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1. Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates

Author

Reiss, E. I. M. M., van Haaren, M. M., van Schooten, J., Claireaux, M. A. F., Maisonnasse, P., Antanasijevic, A., Allen, J. D., Bontjer, I., Torres, J. L., Lee, W-H, Ozorowski, G., Vázquez Bernat, N., Kaduk, M., Aldon, Y., Burger, J. A., Chawla, H., Aartse, A., Tolazzi, M., Gao, H., Mundsperger, P., Crispin, M., Montefiori, D. C., Karlsson Hedestam, G. B., Scarlatti, G., Ward, A. B., Le Grand, R., Shattock, R., Dereuddre-Bosquet, N., Sanders, R. W., and van Gils, M. J.

Published
2022
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2. Pharmacogenetics of Anticoagulation and Clinical Events in Warfarin-Treated Patients: A Register-Based Cohort Study with Biobank Data and National Health Registries in Finland

Author

Vuorinen AL, Lehto M, Niemi M, Harno K, Pajula J, van Gils M, and Lähteenmäki J

Subjects
pharmacogenomics, warfarin, bleeding, inr, cyp2c9, vkorc1, Infectious and parasitic diseases, RC109-216
Abstract

Anna-Leena Vuorinen,1 Mika Lehto,2,3 Mikko Niemi,4,5 Kari Harno,6 Juha Pajula,1 Mark van Gils,1 Jaakko Lähteenmäki7 1VTT Technical Research Centre of Finland, Tampere, Finland; 2Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland; 3University of Helsinki, Helsinki, Finland; 4Department of Clinical Pharmacology and Individualized Drug Therapy Research Program, University of Helsinki, Helsinki, Finland; 5Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland; 6Department of Health and Social Management, University of Eastern Finland, Kuopio, Finland; 7VTT Technical Research Centre of Finland, Espoo, FinlandCorrespondence: Anna-Leena VuorinenVTT Technical Research Centre of Finland, P.O. Box 1300, Tampere, 33101, FinlandTel +358 40 8485966Email anna-leena.vuorinen@vtt.fiPurpose: To assess the association between VKORC1 and CYP2C9 variants and the incidence of adverse drug reactions in warfarin-treated patients in a real-world setting.Materials and Methods: This was a register-based cohort study (PreMed) linking data from Finnish biobanks, national health registries and patient records between January 1st 2007 and June 30th 2018. The inclusion criteria were: 1) ≥ 18 years of age, 2) CYP2C9 and VKORC1 genotype information available, 3) a diagnosis of a cardiovascular disease, 4) at least one warfarin purchase, 5) regular INR tests. Eligible individuals were divided into two warfarin sensitivity groups; normal responders, and sensitive and highly sensitive responders based on their VKORC1 and CYP2C9 genotypes. The incidences of clinical events were compared between the groups using Cox regression models.Results: The cohort consisted of 2508 participants (45% women, mean age of 69 years), of whom 65% were categorized as normal responders and 35% sensitive or highly sensitive responders. Compared to normal responders, sensitive and highly sensitive responders had fewer INR tests below 2 (median: 33.3% vs 43.8%, 95% CI: − 13.3%, − 10.0%) and more above 3 (median: 18.2% vs 6.7%, 95% Cl: 8.3%, 10.8%). The incidence (per 100 patient-years) of bleeding outcomes was 5.4 for normal responders and 5.6 for the sensitive and highly sensitive responder group (HR=1.03, 95% CI: 0.74, 1.44). The incidence of thromboembolic outcomes was 4.9 and 7.8, respectively (HR=1.48, 95% CI: 1.08, 2.03).Conclusion: In a real-world setting, genetically sensitive and highly sensitive responders to warfarin had more high INR tests and required a lower daily dose of warfarin than normal responders. However, the risk for bleeding events was not increased in sensitive and highly sensitive responders. Interestingly, the risk of thromboembolic outcomes was lower in normal responders compared to the sensitive and highly sensitive responders.Trial Registration: NCT04001166.Keywords: pharmacogenomics, warfarin, bleeding, INR, CYP2C9, VKORC1

Published
2021

4. Adherence to Physical Activity in Patients with Heart Disease: Types, Settings and Evaluation Instruments

Author

Livitckaia, K., Koutkias, V., Maglaveras, N., Kouidi, E., van Gils, M., Chouvarda, I., Magjarevic, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Maglaveras, Nicos, editor, Chouvarda, Ioanna, editor, and de Carvalho, Paulo, editor

Published
2018
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9. Robust Vaccine-Induced as Well as Hybrid B- and T-Cell Immunity across SARS-CoV-2 Vaccine Platforms in People with HIV

Author

Verburgh, Myrthe L., primary, van Pul, Lisa, additional, Grobben, Marloes, additional, Boyd, Anders, additional, Wit, Ferdinand W. N. M., additional, van Nuenen, Ad C., additional, van Dort, Karel A., additional, Tejjani, Khadija, additional, van Rijswijk, Jacqueline, additional, Bakker, Margreet, additional, van der Hoek, Lia, additional, Schim van der Loeff, Maarten F., additional, van der Valk, Marc, additional, van Gils, Marit J., additional, Kootstra, Neeltje A., additional, Reiss, Peter, additional, Reiss, P., additional, Wit, F. W. N. M., additional, van der Valk, M., additional, Boyd, A., additional, Verburgh, M. L., additional, van der Wulp, I. A. J., additional, Vanbellinghen, M. C., additional, van Eeden, C. J., additional, Schim van der Loeff, M. F., additional, Koole, J. C. D., additional, del Grande, L., additional, Agard, I., additional, Zaheri, S., additional, Hillebregt, M. M. J., additional, Ruijs, Y. M. C., additional, Benschop, D. P., additional, el Berkaoui, A., additional, Kootstra, N. A., additional, Harskamp-Holwerda, A. M., additional, Maurer, I., additional, Mangas Ruiz, M. M., additional, Boeser-Nunnink, B. D. N., additional, Starozhitskaya, O. S., additional, van der Hoek, L., additional, Bakker, M., additional, van Gils, M. J., additional, Dol, L., additional, Rongen, G., additional, Geerlings, S. E., additional, Goorhuis, A., additional, Hovius, J. W. R., additional, Nellen, F. J. B., additional, Prins, J. M., additional, van der Poll, T., additional, Wiersinga, W. J., additional, van Vugt, M., additional, de Bree, G., additional, Lemkes, B. A., additional, Spoorenberg, V., additional, van Eden, J., additional, Pijnappel, F. J. J., additional, Weijsenfeld, A., additional, Smalhout, S., additional, Hylkema-van den Bout, I. J., additional, Bruins, C., additional, Spelbrink, M. E., additional, Postema, P. G., additional, Bisschop, P. H. L. T., additional, Dekker, E., additional, van der Velde, N., additional, Franssen, R., additional, Willemsen, J. M. R., additional, Vogt, L., additional, Portegies, P., additional, Geurtsen, G. J., additional, Visser, I., additional, Schadé, A., additional, Nieuwkerk, P. T., additional, van Steenwijk, R. P., additional, Jonkers, R. E., additional, Majoie, C. B. L. M., additional, Caan, M. W. A., additional, van den Born, B. J. H., additional, Stroes, E. S. G., additional, and van Oorspronk, S., additional

Published
2023
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10. Medication Incompliance and Vital Signs in Heart Failure Patients

Author

Chouvarda, I. G., Mabote, T., Torabi, A., Caffarel, J., van Gils, M., Cleland, J., Maglaveras, N., Magjarevic, Ratko, Editor-in-chief, Ładyzynsk, Piotr, Series editor, Ibrahim, Fatimah, Series editor, Lackovic, Igor, Series editor, Rock, Emilio Sacristan, Series editor, and Zhang, Yuan-Ting, editor

Published
2014
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14. Older people with well-controlled HIV have similar antibody and higher T-cell responses after vaccination against SARS-CoV-2 compared to demographically and lifestyle-comparable people without HIV

Author

Verburgh, M., van Pul, L., Grobben, M., Boyd, A., Wit, F., van Nuenen, A., van Dort, K., Tejjani, K., van Rijswijk, J., Bakker, M., van der Hoek, L., van der Loeff, M. Schim, van der Valk, M., van Gils, M., Kootstra, N., Reiss, P., AII - Infectious diseases, APH - Global Health, Infectious diseases, Global Health, Graduate School, Experimental Immunology, APH - Methodology, APH - Aging & Later Life, and Medical Microbiology and Infection Prevention

Published
2022

16. SARS-CoV-2 evolution during treatment of chronic infection

Author

Kemp, S. A., Collier, D. A., Datir, R. P., Ferreira, I. A. T. M., Gayed, S., Jahun, A., Hosmillo, M., Rees-Spear, C., Mlcochova, P., Lumb, I. U., Roberts, D. J., Chandra, A., Temperton, N., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Estee Torok, M., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Abnizova, I., Aigrain, L., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Betteridge, E., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Bonfield, J., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Goodwin, S., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Liddle, J., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Makunin, A., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mccarthy, S., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Puethe, C., Quail, M., Rajan, D., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Scott, C., Seekings, P., Shirley, L., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Jansen Van, P., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Whitwham, A., Widaa, S., Williams, M., Wilson, M., Wright, S., Farr, B. W., Quail, M. A., Thurston, S. A. J., Bronner, I. F., Redshaw, N. M., Lensing, S. V., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Sharrocks, K., Blane, E., Modis, Y., Leigh, K. E., Briggs, J. A. G., van Gils, M. J., Smith, K. G. C., Bradley, J. R., Doffinger, R., Ceron-Gutierrez, L., Barcenas-Morales, G., Pollock, D. D., Goldstein, R. A., Smielewska, A., Skittrall, J. P., Gouliouris, T., Goodfellow, I. G., Gkrania-Klotsas, E., Illingworth, C. J. R., Mccoy, L. E., Gupta, R. K., Medical Microbiology and Infection Prevention, AII - Infectious diseases, Collier, Dami A [0000-0001-5446-4423], Jahun, Aminu [0000-0002-4585-1701], Temperton, Nigel [0000-0002-7978-3815], Modis, Yorgo [0000-0002-6084-0429], Briggs, John AG [0000-0003-3990-6910], Goldstein, Richard A [0000-0001-5148-4672], Skittrall, Jordan P [0000-0002-8228-3758], Gkrania-Klotsas, Effrossyni [0000-0002-0930-8330], McCoy, Laura E [0000-0001-9503-7946], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Time Factors, viruses, Passive, Antibodies, Viral, CITIID-NIHR BioResource COVID-19 Collaboration, 2.1 Biological and endogenous factors, Viral, Aetiology, Neutralizing, Lung, Phylogeny, neutralising antibodies, Infectivity, education.field_of_study, Genome, Multidisciplinary, Alanine, biology, High-Throughput Nucleotide Sequencing, Viral Load, Spike Glycoprotein, Virus Shedding, Adenosine Monophosphate, Aged, Antibodies, Neutralizing, COVID-19, Chronic Disease, Genome, Viral, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Mutagenesis, Mutant Proteins, Mutation, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Evolution, Molecular, Infectious Diseases, Pneumonia & Influenza, Antibody, Infection, Viral load, Biotechnology, Evolution, General Science & Technology, antibody escape, Convalescent plasma, 030106 microbiology, Population, evasion, Antibodies, Virus, Article, Vaccine Related, resistance, 03 medical and health sciences, Immune system, COVID-19 Genomics UK (COG-UK) Consortium, Biodefense, Genetics, Viral shedding, education, COVID-19 Serotherapy, QR355, Prevention, Wild type, Molecular, Pneumonia, Virology, COVID-19 Drug Treatment, Coronavirus, Emerging Infectious Diseases, Good Health and Well Being, 030104 developmental biology, biology.protein, Immunization, immune suppression, mutation
Abstract

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.

Published
2021

17. Novel trimer-only (TO) producing HIV-1 envelope glycoprotein constructs for inducing broadly neutralizing antibody responses by genetic vaccination

Author

Sanchez, I. Del Moral, Wee, E.G., Koekkoek, S.M., Schermer, E.E., Lee, W.H., Kumar, S., Zwolsman, R., Allen, J.D., Pena, A. Torrents de la, Haaren, M.M.Van, Reiss, E., Van Gils, M., Crispin, M., Ozorowski, G., and Ward, A.B.

Subjects
Testing, Care and treatment, Development and progression, Genetic aspects, Health aspects, HIV infections -- Genetic aspects -- Development and progression -- Care and treatment, Glycoproteins -- Health aspects, DNA vaccines -- Testing, Gene expression -- Health aspects, HIV infection -- Genetic aspects -- Development and progression -- Care and treatment
Abstract

OA15.03 I. del Moral Sanchez (1); E.G. Wee (2); S.M. Koekkoek (1); E.E. Schermer (1); W.H. Lee (3); S. Kumar (4); R. Zwolsman (1); J.D. Allen (5); A. Torrents de [...], Background: Soluble immunogens that properly mimic the HIV-1 envelope glycoprotein (Env), such as SOSIP and native flexibly linked (NFL) trimers, are used as constituents for a number of HIV-1 vaccine approaches. However, most NFL and SOSIP constructs are not only expressed as trimers, but also produce undesired monomers and dimers that expose non-neutralizing epitopes. Usually, chromatography procedures are used to isolate the desired trimers for vaccination. However, this also implies that conventional SOSIP and NFL constructs might be less suitable for genetic vaccination. Here, we describe a novel HIV-1 Env construct that was designed to express as trimers only (TO). Methods: First, we combined the TO design with BG505 env to generate a BG505 TO-SOSIP construct as a proof-of-concept. Next, we used TO-SOSIP as a design template to generate a number of different HIV-1 Env immunogens: 1) TO-SOSIP in which immunodominant strain-specific glycan holes were hidden by glycan masking (GM) (TOSOSIP.GM). 2) TO-SOSIP containing germline-targeting (GT) mutations that enable binding by naive precursors of CD4bs broadly neutralizing antibodies (bNAbs) (TO-SOSIP.GT). Results: Transient transfection followed by lectin affinity chromatography showed that the BG505 TO-SOSIP construct expressed only as trimers, of which >85% displayed a native-like conformation, while BG505 SOSIP and NFL-SOSIP preparations contained significant amounts of dimers and monomers. Furthermore, TO-SOSIP interacted efficiently with quaternary dependent bNAbs, such as PGT145 and PGT151, while showing weak binding to most non-NAbs. Both glycan masked and germline targeting variants also expressed only trimers. TO-SOSIPGM showed negligible reactivity to glycan hole-targeting antibodies, while several TO-SOSIPGT variants showed efficient binding to inferred germline versions of several CD4bs bNAbs. Remarkably, the TO design approach also allowed us to generate influenza hemagglutinin (HA) immunogens that express only as trimers without heterologous trimerization domains. Conclusions: The TO design is a useful platform for generating Env and HA immunogens and is especially suitable for genetic vaccination purposes. In the context of DNA prime and protein boost vaccination strategies, the glycan masked and germline targeting TO-SOSIP constructs could prove essential for the early activation of potentially cross-neutralizing epitopes.

Published
2021
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18. Evaluation framework for carotid bifurcation lumen segmentation and stenosis grading

Author

Hameeteman, K., Zuluaga, M.A., Freiman, M., Joskowicz, L., Cuisenaire, O., Valencia, L. Flórez, Gülsün, M.A., Krissian, K., Mille, J., Wong, W.C.K., Orkisz, M., Tek, H., Hoyos, M. Hernández, Benmansour, F., Chung, A.C.S., Rozie, S., van Gils, M., van den Borne, L., Sosna, J., Berman, P., Cohen, N., Douek, P.C., Sánchez, I., Aissat, M., Schaap, M., Metz, C.T., Krestin, G.P., van der Lugt, A., Niessen, W.J., and van Walsum, T.

Published
2011
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20. Surveillance of Immunological Status after Vaccination by two Serological Assays based on SARS-CoV-2 Spike Protein

Author

Fresco-Taboada, A., primary, Garcia-Duran, M., additional, Aira, C., additional, López, L., additional, Sastre, P., additional, Van der Hoek, L., additional, Van Gils, M., additional, Brouwer, P.J.M., additional, Sanders, R.W., additional, Holzer, B., additional, Zimpernik, I., additional, López-Collazo, E., additional, Muñoz, P., additional, Rueda, P., additional, and Vela, C., additional

Published
2022
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22. Antibodies from Rabbits Immunized with HIV-1 Clade B SOSIP Trimers Can Neutralize Multiple Clade B Viruses by Destabilizing the Envelope Glycoprotein

Author

van Haaren, M. M., primary, McCoy, L. E., additional, Torres, J. L., additional, Lee, W., additional, Cottrell, C. A., additional, Copps, J. L., additional, van der Woude, P., additional, Yasmeen, A., additional, de Taeye, S. W., additional, Torrents de la Peña, A., additional, Moore, J. P., additional, Burton, D. R., additional, Klasse, P. J., additional, Ward, A. B., additional, Sanders, R. W., additional, and van Gils, M. J., additional

Published
2021
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23. Cross-reactive antibodies after SARS-CoV-2 infection and vaccination

Author

Grobben, M, van der Straten, K, Brouwer, PJM, Brinkkemper, M, Maisonnasse, P, Dereuddre-Bosquet, N, Burger, J, Poniman, M, Oomen, M, Eggink, D, Bijl, TPL, van Willigen, HDG, Wynberg, E, Verkaik, B, Figaroa, OJA, de Vries, P, Boertien, T, Grand, RL, de Jong, M, Prins, M, Chung, A, de Bree, G, Sanders, R, van Gils, M, Grobben, M, van der Straten, K, Brouwer, PJM, Brinkkemper, M, Maisonnasse, P, Dereuddre-Bosquet, N, Burger, J, Poniman, M, Oomen, M, Eggink, D, Bijl, TPL, van Willigen, HDG, Wynberg, E, Verkaik, B, Figaroa, OJA, de Vries, P, Boertien, T, Grand, RL, de Jong, M, Prins, M, Chung, A, de Bree, G, Sanders, R, and van Gils, M

Abstract

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11 to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2 to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 S protein immunization in macaques, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.

Published
2021

32. Metabolic profiles help discriminate mild cognitive impairment from dementia stage in Alzheimer’s disease

Author

Jääskeläinen, O. (Olli), Hall, A. (Anette), Tiainen, M. (Mika), van Gils, M. (Mark), Lötjönen, J. (Jyrki), Kangas, A. J. (Antti J.), Helisalmi, S. (Seppo), Pikkarainen, M. (Maria), Hallikainen, M. (Merja), Koivisto, A. (Anne), Hartikainen, P. (Päivi), Hiltunen, M. (Mikko), Ala-Korpela, M. (Mika), Soininen, P. (Pasi), Soininen, H. (Hilkka), Herukka, S.-K. (Sanna-Kaisa), Jääskeläinen, O. (Olli), Hall, A. (Anette), Tiainen, M. (Mika), van Gils, M. (Mark), Lötjönen, J. (Jyrki), Kangas, A. J. (Antti J.), Helisalmi, S. (Seppo), Pikkarainen, M. (Maria), Hallikainen, M. (Merja), Koivisto, A. (Anne), Hartikainen, P. (Päivi), Hiltunen, M. (Mikko), Ala-Korpela, M. (Mika), Soininen, P. (Pasi), Soininen, H. (Hilkka), and Herukka, S.-K. (Sanna-Kaisa)

Abstract

Accurate differentiation between neurodegenerative diseases is developing quickly and has reached an effective level in disease recognition. However, there has been less focus on effectively distinguishing the prodromal state from later dementia stages due to a lack of suitable biomarkers. We utilized the Disease State Index (DSI) machine learning classifier to see how well quantified metabolomics data compares to clinically used cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD). The metabolic profiles were quantified for 498 serum and CSF samples using proton nuclear magnetic resonance spectroscopy. The patient cohorts in this study were dementia (with a clinical AD diagnosis) (N = 359), mild cognitive impairment (MCI) (N = 96), and control patients with subjective memory complaints (N = 43). DSI classification was conducted for MCI (N = 51) and dementia (N = 214) patients with low CSF amyloid-β levels indicating AD pathology and controls without such amyloid pathology (N = 36). We saw that the conventional CSF markers of AD were better at classifying controls from both dementia and MCI patients. However, quantified metabolic subclasses were more effective in classifying MCI from dementia. Our results show the consistent effectiveness of traditional CSF biomarkers in AD diagnostics. However, these markers are relatively ineffective in differentiating between MCI and the dementia stage, where the quantified metabolomics data provided significant benefit.

Published
2020

33. cCOG:a web‐based cognitive test tool for detecting neurodegenerative disorders

Author

Rhodius-Meester, H. F. (Hanneke F.M.), Paajanen, T. (Teemu), Koikkalainen, J. (Juha), Mahdiani, S. (Shadi), Bruun, M. (Marie), Baroni, M. (Marta), Lemstra, A. W. (Afina W.), Scheltens, P. (Philip), Herukka, S.-K. (Sanna-Kaisa), Pikkarainen, M. (Maria), Hall, A. (Anette), Hänninen, T. (Tuomo), Ngandu, T. (Tiia), Kivipelto, M. (Miia), van Gils, M. (Mark), Hasselbalch, S. G. (Steen Gregers), Mecocci, P. (Patrizia), Remes, A. (Anne), Soininen, H. (Hilkka), van der Flier, W. M. (Wiesje M.), Lötjönen, J. (Jyrki), Rhodius-Meester, H. F. (Hanneke F.M.), Paajanen, T. (Teemu), Koikkalainen, J. (Juha), Mahdiani, S. (Shadi), Bruun, M. (Marie), Baroni, M. (Marta), Lemstra, A. W. (Afina W.), Scheltens, P. (Philip), Herukka, S.-K. (Sanna-Kaisa), Pikkarainen, M. (Maria), Hall, A. (Anette), Hänninen, T. (Tuomo), Ngandu, T. (Tiia), Kivipelto, M. (Miia), van Gils, M. (Mark), Hasselbalch, S. G. (Steen Gregers), Mecocci, P. (Patrizia), Remes, A. (Anne), Soininen, H. (Hilkka), van der Flier, W. M. (Wiesje M.), and Lötjönen, J. (Jyrki)

Abstract

Introduction: Web‐based cognitive tests have potential for standardized screening in neurodegenerative disorders. We examined accuracy and consistency of cCOG, a computerized cognitive tool, in detecting mild cognitive impairment (MCI) and dementia. Methods: Clinical data of 306 cognitively normal, 120 mild cognitive impairment (MCI), and 69 dementia subjects from three European cohorts were analyzed. Global cognitive score was defined from standard neuropsychological tests and compared to the corresponding estimated score from the cCOG tool containing seven subtasks. The consistency of cCOG was assessed comparing measurements administered in clinical settings and in the home environment. Results: cCOG produced accuracies (receiver operating characteristic‐area under the curve [ROC‐AUC]) between 0.71 and 0.84 in detecting MCI and 0.86 and 0.94 in detecting dementia when administered at the clinic and at home. The accuracy was comparable to the results of standard neuropsychological tests (AUC 0.69–0.77 MCI/0.91–0.92 dementia). Conclusions: cCOG provides a promising tool for detecting MCI and dementia with potential for a cost‐effective approach including home‐based cognitive assessments.

Published
2020

37. Impact of a clinical decision support tool on prediction of progression in early-stage dementia:a prospective validation study

Author

Bruun, M. (Marie), Frederiksen, K. S. (Kristian S.), Rhodius-Meester, H. F. (Hanneke F. M.), Baroni, M. (Marta), Gjerum, L. (Le), Koikkalainen, J. (Juha), Urhemaa, T. (Timo), Tolonen, A. (Antti), van Gils, M. (Mark), Rueckert, D. (Daniel), Dyremose, N. (Nadia), Andersen, B. B. (Birgitte B.), Lemstra, A. W. (Afina W.), Hallikainen, M. (Merja), Kurl, S. (Sudhir), Herukka, S.-K. (Sanna-Kaisa), Remes, A. M. (Anne M.), Waldemar, G. (Gunhild), Soininen, H. (Hilkka), Mecocci, P. (Patrizia), van der Flier, W. M. (Wiesje M.), Lötjönen, J. (Jyrki), Hasselbalch, S. G. (Steen G.), Bruun, M. (Marie), Frederiksen, K. S. (Kristian S.), Rhodius-Meester, H. F. (Hanneke F. M.), Baroni, M. (Marta), Gjerum, L. (Le), Koikkalainen, J. (Juha), Urhemaa, T. (Timo), Tolonen, A. (Antti), van Gils, M. (Mark), Rueckert, D. (Daniel), Dyremose, N. (Nadia), Andersen, B. B. (Birgitte B.), Lemstra, A. W. (Afina W.), Hallikainen, M. (Merja), Kurl, S. (Sudhir), Herukka, S.-K. (Sanna-Kaisa), Remes, A. M. (Anne M.), Waldemar, G. (Gunhild), Soininen, H. (Hilkka), Mecocci, P. (Patrizia), van der Flier, W. M. (Wiesje M.), Lötjönen, J. (Jyrki), and Hasselbalch, S. G. (Steen G.)

Abstract

Background: In clinical practice, it is often difficult to predict which patients with cognitive complaints or impairment will progress or remain stable. We assessed the impact of using a clinical decision support system, the PredictND tool, to predict progression in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in memory clinics. Methods: In this prospective multicenter study, we included 429 patients with SCD (n = 230) and MCI (n = 199) (female 54%, age 67 ± 9, MMSE 28 ± 2) and followed them for at least 12 months. Based on all available patient baseline data (demographics, cognitive tests, cerebrospinal fluid biomarkers, and MRI), the PredictND tool provides a comprehensive overview of the data and a classification defining the likelihood of progression. At baseline, a clinician defined an expected follow-up diagnosis and estimated the level of confidence in their prediction using a visual analogue scale (VAS, 0–100%), first without and subsequently with the PredictND tool. As outcome measure, we defined clinical progression as progression from SCD to MCI or dementia, and from MCI to dementia. Correspondence between the expected and the actual clinical progression at follow-up defined the prognostic accuracy. Results: After a mean follow-up time of 1.7 ± 0.4 years, 21 (9%) SCD and 63 (32%) MCI had progressed. When using the PredictND tool, the overall prognostic accuracy was unaffected (0.4%, 95%CI − 3.0%; + 3.9%; p = 0.79). However, restricting the analysis to patients with more certain classifications (n = 203), we found an increase of 3% in the accuracy (95%CI − 0.6%; + 6.5%; p = 0.11). Furthermore, for this subgroup, the tool alone showed a statistically significant increase in the prognostic accuracy compared to the evaluation without tool (6.4%, 95%CI 2.1%; 10.7%; p = 0.004). Specifically, the negative predictive value was high. Moreover, confidence in the prediction increased significantly (∆VAS = 4%, p

Published
2019

38. Detecting frontotemporal dementia syndromes using MRI biomarkers

Author

Bruun, M. (Marie), Koikkalainen, J. (Juha), Rhodius-Meester, H. F. (Hanneke F. M.), Baroni, M. (Marta), Gjerum, L. (Le), van Gils, M. (Mark), Soininen, H. (Hilkka), Remes, A. M. (Anne M.), Hartikainen, P. (Päivi), Waldemar, G. (Gunhild), Mecocci, P. (Patrizia), Barkhof, F. (Frederik), Pijnenburg, Y. (Yolande), van der Flier, W. M. (Wiesje M.), Hasselbalch, S. G. (Steen G.), Lötjönen, J. (Jyrki), Frederiksen, K. S. (Kristian S.), Bruun, M. (Marie), Koikkalainen, J. (Juha), Rhodius-Meester, H. F. (Hanneke F. M.), Baroni, M. (Marta), Gjerum, L. (Le), van Gils, M. (Mark), Soininen, H. (Hilkka), Remes, A. M. (Anne M.), Hartikainen, P. (Päivi), Waldemar, G. (Gunhild), Mecocci, P. (Patrizia), Barkhof, F. (Frederik), Pijnenburg, Y. (Yolande), van der Flier, W. M. (Wiesje M.), Hasselbalch, S. G. (Steen G.), Lötjönen, J. (Jyrki), and Frederiksen, K. S. (Kristian S.)

Abstract

Background: Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another. Methods: In this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer’s disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200). Results: The anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, neg

Published
2019

39. Evaluating combinations of diagnostic tests to discriminate different dementia types

Author

Bruun, M. (Marie), Rhodius-Meester, H. F. (Hanneke F. M.), Koikkalainen, J. (Juha), Baroni, M. (Marta), Gjerum, L. (Le), Lemstra, A. W. (Afina W.), Barkhof, F. (Frederik), Remes, A. M. (Anne M.), Urhemaa, T. (Timo), Tolonen, A. (Antti), Rueckert, D. (Daniel), van Gils, M. (Mark), Frederiksen, K. S. (Kristian S.), Waldemar, G. (Gunhild), Scheltens, P. (Philip), Mecocci, P. (Patrizia), Soininen, H. (Hilkka), Lötjönen, J. (Jyrki), Hasselbalch, S. G. (Steen G.), van der Flier, W. M. (Wiesje M.), Bruun, M. (Marie), Rhodius-Meester, H. F. (Hanneke F. M.), Koikkalainen, J. (Juha), Baroni, M. (Marta), Gjerum, L. (Le), Lemstra, A. W. (Afina W.), Barkhof, F. (Frederik), Remes, A. M. (Anne M.), Urhemaa, T. (Timo), Tolonen, A. (Antti), Rueckert, D. (Daniel), van Gils, M. (Mark), Frederiksen, K. S. (Kristian S.), Waldemar, G. (Gunhild), Scheltens, P. (Philip), Mecocci, P. (Patrizia), Soininen, H. (Hilkka), Lötjönen, J. (Jyrki), Hasselbalch, S. G. (Steen G.), and van der Flier, W. M. (Wiesje M.)

Abstract

Introduction: We studied, using a data-driven approach, how different combinations of diagnostic tests contribute to the differential diagnosis of dementia. Methods: In this multicenter study, we included 356 patients with Alzheimer’s disease, 87 frontotemporal dementia, 61 dementia with Lewy bodies, 38 vascular dementia, and 302 controls. We used a classifier to assess accuracy for individual performance and combinations of cognitive tests, cerebrospinal fluid biomarkers, and automated magnetic resonance imaging features for pairwise differentiation between dementia types. Results: Cognitive tests had good performance in separating any type of dementia from controls. Cerebrospinal fluid optimally contributed to identifying Alzheimer’s disease, whereas magnetic resonance imaging features aided in separating vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Combining diagnostic tests increased the accuracy, with balanced accuracies ranging from 78% to 97%. Conclusions: Different diagnostic tests have their distinct roles in differential diagnostics of dementias. Our results indicate that combining different diagnostic tests may increase the accuracy further.

Published
2018

43. The RESET project: Constructing a European tephra lattice for refined synchronisation of environmental and archaeological events during the last c. 100 ka

Author

Lowe, John J, Ramsey, Christopher Bronk, Housley, Rupert A., Lane, Christine S., Tomlinson, Emma L., Stringer, Chris, Davies, William, Barton, Nick, Pollard, Mark, Gamble, Clive, Menzies, Martin, Rohling, Eelco, Roberts, Andrew, Blockley, Simon, Cullen, Victoria, Grant, Katharine, Lewis, Mark, Macleod, Alison, White, Dustin, Albert, Paul, Hardiman, Mark, Lee, Sharen, Anna, Oh, Satow, Christopher, Cross, Joanna K., Law, Cassian Bramham, Todman, Anna, Bourne, Anna, Matthews, Ian, Müller, Wolfgang, Smith, Victoria, Wulf, Sabine, Anghelinu, M., Antl Weiser, W., Bar Yosef, O., Boric, D., Boscato, P., Ronchitelli, A., Chabai, V., Veselsky, A., Uthmeier, T., Farrand, W., Gjipali, I., Ruka, R., Güleç, E., Karavanic, I., Karkanas, P., King, T., Komšo, D., Koumouzelis, M., Kyparissi, N., Lengyel, G., Mester, Z., Neruda, P., Panagopoulou, E., Shalamanov Korobar, L., Tolevski, I., Sirakov, N., Guadelli, A., Guadelli, J. L., Ferrier, C., Skrdla, P., Slimak, L., Soler, N., Soler, J., Soressi, M., Tushabramishvilii, N., Zilhão, J., Angelucci, D., Albert, P., Bramham Law, C., Cullen, V. L., Lincoln, P., Staff, R., Flower, K., Aouadi Abdeljaouad, N., Belhouchet, L., Barker, G., Bouzouggar, A., Van Peer, P., Kindermann, K., Gerken, K., Niemann, H., Tipping, R., Saville, A., Ward, T., Clausen, I., Weber, M. J., Kaiser, K., Torksdorf, J. F., Turner, F., Veil, S., Nygaard, N., Pyne O'Donnell, S. D. F., Masojc, M., Nalepka, D., Jurochnik, A., Kabacinski, J., Antoine, P., Olive, M., Christensen, M., Bodu, P., Debout, G., Orliac, M., De Bie, M., Van Gils, M., Paulissen, E., Brou, L., Leesch, D., Hadorn, P., Thew, N., Riede, F., Heinen, M., Joris, O., Richter, J., Knipping, M., Stika, H. P., Friedrich, M., Conard, N., Malina, M., Kind, C. J., Beutelspacher, T., Mortensen, M. F., Burdukiewicz, J. M., Szynkiewicz, A., Poltowicz Bobak, M., Bobak, D., Wisniewski, A., Przezdziecki, M., Valde Nowak, P., Muzyczuk, A., Davies, L., Macleod, A., Morgan, P., Aydar, Erkan, Çubukçu, Evren, Brown, Richard, Coltelli, Mauro, Castro, Deborah Lo, Cioni, Raffaello, Derosa, Rosanna, Donato, Paola, Roberto, Alessio Di, Gertisser, Ralf, Giordano, Guido, Branney, Mike, Jordan, Nina, Keller, Jörg, Kinvig, Helen, Gottsman, Jo, Blundy, Jon, Marani, Michael, Orsi, Giovanni, Civetta, Lucia, Arienzo, Ilenia, Carandente, Antonio, Rosi, Mauro, Zanchetta, Giovanni, Seghedi, Ioan, Szakacs, Alex, Sulpizio, Roberto, Thordarson, Thor, Trincardi, Fabio, Vigliotti, Luigi, Asioli, Alesssandra, Piva, Andrea, Andric, M., Brauer, A., de Klerk, P., Filippi, M. L., Finsinger, W., Galovic, L., Jones, T., Lotter, A., Müller, U., Pross, J., Mangerud, J., Lohne, Ø., Pyne O'Donnell, S., Markovic, S., Pini, R., Ravazzi, C., Theuerkauf, M., Tzedakis, C., Margari, V., Veres, D., Wastegård, S., Ortiz, J. E., Torres, T., Díaz Bautista, A., Moreno, A., Valero Garcés, B., Lowick, S., Ottolini, Lusia, John J. Lowe a,, Christopher Bronk Ramsey, B, A, Rupert A. Housley, B, Christine S. Lane, C, Emma L. Tomlinson, Team, Reset, and Giordano, Guido

Subjects
Archeology, Environmental change, Evolution, Dansgaard–Oeschger and Heinrich events, Abrupt environmental transitions (AETs), Dansgaard-Oeschger and Heinrich events, Last Glacial stage, Middle to Upper Palaeolithic, Tephra database, Tephra geochemistry, Volcanic ash isochrons, Geology, Global and Planetary Change, Ecology, Evolution, Behavior and Systematics, Archeology (arts and humanities), Behavior and Systematics, Glacial period, Tephra, Holocene, Isochron dating, Ecology, Volcanic ash isochron, Tephra geochemistr, Quaternary science, Archaeology, Ecology, Evolution, Behavior and Systematic, Dansgaard-Oeschger and Heinrich event, Mainland, Physical geography
Abstract

This paper introduces the aims and scope of the RESET project (. RESponse of humans to abrupt Environmental Transitions), a programme of research funded by the Natural Environment Research Council (UK) between 2008 and 2013; it also provides the context and rationale for papers included in a special volume of Quaternary Science Reviews that report some of the project's findings. RESET examined the chronological and correlation methods employed to establish causal links between the timing of abrupt environmental transitions (AETs) on the one hand, and of human dispersal and development on the other, with a focus on the Middle and Upper Palaeolithic periods. The period of interest is the Last Glacial cycle and the early Holocene (c. 100-8 ka), during which time a number of pronounced AETs occurred. A long-running topic of debate is the degree to which human history in Europe and the Mediterranean region during the Palaeolithic was shaped by these AETs, but this has proved difficult to assess because of poor dating control. In an attempt to move the science forward, RESET examined the potential that tephra isochrons, and in particular non-visible ash layers (cryptotephras), might offer for synchronising palaeo-records with a greater degree of finesse. New tephrostratigraphical data generated by the project augment previously-established tephra frameworks for the region, and underpin a more evolved tephra 'lattice' that links palaeo-records between Greenland, the European mainland, sub-marine sequences in the Mediterranean and North Africa. The paper also outlines the significance of other contributions to this special volume: collectively, these illustrate how the lattice was constructed, how it links with cognate tephra research in Europe and elsewhere, and how the evidence of tephra isochrons is beginning to challenge long-held views about the impacts of environmental change on humans during the Palaeolithic. © 2015 Elsevier Ltd., RESET was funded through Consortium Grants awarded by the Natural Environment Research Council, UK, to a collaborating team drawn from four institutions: Royal Holloway University of London (grant reference NE/E015905/1), the Natural History Museum, London (NE/E015913/1), Oxford University (NE/E015670/1) and the University of Southampton, including the National Oceanography Centre (NE/01531X/1). The authors also wish to record their deep gratitude to four members of the scientific community who formed a consultative advisory panel during the lifetime of the RESET project: Professor Barbara Wohlfarth (Stockholm University), Professor Jørgen Peder Steffensen (Niels Bohr Institute, Copenhagen), Dr. Martin Street (Romisch-Germanisches Zentralmuseum, Neuwied) and Professor Clive Oppenheimer (Cambridge University). They provided excellent advice at key stages of the work, which we greatly valued. We also thank Jenny Kynaston (Geography Department, Royal Holloway) for construction of several of the figures in this paper, and Debbie Barrett (Elsevier) and Colin Murray Wallace (Editor-in-Chief, QSR) for their considerable assistance in the production of this special volume.

Published
2015
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45. Het begin van exit : de ontwikkeling van een beleidskader met daarin de momentkeuze voor het opstellen van een exit strategie bij statebuilding operaties

Author

Ente van Gils, M. H. S. and Ente van Gils, M. H. S.

Abstract

Begeleider: Prof. dr. Ir. G.E. Frerks.; Met literatuuropgave., In deze scriptie wordt onderzoek gedaan naar de ontwikkeling van een beleidskader waaruit overheden kunnen afleiden in hoeverre het opstellen van een exit-strategie voorafgaand aan een statebuilding operatie noodzakelijk en mogelijk is of niet. Het beleidskader is voornamelijk bedoeld voor overheden en IGO's maar is ook toepasbaar voor andere actoren zoals NGO's.

Published
2016

50. Transitie als benchmark

Author

van der Heijden, J, Nooteboom, Sibout, van Gils, M., de Jong, B., and Public Administration

Published
2009

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