, H., Boere, I., van Deurzen, C., Obdeijn, I.-M., van den Ouweland, A., Seynaeve, C., Siesling, S., Verloop, J., van Asperen, C.J., van Cronenburg, T., Blok, R., de Boer, M., Garcia, E.G., Adank, M., Hogervorst, F., Jenner, D., van Leeuwen, F., Rookus, M., Russell, N., Schmidt, M., van den Belt-Dusebout, S., Kets, C., Mensenkamp, A., de Bock, T., van der Hout, A., Mourits, M., Oosterwijk, J., Ausems, M., Koudijs, M., Baxter, R., Yip, D., Carpenter, J., Davis, A., Pathmanathan, N., Graham, D., Sachchithananthan, M., Isaacs, C., Iwasaki, M., Jager, A., Jakimovska, M., Jakubowska, A., James, P.A., Janavicius, R., Jankowitz, R.C., John, E.M., Johnson, N., Jones, M.E., Jukkola-Vuorinen, A., Jung, A., Kaaks, R., Kang, D., Kapoor, P.M., Karlan, B.Y., Keeman, R., Kerin, M.J., Khusnutdinova, E., Kiiski, J.I., Kitahara, C.M., Ko, Y.-D., Konstantopoulou, I., Kosma, V.-M., Koutros, S., Kubelka-Sabit, K., Kwong, A., Kyriacou, K., Laitman, Y., Lambrechts, D., Lee, E., Leslie, G., Lester, J., Lesueur, F., Lindblom, A., Lo, W.-Y., Long, J., Lophatananon, A., Loud, J.T., Lubiński, J., MacInnis, R.J., Maishman, T., Makalic, E., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, M.E., Matsuo, K., Maurer, T., Mavroudis, D., Mayes, R., McGuffog, L., McLean, C., Meindl, A., Miller, A., Miller, N., Montagna, M., Moreno, F., Muir, K., Mulligan, A.M., Muñoz-Garzon, V.M., Muranen, T.A., Narod, S.A., Nassir, R., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Neven, P., Nielsen, F.C., Nikitina-Zake, L., Norman, A., Offit, K., Olah, E., Olopade, O.I., Olsson, H., Orr, N., Osorio, A., Pankratz, V.S., Papp, J., Park, S.K., Park-Simon, T.-W., Parsons, M.T., Paul, J., Pedersen, I.S., Peissel, B., Peshkin, B., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Prajzendanc, K., Prentice, R., Presneau, N., Prokofyeva, D., Pujana, M.A., Pylkäs, K., Radice, P., Ramus, S.J., Rantala, J., Rau-Murthy, R., Rennert, G., Risch, H.A., Robson, M., Romero, A., Rossing, M., Saloustros, E., Sánchez-Herrero, E., Sandler, D.P., Santamariña, M., Sawyer, E.J., Scheuner, M.T., Schmidt, D.F., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Schöttker, B., Schürmann, P., Scott, R.J., Senter, L., Seynaeve, C.M., Shah, M., Sharma, P., Shen, C.-Y., Shu, X.-O., Singer, C.F., Slavin, T.P., Smichkoska, S., Southey, M.C., Spinelli, J.J., Spurdle, A.B., Sutter, C., Swerdlow, A.J., Tamimi, R.M., Tan, Y.Y., Tapper, W.J., Taylor, J.A., Teixeira, M.R., Tengström, M., Teo, S.H., Terry, M.B., Teulé, A., Thomassen, M., Thull, D.L., Toland, A.E., Tollenaar, R.A.E.M., Tomlinson, I., Torres, D., Torres-Mejía, G., Troester, M.A., Truong, T., Tung, N., Tzardi, M., Ulmer, H.-U., Vachon, C.M., van der Kolk, L.E., van Rensburg, E.J., Vega, A., Viel, A., Vijai, J., Vogel, M.J., Wang, Q., Wappenschmidt, B., Weinberg, C.R., Weitzel, J.N., Wendt, C., Wildiers, H., Winqvist, R., Wolk, A., Wu, A.H., Yannoukakos, D., Zhang, Y., Zheng, W., Hunter, D., Pharoah, P.D.P., Chang-Claude, J., García-Closas, M., Schmidt, M.K., Kristensen, V.N., French, J.D., Edwards, S.L., Antoniou, A.C., Simard, J., Easton, D.F., Kraft, P., Dunning, A.M., Collaborators, GEMO Study, Collaborators, EMBRACE, Investigators, KConFab, Investigators, HEBON, Investigators, ABCTB, Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel R, Duijf, Pascal, Dunning, Alison M, GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), European Commission, Government of Canada, Canadian Institutes of Health Research, National Institutes of Health (US), Cancer Research UK, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, University of Cambridge [UK] (CAM), NSCAD, University of Cyprus [Nicosia], Harvard T.H. Chan School of Public Health, This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation), the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492), and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note., We thank all of the individuals who took part in these studies, as well as all of the researchers, clinicians, technicians and administrative staff who enabled this work to be carried out, European Project: 656144,H2020,H2020-MSCA-IF-2014,RADIOGENFF(2016), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), Clinical Genetics, Medical Oncology, Pathology, Radiology & Nuclear Medicine, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia] (UCY), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), Targeted Gynaecologic Oncology (TARGON), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Aschard, Hugues [0000-0002-7554-6783], Barnes, Daniel R [0000-0002-3781-7570], Dennis, Joe [0000-0003-4591-1214], Michailidou, Kyriaki [0000-0001-7065-1237], Lemaçon, Audrey [0000-0002-1817-7029], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Bojesen, Stig E [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Campbell, Ian [0000-0002-7773-4155], Carroll, Jason S [0000-0003-3643-0080], Claes, Kathleen BM [0000-0003-0841-7372], Collée, J Margriet [0000-0002-9272-9346], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dwek, Miriam [0000-0001-7184-2932], Fletcher, Olivia [0000-0001-9387-7116], Floris, Giuseppe [0000-0003-2391-5425], Foulkes, William D [0000-0001-7427-4651], García-Sáenz, José A [0000-0001-6880-0301], Greene, Mark H [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Heemskerk-Gerritsen, Bernadette AM [0000-0002-9724-6693], Hollestelle, Antoinette [0000-0003-1166-1966], Hulick, Peter J [0000-0001-8397-4078], Jakimovska, Milena [0000-0002-1506-0669], Jakubowska, Anna [0000-0002-5650-0501], James, Paul A [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Konstantopoulou, Irene [0000-0002-0470-0309], Leslie, Goska [0000-0001-5756-6222], Lesueur, Fabienne [0000-0001-7404-4549], Matsuo, Keitaro [0000-0003-1761-6314], McLean, Catriona [0000-0002-0302-5727], Miller, Austin [0000-0001-9739-8462], Muir, Kenneth [0000-0001-6429-988X], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Olopade, Olufunmilayo I [0000-0002-9936-1599], Orr, Nick [0000-0003-2866-942X], Pankratz, V Shane [0000-0002-3742-040X], Parsons, Michael T [0000-0003-3242-8477], Paul, James [0000-0001-7367-5816], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Pylkäs, Katri [0000-0002-2449-0521], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Robson, Mark [0000-0002-3109-1692], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Scott, Rodney J [0000-0001-7724-3404], Spurdle, Amanda B [0000-0003-1337-7897], Stone, Jennifer [0000-0001-5077-0124], Sutter, Christian [0000-0003-4051-5888], Tan, Yen Yen [0000-0003-1063-5352], Teixeira, Manuel R [0000-0002-4896-5982], Toland, Amanda E [0000-0002-0271-1792], Tomlinson, Ian [0000-0003-3037-1470], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Wolk, Alicja [0000-0001-7387-6845], Yannoukakos, Drakoulis [0000-0001-7509-3510], Pharoah, Paul DP [0000-0001-8494-732X], Schmidt, Marjanka K [0000-0002-2228-429X], Milne, Roger L [0000-0001-5764-7268], Edwards, Stacey L [0000-0001-7428-4139], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Kraft, Peter [0000-0002-4472-8103], Dunning, Alison M [0000-0001-6651-7166], Apollo - University of Cambridge Repository, Academic Medical Center, ARD - Amsterdam Reproduction and Development, Human genetics, CCA - Cancer biology and immunology, Molecular cell biology and Immunology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, University of Helsinki, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Doctoral Programme in Clinical Research, Staff Services, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, and Department of Obstetrics and Gynecology

Subjects
CHROMATIN, Linkage disequilibrium, Genome-wide association study, Regulatory Sequences, Nucleic Acid, Genome-wide association studies, Linkage Disequilibrium, Basic medicine, 0302 clinical medicine, Breast cancer, MESH: Risk Factors, Risk Factors, COMPREHENSIVE MOLECULAR PORTRAITS, 11 Medical and Health Sciences, HEBON Investigators, Genetics & Heredity, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], PROTEIN FUNCTION, Tumor, breast tumor, MESH: Polymorphism, Single Nucleotide, 1184 Genetics, developmental biology, physiology, MESH: Genetic Predisposition to Disease, apoptosis, Chromosome Mapping, Single Nucleotide, 3. Good health, MESH: Linkage Disequilibrium, Female, MESH: Biomarkers, Tumor, Biomarkers, Tumor/genetics, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Life Sciences & Biomedicine, SUSCEPTIBILITY LOCI, MESH: Bayes Theorem, Quantitative Trait Loci, ABCTB Investigators, INTEGRATIVE ANALYSIS, Breast Neoplasms, Computational biology, Biology, Quantitative trait locus, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, Article, ENHANCER, GEMO Study Collaborators, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, REVEALS, Genetics, Biomarkers, Tumor, MESH: Regulatory Sequences, Nucleic Acid, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, FUNCTIONAL VARIANTS, EMBRACE Collaborators, Gene, 030304 developmental biology, Genetic association, Bayes Theorem, Genome-Wide Association Study, MESH: Humans, Science & Technology, Nucleic Acid, gene mapping, 06 Biological Sciences, MESH: Quantitative Trait Loci, DNA binding site, ESTROGEN-RECEPTOR, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Clinical medicine, Expression quantitative trait loci, MESH: Genome-Wide Association Study, Human genome, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, KConFab Investigators, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Chromosome Mapping, Chromosome Mapping/methods, Regulatory Sequences, MESH: Female, Biomarkers, 030217 neurology & neurosurgery, MESH: Breast Neoplasms, Developmental Biology
Abstract

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes., This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation); the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE; part of the GAME-ON initiative).

Published
2020
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21. Science and decisionmaking

Author

Rykiel, E.J., primary, Berkson, J., additional, Brown, V.A., additional, Krewitt, W., additional, Peters, I., additional, Schwartz, M., additional, Shogren, J., additional, Van der Molen, D., additional, Blok, R., additional, Borsuk, M., additional, Bruins, R., additional, Cover, K., additional, Dale, V., additional, Dew, J., additional, Etnier, C., additional, Fanning, L., additional, Felix, F., additional, Nordin Hasan, M., additional, Hong, H., additional, King, A.W., additional, Krauchi, N., additional, Lubinsky, K., additional, Olson, J., additional, Onigkeit, J., additional, Patterson, G., additional, Rajan, K.S., additional, Reichert, P., additional, Sharma, K., additional, Smith, V., additional, Sonnenschein, M., additional, St-Louis, R., additional, Stuart, D., additional, Supalla, R., additional, and van Latesteijn, H., additional

Published
2002
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23. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Author

Ramus S.J., Carroll J.S., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Scott C., Scott R.J., Senter L., Shah M., Sharma P., Shen C.-Y., Shu X.-O., Singer C.F., Slavin T.P., Smichkoska S., Spinelli J.J., Spurdle A.B., Sutter C., Swerdlow A.J., Tamimi R.M., Tan Y.Y., Tapper W.J., Taylor J., Teixeira M.R., Tengstrom M., Teo S.H., Terry M.B., Teule A., Thomassen M., Thull D.L., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Torres-Mejia G., Troester M.A., Truong T., Tung N., Tzardi M., Ulmer H.-U., Vachon C.M., van der Kolk L.E., van Rensburg E.J., Vega A., Viel A., Vijai J., Vogel M.J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wildiers H., Winqvist R., Wolk A., Wu A.H., Yannoukakos D., Zhang Y., Zheng W., Hunter D., Pharoah P.D.P., Chang-Claude J., Garcia-Closas M., Schmidt M.K., Kristensen V.N., French J.D., Antoniou A.C., Chenevix-Trench G., Simard J., Easton D.F., Kraft P., Allen J., Harris M., Fachal L., Aschard H., Beesley J., Barnes D.R., Kar S., Pooley K.A., Dennis J., Michailidou K., Turman C., Soucy P., Lemacon A., Lush M., Tyrer J.P., Ghoussaini M., Marjaneh M.M., Jiang X., Agata S., Aittomaki K., Alonso M.R., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arason A., Arndt V., Aronson K.J., Arun B.K., Auber B., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Beeghly-Fadiel A., Benitez J., Bermisheva M., Bialkowska K., Blanco A.M., Blomqvist C., Blot W., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Bosse K., Brauch H., Brenner H., Briceno I., Brock I.W., Brooks-Wilson A., Bruning T., Burwinkel B., Buys S.S., Cai Q., Caldes T., Caligo M.A., Camp N.J., Campbell I., Carter B.D., Castelao J.E., Chiquette J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Mari V., Berthet P., Castera L., Vaur D., Lallaoui H., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Revillion F., Vennin P., Muller D., Gomes D.M., Ingster O., Coupier I., Pujol P., Collonge-Rame M.-A., Mortemousque I., Bera O., Rose M., Baurand A., Bertolone G., Faivre L., Dreyfus H., Leroux D., Venat-Bouvet L., Bezieau S., Delnatte C., Chiesa J., Gilbert-Dussardier B., Gesta P., Prieur F.P., Bronner M., Sokolowska J., Coulet F., Boutry-Kryza N., Calender A., Giraud S., Leone M., Fert-Ferrer S., Stoppa-Lyonnet D., Jiao Y., Lesueur F.L., Mebirouk N., Barouk-Simonet E., Bubien V., Longy M., Sevenet N., Gladieff L., Toulas C., Reimineras A., Sobol H., Paillerets B.B.-D., Cabaret O., Caron O., Guillaud-Bataille M., Rouleau E., Belotti M., Buecher B., Caputo S., Colas C., Pauw A.D., Fourme E., Gauthier-Villars M., Golmard L., Moncoutier V., Saule C., Donaldson A., Murray A., Brady A., Brewer C., Pottinger C., Miller C., Gallagher D., Gregory H., Cook J., Eason J., Adlard J., Barwell J., Ong K.-R., Snape K., Walker L., Izatt L., Side L., Tischkowitz M., Rogers M.T., Porteous M.E., Ahmed M., Morrison P.J., Brennan P., Eeles R., Davidson R., Collee J.M., Cornelissen S., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Domchek S.M., Dork T., dos-Santos-Silva I., Droit A., Dubois S., Dumont M., Duran M., Durcan L., Dwek M., Eccles D.M., Engel C., Eriksson M., Evans D.G., Fasching P.A., Fletcher O., Floris G., Flyger H., Foretova L., Foulkes W.D., Friedman E., Fritschi L., Frost D., Gabrielson M., Gago-Dominguez M., Gambino G., Ganz P.A., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Georgoulias V., Giles G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Tibiletti M.G., Greene M.H., Grip M., Gronwald J., Grundy A., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hartikainen J.M., Hartman M., He W., Healey C.S., Heemskerk-Gerritsen B.A.M., Heyworth J., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Hooning M., Hopper J., Howell A., Huang G., Hulick P.J., Imyanitov E.N., Sexton A., Christian A., Trainer A., Spigelman A., Fellows A., Shelling A., Fazio A.D., Blackburn A., Crook A., Meiser B., Patterson B., Clarke C., Saunders C., Hunt C., Amor D., Marsh D., Edkins E., Salisbury E., Haan E., Neidermayr E., Macrea F., Farshid G., Lindeman G., Trench G., Mann G., Gill G., Thorne H., Hickie I., Winship I., Flanagan J., Kollias J., Visvader J., Stone J., Burke J., Saunus J., Forbes J., French J., Tucker K., Wu K., Phillips K., Lipton L., Andrews L., Lobb L., Kentwell M., Spurdle M., Cummings M., Gleeson M., Jenkins M., Young M.A., Delatycki M., Wallis M., Burgess M., Price M., Brown M., Southey M., Bogwitz M., Field M., Friedlander M., Gattas M., Saleh M., Hayward N., Pachter N., Cohen P., Duijf P., James P., Simpson P., Fong P., Butow P., Williams R., Kefford R., Scott R., Milne R.L., Balleine R., Dawson S.-J., Lok S., O'Connell S., Greening S., Nightingale S., Edwards S., Fox S., McLachlan S.-A., Lakhani S., Antill Y., Aalfs C., Meijers-Heijboer H., van Engelen K., Gille H., Boere I., Collee M., van Deurzen C., Obdeijn I.-M., van den Ouweland A., Seynaeve C., Siesling S., Verloop J., van Asperen C., van Cronenburg T., Blok R., de Boer M., Garcia E.G., Adank M., Hogervorst F., Jenner D., van Leeuwen F., Rookus M., Russell N., Schmidt M., van den Belt-Dusebout S., Kets C., Mensenkamp A., de Bock T., van der Hout A., Mourits M., Oosterwijk J., Ausems M., Koudijs M., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Isaacs C., Iwasaki M., Jager A., Jakimovska M., Jakubowska A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Jones M.E., Jukkola-Vuorinen A., Jung A., Kaaks R., Kang D., Kapoor P.M., Karlan B.Y., Keeman R., Kerin M.J., Khusnutdinova E., Kiiski J.I., Kirk J., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Kosma V.-M., Koutros S., Kubelka-Sabit K., Kwong A., Kyriacou K., Laitman Y., Lambrechts D., Lee E., Leslie G., Lester J., Lesueur F., Lindblom A., Lo W.-Y., Long J., Lophatananon A., Loud J.T., Lubinski J., MacInnis R.J., Maishman T., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matsuo K., Maurer T., Mavroudis D., Mayes R., McGuffog L., McLean C., Meindl A., Miller A., Miller N., Montagna M., Moreno F., Muir K., Mulligan A.M., Munoz-Garzon V.M., Muranen T.A., Narod S.A., Nassir R., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Nielsen F.C., Nikitina-Zake L., Norman A., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Osorio A., Pankratz V.S., Papp J., Park S.K., Park-Simon T.-W., Parsons M.T., Paul J., Pedersen I.S., Peissel B., Peshkin B., Peterlongo P., Peto J., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Prokofyeva D., Pujana M.A., Pylkas K., Radice P., Canzian F., Rantala J., Rau-Murthy R., Rennert G., Risch H.A., Robson M., Romero A., Rossing M., Saloustros E., Sanchez-Herrero E., Sandler D.P., Santamarina M., Sawyer E.J., Scheuner M.T., Schmidt D.F., Schmutzler R.K., Ramus S.J., Carroll J.S., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Scott C., Scott R.J., Senter L., Shah M., Sharma P., Shen C.-Y., Shu X.-O., Singer C.F., Slavin T.P., Smichkoska S., Spinelli J.J., Spurdle A.B., Sutter C., Swerdlow A.J., Tamimi R.M., Tan Y.Y., Tapper W.J., Taylor J., Teixeira M.R., Tengstrom M., Teo S.H., Terry M.B., Teule A., Thomassen M., Thull D.L., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Torres-Mejia G., Troester M.A., Truong T., Tung N., Tzardi M., Ulmer H.-U., Vachon C.M., van der Kolk L.E., van Rensburg E.J., Vega A., Viel A., Vijai J., Vogel M.J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wildiers H., Winqvist R., Wolk A., Wu A.H., Yannoukakos D., Zhang Y., Zheng W., Hunter D., Pharoah P.D.P., Chang-Claude J., Garcia-Closas M., Schmidt M.K., Kristensen V.N., French J.D., Antoniou A.C., Chenevix-Trench G., Simard J., Easton D.F., Kraft P., Allen J., Harris M., Fachal L., Aschard H., Beesley J., Barnes D.R., Kar S., Pooley K.A., Dennis J., Michailidou K., Turman C., Soucy P., Lemacon A., Lush M., Tyrer J.P., Ghoussaini M., Marjaneh M.M., Jiang X., Agata S., Aittomaki K., Alonso M.R., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arason A., Arndt V., Aronson K.J., Arun B.K., Auber B., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Beeghly-Fadiel A., Benitez J., Bermisheva M., Bialkowska K., Blanco A.M., Blomqvist C., Blot W., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Bosse K., Brauch H., Brenner H., Briceno I., Brock I.W., Brooks-Wilson A., Bruning T., Burwinkel B., Buys S.S., Cai Q., Caldes T., Caligo M.A., Camp N.J., Campbell I., Carter B.D., Castelao J.E., Chiquette J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Mari V., Berthet P., Castera L., Vaur D., Lallaoui H., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Revillion F., Vennin P., Muller D., Gomes D.M., Ingster O., Coupier I., Pujol P., Collonge-Rame M.-A., Mortemousque I., Bera O., Rose M., Baurand A., Bertolone G., Faivre L., Dreyfus H., Leroux D., Venat-Bouvet L., Bezieau S., Delnatte C., Chiesa J., Gilbert-Dussardier B., Gesta P., Prieur F.P., Bronner M., Sokolowska J., Coulet F., Boutry-Kryza N., Calender A., Giraud S., Leone M., Fert-Ferrer S., Stoppa-Lyonnet D., Jiao Y., Lesueur F.L., Mebirouk N., Barouk-Simonet E., Bubien V., Longy M., Sevenet N., Gladieff L., Toulas C., Reimineras A., Sobol H., Paillerets B.B.-D., Cabaret O., Caron O., Guillaud-Bataille M., Rouleau E., Belotti M., Buecher B., Caputo S., Colas C., Pauw A.D., Fourme E., Gauthier-Villars M., Golmard L., Moncoutier V., Saule C., Donaldson A., Murray A., Brady A., Brewer C., Pottinger C., Miller C., Gallagher D., Gregory H., Cook J., Eason J., Adlard J., Barwell J., Ong K.-R., Snape K., Walker L., Izatt L., Side L., Tischkowitz M., Rogers M.T., Porteous M.E., Ahmed M., Morrison P.J., Brennan P., Eeles R., Davidson R., Collee J.M., Cornelissen S., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Domchek S.M., Dork T., dos-Santos-Silva I., Droit A., Dubois S., Dumont M., Duran M., Durcan L., Dwek M., Eccles D.M., Engel C., Eriksson M., Evans D.G., Fasching P.A., Fletcher O., Floris G., Flyger H., Foretova L., Foulkes W.D., Friedman E., Fritschi L., Frost D., Gabrielson M., Gago-Dominguez M., Gambino G., Ganz P.A., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Georgoulias V., Giles G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Tibiletti M.G., Greene M.H., Grip M., Gronwald J., Grundy A., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hartikainen J.M., Hartman M., He W., Healey C.S., Heemskerk-Gerritsen B.A.M., Heyworth J., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Hooning M., Hopper J., Howell A., Huang G., Hulick P.J., Imyanitov E.N., Sexton A., Christian A., Trainer A., Spigelman A., Fellows A., Shelling A., Fazio A.D., Blackburn A., Crook A., Meiser B., Patterson B., Clarke C., Saunders C., Hunt C., Amor D., Marsh D., Edkins E., Salisbury E., Haan E., Neidermayr E., Macrea F., Farshid G., Lindeman G., Trench G., Mann G., Gill G., Thorne H., Hickie I., Winship I., Flanagan J., Kollias J., Visvader J., Stone J., Burke J., Saunus J., Forbes J., French J., Tucker K., Wu K., Phillips K., Lipton L., Andrews L., Lobb L., Kentwell M., Spurdle M., Cummings M., Gleeson M., Jenkins M., Young M.A., Delatycki M., Wallis M., Burgess M., Price M., Brown M., Southey M., Bogwitz M., Field M., Friedlander M., Gattas M., Saleh M., Hayward N., Pachter N., Cohen P., Duijf P., James P., Simpson P., Fong P., Butow P., Williams R., Kefford R., Scott R., Milne R.L., Balleine R., Dawson S.-J., Lok S., O'Connell S., Greening S., Nightingale S., Edwards S., Fox S., McLachlan S.-A., Lakhani S., Antill Y., Aalfs C., Meijers-Heijboer H., van Engelen K., Gille H., Boere I., Collee M., van Deurzen C., Obdeijn I.-M., van den Ouweland A., Seynaeve C., Siesling S., Verloop J., van Asperen C., van Cronenburg T., Blok R., de Boer M., Garcia E.G., Adank M., Hogervorst F., Jenner D., van Leeuwen F., Rookus M., Russell N., Schmidt M., van den Belt-Dusebout S., Kets C., Mensenkamp A., de Bock T., van der Hout A., Mourits M., Oosterwijk J., Ausems M., Koudijs M., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Isaacs C., Iwasaki M., Jager A., Jakimovska M., Jakubowska A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Jones M.E., Jukkola-Vuorinen A., Jung A., Kaaks R., Kang D., Kapoor P.M., Karlan B.Y., Keeman R., Kerin M.J., Khusnutdinova E., Kiiski J.I., Kirk J., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Kosma V.-M., Koutros S., Kubelka-Sabit K., Kwong A., Kyriacou K., Laitman Y., Lambrechts D., Lee E., Leslie G., Lester J., Lesueur F., Lindblom A., Lo W.-Y., Long J., Lophatananon A., Loud J.T., Lubinski J., MacInnis R.J., Maishman T., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matsuo K., Maurer T., Mavroudis D., Mayes R., McGuffog L., McLean C., Meindl A., Miller A., Miller N., Montagna M., Moreno F., Muir K., Mulligan A.M., Munoz-Garzon V.M., Muranen T.A., Narod S.A., Nassir R., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Nielsen F.C., Nikitina-Zake L., Norman A., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Osorio A., Pankratz V.S., Papp J., Park S.K., Park-Simon T.-W., Parsons M.T., Paul J., Pedersen I.S., Peissel B., Peshkin B., Peterlongo P., Peto J., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Prokofyeva D., Pujana M.A., Pylkas K., Radice P., Canzian F., Rantala J., Rau-Murthy R., Rennert G., Risch H.A., Robson M., Romero A., Rossing M., Saloustros E., Sanchez-Herrero E., Sandler D.P., Santamarina M., Sawyer E.J., Scheuner M.T., Schmidt D.F., and Schmutzler R.K.

Abstract

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2020

24. Taalgebruik en taalattitudes onder expats in Nederland: een onderzoek naar communicatie in de huisartsenpraktijk en naar voorlichting over het coronavirus

Author

Blok, R., Kester, P. M. (Thesis Advisor), Blok, R., and Kester, P. M. (Thesis Advisor)

Abstract

In deze masterscriptie wordt op een exploratieve wijze onderzoek gedaan naar taalgebruik, taalattitudes en communicatie binnen de huisartsenpraktijk en bij voorlichting over het coronavirus. De groep expats in Nederland, vooral in de Randstad, is erg groot, al kent de term ‘expat’ geen eenduidige definitie. Het is van belang dat expats communicatie binnen de zorg en rondom de coronacrisis ook kunnen begrijpen. Uit dit onderzoek blijkt dat de respondenten meer informele dan formele gesprekken in het Nederlands voeren. Dit kan komen doordat ze hun eigen Nederlands nog niet als vloeiend inschatten. Vooral het spreken blijkt (nog) lastig. Wel wil de grote meerderheid beter Nederlands leren spreken en een nog grotere groep vindt het belangrijk om Nederlands te spreken wanneer je in Nederland woont. Het Engels wordt het liefst gebruikt als voertaal bij de huisarts, ook al vond minder dan de helft van de respondenten dat hun huisarts het Engels vloeiend beheerst. De meerderheid van de respondenten met kinderen geeft aan dat hun kinderen het liefst Nederlands praten met de huisarts. Het is interessant om te zien dat deze expats hun eigen Nederlands beter inschatten dan de expats zonder kinderen. Ook vinden zij het belangrijker om Nederlands te leren wanneer je in Nederland woont. Ongeveer de helft van alle respondenten is tevreden over zijn of haar huisarts in Nederland. De respondenten maken tijdens de coronacrisis gebruik van andere mediabronnen dan waar ze voor de crisis gebruik van maakten. Zo lazen ze minder de (online) krant en keken ze vaker naar de Engelse versie van de website van de Rijksoverheid. Ze gaven aan te kunnen begrijpen wat de situatie is in Nederland en wat de maatregelen zijn die hierbij horen. Daarnaast vindt de grote meerderheid dat er via de Nederlandse overheid redelijk wat informatie in het Engels beschikbaar is en dat de overheid dus redelijk rekening houdt met mensen die geen Nederlands spreken. In de toekomst moet er meer onderzoek komen naar e

Published
2020

27. Demolition versus transformation, 'mortality of building structures' depending on their technical building properties

Author

Blok, R., Teuffel, P.M., Blok, R., and Teuffel, P.M.

Abstract

This paper describes the assessment of 60 multi-story buildings in the Netherlands, the followed approach and the main results. The 60 buildings have been assessed on their technical building properties to see which building parameters could be influential on the probability of an elongated Service Life for the building structure. The buildings, (of which 40 buildings have been given a "Second Life" through Transformation and 20 buildings have been demolished) have been assessed, initially on 64 different parameters. The number of parameters has then been reduced to 20, more or less influential parameters. A "quick scan" of building structures has been derived from these parameters. This quick scan uses an aggregated value expressing the re-use potential in a single adaptability/flexibility score. In a similar approach as often is used in medical survival analysis, the "Mortality of Buildings" have been calculated for different Flexibility Scores. Further elaboration will make it possible to assess building structures and then give an indication on their probability for (future) transformation. This is important, not only to assess our existing building stock but also to improve elongated Service Live's for new buildings. By optimizing the Service Life of buildings structures, negative material impacts can be further reduced and the Re-use and Transformation on building level, rather than on material level, can be improved. More realistic Service Life Estimations will make comparisons of different solutions with different levels of Flexibility much more feasible.

Published
2019

30. Optimized plankton imaging, clustering and visualization workflows through integrative data management and application of artificial intelligence

Author

Debusschere, E., Mortelmans, J., Tyberghein, L., Artigas, L.F., Creach, V., de Blok, R., Everaert, G., Kromkamp, J., Lizon, F., Louchart, A., Rijkeboer, M., and Deneudt, K.

Abstract

Phytoplankton is a diverse group of photosynthesizing organisms which account for approximately fifty percent of the primary production on Earth. Increasing our knowledge on phytoplankton dynamics (and plankton in general) is therefore of major importance. In the present research, we aimed to reveal the spatiotemporal dynamics of the phyto- and zooplankton community in the Eastern English Channel, Southern Bight of the North Sea and the Thames estuary. To do so, we organized a JERICO-NEXT Lifewatch cruise in May 2017 on board of the RV Simon Stevin and sampled 44 stations, involving five research institutions from France (CNRS-LOG,), The Netherlands (RWS, NIOZ) and Belgium (UGENT, VLIZ). To quantify the biomass of the phytoplankton community we used a unique combination of three flow cytometers and two Fast Repetition Rate Fluorometerss that were coupled to the underway ferrybox system. These observations were complemented with Water Insight Spectrometer and water profile data (by means of a CTD) and samples for zooplankton, pigment and nutrient analysis. A dedicated data workshop was organized with all partners to conduct a joint analysis on both the biotic and abiotic data. A first exploration of the data, by means of regression-based models and multivariate statistics, suggested that mainly nutrient discharges from the rivers influence the plankton structure. Furthermore, water turbidity is controlling photosynthetic activity and horizontal and vertical variations of photosynthetic properties can be discriminated.

Published
2018

33. Resource-efficient structural design

Author

Blok, R., Habraken, A.P.H.W., Pronk, A.D.C., Teuffel, P.M., Mueller, Caitlin, Adriaenssens, Sigrid, and Innovative Structural Design

Subjects
SDG 7 - Affordable and Clean Energy
Abstract

The building and construction industry is by far the most resource intensive sector in the European Union [1] and the numbers worldwide are comparable. This sector, which is based on a very strong responsibility of architects as well structural engineers takes approximately 50% of all primary raw materials and therefor exhausting natural resources substantially. In the past decades the focus in the construction industry was mainly on the reduction of energy consumption of buildings as well as use of renewable energy, but the impact of material use will be in the spotlight in the future as well.

Published
2018

35. Fully bio-based composite pedestrian bridge : design, production, and monitoring

Author

Luyckx, G., Coene, K., Voet, E., Blok, R., Teuffel, P.M., Wijen, H.L.M., Innovative Structural Design, and Laboratory for SED

Subjects
Structural health monitoring, Fibre Brag Gratings, Fiber Reinforced Structures, Bio based Structures, Bridge engineering
Abstract

The study deals with the development of a fully bio-based composite pedestrian bridge with sensor technology embedded to measure its long term behavior. The bridge was produced in different parts using vacuum infusion and was assembled afterwards. Optical fiber sensor lines with 7 equally spaced FBGs were embedded one in the top laminate and two in the bottom laminate during production. Consequently, the sensors have been compared with LVDT readings. During a lab reference measurement a linear trend with increasing load was seen for both techniques. The field tests afterwards shows the potential of the sensor network to in-situ measure the dynamic behavior e.g. damping and 1st eigenfrequency of the bridge and its long term static behavior e.g. creep effects.

Published
2017

37. The urban wind energy potential for integrated roof wind energy systems based on local building height distributions

Author

Blok, R., Coers, M.D., Innovative Structural Design, and Built Environment

Subjects
SDG 7 - Affordable and Clean Energy
Abstract

An Integrated Roof Wind Energy System (IRWES) is a roof mounted structure with an internal wind turbine that uses smart aerodynamics to catch and accelerate wind flow. It has been designed for application on (existing) buildings in the urban environment. To estimate the maximum total wind energy harvesting potential of cities, while using these kind of roof mounted units, a method has been developed. The method analyses actual height measurement data files, estimates surface roughness, and calculates wind energy potential for different building height categories. This wind energy potential is based on theoretical calculated additional building heights for these roof mounted systems, based on building strength and stiffness capacity estimations, local (average) wind velocities as well as the IRWES wind energy efficiency characteristics. The method has been applied to the cities of Amsterdam, Rotterdam as well as Eindhoven, Netherlands, but could also be applied to any City in the World. Results make it possible to compare Urban Wind Energy Potential of whole cities but also to compare height categories of buildings as well as to quickly estimate what an IRWES unit could provide for a single building.

Published
2017

40. Vragen bij Alzheimer: Een literatuurstudie naar de moeilijkheid van het begrijpen en beantwoorden van vragen bij alzheimerpatiënten.

Author

Blok, R., Wijnen, F. N. K. (Thesis Advisor), Blok, R., and Wijnen, F. N. K. (Thesis Advisor)

Abstract

De ziekte van Alzheimer veroorzaakt moeilijkheden in de communicatie tussen alzheimerpatiënten en hun omgeving. In het boek ‘Ondersteunend communiceren bij dementie’ wordt de tip gegeven ‘Niet alleen vragen stellen’, maar de evidence base wordt in het boek niet vermeld. Dat wordt in deze scriptie wel gedaan. Bij mensen met dementie gaan zenuwcellen in de hersenen kapot en hierdoor vindt er steeds minder communicatie tussen hersencellen plaats. Dit heeft onder andere tot gevolg dat het taalvermogen van alzheimerpatiënten achteruit gaat. In deze scriptie concentreer ik me op de taal van alzheimerpatiënten vanuit de syntaxis, het semantische systeem, de pragmatiek en vanuit literatuur over het werkgeheugen. Het lijkt erop dat vooral het mentale lexicon in het semantische systeem aangedaan is. Er is ook literatuur over storingen in het werkgeheugen en in de pragmatiek bij mensen met Alzheimer, maar er is meer onderzoek nodig om hier conclusies uit te kunnen trekken. Het blijft onduidelijk wat Scheres en De Rijdt (2017) precies bedoelden met de bovenstaande tip. Het zou zo kunnen zijn dat het vooral gaat om het niet teveel stellen van vraagwoordvragen. Deze vraagwoordvragen veroorzaken namelijk eerder een communicatiestoring dan ja/nee-vragen. In de toekomst kan er onder andere gekeken worden naar de pragmatiek en het werkgeheugen bij mensen met Alzheimer om zo de communicatie tussen alzheimerpatiënten en hun omgeving te verbeteren.

Published
2018

42. The Twist: innovative architectural and structural integrated high rise building design

Author

van Weersch, I.E.A., Ploegmakers, D.G., Blok, R., Built Environment, and Innovative Structural Design

Subjects
high rise building, innovative design concept, architecture, structural design, diagrid, integrated design
Abstract

When city’s become more dense, the need for high rise buildings increases. However, implementation of high rise buildings in a crowded city is difficult on street level. Common high rise designs have a discrete transition between public and private area, subsequently losing interaction with the city. In this research a new high rise building concept has been developed. An integrated design approach combining architectural and structural solutions has been used. The final design consists of three slender buildings with public space between them combined through a diagrid structure. This diagrid structure ensures the lateral stiffness of the buildings. This innovative high rise building concept is a new possibility to implement high rise in a city that combines all important design criteria. Keywords-component; high rise building; innovative design concept; architecture; structural design; diagrid; integrated design

Published
2017

43. Bio-Based Composite Bridge – Lessons Learned

Author

Blok, R., Teuffel, P.M., Bögle, A., Grohmann, M., and Innovative Structural Design

Subjects
Footbridge, bio-composites, innovative structural design, new materials, bio-based structures, fibre bragg optical sensors
Abstract

The concept and design process of the world’s first bio-based composite pedestrian bridge at the campus of Eindhoven University of Technology was described and presented at the previous IASS conference in Tokyo [1], [2]. The bridge has a span of 14 m and uses a bio-composite as the main structural material, which is based on hemp, flax and Greenpoxy. In the meantime the project has been successfully realized and finished in November 2016. The focus of this paper will be on a couple of major aspects, that can be helpful for future projects using bio-based composite materials: evaluation of the material tests, comparison of the FEM analysis with the 1:1 scale load test, production process as well as the monitoring of the bridge after installation. In order to understand the material properties in a better way a series of tests have been and still are being conducted in the laboratory at TU/e. Apart from the prior essential tests, such as strength and stiffness, further ongoing tests look at the creep behaviour of the composite material. The installation of the bridge was carried out in public space, so full approval of the authorities had to be obtained. Due to the fact that no building codes exist for bio-based composite materials the authors had to prove the correctness of their calculations with a full scale load test. At the moment the longterm behaviour of the bridge is monitored with in total 27 fibre-optical sensors to further study and evaluate the strain properties over a period of 1 year with varying environmental conditions. It can be concluded that bio-based composite materials show a great potential for applications in the built environment, while also a long list of questions remains for researcher to be answered.

Published
2017

44. Fully bio-based-composite footbridge : strain monitoring during use phase

Author

Blok, R., Teuffel, P.M., and Innovative Structural Design

Abstract

Last year a bio based pedestrian bridge, first in its kind, has been installed at the TU/e University campus in Eindhoven. Material test formed the basis for the innovative design and the research project resulted in the production and installation of the bridge. Because there are still a lot of unknowns in the material behaviour of the used bio-composites, it was decided to monitor and test the bridge further after production. For this purpose optical FBG sensors have been installed. The FBG sensors show the material strains in good detail and the results of the thus measured strains in load tests are shown. The test results are compared with results from earlier material tests. The short term structural behaviour follows closely the used elastic models based on calculated as well as measured stiffnesses. The long term time dependent behaviour however shows a number of different influences from creep, temperature and moisture content that can not yet be fully explained by earlier measurements and tests.

Published
2017

45. Design of Da Vinci’s bridge in ice

Author

Pronk, A.D.C., Blok, R., van Brunschot, Maikel Cornelis Adolf Johannes, van Lier, Arthur J., van de Mortel, F.F.H., Williams, K.K., Arntz, M.G.A.J., Hermens, L.J., Koekkoek, R., van de Nieuwenhof, T.A.H., Cruz, Paulo J.S., Innovative Structural Design, and Built Environment

Subjects
ice composite, ice dome, Engineering, business.industry, Pykrete, Shell (structure), ComputingMilieux_LEGALASPECTSOFCOMPUTING, Structural engineering, textile fabrics, Shotcrete, Bridge (interpersonal), Sagrada Familia, shell, business, shotcrete, Pykrete, shotcrete, ice composite, ice dome, Sagrada Familia, Gaudí, textile fabrics, shell, Gaudí
Published
2016
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48. Simple clamped connection for bamboo truss systems

Author

Blok, R. and Innovative Structural Design

Abstract

“How to make fast and simple tension connections for truss systems?” The Solution: The innovation is a connection that uses only widely available base components (boltsand threaded steel bars) and simple hand tools to install it. With a handsaw and aspanner, the bamboo stems can be combined into to structural truss-systems for buildings.

Published
2016

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