99 results on '"Brolin K"'
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2. The learning environment and supportive supervision promote learning and are based on the relationship between students and supervisors - A qualitative study
- Author
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Nyqvist, J., Brolin, K., Nilsson, T., and Lindström, V.
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- 2020
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3. Evaluation of prophylactic therapy in haemophilia with global coagulation tests
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Zetterberg, E., Brolin, K., Lindahl, R., Knobe, K., and Berntorp, E.
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- 2018
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4. Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
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Krohn, L., Heilbron, K., Blauwendraat, C., Reynolds, R. H., Yu, E., Senkevich, K., Rudakou, U., Estiar, M. A., Gustavsson, E. K., Brolin, K., Ruskey, J. A., Freeman, K., Asayesh, F., Chia, R., Arnulf, I., M. T. M., Hu, Montplaisir, J. Y., Gagnon, J. -F., Desautels, A., Dauvilliers, Y., Gigli, G. L., Valente, M., Janes, F., Bernardini, A., Hogl, B., Stefani, A., Ibrahim, A., Sonka, K., Kemlink, D., Oertel, W., Janzen, A., Plazzi, G., Biscarini, F., Antelmi, E., Figorilli, M., Puligheddu, M., Mollenhauer, B., Trenkwalder, C., Sixel-Doring, F., Cochen De Cock, V., Monaca, C. C., Heidbreder, A., Ferini-Strambi, L., Dijkstra, F., Viaene, M., Abril, B., Boeve, B. F., Aslibekyan, S., Auton, A., Babalola, E., Bell, R. K., Bielenberg, J., Bryc, K., Bullis, E., Coker, D., Partida, G. C., Dhamija, D., Das, S., Elson, S. L., Filshtein, T., Fletez-Brant, K., Fontanillas, P., Freyman, W., Gandhi, P. M., Hicks, B., Hinds, D. A., Jewett, E. M., Jiang, Y., Kukar, K., Lin, K. -H., Lowe, M., Mccreight, J. C., Mcintyre, M. H., Micheletti, S. J., Moreno, M. E., Mountain, J. L., Nandakumar, P., Noblin, E. S., O'Connell, J., Petrakovitz, A. A., Poznik, G. D., Schumacher, M., Shastri, A. J., Shelton, J. F., Shi, J., Shringarpure, S., Tran, V., Tung, J. Y., Wang, X., Wang, W., Weldon, C. H., Wilton, P., Hernandez, A., Wong, C., Tchakoute, C. T., Scholz, S. W., Ryten, M., Bandres-Ciga, S., Noyce, A., Cannon, P., Pihlstrom, L., Nalls, M. A., Singleton, A. B., Rouleau, G. A., Postuma, R. B., Gan-Or, Z., and 23andMe Research Team
- Subjects
Multidisciplinary ,Risk factors ,General Physics and Astronomy ,Genomics ,General Chemistry ,Human medicine ,Genome-wide association studies ,General Biochemistry, Genetics and Molecular Biology - Abstract
Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention. REM-sleep behavior disorder often precedes Parkinson's disease or dementia. Here, the authors perform a genome-wide association study for REM-sleep behavior disorder, and discover how it potentially affects gene expression in the brain.
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- 2022
5. Low prevalence of known pathogenic mutations in dominant PD genes: A Swedish multicenter study
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Puschmann, A. (Andreas), Jiménez-Ferrer, I. (Itzia), Lundblad-Andersson, E. (Elin), Mårtensson, E. (Emma), Hansson, O. (Oskar), Odin, P. (Per), Widner, H. (Håkan), Brolin, K. (Kajsa), Mzezewa, R. (Ropafadzo), Kristensen, J. (Jonas), Soller, M. (Maria), Rödström, E.Y. (Emil Ygland), Ross, O.A. (Owen), Toft, M. (Mathias), Breedveld, G.J. (Guido), Bonifati, V. (Vincenzo), Brodin, L. (Lovisa), Zettergren, A. (Anna), Sydow, O. (Olof), Linder, J. (Jan), Wirdefeldt, K. (Karin), Svenningsson, P. (Per), Nissbrandt, H. (Hans), Belin, A.C. (Andrea Carmine), Forsgren, L. (Lars), Swanberg, M. (Maria), Puschmann, A. (Andreas), Jiménez-Ferrer, I. (Itzia), Lundblad-Andersson, E. (Elin), Mårtensson, E. (Emma), Hansson, O. (Oskar), Odin, P. (Per), Widner, H. (Håkan), Brolin, K. (Kajsa), Mzezewa, R. (Ropafadzo), Kristensen, J. (Jonas), Soller, M. (Maria), Rödström, E.Y. (Emil Ygland), Ross, O.A. (Owen), Toft, M. (Mathias), Breedveld, G.J. (Guido), Bonifati, V. (Vincenzo), Brodin, L. (Lovisa), Zettergren, A. (Anna), Sydow, O. (Olof), Linder, J. (Jan), Wirdefeldt, K. (Karin), Svenningsson, P. (Per), Nissbrandt, H. (Hans), Belin, A.C. (Andrea Carmine), Forsgren, L. (Lars), and Swanberg, M. (Maria)
- Abstract
Objective: To determine the frequency of mutations known to cause autosomal dominant Parkinson disease (PD) in a series with more than 10% of Sweden's estimated number of PD patients. Methods: The Swedish Parkinson Disease Genetics Network was formed as a national multicenter consortium of clinical researchers who together have access to DNA from a total of 2,206 PD patients; 85.4% were from population-based studies. Samples were analyzed centrally for known pathogenic mutations in SNCA (duplications/triplications, p.Ala30Pro, p.Ala53Thr) and LRRK2 (p.Asn1437His, p.Arg1441His, p.Tyr1699Cys, p.Gly2019Ser, p.Ile2020Thr). We compared the frequency of these mutations in Swedish patients with published PD series and the gnomAD database. Results: A family history of PD in first- and/or second-degree relatives was reported by 21.6% of participants. Twelve patients (0.54%) carried LRRK2 p.(Gly2019Ser) mutations, one patient (0.045%) an SNCA duplication. The frequency of LRRK2 p.(Gly2019Ser) carriers was 0.11% in a matched Swedish control cohort and a similar 0.098% in total gnomAD, but there was a marked difference between ethnicities in gnomAD, with 42-fold higher frequency among Ashkenazi Jews than all others combined. Conclusions: In relative terms, the LRRK2 p.(Gly2019Ser) variant is the most frequent mutation among Swedish or international PD patients, and in gnomAD. SNCA duplications were the second most common of the mutations examined. In absolute terms, however, these known pathogenic variants in dominant PD genes are generally very rare and can only explain a minute fraction of familial aggregation of PD. Additional genetic and environmental mechanisms may explain the frequent co-occurrence of PD in close relatives.
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- 2019
- Full Text
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6. Low prevalence of known pathogenic mutations in dominant PD genes: A Swedish multicenter study
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Puschmann, A, Jimenez-Ferrer, I, Lundblad-Andersson, E, Martensson, E, Hansson, O, Odin, P, Widner, H, Brolin, K, Mzezewa, R, Kristensen, J, Soller, M, Rodstrom, EY, Ross, OA, Toft, M, Breedveld, Guido, Bonifati, Vincenzo, Brodin, L, Zettergren, A, Sydow, O, Linder, J, Wirdefeldt, K, Svenningsson, P, Nissbrandt, H, Belin, A C, Forsgren, L, Swanberg, M, Puschmann, A, Jimenez-Ferrer, I, Lundblad-Andersson, E, Martensson, E, Hansson, O, Odin, P, Widner, H, Brolin, K, Mzezewa, R, Kristensen, J, Soller, M, Rodstrom, EY, Ross, OA, Toft, M, Breedveld, Guido, Bonifati, Vincenzo, Brodin, L, Zettergren, A, Sydow, O, Linder, J, Wirdefeldt, K, Svenningsson, P, Nissbrandt, H, Belin, A C, Forsgren, L, and Swanberg, M
- Published
- 2019
7. Ezetimibe added to statin therapy after acute coronary syndromes
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Cannon, Christopher P., Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, Califf, Musliner T, Robert M., Tershakovec, A, Gurfinkel, E, Aylward, P, Tonkin, A, Maurer, G, Van de Werf, F, Nicolau, Jc, Theroux, P, Genest, J, Armstrong, P, Corbalan, R, Isaza, D, Spinar, J, Grande, P, Voitk, J, Kesaniemi, A, Bassand, Jp, Farnier, M, Darius, H, Keltai, M, Mathur, A, Mittal, S, Reddy, K, Lewis, B, De Ferrari GM, Ophuis, To, Jukema, J, White, H, Pedersen, T, Britto, F, Ruzyllo, W, Carrageta, M, Duris, T, Dalby, A, Seung, Kb, Lopez-Sendon, J, Dellborg, M, Mach, F, Guneri, S, Parkhomenko, A, Brady, A, Cannon, C, Blazing, M, Ballantyne, C, de Lemos, J, Kleiman, N, Mcguire, Dk, Centeno, E, Casalins, M, Cartasegna, L, Beltrano, Mc, Guerrero, R, Fanuele, M, Berra, F, Egido, J, Colombo, H, Dellatorre, M, Terns, P, Blumberg, E, Reges, P, Azize, G, Ramos, H, Fernandez, R, Carlessi, C, Milesi, R, Schmuck, R, Duronto, E, Procopio, G, Carlevaro, O, Maffeo, H, Beloscar, J, Viso, M, Hominal, M, Castoldi, M, Bluguermann, J, Mauro, D, Macin, S, Cocco, N, Ruiz, N, Ricart, J, Lozada, A, Nani, S, Turri, D, Fernandez, H, Caruso, O, Zarandon, R, Bono, J, Arias, V, Allall, O, Marino, J, Cusimano, S, Schygiel, P, Buzetti, C, Penaloza, N, Berli, M, Worthley, S, Roach, A, Chew, D, Wright, T, Leitch, J, Hicks, E, Rankin, J, Venn-Edmonds, C, Lehman, R, Morrison, H, Shaw, J, Mak, V, Hii, C, Smith, K, Cross, D, Lilwall, L, Nelson, G, Loxton, A, Horowitz, J, Rose, J, Steinwender, C, Leisch, F, Kammler, J, Brussee, H, Zweiker, R, Niederl, E, Weihs, W, Giorgio, G, Lang, I, Drexel, H, Zanolin, D, Hoppe, U, Atzenhofer-Baumgartner, K, Pichler, M, Hainzer, D, Eber, B, Pichler, F, Foeger, B, Wechselberger, T, Mayr, H, Hofer, J, Stockenhuber, F, Warlits, B, Huber, K, Egger, F, Weidinger, F, Ziegler, B, Jirak, P, Metzler, B, Pachinger, O, Wanitschek, M, Auer, J, Grabscheit, G, Podczeck-Schweighofer, A, Priesnitz, T, Frank, H, El Allaf, D, Marechal, P, Roosen, J, Joly, E, Lefebvre, P, Arend, C, Sinnaeve, P, De Velder, L, Hellemans, S, Vanhauwaert, B, Van Dorpe, A, Heyse, A, Vantomme, C, Striekwold, H, Van Den Broeck, D, Lancellotti, P, Schoors, D, Lemoine, I, Taeymans, Y, De Wolf, L, Brike, C, Vercauteren, S, Tahon, S, Vervoort, G, Mestdagh, I, Pirenne, B, Cardinal, F, Lips, S, Dujardin, K, Debrouwer, K, Dhooghe, G, Holvoet, G, van de Borne, P, Renard, M, De Clippel, M, Lesseliers, H, Van Miert, N, Saraiva, J, Vicente, C, Rossi, P, Dos Santos LB, Duda, N, Tognon, Ap, Serrano, C, Gomes, Fl, Manenti, Er, Silveira, Ds, Maia, L, Mouco, Om, Paiva, M, Antonangelo, A, de Souza, J, Lino, Ea, Leães, P, Blacher, Mg, Kormann, A, Ultramari, Ft, Dutra, O, Mendelski, Am, Morgado, S, Ardito, W, Greque, G, Ardito, Rv, Pimentel Filho, P, Zucchetti, C, Alves, A, Seabra, Am, Mattos, M, Miranda, Lf, Silva, D, Uehara, Rm, Marin Neto, J, Schmidt, A, Braga, J, Rodrigues, A, Abrantes, J, Pinheiro, L, Bodanese, L, Magedanz, Éh, Piegas, L, Dos Santos ES, Wainstein, M, Ribeiro, J, Stein, R, Marino, R, Machado, Vm, Moraes Junior, J, Guimarães, S, da Costa FA, Ferraz, Rf, Albuquerque, D, Rocha, Rm, de Carvalho Moreira, R, Dohmann, H, Costantini, C, Tarastchuk, Jc, Coelho, O, Cirillo, W, Sousa, A, Almeira, As, Stefanini, E, Silva, F, Teixeira, M, da Cunha, C, Précoma, D, Facchi, Tl, Rupka, D, Thiessen, S, Warnica, J, Smith, B, Della Siega, A, Klinke, P, Nelson, S, Dion, D, Gilbert, N, Hui, W, Kvill, L, Sussex, B, Luther, A, Dupuis, R, Ouimet, F, Pandey, A, Clarus, S, Senaratne, M, Ferdinandis, H, Mukherjee, A, Bozek, B, Vizel, S, Markov, G, Zimmermann, R, Stephens, W, Tremblay, B, Wong, G, Uchida, N, Brossoit, R, Peck, C, Van Kieu, C, Forgione, M, Bata, I, Cossett, J, Kostuk, W, Arnold, M, Bone, C, Grondin, F, Bilodeau, N, Gosselin, G, David, M, Giannoccaro, J, Beresford, P, Polasek, P, Roberts, P, Doucet, M, Beaudry, M, Cheung, S, Cleveland, T, Bhargava, R, Mccallum, A, Ma, P, Morrissette, J, Cleveland, D, Chadwyn, D, Nigro, F, Weeks, A, Cryderman, C, Leader, R, Houde, G, Rousseau, S, Pearce, M, Radyk, M, Lonn, E, Magi, A, Lefkowitz, C, Sandrin, F, Coffin, N, Lubelsky, B, Coldwell, J, Habot, J, Mcpherson, C, De Larochelliere, R, Roy, M, Haichin, R, Barber, C, Bhesania, T, Kitagawa, H, To, T, Donnelly, B, Tymchak, W, Harris, L, Kouz, S, Huynh, T, St Jacques, B, Lamy, A, Rizzo, A, Stein, J, Childs, C, Wong, B, Poirier, R, Gupta, M, Dela Cruz, C, Constance, C, Gauthier, M, Ervin, F, Ouellette, M, Kokis, A, Lemay, C, Kwok, K, Leung, C, Lee, D, Nesmith, J, Renton, J, Syan, G, Turek, M, Hogan, D, Griffin, P, Lipson, A, Winestock, J, Abramson, B, Fogel, A, Gagne, C, Bergeron, J, Clarke, A, Slipp, S, Darcel, I, Carling-Chambers, L, Kannampuzha, P, Pallie, S, Krekorian, S, Vertes, G, Roth, S, Lai, K, Heath, J, Perez, L, Arriagada, G, Castro, P, Villa, F, Rodríguez, M, Ramos, G, Baraona, F, Núñez, A, García, M, Jofre, C, Silva, P, Lamich, R, Yovaniniz, P, Escobar, E, Dussaubat, A, Segura, E, Ramirez, M, Lapostol, C, Palma, A, Encina, L, Zapata, M, Baeza, N, Varela, P, Pérez, L, Jaramillo, C, Ruiz, S, Sanchez, G, Perdomo, I, Manzur, F, Cohen, Le, Velasquez, J, Arana, C, Alvarez, Y, Triana, M, Balaguera, J, de Salazar, D, Rendon, N, Botero, R, Ruiz, A, Saaibi, J, Medina, J, Jaramillo, M, Calderón, Mj, Delgado, J, Bohorquez, R, Medina, Mf, Herrera, M, Rosales, D, Mendoza, F, Martinez, S, Ternera, A, Castro, R, Baiz, A, Martinez, M, Orozco, A, Suarez, M, Fonseca, Y, Beltran, R, Cepeda, M, Jaramillo, N, Valenzuela, C, Gutierrez, M, Sanchez, A, Vitovec, J, Hlinomaz, O, Poloczek, M, Mayer, O, Veselka, J, Vejvoda, J, Soucek, M, Spac, J, Novobilsky, K, Srp, V, Francek, L, Branny, M, Sknouril, L, Motovska, Z, Rohac, F, Stankova, A, Fiala, T, Holub, M, Zeman, K, Pohludkova, L, Pospisilova, E, Tuma, P, Cihalik, C, Oral, I, Podpera, I, Stepanovova, R, Uricar, M, Solar, M, Pelouch, R, Porzer, M, Grussmannova, K, Stipal, R, Reichert, P, Hradec, J, Kral, J, Sejkova, B, Janek, B, Pitha, J, Linhart, A, Polacek, P, Koeber, L, Clemmensen, P, Hebin, Ch, Schmidt, E, Pedersen, Ms, Roseva-Nielsen, N, Kristensen, K, Bang-Hansen, T, Jensen, J, Laage-Petersen, J, Nielsen, H, Stokholm, E, Thayssen, P, Cappelen, H, Jensen, T, Winther-Friis, B, Klausen, I, Hedegaard, B, May, O, Andersen, M, Bottzauw, J, Lush, A, Markenvard, J, Vestager, Km, Bronnum-Schou, J, Hempel, H, Petersen, J, Nielsen, Aj, Thomsen, K, Nielsen, T, Nygaard, A, Sykulski, R, Jensen, Bs, Ralfkiaer, N, Gottschalck, H, Rasmussen, S, Pedersen, Lr, Dodt, K, Skovsbøl, M, Andersen, O, Tuxen, C, Meier, Aw, Kristensen, T, Rasmussen, O, Lopez, J, Salazar, D, Sanchez, L, Rosero, F, Penaherrera, E, Duarte, Yc, Marmol, R, Andrade, G, Guzman, E, Morillo, A, Aug, L, Loogna, I, Laanmets, P, Mustonen, J, Mäntylä, P, Kesäniemi, A, Ukkola, O, Kervinen, H, Juhela, S, Juvonen, J, Toppinen, A, Jarvenpaa, J, Syvanne, M, Svahn, T, Voutilainen, S, Huotari, A, Nikkila, M, Raiskinmäki, S, Kotila, M, Rajala, A, Laukkanen, J, Hiltunen, P, Melin, J, Nyman, K, Luukkonen, J, Kosonen, P, Huttunen, M, Seppänen, V, Airaksinen, J, Juonala, M, Lehto, S, Savolainen, K, Halkosaari, M, Sia, J, Palomaki, A, Luoma, J, Utriainen, S, Valpas, S, Tiensuu, T, Lilleberg, J, Kainulainen, R, Schiele, F, Bassand, J, Meneveau, N, Galinier, M, Jean, M, Martelet, M, Mouallem, J, Elbaz, M, Puel, J, Carrié, D, Coisne, D, Varroud-Vial, N, Jaboureck, O, Dujardin, J, Leroy, F, Mansourati, J, Funck, F, Jourdain, P, Guillard, N, Coviaux, F, Gay, A, Dourmap-Collas, C, Froger-Bompas, C, Paillard, F, Tricot, O, Maquin-Mavier, I, Dubois-Rande, Jl, Pongas, D, Paris, Ap, Delahaye, F, Ovize, M, Benyahya, L, Bonnet, J, Belle, L, Mangin, L, Lafitte, B, Zemour, G, Doux, N, Agraou, B, El Mansour, N, Traisnel, G, El Jarroudi, M, Ohlmann, P, Diadema, B, Escande, M, Legros, G, Demarcq, Jm, Haftel, Y, Alsagheer, S, Dambrine, P, Cottin, Y, Ghostine, S, Caussin, C, Gacem, A, Bouvier, Jm, Poulard, J, Davy, J, Furber, A, Prunier, F, Muenzel, T, Genth-Zotz, S, Appel, K, Kretzschmar, D, Ferrari, M, Terres, W, Uher, T, Schulze, H, Ochs, H, Morbach, S, Duengen, H, Gross, M, Oezcelik, C, Tahirovic, E, Heuer, H, Laschewski, B, Kadel, C, Rahn, G, Steiner, S, Kreuzer, J, Tsoy, I, Zeiher, A, Muegge, A, Hanefeld, C, Boehm, S, Boudriot, E, Hodenberg, E, Lippe, B, Hausdorf, C, Sydow, K, Baldus, S, Schlesner, C, Tiroch, K, Haltern, G, Guelker, H, Wilhelm, J, Dietz, S, Ebelt, H, Buerke, M, Rupprecht, H, Rittgen, J, Schaeufele, T, Meinhardt, G, Schieber, M, Honold, M, Sieprath, S, Nienaber, C, Hacker, J, Butter, C, Lapp, H, Hirn, S, Pauschinger, M, Zahn, R, Scheffler, U, Schaefer, A, Schieffer, B, Tebbe, U, Kriete, M, Mudra, H, Raeder, T, Braun, P, Zeymer, U, Kouraki, K, Reppel, M, Schunkert, H, Weil, J, Olbrich, H, Schwaiger, P, Mueller, O, Blessing, E, Buss, I, Bohlscheid, V, Kaddatz, J, Skowasch, D, Nickenig, G, Twelker, K, Osterhues, H, Varghese, T, Burghard, S, Kaeaeb, S, Klauss, V, Sohn, Hy, Hauptmann, K, 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Mueller, H., Ash, Y., Wilson, V., Bayer, M., Marshall, J., Dobies, D., Dawson, G., Osman, A., Saba, F., Costello, T., Fuentes, F., Underwood, C., Vijay, N., Washam, M., Dietz, W., Glasgow, B., Mukherjee, S., Hinchion, N., Speirs, S., Thornley, A., Lee, K., Movahed, M., Strootman, D., Chernick, R., Parrott, C., Flock, C., Marques, V., Syzmanski, E., Rama, P., Domingo, D., Wu, L., Bauer, B., Dionisopoulos, P., Aggarwal, A., Holcomb, R., Foster, R., Hancock, T., Hargrove, J., Fletcher, A., Stine, R., Bullivant, M., Adams, K., Lohman, J., Klepper, V., Kabour, A., Neidhardt, J., Phillips, W., Tardiff, S., Aji, J., Corut, S., Foster, G., Firek, C., St Goar, F., Sumner, R., Davis, T., Schneider, R., Schneider, W., Villa, A., Desai, V., Chhabra, A., Banks, K., Herzog, W., Burley, T., Quyyumi, A., Smiley, W., Manocha, P., Fishbein, G., Weller, C., Coffman, A., Kim, C., Kedia, A., Firth, B., Rizvi, M., Dahiya, R., Foster, B., Balcells, E., Metzger, D.C., Lester, J., Bissett, J., Fahdi, I., Sides, E.A., Azrin, M., Martin, C., Quick, A., Conaway, D., Garg, M., Schallert, G., Lancaster, L., Mckissick, S., Atieh, M., Garbarino, J., Eisenberg, D., Uusinarkaus, K., Wirtemburg, P., Ellis, J., Cristaldi, J., Berglund, R., Negus, B., Pappas, J., Rocha, R., Nguyen, T., Stone, J., Janosik, D., Labovitz, A., Elmore, N., Dave, R., Loffredo, K., Gabriel, G., Snyder, C., Ahmed, O., Stone, H., Kelley, M., Diffenback, M., Friedman, B., Zirkle, J., Severa, L., Sample, S., Dignen, K., Raisinghani, A., Ben-Yehuda, O., Ghannadian, B., Moscoso, R., Mankowski, J., Boliek, W., Rukavina, M., Davis, W., Ledbetter, S., Handel, F., Mastouri, R., Mahenthiran, J., Foltz, J., Malhotra, V., Jonas, J., Berk, M., Singh, V., Nelson, M., Elsner, G., Gall, J., Kondo, N., Frank, S., Chandraratna, P., Ranasinghe, S., Ebrahimi, R., Treadwell, M., Walters, B., Hughes, L., Kramer, J., Kumar, K., Mente, T., Lachterman, B., Schifferdecker, B., Munshi, K., Sease, D., Waldo, D., Chandler, G., Manns, D., Nahhas, A., Kamalesh, M., Williams, V., Reich, D., Desalca, M., Sharma, S., Liston, M., Gupta, K., Costa, M., Altschuller, A., Lemmertz, K., Shanes, J., Hansen, C., Therrien, M., Mendelson, R., Ramnarine, R., Myers, G., Donovan, C., Klein, M., Fine, D., Owens, S., Murray, C., Ketroser, R., Heifetz, S., Darnell, Z., Touchon, R., Taghizadeh, B., Bohle, D., Norwood, D., Forrest, T., Jackson, S., Shumate, K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, Cp, Blazing, Ma, Giugliano, Rp, Mccagg, A, White, Ja, Theroux, P, Darius, H, Lewis, B, Ophuis, To, Jukema, Jw, De Ferrari, Gm, Ruzyllo, W, De Lucca, P, Im, K, Bohula, Ea, Reist, C, Wiviott, Sd, Tershakovec, Am, Musliner, Ta, Braunwald, E, Califf, Rm, for the IMPROVE-IT, Investigator, Cianflone, D, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], College of Information Science and Engineering, Ritsumeikan University, Montreal Heart Institute (MONTREAL HEART INSTITUTE), Laboratoire des Micro-algues toxiques, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD), Interuniversity Cardiology Institute Netherlands, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Merck Sharp & Dohme Corp., Merck & Co. Inc, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Cannon, C.P., Blazing, M.A., Giugliano, R.P., Mccagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., Califf, R.M., for the IMPROVE-IT Investigators [.., C. Rapezzi, ], Other departments, Cannon, Christopher P, Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, and Califf, Robert M.
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Male ,Simvastatin ,acute coronary syndrome ,aged ,anticholesteremic agents ,azetidines ,cardiovascular diseases ,cholesterol, ldl ,double-blind method ,drug therapy, combination ,ezetimibe ,female ,humans ,hydroxymethylglutaryl-coa reductase inhibitors ,kaplan-meier estimate ,male ,middle aged ,simvastatin ,triglycerides ,medicine (all ,[SDV]Life Sciences [q-bio] ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Bococizumab ,Triglyceride ,chemistry.chemical_compound ,0302 clinical medicine ,Azetidine ,Cardiovascular Disease ,Anticholesteremic Agent ,Acute Coronary Syndrome ,Aged ,Anticholesteremic Agents ,Azetidines ,Cardiovascular Diseases ,Cholesterol, LDL ,Double-Blind Method ,Drug Therapy, Combination ,Female ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Middle Aged ,Triglycerides ,030212 general & internal medicine ,Medicine (all) ,Research Support, Non-U.S. Gov't ,Hazard ratio ,General Medicine ,Acute Coronary Syndrome, Aged ,Anticholesteremic Agents, Azetidines, Cardiovascular Diseases ,Ezetimibe, Female, Humans ,Male, Middle Aged ,3. Good health ,Multicenter Study ,Editorial ,Cholesterol ,Randomized Controlled Trial ,Combination ,Ezetimibe ,lipids (amino acids, peptides, and proteins) ,Human ,medicine.drug ,medicine.medical_specialty ,Acute Coronary Syndroms ,Urology ,Acute Coronary Syndrome/drug therapy ,Anticholesteremic Agents/adverse effects ,Anticholesteremic Agents/therapeutic use ,Azetidines/adverse effects ,Azetidines/therapeutic use ,Cardiovascular Diseases/epidemiology ,Cardiovascular Diseases/mortality ,Cardiovascular Diseases/prevention & control ,Cholesterol, LDL/blood ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ,Simvastatin/therapeutic use ,Triglycerides/blood ,NO ,LDL ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Drug Therapy ,Internal medicine ,Journal Article ,medicine ,Comparative Study ,Alirocumab ,business.industry ,PCSK9 ,ta3121 ,Lomitapide ,DOENÇAS CARDIOVASCULARES ,Endocrinology ,chemistry ,Statin Therapy ,Hydroxymethylglutaryl-CoA Reductase Inhibitor ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (PCONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).
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- 2015
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8. Evaluation of prophylactic therapy in haemophilia with global coagulation tests
- Author
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Zetterberg, E., primary, Brolin, K., additional, Lindahl, R., additional, Knobe, K., additional, and Berntorp, E., additional
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- 2017
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9. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.
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IMPROVE-IT Investigators, Musliner, T., Tershakovec, A., Gurfinkel, E., Aylward, P., Tonkin, A., Maurer, G., Van de Werf, F., Nicolau, J.C., Theroux, P., Genest, J., Armstrong, P., Corbalan, R., Isaza, D., Spinar, J., Grande, P., Voitk, J., Kesaniemi, A., Bassand, J.P., Farnier, M., Darius, H., Keltai, M., Mathur, A., Mittal, S., Reddy, K., Lewis, B., De Ferrari, G.M., Ophuis, T.O., Jukema, J., White, H., Pedersen, T., Britto, F., Ruzyllo, W., Carrageta, M., Duris, T., Dalby, A., Seung, K.B., Lopez-Sendon, J., Dellborg, M., Mach, F., Guneri, S., Parkhomenko, A., Brady, A., Cannon, C., Blazing, M., Ballantyne, C., de Lemos, J., Kleiman, N., McGuire, D.K., Centeno, E., Casalins, M., Cartasegna, L., Beltrano, M.C., Guerrero, R., Fanuele, M., Berra, F., Egido, J., Colombo, H., Dellatorre, M., Terns, P., Blumberg, E., Reges, P., Azize, G., Ramos, H., Fernandez, R., Carlessi, C., Milesi, R., Schmuck, R., Duronto, E., Procopio, G., Carlevaro, O., Maffeo, H., Beloscar, J., Viso, M., Hominal, M., Castoldi, M., Bluguermann, J., Mauro, D., Macin, S., Cocco, N., Ruiz, N., Ricart, J., Lozada, A., Nani, S., Turri, D., Fernandez, H., Caruso, O., Zarandon, R., Bono, J., Arias, V., Allall, O., Marino, J., Cusimano, S., Schygiel, P., Buzetti, C., Penaloza, N., Berli, M., Worthley, S., Roach, A., Chew, D., Wright, T., Leitch, J., Hicks, E., Rankin, J., Venn-Edmonds, C., Lehman, R., Morrison, H., Shaw, J., Mak, V., Hii, C., Smith, K., Cross, D., Lilwall, L., Nelson, G., Loxton, A., Horowitz, J., Rose, J., Steinwender, C., Leisch, F., Kammler, J., Brussee, H., Zweiker, R., Niederl, E., Weihs, W., Giorgio, G., Lang, I., Drexel, H., Zanolin, D., Hoppe, U., Atzenhofer-Baumgartner, K., Pichler, M., Hainzer, D., Eber, B., Pichler, F., Foeger, B., Wechselberger, T., Mayr, H., Hofer, J., Stockenhuber, F., Warlits, B., Huber, K., Egger, F., Weidinger, F., Ziegler, B., Jirak, P., Metzler, B., Pachinger, O., Wanitschek, M., Auer, J., Grabscheit, G., Podczeck-Schweighofer, A., Priesnitz, T., Frank, H., El Allaf, D., Marechal, P., Roosen, J., Joly, E., Lefebvre, P., Arend, C., Sinnaeve, P., De Velder, L., Hellemans, S., Vanhauwaert, B., Van Dorpe, A., Heyse, A., Vantomme, C., Striekwold, H., Van Den Broeck, D., Lancellotti, P., Schoors, D., Lemoine, I., Taeymans, Y., De Wolf, L., Brike, C., Vercauteren, S., Tahon, S., Vervoort, G., Mestdagh, I., Pirenne, B., Cardinal, F., Lips, S., Dujardin, K., Debrouwer, K., Dhooghe, G., Holvoet, G., van de Borne, P., Renard, M., De Clippel, M., Lesseliers, H., Van Miert, N., Saraiva, J., Vicente, C., Rossi, P., Dos Santos, L.B., Duda, N., Tognon, A.P., Serrano, C., Gomes, F.L., Manenti, E.R., Silveira, D.S., Maia, L., Mouco, O.M., Paiva, M., Antonangelo, A., de Souza, J., Lino, E.A., Leães, P., Blacher, M.G., Kormann, A., Ultramari, F.T., Dutra, O., Mendelski, A.M., Morgado, S., Ardito, W., Greque, G., Ardito, R.V., Pimentel Filho, P., Zucchetti, C., Alves, A., Seabra, A.M., Mattos, M., Miranda, L.F., Silva, D., Uehara, R.M., Marin Neto, J., Schmidt, A., Braga, J., Rodrigues, A., Abrantes, J., Pinheiro, L., Bodanese, L., Magedanz, É.H., Piegas, L., Dos Santos, E.S., Wainstein, M., Ribeiro, J., Stein, R., Marino, R., Machado, V.M., Moraes Junior, J., Guimarães, S., da Costa, F.A., Ferraz, R.F., Albuquerque, D., Rocha, R.M., de Carvalho Moreira, R., Dohmann, H., Costantini, C., Tarastchuk, J.C., Coelho, O., Cirillo, W., Sousa, A., Almeira, A.S., Stefanini, E., Silva, F., Teixeira, M., da Cunha, C., Précoma, D., Facchi, T.L., Rupka, D., Thiessen, S., Warnica, J., Smith, B., Della Siega, A., Klinke, P., Nelson, S., Dion, D., Gilbert, N., Hui, W., Kvill, L., Sussex, B., Luther, A., Dupuis, R., Ouimet, F., Pandey, A., Clarus, S., Senaratne, M., Ferdinandis, H., Mukherjee, A., Bozek, B., Vizel, S., Markov, G., Zimmermann, R., Stephens, W., Tremblay, B., Wong, G., Uchida, N., Brossoit, R., Peck, C., Van Kieu, C., Forgione, M., Bata, I., Cossett, J., Kostuk, W., Arnold, M., Bone, C., Grondin, F., Bilodeau, N., Gosselin, G., David, M., Giannoccaro, J., Beresford, P., Polasek, P., Roberts, P., Doucet, M., Beaudry, M., Cheung, S., Cleveland, T., Bhargava, R., McCallum, A., Ma, P., Morrissette, J., Cleveland, D., Chadwyn, D., Nigro, F., Weeks, A., Cryderman, C., Leader, R., Houde, G., Rousseau, S., Pearce, M., Radyk, M., Lonn, E., Magi, A., Lefkowitz, C., Sandrin, F., Coffin, N., Lubelsky, B., Coldwell, J., Habot, J., McPherson, C., De Larochelliere, R., Roy, M., Haichin, R., Barber, C., Bhesania, T., Kitagawa, H., To, T., Donnelly, B., Tymchak, W., Harris, L., Kouz, S., Huynh, T., St Jacques, B., Lamy, A., Rizzo, A., Stein, J., Childs, C., Wong, B., Poirier, R., Gupta, M., Dela Cruz, C., Constance, C., Gauthier, M., Ervin, F., Ouellette, M., Kokis, A., Lemay, C., Kwok, K., Leung, C., Lee, D., Nesmith, J., Renton, J., Syan, G., Turek, M., Hogan, D., Griffin, P., Lipson, A., Winestock, J., Abramson, B., Fogel, A., Gagne, C., Bergeron, J., Clarke, A., Slipp, S., Darcel, I., Carling-Chambers, L., Kannampuzha, P., Pallie, S., Krekorian, S., Vertes, G., Roth, S., Lai, K., Heath, J., Perez, L., Arriagada, G., Castro, P., Villa, F., Rodríguez, M., Ramos, G., Baraona, F., Núñez, A., García, M., Jofre, C., Silva, P., Lamich, R., Yovaniniz, P., Escobar, E., Dussaubat, A., Segura, E., Ramirez, M., Lapostol, C., Palma, A., Encina, L., Zapata, M., Baeza, N., Varela, P., Pérez, L., Jaramillo, C., Ruiz, S., Sanchez, G., Perdomo, I., Manzur, F., Cohen, L.E., Velasquez, J., Arana, C., Alvarez, Y., Triana, M., Balaguera, J., de Salazar, D., Rendon, N., Botero, R., Ruiz, A., Saaibi, J., Medina, J., Jaramillo, M., Calderón, M.J., Delgado, J., Bohorquez, R., Medina, M.F., Herrera, M., Rosales, D., Mendoza, F., Martinez, S., Ternera, A., Castro, R., Baiz, A., Martinez, M., Orozco, A., Suarez, M., Fonseca, Y., Beltran, R., Cepeda, M., Jaramillo, N., Valenzuela, C., Gutierrez, M., Sanchez, A., Vitovec, J., Hlinomaz, O., Poloczek, M., Mayer, O., Veselka, J., Vejvoda, J., Soucek, M., Spac, J., Novobilsky, K., 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C., Froger-Bompas, C., Paillard, F., Tricot, O., Maquin-Mavier, I., Dubois-Rande, J.L., Pongas, D., Paris, A.P., Delahaye, F., Ovize, M., Benyahya, L., Bonnet, J., Belle, L., Mangin, L., Lafitte, B., Zemour, G., Doux, N., Agraou, B., El Mansour, N., Traisnel, G., El Jarroudi, M., Ohlmann, P., Diadema, B., Escande, M., Legros, G., Demarcq, J.M., Haftel, Y., Alsagheer, S., Dambrine, P., Cottin, Y., Ghostine, S., Caussin, C., Gacem, A., Bouvier, J.M., Poulard, J., Davy, J., Furber, A., Prunier, F., Muenzel, T., Genth-Zotz, S., Appel, K., Kretzschmar, D., Ferrari, M., Terres, W., Uher, T., Schulze, H., Ochs, H., Morbach, S., Duengen, H., Gross, M., Oezcelik, C., Tahirovic, E., Heuer, H., Laschewski, B., Kadel, C., Rahn, G., Steiner, S., Kreuzer, J., Tsoy, I., Zeiher, A., Muegge, A., Hanefeld, C., Boehm, S., Boudriot, E., Hodenberg, E., Lippe, B., Hausdorf, C., Sydow, K., Baldus, S., Schlesner, C., Tiroch, K., Haltern, G., Guelker, H., Wilhelm, J., Dietz, S., Ebelt, H., Buerke, M., Rupprecht, H., Rittgen, J., Schaeufele, T., Meinhardt, G., Schieber, M., Honold, M., Sieprath, S., Nienaber, C., Hacker, J., Butter, C., Lapp, H., Hirn, S., Pauschinger, M., Zahn, R., Scheffler, U., Schaefer, A., Schieffer, B., Tebbe, U., Kriete, M., Mudra, H., Raeder, T., Braun, P., Zeymer, U., Kouraki, K., Reppel, M., Schunkert, H., Weil, J., Olbrich, H., Schwaiger, P., Mueller, O., Blessing, E., Buss, I., Bohlscheid, V., Kaddatz, J., Skowasch, D., Nickenig, G., Twelker, K., Osterhues, H., Varghese, T., Burghard, S., Kaeaeb, S., Klauss, V., Sohn, H.Y., Hauptmann, K., Schulze, M., Gall, K., Felix, S., Doerr, M., Mante, J., Gulba, D., Freick, M., Werner, G., Kleinertz, K., Hobbach, H.P., Halbach, M., Mueller-Ehmsen, J., Mueller, M.E., Mitrovic, V., Peil, A., Laufs, U., vom Dahl, J., Baumanns, S., Scholtz, W., Wiemer, M., Haude, M., Van de Loo, A., Pistorius, K., Schaefer, J., Schwinger, R., Goeing, O., Jung, W., Birkemeyer, R., Lee, W., Kong, S., Yu, C., Chui, K., Merkely, B., 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Melegrito, K., Mostel, E., Harris, R., Chang, M., Hatfield, G., Makam, S., Garvey, M., Levite, H., White, J., Abdel-Latief, A., Pelletier, L., Carr, K., Mckenna, K., De Lemos, J., Soto, G., Kozina, J., Harris, D., Vlastaris, A., Bittel, B., Riba, A., Gugudis, J., Singh, N., Qureshi, I., Doty, W., Lehmann, J., Lieber, I., Martin, S., Nicu, M., Bhalodkar, N., Ravi, P., Canto, J., Bass, M., Campbell, C., Steinhubl, S., Moles, K., Harjai, K., Stapleton, D.D., Hoey, K., Erwin, J., Fikes, W., Stein, B., Sabatino, K., Teklinski, A., Colfer, H., Ward, P., Langevin, E., Faucett, S., Mamdani, S., DeSimone, L., Tuohy, E., Cullen, T., Eisenberg, S., Chronos, N., Allen, R.P., Erickson, B., Mahon, K., Kirby, A., Siegel, C., Stroud, L., Johnson, J., Panchal, V., Pearson, A., Abell, T., De Gregorio, M., Boomer, L., Vahdat, O., VanNatta, B., Long, P., Chalavarya, G., Skatrud, L., Carey, C., Wright, W., Mechem, C., Matthews, B., Adams, A., Vora, K., Wead, J., Koren, M., Gregory, D., El Khadra, M., Peacock, G., Kieval, J., Barron, M., Lewis, D., Grice, R., Bobek, M., Moore, C., Nygaard, T., Fischell, T., Salman, W., Schneider, C., Muhlestein, B., Peeler, D., Chang, D., Todd, A., Chilakamarri, V., Hanley, P., Gelormini, J., Iacona, M.A., Effron, B., Mazzurco, S., Mazzella, M., Wyman, P., Orchard, R., Battin, D., Rezkalla, S., Bishop, C., Sharp, S., Gredler, F., Knap, P., Fadel, M., Saucedo, J., Keng, A., Imburgia, M., Blank, E., Effat, M., Khoury, S., Mardis, R., Baldari, D., Tafuri, L., Mascolo, R., Taylor, D., Mandviwala, M., Khan, W., Mumford, T., Mayer, N., Mitchell, B., Oliver, T., Lombardi, W., Zimmerman, T., Rohrbeck, S., Cooke, L., Craig, M., Mego, D., Griffin, B., Perez, J., LeClerc, K., Addington, J., Aboufakher, R., Ahmed, A., Westecott, B., Steel, K., Hawkins, K., Shah, A., Ward, U., McGreevy, M., Goldberg, R., Prashad, R., McDonough, C., Silver, K., Josephson, R., Witsaman, S., Labib, S., Woodhead, G., Schrank, J., Bell, K., Chandna, H., Holly, D., Bethea, C., Fife, B., Gruberg, L., Singer, A., Ramgadoo, M., Lalonde, T., Morin, R., French, W., Barillas, O., Gradner, G., Kahn, Z., Gress, J., Rocco, D., Thew, S., Stifter, W., Fisher, M., McNamara, J., Kupfer, J., Agocha, A., Cush, S., Jones, S., Whitaker, T., Stover, T., Kumkumian, G., Kent, K., Greenberg, A., Pandey, P., Pytlewski, G., Matsumura, M., Kai, W., Sameshima, S., Thomas, J., MacNicholas, D., Pillai, K., Jones, D., Navas, J.P., Laskoe, B., Patel, P., Fini, G., Minor, S., Shipwash, T., Cabrera-Santamaria, A., Rivera, E., Mincher, L., Jafar, M., Yen, M., Finkle, C., Rahimtoola, A., Severson, L., Labroo, A., Jinich, D., Tam, K., Vogel, C., Aggarwal, R., Zakhary, B., Curtis, S., Lyster, M., Humphrey, K., Lavine, P., Fujise, K., Birnbaum, Y., Allen, J., Kesselbrenner, M., Michel, K., Staniloae, C., Liu, M., Sonel, A., Macioce-Caffas, A., Amidon, T., Leggett, J., Yedinak, S., Gudmundsson, G., Sabharwal, J., Dagefoerde, N., Wu, W., Meyerrose, G., Roongsritong, C., Jenkins, L., Lieberman, S., Sokol, S., Gutierrez, C., Nelson, C., Barrett, J., Hotchkiss, D., Farley, A., Atassi, K., Christy, L., Baig, M., Di Fazio, J., Meengs, M., Thomas, K., Surmitis, J., DeVault, S., Farhat, N., Hulyalkar, A., Riddell, L., Rivera, W., Sheynberg, B., Kobayashi, J., Katsaropoulos, J., Jan, M., Krucoff, M., Paterno, C., Chandrasekaran, S., Curry, R., Cassavar, D., Wheeler, M., McGarvey, J., Schwarz, L., Miller, E., Andrea, B., Carswell, B.S., Lurie, M., Patti, J., Bowden, W., Vasiliauskas, T., Latham, R., Schwartz, B., Bradford, L., Mattleman, S., Wertheimer, J., Goulden, D., Khan, M., Hawkins, B., Ostfeld, R., Mueller, H., Ash, Y., Wilson, V., Bayer, M., Marshall, J., Dobies, D., Dawson, G., Osman, A., Saba, F., Costello, T., Fuentes, F., Underwood, C., Vijay, N., Washam, M., Dietz, W., Glasgow, B., Mukherjee, S., Hinchion, N., Speirs, S., Thornley, A., Lee, K., Movahed, M., Strootman, D., Chernick, R., Parrott, C., Flock, C., Marques, V., Syzmanski, E., Rama, P., Domingo, D., Wu, L., Bauer, B., Dionisopoulos, P., Aggarwal, A., Holcomb, R., Foster, R., Hancock, T., Hargrove, J., Fletcher, A., Stine, R., Bullivant, M., Adams, K., Lohman, J., Klepper, V., Kabour, A., Neidhardt, J., Phillips, W., Tardiff, S., Aji, J., Corut, S., Foster, G., Firek, C., St Goar, F., Sumner, R., Davis, T., Schneider, R., Schneider, W., Villa, A., Desai, V., Chhabra, A., Banks, K., Herzog, W., Burley, T., Quyyumi, A., Smiley, W., Manocha, P., Fishbein, G., Weller, C., Coffman, A., Kim, C., Kedia, A., Firth, B., Rizvi, M., Dahiya, R., Foster, B., Balcells, E., Metzger, D.C., Lester, J., Bissett, J., Fahdi, I., Sides, E.A., Azrin, M., Martin, C., Quick, A., Conaway, D., Garg, M., Schallert, G., Lancaster, L., Mckissick, S., Atieh, M., Garbarino, J., Eisenberg, D., Uusinarkaus, K., Wirtemburg, P., Ellis, J., Cristaldi, J., Berglund, R., Negus, B., Pappas, J., Rocha, R., Nguyen, T., Stone, J., Janosik, D., Labovitz, A., Elmore, N., Dave, R., Loffredo, K., Gabriel, G., Snyder, C., Ahmed, O., Stone, H., Kelley, M., Diffenback, M., Friedman, B., Zirkle, J., Severa, L., Sample, S., Dignen, K., Raisinghani, A., Ben-Yehuda, O., Ghannadian, B., Moscoso, R., Mankowski, J., Boliek, W., Rukavina, M., Davis, W., Ledbetter, S., Handel, F., Mastouri, R., Mahenthiran, J., Foltz, J., Malhotra, V., Jonas, J., Berk, M., Singh, V., Nelson, M., Elsner, G., Gall, J., Kondo, N., Frank, S., Chandraratna, P., Ranasinghe, S., Ebrahimi, R., Treadwell, M., Walters, B., Hughes, L., Kramer, J., Kumar, K., Mente, T., Lachterman, B., Schifferdecker, B., Munshi, K., Sease, D., Waldo, D., Chandler, G., Manns, D., Nahhas, A., Kamalesh, M., Williams, V., Reich, D., Desalca, M., Sharma, S., Liston, M., Gupta, K., Costa, M., Altschuller, A., Lemmertz, K., Shanes, J., Hansen, C., Therrien, M., Mendelson, R., Ramnarine, R., Myers, G., Donovan, C., Klein, M., Fine, D., Owens, S., Murray, C., Ketroser, R., Heifetz, S., Darnell, Z., Touchon, R., Taghizadeh, B., Bohle, D., Norwood, D., Forrest, T., Jackson, S., Shumate, K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, C.P., Blazing, M.A., Giugliano, R.P., McCagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., and Califf, R.M.
- Abstract
Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benef
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- 2015
10. A method to model anticipatory postural control in driver braking events
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Osth, J. (author), Eliasson, E. (author), Happee, R. (author), Brolin, K. (author), Osth, J. (author), Eliasson, E. (author), Happee, R. (author), and Brolin, K. (author)
- Abstract
Human body models (HBMs) for vehicle occupant simulations have recently been extended with active muscles and postural control strategies. Feedback control has been used to model occupant responses to autonomous braking interventions. However, driver postural responses during driver initiated braking differ greatly from autonomous braking. In the present study, an anticipatory postural response was hypothesized, modelled in a whole-body HBM with feedback controlled muscles, and validated using existing volunteer data. The anticipatory response was modelled as a time dependent change in the reference value for the feedback controllers, which generates correcting moments to counteract the braking deceleration. The results showed that, in 11 m/s2 driver braking simulations, including the anticipatory postural response reduced the peak forward displacement of the head by 100 mm, of the shoulder by 30 mm, while the peak head flexion rotation was reduced by 18°. The HBM kinematic response was within a one standard deviation corridor of corresponding test data from volunteers performing maximum braking. It was concluded that the hypothesized anticipatory responses can be modelled by changing the reference positions of the individual joint feedback controllers that regulate muscle activation levels. The addition of anticipatory postural control muscle activations appears to explain the difference in occupant kinematics between driver and autonomous braking. This method of modelling postural reactions can be applied to the simulation of other driver voluntary actions, such as emergency avoidance by steering., Biomechanical Engineering, Mechanical, Maritime and Materials Engineering
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- 2014
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11. The importance of muscle tension on the outcome of impacts with a major vertical component
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Brolin, K., Hedenstierna, S., Halldin, P., Bass, C., Alem, N., Brolin, K., Hedenstierna, S., Halldin, P., Bass, C., and Alem, N.
- Abstract
The hypothesis that muscle tension protects the spine from injuries in helicopter scenarios was tested using a finite-element model of the human head and neck. It was compared with cadaver crash sled experiment with good correlation. Then, simulations were performed with a sinusoidal velocity (5-22 G) applied at T1 60 to the horizontal plane. The model with relaxed muscle activation had delayed and decreased peak head rotation compared with passive properties only. Full muscle activation decreased the injury risk for the 13.5-22 G impacts. A sensitivity study of the impact angle showed a very slight variation of the resulting neck flexion, and 1 change affected all ligament injury predictions less than 4%. Finally, simulations with helmets resulted in increased ligament and disc strains with increasing helmet mass and with an anterior or inferior shift of the centre of gravity. It is concluded that the hypothesis seems to hold.
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- 2008
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12. Evaluation of a combination of continuum and truss finite elements in a model of passive and active muscle tissue
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Hedenstierna, S., primary, Halldin, P., additional, and Brolin, K., additional
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- 2008
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13. The importance of muscle tension on the outcome of impacts with a major vertical component
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Brolin, K., primary, Hedenstierna, S., additional, Halldin, P., additional, Bass, C., additional, and Alem, N., additional
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- 2008
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14. Development and evaluation of a continuum neck muscle model
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Hedenstierna, S., primary, Halldin, P., additional, Brolin, K., additional, and von Holst, H., additional
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- 2006
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15. Finite element simulation of chiropratic adjustment in the cervical spine
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Dahlkvist, J., primary, Brolin, K., additional, and Halldin, P., additional
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- 2006
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16. Stability and fibre reinforced adhesive fixation of vertebral fracture in the upper cervical spine
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Brolin, K., primary, Nordberg, A., additional, and von Holst, H., additional
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- 2006
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17. FE modelling of the neck responses in 3D loading and the influence of muscle activation for HSM evaluations
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Halldin, P., primary, Brolin, K., additional, Hedenstierna, S., additional, and Alem, N., additional
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- 2006
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18. The occupant response to autonomous braking: a modeling approach that accounts for active musculature.
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Osth J, Brolin K, Carlsson S, Wismans J, and Davidsson J
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- 2012
19. Vertebral fractures fixation with composite patch fibre reinforced adhesives.
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Nordberg, A., von Holst, H., Brolin, K., and Beckman, A.
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CERVICAL vertebrae ,FRACTURE fixation ,CYANOACRYLATES ,BONESETTERS ,MEDICAL research - Abstract
Purpose: The aim is to investigate fixation of cervical vertebral fractures by patching it with a composite laminate of adhesive and fibres, in comparison with use of only adhesives. Material and methods: The composite fixation was tested on bonded roe deer vertebrae. 25 specimens were sawed in two halves, creating a generic fracture, and thereafter bonded. The adhesives used were a dental system, Scotchbond XT, and a cyanoacrylate, M-bond 200. The fibres used were unidirectional carbon fibres and randomly distributed E-glass fibres. The composites were applied as a 7 mm wide patch circumferential along the induced fracture. Reference specimens for comparison were also made. The ultimate tensile strength was tested in an Instron 5567. The failure site was examined with a microscope. Strain vectors were tracked using Digital Speckle Analysis. Results: Scotchbond XT + E-glass fibres gave best results, with a tensile strength of 3.5 N/mm circumferential length (24.3% of reference). All composites had lower stiffness than cortical bone. The dental adhesive fibre composites gave better results than the cyanoacrylate fibre composites. In all cases fibre reinforced adhesive composite gave better results than adhesive without fibre reinforcement. Conclusion: Fibre-adhesive composite is a promising technique for fixating cervical vertebral fractures. [ABSTRACT FROM AUTHOR]
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- 2007
20. Dynamic cervical vertebral motion of female and male volunteers and analysis of its interaction with head/neck/torso behavior during low-speed rear impact
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Sato, F., Nakajima, T., Ono, K., Mats Svensson, Brolin, K., and Kaneoka, K.
21. Restrained male and female occupants in frontal crashes: Are we different?
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Parenteau, C. S., Zuby, D., Brolin, K. B., Mats Svensson, Palmertz, C., and Wang, S. C.
22. The effect of seat back inclination on spinal segmental angles in automotive seated postures
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Sato, F., Miyazaki, Y., Mats Svensson, Brolin, K., Yamazaki, K., Konosu, A., Morikawa, S., and Ferreiro Perez, A.
23. Development of a 50th percentile female human body model
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Östh, J., Mendoza-Vazquez, M., Mats Svensson, Linder, A., and Brolin, K.
24. Challenges in steering wheel rim to thorax impacts using finite element Hybrid III and human body models for heavy vehicle frontal crash applications
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Holmqvist, K., Svensson, M. Y., Thorn, S., Brolin, K., and Johan Davidsson
25. Gender differences in Occupant Posture during Driving and Riding
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Hattie Cutcliffe, Ólafsdóttir, J. M., Östh, J., Davidsson, J., and Brolin, K.
26. Challenges in implementing PBL: Chalmers formula student as a case
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Malin Kjellberg, Adawi, T., and Brolin, K.
27. Passenger kinematics and muscle responses in autonomous braking events with standard and reversible pre-tensioned restraints
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Ólafsdóttir, J. M., Östh, J. K. H., Johan Davidsson, and Brolin, K. B.
28. Active human body model predictions compared to volunteer response in experiments with braking, lane change, and combined manoeuvres
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Larsson, E., Johan Iraeus, Fice, J., Pipkorn, B., Jakobsson, L., Brynskog, E., Brolin, K., and Davidsson, J.
29. Design implications for improving an anthropomorphic test device based on human body simulations
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Brolin, K., Mendoza-Vazquez, M., Song, E., Lecuyer, E., and Johan Davidsson
30. Development of an active 6-year-old child human body model for simulation of emergency events
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Brolin, K., Stockman, I., Subramanian, H., Laure-Lise Gras, and Östh, J.
31. Correlation of global head and brain tissue injury criteria to experimental concussion derived from monkey head trauma experiments
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Antona-Makoshi, J., Johan Davidsson, Ejima, S., Ono, K., Brolin, K., and Anata, K.
32. Evaluation of thoracic injury criteria for THUMS finite element human body model using real-world crash data
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Mendoza-Vázquez, M., Jakobsson, L., Johan Davidsson, Brolin, K., and Östmann, M.
33. Relative effectiveness of the second booster COVID-19 vaccines against laboratory confirmed SARS-CoV-2 infection in healthcare workers: VEBIS HCW VE cohort study (1 October 2022-2 May 2023).
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Savulescu C, Prats-Uribe A, Brolin K, Uusküla A, Bergin C, Fleming C, Zvirbulis V, Zavadska D, Szułdrzyński K, Gaio V, Popescu CP, Craiu M, Cisneros M, Latorre-Millán M, Lohur L, McGrath J, Ferguson L, Abolina I, Gravele D, Machado A, Florescu SA, Lazar M, Subirats P, Clusa Cuesta L, Sui J, Kenny C, Krievins D, Barzdina EA, Melo A, Kosa AG, Miron VD, Muñoz-Almagro C, Milagro AM, Bacci S, Kramarz P, and Nardone A
- Abstract
Introduction: Repeated COVID-19 booster vaccination was recommended in healthcare workers (HCWs) to maintain protection. We measured the relative vaccine effectiveness (rVE) of the second booster dose of COVID-19 vaccine compared to the first booster, against laboratory-confirmed SARS-CoV-2 infection in HCWs., Methods: In a prospective cohort study among HCWs from 12 European hospitals, we collected nasopharyngeal or saliva samples at enrolment and during weekly/fortnightly follow-up between October 2022 and May 2023. We estimated rVE of the second versus first COVID-19 vaccine booster dose against SARS-CoV-2 infection, overall, by time since second booster and restricted to the bivalent vaccines only. Using Cox regression, we calculated the rVE as (1-hazard ratio)*100, adjusting for hospital, age, sex, prior SARS-CoV-2 infection and at least one underlying condition., Results: Among the 979 included HCWs eligible for a second booster vaccination, 392 (40 %) received it and 192 (20 %) presented an infection during the study period. The rVE of the second versus first booster dose was -5 % (95 %CI: -46; 25) overall, 3 % (-46; 36) in the 7-89 days after receiving the second booster dose. The rVE was 11 % (-43; 45) when restricted to the use of bivalent vaccines only., Conclusion: The bivalent COVID-19 could have reduced the risk of SARS-CoV-2 infection among HCWs by 11 %. However, we note the limitation of imprecise rVE estimates due to the proportion of monovalent vaccine used in the study, the small sample size and the study being conducted during the predominant circulation of XBB.1.5 sub-lineage. COVID-19 vaccine effectiveness studies in HCWs can provide important evidence to inform the optimal timing and the use of updated COVID-19 vaccines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: APU reported payment under EMA DARWIN EU project outside of the submitted work. MLM, AM, LCC reported additional support received from ISIDORe (EATRIS) Network for carrying out the local SARS-CoV-2 sequencing. CPP reported speaker fees from Pfizer and MSD. SAF reported speaker fees from and participation in Advisory board of Pfizer, MSD and Gilead. CMA reported speaker fees from MSD, Pfizer and Sanofi. JS reported support for attending ESID conference 2022 from Takeda Pharmaceutical. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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34. Environmental Risk Factors for Parkinson's Disease: A Critical Review and Policy Implications.
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Atterling Brolin K, Schaeffer E, Kuri A, Rumrich IK, Schumacher Schuh AF, Darweesh SKL, Kaasinen V, Tolppanen AM, Chahine LM, and Noyce AJ
- Abstract
The age-standardized prevalence of Parkinson's disease (PD) has increased substantially over the years and is expected to increase further. This emphasizes the need to identify modifiable risk factors of PD, which could form a logical entry point for the prevention of PD. The World Health Organization (WHO) has recommended reducing exposure to specific environmental factors that have been reported to be associated with PD, in particular pesticides, trichloroethylene (TCE), and air pollution. In this review we critically evaluate the epidemiological and biological evidence on the associations of these factors with PD and review evidence on whether these putative associations are causal. We conclude that when considered in isolation, it is difficult to determine whether these associations are causal, in large part because of the decades-long lag between relevant exposures and the incidence of manifest PD. However, when considered in tandem with evidence from complementary research lines (such as animal models), it is increasingly likely that these associations reflect harmful causal effects. Fundamentally, whilst we highlight some evidence gaps that require further attention, we believe the current evidence base is sufficiently strong enough to support our call for stronger policy action. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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- 2024
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35. Incidence of SARS-CoV-2 Infection Among European Healthcare Workers and Effectiveness of the First Booster COVID-19 Vaccine, VEBIS HCW Observational Cohort Study, May 2021-May 2023.
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Savulescu C, Prats-Uribe A, Brolin K, Lovrić Makarić Z, Uusküla A, Panagiotakopoulos G, Bergin C, Fleming C, Agodi A, Bonfanti P, Murri R, Zvirbulis V, Zavadska D, Szuldrzynski K, Machado A, Popescu CP, Craiu M, Cisneros M, Latorre-Millán M, Petrović G, Lohur L, Tryfinopoulou K, McGrath J, Ferguson L, Barchitta M, Spolti A, de Gaetano Donati K, Abolina I, Gravele D, Gaio V, Florescu SA, Lazar M, Subirats P, Clusa Cuesta L, Sarajlić G, Amerali M, Sui J, Kenny C, Rapisarda V, Rossi M, Lamonica S, Krievins D, Barzdina EA, Palmira Amaral A, Kosa AG, Miron VD, Muñoz-Almagro C, Milagro AM, Bacci S, Kramarz P, Nardone A, and The Vebis Hcw Ve Study Group
- Abstract
Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up. We measured the incidence during pre-Delta (2 May-6 September 2021), Delta (7 September-14 December 2021), and Omicron (15 December 2021-2 May 2023) waves. Using Cox regression, we measured the relative vaccine effectiveness (rVE) of the first COVID-19 booster dose versus primary course alone during Delta and Omicron waves. Results: We included a total of 3015 HCWs. Participants were mostly female (2306; 79%), with a clinical role (2047; 68%), and had a median age of 44 years. The overall incidence of SARS-CoV-2 infection was 3.01/10,000 person-days during pre-Delta, 4.21/10,000 during Delta, and 23.20/10,000 during Omicron waves. rVE was 59% (95% CI: -25; 86) during Delta and 22% (1; 39) during Omicron waves. rVE was 51% (30; 65) 7-90 days after the first booster dose during the Omicron wave. Conclusions: The incidence of SARS-CoV-2 infection among HCWs was higher during the Omicron circulation period. The first COVID-19 vaccine booster provided additional protection against SARS-CoV-2 infection compared to primary course vaccination when recently vaccinated <90 days. This multi-country HCW cohort study addressing infection as the main outcome is crucial for informing public health interventions for HCWs.
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- 2024
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36. Effectiveness of the autumn 2023 COVID-19 vaccine dose in hospital-based healthcare workers: results of the VEBIS healthcare worker vaccine effectiveness cohort study, seven European countries, season 2023/24.
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Savulescu C, Prats-Uribe A, Brolin K, Uusküla A, Bergin C, Fleming C, Murri R, Zvirbulis V, Zavadska D, Gaio V, Popescu CP, Hrisca R, Cisneros M, Latorre-Millán M, Lohur L, McGrath J, Ferguson L, De Gaetano Donati K, Abolina I, Gravele D, Machado A, Florescu SA, Lazar M, Subirats P, Clusa Cuesta L, Sui J, Kenny C, Santangelo R, Krievins D, Barzdina EA, Valadas Henriques C, Kosa AG, Pohrib SM, Muñoz-Almagro C, Milagro A, Bacci S, and Nardone A
- Subjects
- Humans, Europe epidemiology, Female, Adult, Male, Prospective Studies, Middle Aged, Vaccine Efficacy, Seasons, Incidence, Cohort Studies, Hospitals, COVID-19 Vaccines administration & dosage, COVID-19 Vaccines immunology, COVID-19 prevention & control, COVID-19 epidemiology, SARS-CoV-2 immunology, Health Personnel statistics & numerical data, Vaccination statistics & numerical data
- Abstract
COVID-19 vaccination recommendations include healthcare workers (HCWs). We measured COVID-19 vaccine effectiveness (CVE) of the autumn 2023 dose against laboratory-confirmed SARS-CoV-2 infection in a prospective cohort study of 1,305 HCWs from 13 European hospitals. Overall CVE was 22% (95% CI: -17 to 48), 49% (95% CI: -8 to 76) before and -11% (95% CI: -84 to 34) after the start of BA.2.86/JN.1 predominant circulation. Autumn 2023 COVID-19 vaccination led to a moderate-to-low reduction in SARS-CoV-2 infection incidence in HCWs. Monitoring of CVE is crucial for COVID-19 prevention.
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- 2024
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37. Rethinking Human Factors in Obesity: Development of Simulation and Physical Test Models of Human Soft Tissue to Study Autoinjector Activation Performance.
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Linvill E, Tsai C, Ravaynia P, Chang C, Brolin K, Alvarez V, and Jonasson S
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- Humans, Computer Simulation, Equipment Design, Injections, Subcutaneous instrumentation, Viscosity, Models, Biological, Elasticity, Obesity
- Abstract
Activation against a hard surface according to ISO 11608-1 is not always representative of device use on a soft injection site. A softer injection site - which is an anthropometric property found in obese patients - presents a distinct viscoelastic property which can lead to greater autoinjector activation forces that are not captured in standardized activation testing methodology. Soft tissue simulation and physical testing were developed at SHL to advance the development of autoinjectors, allowing for rigorous testing and challenging these in scenarios involving even the softest injection sites., (© PDA, Inc. 2024.)
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- 2024
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38. Author Correction: The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data.
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Leonard HL, Murtadha R, Martinez-Carrasco A, Jama A, Müller-Nedebock AC, Gil-Martinez AL, Illarionova A, Moore A, Bustos BI, Jadhav B, Huxford B, Storm C, Towns C, Vitale D, Chetty D, Yu E, Grenn FP, Salazar G, Rateau G, Iwaki H, Elsayed I, Foote IF, Jansen van Rensburg Z, Kim JJ, Yuan J, Lake J, Brolin K, Senkevich K, Wu L, Tan MMX, Periñán MT, Makarious MB, Ta M, Pillay NS, Betancor OL, Reyes-Pérez PR, Alvarez Jerez P, Saini P, Al-Ouran R, Sivakumar R, Real R, Reynolds RH, Hu R, Abrahams S, Rao SC, Antar T, Leal TP, Iankova V, Scotton WJ, Song Y, Singleton A, Nalls MA, Dey S, Bandres-Ciga S, Blauwendraat C, and Noyce AJ
- Published
- 2023
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39. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data.
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Leonard HL, Murtadha R, Martinez-Carrasco A, Jama A, Müller-Nedebock AC, Gil-Martinez AL, Illarionova A, Moore A, Bustos BI, Jadhav B, Huxford B, Storm C, Towns C, Vitale D, Chetty D, Yu E, Grenn FP, Salazar G, Rateau G, Iwaki H, Elsayed I, Foote IF, Jansen van Rensburg Z, Kim JJ, Yuan J, Lake J, Brolin K, Senkevich K, Wu L, Tan MMX, Periñán MT, Makarious MB, Ta M, Pillay NS, Betancor OL, Reyes-Pérez PR, Alvarez Jerez P, Saini P, Al-Ouran R, Sivakumar R, Real R, Reynolds RH, Hu R, Abrahams S, Rao SC, Antar T, Leal TP, Iankova V, Scotton WJ, Song Y, Singleton A, Nalls MA, Dey S, Bandres-Ciga S, Blauwendraat C, and Noyce AJ
- Abstract
Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD., (© 2023. The Author(s).)
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- 2023
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40. Effect Modification between Genes and Environment and Parkinson's Disease Risk.
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Periñán MT, Brolin K, Bandres-Ciga S, Blauwendraat C, Klein C, Gan-Or Z, Singleton A, Gomez-Garre P, Swanberg M, Mir P, and Noyce A
- Subjects
- Humans, Penetrance, Parkinson Disease epidemiology, Parkinson Disease genetics
- Abstract
Parkinson's disease (PD) is a complex neurodegenerative condition in which genetic and environmental factors interact to contribute to its etiology. Remarkable progress has been made in deciphering disease etiology through genetic approaches, but there is limited data about how environmental and genetic factors interact to modify penetrance, risk, and disease severity. Here, we provide insights into environmental modifiers of PD, discussing precedents from other neurological and non-neurological conditions. Based on these examples, we outline genetic and environmental factors contributing to PD and review potential environmental modifiers of penetrance and clinical variability in monogenic and idiopathic PD. We also highlight the potential challenges and propose how future studies might tackle these important questions. ANN NEUROL 2022;92:715-724., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2022
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41. Insights on Genetic and Environmental Factors in Parkinson's Disease from a Regional Swedish Case-Control Cohort.
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Brolin K, Bandres-Ciga S, Blauwendraat C, Widner H, Odin P, Hansson O, Puschmann A, and Swanberg M
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- Case-Control Studies, Cohort Studies, Female, Genetic Predisposition to Disease genetics, Humans, Male, Polymorphism, Single Nucleotide, Risk Factors, Sweden epidemiology, Genome-Wide Association Study, Parkinson Disease epidemiology, Parkinson Disease genetics
- Abstract
Background: Risk factors for Parkinson's disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology., Objective: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort., Methods: PD patients (n = 929) and matched population-based controls (n = 935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores., Results: The cohort is a representative PD case-control cohort (64% men, mean age at diagnosis = 67 years, median Hoehn and Yahr score 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA. In addition, we nominate an unconfirmed and potentially population-specific genome-wide significant association in the PLPP4 locus (rs12771445)., Conclusion: This work provides an in-depth description of a new PD case-control cohort from southern Sweden, giving insights into environmental and genetic risk factors for PD in the Swedish population.
- Published
- 2022
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42. RIC3 variants are not associated with Parkinson's disease in large European, Latin American, or East Asian cohorts.
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Brolin K, Bandres-Ciga S, Leonard H, Makarious MB, Blauwendraat C, Mata IF, Foo JN, Pihlstrøm L, Swanberg M, Gan-Or Z, and Tan MM
- Subjects
- Asian People, Cohort Studies, Europe, Asia, Eastern, Female, Genotyping Techniques methods, Hispanic or Latino, Humans, Latin America, Male, White People, Whole Genome Sequencing, Genetic Variation genetics, Genome-Wide Association Study methods, Intracellular Signaling Peptides and Proteins genetics, Negative Results, Parkinson Disease etiology, Parkinson Disease genetics
- Abstract
Parkinson's disease (PD) is a complex neurodegenerative disorder in which both rare and common genetic variants contribute to disease risk. Multiple genes have been reported to be linked to monogenic PD but these only explain a fraction of the observed familial aggregation. Rare variants in RIC3 have been suggested to be associated with PD in the Indian population. However, replication studies yielded inconsistent results. We further investigate the role of RIC3 variants in PD in European cohorts using individual-level genotyping data from 14,671 PD patients and 17,667 controls, as well as whole-genome sequencing data from 1,615 patients and 961 controls. We also investigated RIC3 using summary statistics from a Latin American cohort of 1,481 individuals, and from a cohort of 31,575 individuals of East Asian ancestry. We did not identify any association between RIC3 and PD in any of the cohorts. However, more studies of rare variants in non-European ancestry populations, in particular South Asian populations, are necessary to further evaluate the world-wide role of RIC3 in PD etiology., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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43. The Effect of Seat Back Inclination on Spinal Alignment in Automotive Seating Postures.
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Sato F, Miyazaki Y, Morikawa S, Ferreiro Perez A, Schick S, Brolin K, and Svensson M
- Abstract
Experimental studies have demonstrated a relationship between spinal injury severity and vertebral kinematics, influenced by the initial spinal alignment of automotive occupants. Spinal alignment has been considered one of the possible causes of gender differences in the risk of sustaining spinal injuries. To predict vertebral kinematics and investigate spinal injury mechanisms, including gender-related mechanisms, under different seat back inclinations, it is needed to investigate the effect of the seat back inclination on initial spinal alignment in automotive seating postures for both men and women. The purpose of this study was to investigate the effect of the seat back inclination on spinal alignments, comparing spinal alignments of automotive seating postures in the 20° and 25° seat back angle and standing and supine postures. The spinal columns of 11 female and 12 male volunteers in automotive seating, standing, and supine postures were scanned in an upright open magnetic resonance imaging system. Patterns of their spinal alignments were analyzed using Multidimensional Scaling presented in a distribution map. Spinal segmental angles (cervical curvature, T1 slope, total thoracic kyphosis, upper thoracic kyphosis, lower thoracic kyphosis, lumbar lordosis, and sacral slope) were also measured using the imaging data. In the maximum individual variances in spinal alignment, a relationship between the cervical and thoracic spinal alignment was found in multidimensional scaling analyses. Subjects with a more lordotic cervical spine had a pronounced kyphotic thoracic spine, whereas subjects with a straighter to kyphotic cervical spine had a less kyphotic thoracic spine. When categorizing spinal alignments into two groups based on the spinal segmental angle of cervical curvature, spinal alignments with a lordotic cervical spine showed significantly greater absolute average values of T1 slope, total thoracic kyphosis, and lower thoracic kyphosis for both the 20° and 25° seat back angles. For automotive seating postures, the gender difference in spinal alignment was almost straight cervical and less-kyphotic thoracic spine for the female subjects and lordotic cervical and more pronounced kyphotic thoracic spine for the male subjects. The most prominent influence of seatback inclination appeared in Total thoracic kyphosis, with increased angles for 25° seat back, 8.0° greater in spinal alignments with a lordotic cervical spine, 3.2° greater in spinal alignments with a kyphotic cervical spine. The difference in total thoracic kyphosis between the two seatback angles and between the seating posture with the 20° seat back angle and the standing posture was greater for spinal alignments with a lordotic cervical spine than for spinal alignments with a kyphotic cervical spine. The female subjects in this study had a tendency toward the kyphotic cervical spine. Some of the differences between average gender-specific spinal alignments may be explained by the findings observed in the differences between spinal alignments with a lordotic and kyphotic cervical spine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sato, Miyazaki, Morikawa, Ferreiro Perez, Schick, Brolin and Svensson.)
- Published
- 2021
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44. Neck Muscle and Head/Neck Kinematic Responses While Bracing Against the Steering Wheel During Front and Rear Impacts.
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Fice JB, Mang DWH, Ólafsdóttir JM, Brolin K, Cripton PA, Blouin JS, and Siegmund GP
- Subjects
- Adult, Biomechanical Phenomena, Female, Head physiology, Humans, Male, Middle Aged, Neck physiology, Torso physiology, Young Adult, Accidents, Traffic, Automobile Driving, Neck Muscles physiology, Posture physiology
- Abstract
Drivers often react to an impending collision by bracing against the steering wheel. The goal of the present study was to quantify the effect of bracing on neck muscle activity and head/torso kinematics during low-speed front and rear impacts. Eleven seated subjects (3F, 8 M) experienced multiple sled impacts (Δv = 0.77 m/s; a
peak = 19.9 m/s2 , Δt = 65.5 ms) with their hands on the steering wheel in two conditions: relaxed and braced against the steering wheel. Electromyographic activity in eight neck muscles (sternohyoid, sternocleidomastoid, splenius capitis, semispinalis capitis, semispinalis cervicis, multifidus, levator scapulae, and trapezius) was recorded unilaterally with indwelling electrodes and normalized by maximum voluntary contraction (MVC) levels. Head and torso kinematics (linear acceleration, angular velocity, angular rotation, and retraction) were measured with sensors and motion tracking. Muscle and kinematic variables were compared between the relaxed and braced conditions using linear mixed models. We found that pre-impact bracing generated only small increases in the pre-impact muscle activity (< 5% MVC) when compared to the relaxed condition. Pre-impact bracing did not increase peak neck muscle responses during the impacts; instead it reduced peak trapezius and multifidus muscle activity by about half during front impacts. Bracing led to widespread changes in the peak amplitude and timing of the torso and head kinematics that were not consistent with a simple stiffening of the head/neck/torso system. Instead pre-impact bracing served to couple the torso more rigidly to the seat while not necessarily coupling the head more rigidly to the torso.- Published
- 2021
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45. The Parkinson's Disease Genome-Wide Association Study Locus Browser.
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Grenn FP, Kim JJ, Makarious MB, Iwaki H, Illarionova A, Brolin K, Kluss JH, Schumacher-Schuh AF, Leonard H, Faghri F, Billingsley K, Krohn L, Hall A, Diez-Fairen M, Periñán MT, Foo JN, Sandor C, Webber C, Fiske BK, Gibbs JR, Nalls MA, Singleton AB, Bandres-Ciga S, Reed X, and Blauwendraat C
- Subjects
- Age of Onset, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Risk Factors, Neurodegenerative Diseases, Parkinson Disease genetics
- Abstract
Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus., Methods: We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data., Results: We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets., Conclusions: Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA., (© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)
- Published
- 2020
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46. Generic finite element models of human ribs, developed and validated for stiffness and strain prediction - To be used in rib fracture risk evaluation for the human population in vehicle crashes.
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Iraeus J, Brolin K, and Pipkorn B
- Subjects
- Biomechanical Phenomena, Cross-Sectional Studies, Humans, Male, Ribs, Risk Assessment, Accidents, Traffic, Finite Element Analysis, Rib Fractures
- Abstract
To enable analysis of the risk of occupants sustaining rib fractures in a crash, generic finite element models of human ribs, one through twelve, were developed. The generic ribs representing an average sized male, were created based on data from several sources and publications. The generic ribs were validated for stiffness and strain predictions in anterior-posterior bending. Essentially, both predicted rib stiffness and rib strain, measured at six locations, were within one standard deviation of the average result in the physical tests. These generic finite elements ribs are suitable for strain-based rib fracture risk predictions, when loaded in anterior-posterior bending. To ensure that human variability is accounted for in future studies, a rib parametric study was conducted. This study shows that the rib cross-sectional height, i.e., the smallest of the cross-sectional dimensions, accounted for most of the strain variance during anterior-posterior loading of the ribs. Therefore, for future rib fracture risk predictions with morphed models of the human thorax, it is important to accurately address rib cross-sectional height., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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47. Relationship Between Cervical, Thoracic, and Lumbar Spinal Alignments in Automotive Seated Posture.
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Sato F, Miyazaki Y, Morikawa S, Perez AF, Schick S, Yamazaki K, Brolin K, and Svensson MY
- Abstract
The purpose of this study was to investigate the relationship between cervical, thoracic, and lumbar spinal alignments in one automotive occupant seated posture. An image dataset of the spinal column in the automotive seated posture, previously acquired by an upright open magnetic resonance imaging (MRI) system, was re-analyzed in this study. Spinal alignments were presented by the geometrical centers of the vertebral bodies extracted from the image data. Cervical, thoracic, and lumbar spinal alignments were analyzed separately with multidimensional scaling (MDS). Based on distribution maps of cervical, thoracic, and lumbar spinal alignments created by MDS, representative spinal alignment patterns of the cervical, thoracic, and lumbar spines and the relationship between cervical, thoracic, and lumbar spinal alignments were investigated. As a result, this study found a correlation between cervical and thoracic spinal alignments in an automotive occupant seated posture. According to representative spinal alignment patterns illustrated by the distribution map of spinal alignments, subjects who had kyphotic cervical spinal alignment tended to have less kyphotic thoracic spinal alignment, while subjects who had lordotic cervical spinal alignment tended to have more kyphotic thoracic spinal alignment. For lumbar spinal alignments, no prominent relationship was found between cervical and thoracic spinal alignment in the seated condition of this study., (Copyright © 2019 by ASME.)
- Published
- 2019
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48. Low prevalence of known pathogenic mutations in dominant PD genes: A Swedish multicenter study.
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Puschmann A, Jiménez-Ferrer I, Lundblad-Andersson E, Mårtensson E, Hansson O, Odin P, Widner H, Brolin K, Mzezewa R, Kristensen J, Soller M, Rödström EY, Ross OA, Toft M, Breedveld GJ, Bonifati V, Brodin L, Zettergren A, Sydow O, Linder J, Wirdefeldt K, Svenningsson P, Nissbrandt H, Belin AC, Forsgren L, and Swanberg M
- Subjects
- DNA Copy Number Variations, Databases, Genetic, Humans, Jews genetics, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Mutation, Parkinson Disease ethnology, Sweden ethnology, alpha-Synuclein genetics, Genetic Predisposition to Disease genetics, Parkinson Disease genetics
- Abstract
Objective: To determine the frequency of mutations known to cause autosomal dominant Parkinson disease (PD) in a series with more than 10% of Sweden's estimated number of PD patients., Methods: The Swedish Parkinson Disease Genetics Network was formed as a national multicenter consortium of clinical researchers who together have access to DNA from a total of 2,206 PD patients; 85.4% were from population-based studies. Samples were analyzed centrally for known pathogenic mutations in SNCA (duplications/triplications, p.Ala30Pro, p.Ala53Thr) and LRRK2 (p.Asn1437His, p.Arg1441His, p.Tyr1699Cys, p.Gly2019Ser, p.Ile2020Thr). We compared the frequency of these mutations in Swedish patients with published PD series and the gnomAD database., Results: A family history of PD in first- and/or second-degree relatives was reported by 21.6% of participants. Twelve patients (0.54%) carried LRRK2 p.(Gly2019Ser) mutations, one patient (0.045%) an SNCA duplication. The frequency of LRRK2 p.(Gly2019Ser) carriers was 0.11% in a matched Swedish control cohort and a similar 0.098% in total gnomAD, but there was a marked difference between ethnicities in gnomAD, with 42-fold higher frequency among Ashkenazi Jews than all others combined., Conclusions: In relative terms, the LRRK2 p.(Gly2019Ser) variant is the most frequent mutation among Swedish or international PD patients, and in gnomAD. SNCA duplications were the second most common of the mutations examined. In absolute terms, however, these known pathogenic variants in dominant PD genes are generally very rare and can only explain a minute fraction of familial aggregation of PD. Additional genetic and environmental mechanisms may explain the frequent co-occurrence of PD in close relatives., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
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49. Passenger muscle responses in lane change and lane change with braking maneuvers using two belt configurations: Standard and reversible pre-pretensioner.
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Ghaffari G, Brolin K, Pipkorn B, Jakobsson L, and Davidsson J
- Subjects
- Adult, Aged, Biomechanical Phenomena, Equipment Design, Humans, Male, Middle Aged, Young Adult, Accidents, Traffic prevention & control, Automobile Driving statistics & numerical data, Deceleration, Muscles physiology, Seat Belts statistics & numerical data
- Abstract
Objective: The introduction of integrated safety technologies in new car models calls for an improved understanding of the human occupant response in precrash situations. The aim of this article is to extensively study occupant muscle activation in vehicle maneuvers potentially occurring in precrash situations with different seat belt configurations. Methods: Front seat male passengers wearing a 3-point seat belt with either standard or pre-pretensioning functionality were exposed to multiple autonomously carried out lane change and lane change with braking maneuvers while traveling at 73 km/h. This article focuses on muscle activation data (surface electromyography [EMG] normalized using maximum voluntary contraction [MVC] data) obtained from 38 muscles in the neck, upper extremities, the torso, and lower extremities. The raw EMG data were filtered, rectified, and smoothed. All muscle activations were presented in corridors of mean ± one standard deviation. Separate Wilcoxon signed ranks tests were performed on volunteers' muscle activation onset and amplitude considering 2 paired samples with the belt configuration as an independent factor. Results: In normal driving conditions prior to any of the evasive maneuvers, activity levels were low (<2% MVC) in all muscles except for the lumbar extensors (3-5.5% MVC). During the lane change maneuver, selective muscles were activated and these activations restricted the sideway motions due to inertial loading. Averaged muscle activity, predominantly in the neck, lumbar extensor, and abdominal muscles, increased up to 24% MVC soon after the vehicle accelerated in lateral direction for all volunteers. Differences in activation time and amplitude between muscles in the right and left sides of the body were observed relative to the vehicle's lateral motion. For specific muscles, lane changes with the pre-pretensioner belt were associated with earlier muscle activation onsets and significantly smaller activation amplitudes than for the standard belt ( P < .05). Conclusions: Applying a pre-pretensioner belt affected muscle activations; that is, amplitude and onset time. The present muscle activation data complement the results in a preceding publication, the volunteers' kinematics and the boundary conditions from the same data set. An effect of belt configuration was also seen on previously published volunteers' kinematics with lower lateral and forward displacements for head and upper torso using the pre-pretensioner belt versus the standard belt. The data provided in this article can be used for validation and further improvement of active human body models with active musculature in both sagittal and lateral loading scenarios intended for simulation of some evasive maneuvers that potentially occur prior to a crash.
- Published
- 2019
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50. Glutathione S -Transferase Alpha 4 Prevents Dopamine Neurodegeneration in a Rat Alpha-Synuclein Model of Parkinson's Disease.
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Jewett M, Dickson E, Brolin K, Negrini M, Jimenez-Ferrer I, and Swanberg M
- Abstract
Parkinson's disease (PD) is a common, progressive neurodegenerative disease, which typically presents itself with a range of motor symptoms, like resting tremor, bradykinesia, and rigidity, but also non-motor symptoms such as fatigue, constipation, and sleep disturbance. Neuropathologically, PD is characterized by loss of dopaminergic cells in the substantia nigra pars compacta (SNpc) and Lewy bodies, neuronal inclusions containing α-synuclein (α-syn). Mutations and copy number variations of SNCA , the gene encoding α-syn, are linked to familial PD and common SNCA gene variants are associated to idiopathic PD. Large-scale genome-wide association studies have identified risk variants across another 40 loci associated to idiopathic PD. These risk variants do not, however, explain all the genetic contribution to idiopathic PD. The rat Vra1 locus has been linked to neuroprotection after nerve- and brain injury in rats. Vra1 includes the glutathione S -transferase alpha 4 ( Gsta4 ) gene, which encodes a protein involved in clearing lipid peroxidation by-products. The DA.VRA1 congenic rat strain, carrying PVG alleles in Vra1 on a DA strain background, was recently reported to express higher levels of Gsta4 transcripts and to display partial neuroprotection of SNpc dopaminergic neurons in a 6-hydroxydopamine (6-OHDA) induced model for PD. Since α-syn expression increases the risk for PD in a dose-dependent manner, we assessed the neuroprotective effects of Vra1 in an α-syn-induced PD model. Human wild-type α-syn was overexpressed by unilateral injections of the rAAV6-α-syn vector in the SNpc of DA and DA.VRA1 congenic rats. Gsta4 gene expression levels were significantly higher in the striatum and midbrain of DA.VRA1 compared to DA rats at 3 weeks post surgery, in both the ipsilateral and contralateral sides. At 8 weeks post surgery, DA.VRA1 rats suffered significantly lower fiber loss in the striatum and lower loss of dopaminergic neurons in the SNpc compared to DA. Immunofluorescent stainings showed co-expression of Gsta4 with Gfap at 8 weeks suggesting that astrocytic expression of Gsta4 underlies Vra1 -mediated neuroprotection to α-syn induced pathology. This is the second PD model in which Vra1 is linked to protection of the nigrostriatal pathway, solidifying Gsta4 as a potential therapeutic target in PD.
- Published
- 2018
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