124 results on '"Mittag, F."'
Search Results
2. Alteration of bone sialoprotein expression in osseous metastasized renal cell carcinomas and the tumor surrounding tissue
- Author
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Mittag, F., Hennenlotter, J., Minkley, L., Ipach, I., Schilling, D., Scharpf, M., Stenzl, A., Leichtle, U., and Kluba, T.
- Published
- 2012
- Full Text
- View/download PDF
3. Rezidive nach Korrektur von Hammer- und Krallenzehen
- Author
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Mittag, F. and Wülker, N.
- Published
- 2011
- Full Text
- View/download PDF
4. SBML Level 3: an extensible format for the exchange and reuse of biological models
- Author
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Keating, S, Waltemath, D, König, M, Zhang, F, Dräger, A, Chaouiya, C, Bergmann, F, Finney, A, Gillespie, C, Helikar, T, Hoops, S, Malik-Sheriff, R, Moodie, S, Moraru, I, Myers, C, Naldi, A, Olivier, B, Sahle, S, Schaff, J, Smith, L, Swat, M, Thieffry, D, Watanabe, L, Wilkinson, D, Blinov, M, Begley, K, Faeder, J, Gómez, H, Hamm, T, Inagaki, Y, Liebermeister, W, Lister, A, Lucio, D, Mjolsness, E, Proctor, C, Raman, K, Rodriguez, N, Shaffer, C, Shapiro, B, Stelling, J, Swainston, N, Tanimura, N, Wagner, J, Meier-Schellersheim, M, Sauro, H, Palsson, B, Bolouri, H, Kitano, H, Funahashi, A, Hermjakob, H, Doyle, J, Hucka, M, Adams, R, Allen, N, Angermann, B, Antoniotti, M, Bader, G, Červený, J, Courtot, M, Cox, C, Dalle Pezze, P, Demir, E, Denney, W, Dharuri, H, Dorier, J, Drasdo, D, Ebrahim, A, Eichner, J, Elf, J, Endler, L, Evelo, C, Flamm, C, Fleming, R, Fröhlich, M, Glont, M, Gonçalves, E, Golebiewski, M, Grabski, H, Gutteridge, A, Hachmeister, D, Harris, L, Heavner, B, Henkel, R, Hlavacek, W, Hu, B, Hyduke, D, Jong, H, Juty, N, Karp, P, Karr, J, Kell, D, Keller, R, Kiselev, I, Klamt, S, Klipp, E, Knüpfer, C, Kolpakov, F, Krause, F, Kutmon, M, Laibe, C, Lawless, C, Li, L, Loew, L, Machne, R, Matsuoka, Y, Mendes, P, Mi, H, Mittag, F, Monteiro, P, Natarajan, K, Nielsen, P, Nguyen, T, Palmisano, A, Jean-Baptiste, P, Pfau, T, Phair, R, Radivoyevitch, T, Rohwer, J, Ruebenacker, O, Saez-Rodriguez, J, Scharm, M, Schmidt, H, Schreiber, F, Schubert, M, Schulte, R, Sealfon, S, Smallbone, K, Soliman, S, Stefan, M, Sullivan, D, Takahashi, K, Teusink, B, Tolnay, D, Vazirabad, I, Kamp, A, Wittig, U, Wrzodek, C, Wrzodek, F, Xenarios, I, Zhukova, A, Zucker, J, Keating, SM, Bergmann, FT, Gillespie, CS, Malik-Sheriff, RS, Moodie, SL, Moraru, II, Myers, CJ, Olivier, BG, Schaff, JC, Smith, LP, Swat, MJ, Wilkinson, DJ, Blinov, ML, Faeder, JR, Gómez, HF, Hamm, TM, Lister, AL, Proctor, CJ, Shaffer, CA, Shapiro, BE, Sauro, HM, Doyle, JC, Adams, RR, Allen, NA, Angermann, BR, Bader, GD, Cox, CD, Denney, WS, Evelo, CT, Fleming, RM, Harris, LA, Heavner, BD, Hlavacek, WS, Hyduke, DR, Karp, PD, Karr, JR, Kell, DB, Loew, LM, Monteiro, PT, Natarajan, KN, Nielsen, PM, Phair, RD, Rohwer, JM, Ruebenacker, OA, Sealfon, SC, Stefan, MI, Sullivan, DP, Keating, S, Waltemath, D, König, M, Zhang, F, Dräger, A, Chaouiya, C, Bergmann, F, Finney, A, Gillespie, C, Helikar, T, Hoops, S, Malik-Sheriff, R, Moodie, S, Moraru, I, Myers, C, Naldi, A, Olivier, B, Sahle, S, Schaff, J, Smith, L, Swat, M, Thieffry, D, Watanabe, L, Wilkinson, D, Blinov, M, Begley, K, Faeder, J, Gómez, H, Hamm, T, Inagaki, Y, Liebermeister, W, Lister, A, Lucio, D, Mjolsness, E, Proctor, C, Raman, K, Rodriguez, N, Shaffer, C, Shapiro, B, Stelling, J, Swainston, N, Tanimura, N, Wagner, J, Meier-Schellersheim, M, Sauro, H, Palsson, B, Bolouri, H, Kitano, H, Funahashi, A, Hermjakob, H, Doyle, J, Hucka, M, Adams, R, Allen, N, Angermann, B, Antoniotti, M, Bader, G, Červený, J, Courtot, M, Cox, C, Dalle Pezze, P, Demir, E, Denney, W, Dharuri, H, Dorier, J, Drasdo, D, Ebrahim, A, Eichner, J, Elf, J, Endler, L, Evelo, C, Flamm, C, Fleming, R, Fröhlich, M, Glont, M, Gonçalves, E, Golebiewski, M, Grabski, H, Gutteridge, A, Hachmeister, D, Harris, L, Heavner, B, Henkel, R, Hlavacek, W, Hu, B, Hyduke, D, Jong, H, Juty, N, Karp, P, Karr, J, Kell, D, Keller, R, Kiselev, I, Klamt, S, Klipp, E, Knüpfer, C, Kolpakov, F, Krause, F, Kutmon, M, Laibe, C, Lawless, C, Li, L, Loew, L, Machne, R, Matsuoka, Y, Mendes, P, Mi, H, Mittag, F, Monteiro, P, Natarajan, K, Nielsen, P, Nguyen, T, Palmisano, A, Jean-Baptiste, P, Pfau, T, Phair, R, Radivoyevitch, T, Rohwer, J, Ruebenacker, O, Saez-Rodriguez, J, Scharm, M, Schmidt, H, Schreiber, F, Schubert, M, Schulte, R, Sealfon, S, Smallbone, K, Soliman, S, Stefan, M, Sullivan, D, Takahashi, K, Teusink, B, Tolnay, D, Vazirabad, I, Kamp, A, Wittig, U, Wrzodek, C, Wrzodek, F, Xenarios, I, Zhukova, A, Zucker, J, Keating, SM, Bergmann, FT, Gillespie, CS, Malik-Sheriff, RS, Moodie, SL, Moraru, II, Myers, CJ, Olivier, BG, Schaff, JC, Smith, LP, Swat, MJ, Wilkinson, DJ, Blinov, ML, Faeder, JR, Gómez, HF, Hamm, TM, Lister, AL, Proctor, CJ, Shaffer, CA, Shapiro, BE, Sauro, HM, Doyle, JC, Adams, RR, Allen, NA, Angermann, BR, Bader, GD, Cox, CD, Denney, WS, Evelo, CT, Fleming, RM, Harris, LA, Heavner, BD, Hlavacek, WS, Hyduke, DR, Karp, PD, Karr, JR, Kell, DB, Loew, LM, Monteiro, PT, Natarajan, KN, Nielsen, PM, Phair, RD, Rohwer, JM, Ruebenacker, OA, Sealfon, SC, Stefan, MI, and Sullivan, DP
- Abstract
Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.
- Published
- 2020
5. Clear-cell sarcoma of the soft tissue – a rare diagnosis with a fatal outcome
- Author
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IPACH, I., MITTAG, F., KOPP, H.-G., KUNZE, B., WOLF, P., and KLUBA, T.
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- 2012
- Full Text
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6. Close localization of DAP-kinase positive tumour-associated macrophages and apoptotic colorectal cancer cells
- Author
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Schneider-Stock, R, Kuester, D, Ullrich, O, Mittag, F, Habold, C, Boltze, C, Peters, B, Krueger, S, Hintze, C, Meyer, F, Hartig, R, and Roessner, A
- Published
- 2006
- Full Text
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7. Prévalence des anomalies acétabulaires associées à une déformation en crosse de pistolet dans la coxarthrose
- Author
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Ipach, I., Mittag, F., Walter, C., Syha, R., Wolf, P., and Kluba, T.
- Published
- 2013
- Full Text
- View/download PDF
8. Vergleich von korrigierender Arthrodese versus Resektionsarthroplastik bei kontrakten Kleinzehendeformitäten der der proximalen Interphalangealgelenke - prospektiv randomisierte Studie
- Author
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Hofmann, UK, Nowak, V, Götze, M, Wülker, N, Mittag, F, Hofmann, UK, Nowak, V, Götze, M, Wülker, N, and Mittag, F
- Published
- 2019
9. Die Rolle des Patientenalters bei der Beurteilung von röntgenologischen Parametern zur Beschreibung von Hüftgelenksgeometrie und -pathologie
- Author
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Hofmann, UK, Ipach, I, Rondak, IC, Syha, R, Götze, M, and Mittag, F
- Subjects
ddc: 610 ,Impingement ,Röntgen Beckenübersicht ,Hüftgelenksarthrose ,610 Medical sciences ,Medicine ,CE-Winkel - Abstract
Fragestellung: Während in der Literatur zahlreiche röntgenologische Parameter etabliert sind und die Geometrie und auch pathologische Zustände des Hüftgelenkes zu beschreiben, sind die hierfür zu empfehlenden Referenzwerte und auch ihre klinische Einordnung nach wie vor Gegenstand[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017)
- Published
- 2017
- Full Text
- View/download PDF
10. Der Einfluss von Training und Berufserfahrung auf die Interobserver Reliabilität bei der Klassifikation degenerativer Wirbelsäulenveränderungen
- Author
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Hofmann, UK, Keller, R, Gesicki, M, Mittag, F, Hofmann, UK, Keller, R, Gesicki, M, and Mittag, F
- Published
- 2017
11. Radiologischer Befund bei 516 Patienten mit Hallux valgus und daraus resultierende Methode der operativen Korrektur - Ein Schema zur Indikationsstellung
- Author
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Götze, M, Ipach, I, Walter, C, Wülker, N, Mittag, F, Götze, M, Ipach, I, Walter, C, Wülker, N, and Mittag, F
- Published
- 2015
12. Pedobarographische Analyse von Hallux valgus-Patienten nach Chevron-Osteotomie, Basisosteotomie, Großzehengrundgelenksarthrodese und Resektionsarthroplastik
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Mittag, F, Wallek, H, Lorenz, A, Wülker, N, and Wünschel, M
- Subjects
Hallux valgus ,Resektionsarthroplastik ,ddc: 610 ,Großzehengrundgelenksarthrodese ,610 Medical sciences ,Medicine ,Pedobarographie ,Basisosteotomie ,Chevronosteotomie - Abstract
Fragestellung: Bei Hallux valgus-Patienten führt die gestörte Mechanik des ersten Metatarsophalangealgelenks zu einer Fehlbelastung mit Verlagerung der Belastung auf die lateral gelegenen Strahlen. Die daraus resultierenden Beschwerden werden als Transfermetatarsalgie bezeichnet. In einer [for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2013)
- Published
- 2013
- Full Text
- View/download PDF
13. Pedobarographische Analyse von Hallux valgus – Patienten im Vergleich zu Fußgesunden
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Mittag, F, Schiek, K, Wülker, N, and Wünschel, M
- Subjects
Hallux valgus ,pedobarographische Untersuchung ,ddc: 610 ,Druckverteilung ,Ganganalyse ,Vorfuß ,610 Medical sciences ,Medicine - Abstract
Fragestellung: Hallux valgus-Patienten klagen neben der eigentlichen Deformität meist über eine Pseudoexostose, welche beim Tragen von geschlossenen Schuhen schmerzhaft ist. Die gestörte Mechanik des Metatarsophalangealgelenks der Großzehe führt zu einer Fehlbelastung und zu[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2012)
- Published
- 2012
- Full Text
- View/download PDF
14. Second CW and LP Operation Test of XFEL Prototype Cryomodule
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Sekutowicz, J., Ayvazyan, V., Branlard, J., Ebert, M., Eschke, J., Gössel, A., Kostin, D., Mittag, F., Merz, W., Onken, R., Cichalewski, W., Jałmuzna, W., Piotrowski, A., Przygoda, K., Czuba, K., Zembala, Ł., Kudla, I., and Szewinski, J.
- Published
- 2012
15. CW and LP Operation Test of XFEL-Like Cryomodule
- Author
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Sekutowicz, J., Ayvazyan, V., Ebert, M., Eschke, J., Gössel, A., Kostin, D., Mittag, F., Merz, W., Onken, R., Cichalewski, W., Jałmuz̊na, W., Przygoda, K., Czuba, K., Zembala, Ł., Kudla, I., and Jarosław Szewiński
- Published
- 2012
16. Eine neue Einteilung der 'pistol-grip-Deformität' – Zusammenhang zwischen Schwere der Deformität und dem Grad der Arthrose
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Ipach, I, Mittag, F, Kunze, B, Wolf, P, and Kluba, T
- Subjects
ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Fragestellung: Zwei Arten von Impingement werden für die Entstehung einer Coxarthrose verantwortlich gemacht. Beim sogenannten Pincer-Impingement kommt es zu einer übermäßige lokalen bzw. kompletten Überdachung des Femurkopfes. Das Cam-Impingement entsteht auf Grund einer St[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 75. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 97. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 52. Tagung des Berufsverbandes der Fachärzte für Orthopädie
- Published
- 2011
- Full Text
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17. Hüftprothesen bei unter Sechzigjährigen – Was sind die häufigsten Ursachen für die frühe Entstehung einer Coxarthrose?
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Ipach, I, Mittag, F, Kunze, B, Wolf, P, and Kluba, T
- Subjects
ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Fragestellung: In Deutschland werden jährlich etwa 160.000 primäre Hüft-Endoprothesenimplantationen durchgeführt. Hierbei machen die Patienten mit einem Alter von, Deutscher Kongress für Orthopädie und Unfallchirurgie; 75. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 97. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 52. Tagung des Berufsverbandes der Fachärzte für Orthopädie
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- 2011
- Full Text
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18. Blutgruppenabhängige ossäre Integration von allogenem (fresh frozen) Knochen in der Hüftrevisionsendoprothetik
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Mittag, F, Ipach, I, Straub, M, and Kluba, T
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Fragestellung: Die aktuellen EU-Richtlinien erschweren das Führen einer hauseigenen Knochenbank, da eine Herstellererlaubnis nach AMG nur unter Beachtung strenger Vorschriften erteilt wird. Alternativ wird neben künstlichen Knochenersatzstoffen autoklavierter/bestrahlter Knochen verwe[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 75. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 97. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 52. Tagung des Berufsverbandes der Fachärzte für Orthopädie
- Published
- 2011
- Full Text
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19. Alterationen von Bone Sialoprotein im tumorumgebenden Gewebe von ossär metastasierten Nierenzellkarzinomen
- Author
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Mittag, F., Minkley, L., Kluba, T., Schilling, D., Aicher, W.K., and Wülker, N.
- Subjects
ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Fragestellung: Bone Sialoprotein (BSP) ist ein extrazellulärer Bestandteil mineralisierter Gewebe wie Knochen und kalzifiziertem Knorpel. BSP steuert den Knochenstoffwechsel indem es direkt die Osteoblasten- und Osteoklastenaktivität beeinflusst. Neuerdings ist gezeigt worden, dass BSP in [for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 74. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 96. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 51. Tagung des Berufsverbandes der Fachärzte für Orthopädie
- Published
- 2010
20. DAPK promotor hypermethylation correlates with reduced Fas/FasL-induced apoptosis in colorectal cancer
- Author
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Meyer, F, primary, Boltze, C, additional, Mittag, F, additional, Vieth, M, additional, Höpfner, T, additional, Peters, B, additional, Lippert, H, additional, Roessner, A, additional, and Schneider-Stock, R, additional
- Published
- 2015
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21. How do ankle braces affect braking performance? An experimental driving simulation study with healthy volunteers
- Author
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Hofmann, U, primary, Thumm, S, additional, Jordan, M, additional, Mittag, F, additional, Rondak, I, additional, and Ipach, I, additional
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- 2015
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22. Profil- und Lotändeungen durch das Tragen von Schulranzen
- Author
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Mittag, F., Alagalingam, M., Reize, P., Leichtle, U., Niemeyer, T., and Leichtle, C.I.
- Subjects
ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Fragestellung: Ist der Schulranzen trotz aller Bemühungen der Eltern, Industrie und von Schulen immer noch ein Problem für den Rücken? Welche Beziehungen gibt es zwischen dem Schulranzengewicht und dem Auftreten von Rückenschmerzen? Erstmals wurden im Rahmen dieser Studie[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 50. Tagung des Berufsverbandes der Fachärzte für Orthopädie
- Published
- 2009
23. Case report - ein aseptisch gelockerter Schneider-Burch-Ring verursacht ein chronisch blutendes Aneurysma der Arteria femoralis
- Author
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Mittag, F and Kluba, T
- Subjects
ddc: 610 - Published
- 2008
24. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease
- Author
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Holmans, P., Moskvina, V., Jones, L., Sharma, M., Vedernikov, A., Buchel, F., Sadd, M., Bras, J.M., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Gibbs, J.R., Schulte, C., Durr, A., Guerreiro, R., Hernandez, D., Brice, A., Stefansson, H., Majamaa, K., Gasser, T., Heutink, P., Wood, N.W., Martinez, M., Singleton, A.B., Nalls, M.A., Hardy, J., Morris, H.R., Williams, N.M., Bloem, B., Post, B., Warrenburg, B.P.C. van de, Ravina, B., Shoulson, I., et al., Holmans, P., Moskvina, V., Jones, L., Sharma, M., Vedernikov, A., Buchel, F., Sadd, M., Bras, J.M., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Gibbs, J.R., Schulte, C., Durr, A., Guerreiro, R., Hernandez, D., Brice, A., Stefansson, H., Majamaa, K., Gasser, T., Heutink, P., Wood, N.W., Martinez, M., Singleton, A.B., Nalls, M.A., Hardy, J., Morris, H.R., Williams, N.M., Bloem, B., Post, B., Warrenburg, B.P.C. van de, Ravina, B., Shoulson, I., and et al.
- Abstract
Item does not contain fulltext, Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1-2% in people >60 and 3-4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 x 10(-16)) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the 'regulation of leucocyte/lymphocyte activity' and also 'cytokine-mediated signalling' as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated.
- Published
- 2013
25. Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease
- Author
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Keller, M.F., Saad, M., Bras, J., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Buchel, F., Sharma, M., Gibbs, J.R., Schulte, C., Moskvina, V., Durr, A., Holmans, P., Kilarski, L.L., Guerreiro, R., Hernandez, D.G., Brice, A., Ylikotila, P., Stefansson, H., Majamaa, K., Morris, H.R., Williams, N., Gasser, T., Heutink, P., Wood, N.W., Hardy, J., Martinez, M., Singleton, A.B., Nalls, M.A., Donnelly, P., Bloem, B., et al., Keller, M.F., Saad, M., Bras, J., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Buchel, F., Sharma, M., Gibbs, J.R., Schulte, C., Moskvina, V., Durr, A., Holmans, P., Kilarski, L.L., Guerreiro, R., Hernandez, D.G., Brice, A., Ylikotila, P., Stefansson, H., Majamaa, K., Morris, H.R., Williams, N., Gasser, T., Heutink, P., Wood, N.W., Hardy, J., Martinez, M., Singleton, A.B., Nalls, M.A., Donnelly, P., Bloem, B., and et al.
- Abstract
Item does not contain fulltext, Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17-38, P = 8.08E - 08) phenotypic variance associated with all types of PD, 15% (95% CI -0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17-44, P = 1.34E - 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered.
- Published
- 2012
26. Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease
- Author
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Keller, M. F., Saad, M., Bras, J., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Buchel, F., Sharma, M., Gibbs, J. R., Schulte, C., Moskvina, V., Durr, A., Holmans, P., Kilarski, L. L., Guerreiro, R., Hernandez, D. G., Brice, A., Ylikotila, P., Stefansson, H., Majamaa, K., Morris, H. R., Williams, N., Gasser, T., Heutink, P., Wood, N. W., Hardy, J., Martinez, M., Jankowski, Janusz, Nalls, M. A., Singleton, A. B., Keller, M. F., Saad, M., Bras, J., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Buchel, F., Sharma, M., Gibbs, J. R., Schulte, C., Moskvina, V., Durr, A., Holmans, P., Kilarski, L. L., Guerreiro, R., Hernandez, D. G., Brice, A., Ylikotila, P., Stefansson, H., Majamaa, K., Morris, H. R., Williams, N., Gasser, T., Heutink, P., Wood, N. W., Hardy, J., Martinez, M., Jankowski, Janusz, Nalls, M. A., and Singleton, A. B.
- Abstract
Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17–38, P = 8.08E − 08) phenotypic variance associated with all types of PD, 15% (95% CI −0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17–44, P = 1.34E − 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered.
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- 2012
27. Haftung und osteogene Differenzierung von humanen mesenchymalen Stammzellen auf Laminin-5 in vitro
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Mittag, F, Falkenberg, E, Wülker, N, Aicher, WK, Mittag, F, Falkenberg, E, Wülker, N, and Aicher, WK
- Published
- 2012
28. Alterationen von Bone Sialoprotein im tumorumgebenden Gewebe von ossär metastasierten Nierenzellkarzinomen
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Mittag, F, Minkley, L, Kluba, T, Schilling, D, Aicher, WK, Wülker, N, Mittag, F, Minkley, L, Kluba, T, Schilling, D, Aicher, WK, and Wülker, N
- Published
- 2010
29. Profil- und Lotändeungen durch das Tragen von Schulranzen
- Author
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Mittag, F, Alagalingam, M, Reize, P, Leichtle, U, Niemeyer, T, Leichtle, CI, Mittag, F, Alagalingam, M, Reize, P, Leichtle, U, Niemeyer, T, and Leichtle, CI
- Published
- 2009
30. Indications for Total Hip Arthroplasty in Young Adults – Idiopathic Osteoarthritis Seems To Be Overestimated
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Ipach, I., additional, Mittag, F., additional, Syha, R., additional, Kunze, B., additional, Wolf, P., additional, and Kluba, T., additional
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- 2012
- Full Text
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31. Clear-cell sarcoma of the soft tissue - a rare diagnosis with a fatal outcome
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IPACH, I., primary, MITTAG, F., additional, KOPP, H.-G., additional, KUNZE, B., additional, WOLF, P., additional, and KLUBA, T., additional
- Published
- 2011
- Full Text
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32. Alteration of bone sialoprotein expression in osseous metastasized renal cell carcinomas and the tumor surrounding tissue
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Mittag, F., primary, Hennenlotter, J., additional, Minkley, L., additional, Ipach, I., additional, Schilling, D., additional, Scharpf, M., additional, Stenzl, A., additional, Leichtle, U., additional, and Kluba, T., additional
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- 2011
- Full Text
- View/download PDF
33. A New Classification for ”Pistol Grip Deformity”-Correlation Between the Severity of the Deformity and the Grade of Osteoarthritis of the Hip
- Author
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Ipach, I., primary, Mittag, F., additional, Sachsenmaier, S., additional, Heinrich, P., additional, and Kluba, T., additional
- Published
- 2010
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34. DAPK promotor hypermethylation correlates with reduced apoptosis in colorectal cancer
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Schneider-Stock, R., primary, Boltze, C., additional, Mittag, F., additional, Vieth, M., additional, Peters, B., additional, Hartig, R., additional, Meyer, F., additional, and Roessner, A., additional
- Published
- 2004
- Full Text
- View/download PDF
35. Indications for Total Hip Arthroplasty in Young Adults -- Idiopathic Osteoarthritis Seems To Be Overestimated.
- Author
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Ipach, I., Mittag, F., Syha, R., Kunze, B., Wolf, P., and Kluba, T.
- Published
- 2012
- Full Text
- View/download PDF
36. Feasibility of CW and lp operation of the xfel linac
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Sekutowicz, J., Ayvazyan, V., Branlard, J., Ebert, M., Eschke, J., Feldmann, T., Gössel, A., Kostin, D., Kudla, M., Mittag, F., Merz, W., Müller, C., Onken, R., Sandvoss, I., Schneidmiller, E., Sulimov, A., Yurkov, M., Wojciech Cichalewski, Piotrowski, A., Przygoda, K., Jalmuzna, W., Czuba, K., and Szewinski, J.
37. Test results of components for cw and near-cw operation of a superconducting linac
- Author
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Sekutowicz, J., Ebert, M., Mittag, F., Kneisel, P., Robert Nietubyć, and Sołtan, A.
38. Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinson's disease
- Author
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Mf, Keller, Saad M, Bras J, Bettella F, Nicolaou N, Simón-Sánchez J, Mittag F, Büchel F, Sharma M, Jr, Gibbs, Schulte C, Moskvina V, Durr A, Peter Holmans, Ll, Kilarski, Guerreiro R, Dg, Hernandez, Brice A, Ylikotila P, and Stefánsson H
39. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease
- Author
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Holmans P, Moskvina V, Jones L, Sharma M, Vedernikov A, Buchel F, Saad M, Jose Bras, Bettella F, Nicolaou N, Simón-Sánchez J, Mittag F, Jr, Gibbs, Schulte C, Durr A, Guerreiro R, Hernandez D, Brice A, Stefánsson H, and Majamaa K
40. SBML Level 3: an extensible format for the exchange and reuse of biological models
- Author
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Edda Klipp, Marco Antoniotti, Frank Bergmann, James C. Schaff, Peter D. Karp, Daniel Lucio, Kedar Nath Natarajan, Thomas M. Hamm, Leandro Watanabe, Henning Hermjakob, David Tolnay, John Wagner, Joerg Stelling, Alida Palmisano, Falk Schreiber, Yukiko Matsuoka, Harold F. Gómez, Huaiyu Mi, Carole J. Proctor, Ulrike Wittig, Neil Swainston, Jan Červený, Denis Thieffry, Piero Dalle Pezze, Julio Saez-Rodriguez, Maciej J. Swat, Bin Hu, Martina Kutmon, Thomas Pfau, Bas Teusink, Sarah M. Keating, Fedor A. Kolpakov, Andreas Dräger, Pedro Mendes, Martin Scharm, Emek Demir, Ioannis Xenarios, Christoph Flamm, Axel von Kamp, Darren J. Wilkinson, Nick Juty, Fengkai Zhang, Leonard A. Harris, Michael Schubert, Dagmar Waltemath, Lucian P. Smith, Steffen Klamt, Herbert M. Sauro, Ali Ebrahim, Wolfram Liebermeister, Christian Knüpfer, Nicolas Rodriguez, Tramy Nguyen, Naoki Tanimura, Christopher Cox, Stuart C. Sealfon, Nicholas Alexander Allen, Clemens Wrzodek, Bastian R. Angermann, Martin Meier-Schellersheim, Anna Zhukova, Jean-Baptiste Pettit, Hovakim Grabski, Devin P. Sullivan, Claudine Chaouiya, Michael L. Blinov, John Doyle, Ilya Kiselev, Roman Schulte, Alex Gutteridge, Mélanie Courtot, Eric Mjolsness, Finja Wrzodek, Rahuman S Malik-Sheriff, Ronan M. T. Fleming, Bruce E. Shapiro, Kimberly Begley, Leslie M. Loew, Colin S. Gillespie, Ibrahim Vazirabad, Michael Hucka, Akira Funahashi, Bernhard O. Palsson, Hamid Bolouri, Tomáš Helikar, Camille Laibe, William S. Denney, Chris T. Evelo, Florian Mittag, William S. Hlavacek, Ron Henkel, Harish Dharuri, Julien Dorier, Karthik Raman, Martina Fröhlich, Conor Lawless, Rainer Machné, Falko Krause, Damon Hachmeister, Matthias König, Clifford A. Shaffer, Benjamin D. Heavner, Douglas B. Kell, Jonathan R. Karr, Mihai Glont, Lukas Endler, Melanie I. Stefan, Robert Phair, Lu Li, Henning Schmidt, Dirk Drasdo, Johan Elf, Allyson L. Lister, Hiroaki Kitano, Richard R. Adams, Oliver A. Ruebenacker, Roland Keller, Sven Sahle, Ion I. Moraru, Gary D. Bader, Poul M. F. Nielsen, Johann M. Rohwer, Johannes Eichner, Daniel R. Hyduke, James R. Faeder, Stefan Hoops, Emanuel Gonçalves, Yuichiro Inagaki, Aurélien Naldi, Koichi Takahashi, Sylvain Soliman, Brett G. Olivier, Kieran Smallbone, Stuart L. Moodie, Pedro T. Monteiro, Chris J. Myers, Martin Golebiewski, Tomas Radivoyevitch, Jeremy Zucker, Hidde de Jong, Andrew Finney, Keating, S, Waltemath, D, König, M, Zhang, F, Dräger, A, Chaouiya, C, Bergmann, F, Finney, A, Gillespie, C, Helikar, T, Hoops, S, Malik-Sheriff, R, Moodie, S, Moraru, I, Myers, C, Naldi, A, Olivier, B, Sahle, S, Schaff, J, Smith, L, Swat, M, Thieffry, D, Watanabe, L, Wilkinson, D, Blinov, M, Begley, K, Faeder, J, Gómez, H, Hamm, T, Inagaki, Y, Liebermeister, W, Lister, A, Lucio, D, Mjolsness, E, Proctor, C, Raman, K, Rodriguez, N, Shaffer, C, Shapiro, B, Stelling, J, Swainston, N, Tanimura, N, Wagner, J, Meier-Schellersheim, M, Sauro, H, Palsson, B, Bolouri, H, Kitano, H, Funahashi, A, Hermjakob, H, Doyle, J, Hucka, M, Adams, R, Allen, N, Angermann, B, Antoniotti, M, Bader, G, Červený, J, Courtot, M, Cox, C, Dalle Pezze, P, Demir, E, Denney, W, Dharuri, H, Dorier, J, Drasdo, D, Ebrahim, A, Eichner, J, Elf, J, Endler, L, Evelo, C, Flamm, C, Fleming, R, Fröhlich, M, Glont, M, Gonçalves, E, Golebiewski, M, Grabski, H, Gutteridge, A, Hachmeister, D, Harris, L, Heavner, B, Henkel, R, Hlavacek, W, Hu, B, Hyduke, D, Jong, H, Juty, N, Karp, P, Karr, J, Kell, D, Keller, R, Kiselev, I, Klamt, S, Klipp, E, Knüpfer, C, Kolpakov, F, Krause, F, Kutmon, M, Laibe, C, Lawless, C, Li, L, Loew, L, Machne, R, Matsuoka, Y, Mendes, P, Mi, H, Mittag, F, Monteiro, P, Natarajan, K, Nielsen, P, Nguyen, T, Palmisano, A, Jean-Baptiste, P, Pfau, T, Phair, R, Radivoyevitch, T, Rohwer, J, Ruebenacker, O, Saez-Rodriguez, J, Scharm, M, Schmidt, H, Schreiber, F, Schubert, M, Schulte, R, Sealfon, S, Smallbone, K, Soliman, S, Stefan, M, Sullivan, D, Takahashi, K, Teusink, B, Tolnay, D, Vazirabad, I, Kamp, A, Wittig, U, Wrzodek, C, Wrzodek, F, Xenarios, I, Zhukova, A, Zucker, J, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Heidelberg University Hospital [Heidelberg], Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), European Molecular Biology Laboratory (EMBL), University of Connecticut (UCONN), National Institutes of Health [Bethesda] (NIH), Chercheur indépendant, Amazon Web Services [Seattle] (AWS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), University of Toronto, Masaryk University [Brno] (MUNI), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, The University of Tennessee [Knoxville], The Babraham Institute [Cambridge, UK], Oregon Health and Science University [Portland] (OHSU), Human Predictions LLC, Illumina, Swiss-Prot Group, Swiss Institute of Bioinformatics [Genève] (SIB), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California [San Diego] (UC San Diego), University of California (UC), Center for Bioinformatics (ZBIT), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Uppsala University, Institut für Populationsgenetik [Vienna], Veterinärmedizinische Universität Wien, Maastricht University [Maastricht], Alpen-Adria-Universität Klagenfurt [Klagenfurt, Austria], Medizinische Universität Wien = Medical University of Vienna, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg Institute for Theoretical Studies (HITS ), Russian-Armenian University (RAU), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Microsoft Technology Licensing (MTL), Microsoft Corporation [Redmond, Wash.], Vanderbilt University School of Medicine [Nashville], University of Washington [Seattle], University of Rostock, Los Alamos National Laboratory (LANL), Lorentz Institute, Universiteit Leiden, Tegmine Therapeutics, Modeling, simulation, measurement, and control of bacterial regulatory networks (IBIS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Jean Roget, SRI International [Menlo Park] (SRI), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Liverpool, Universitätsklinikum Tübingen - University Hospital of Tübingen, Institute of Information and Computational Technologies (IICT), Max Planck Institute for Dynamics of Complex Technical Systems, Max-Planck-Gesellschaft, Max-Planck-Institut für Molekulare Genetik (MPIMG), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Humboldt University Of Berlin, Newcastle University [Newcastle], École polytechnique (X), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], The Systems Biology Institute [Tokyo] (SBI), Centro de Quimica Estrutural (CQE), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST), University of Southern California (USC), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, University of Southern Denmark (SDU), University of Auckland [Auckland], University of Utah, Virginia Tech [Blacksburg], University of Luxembourg [Luxembourg], Integrative Bioinformatics Inc [Mountain View], Cleveland Clinic, Stellenbosch University, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Universität Heidelberg [Heidelberg] = Heidelberg University, Leibniz Institute of Plant Genetics and Crop Plant Research [Gatersleben] (IPK-Gatersleben), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Manchester [Manchester], Computational systems biology and optimization (Lifeware), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), California Institute of Technology (CALTECH), Encodia Inc [San Diego], Shinshu University [Nagano], University of Amsterdam [Amsterdam] (UvA), Versiti Blood Center of Wisconsin, Greifswald University Hospital, Bioinformatique évolutive - Evolutionary Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Pacific Northwest National Laboratory (PNNL), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), Department of Bioengineering, University of California (UC)-University of California (UC), ANSYS, Virginia Polytechnic Institute and State University [Blacksburg], Eight Pillars Ltd, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Universität Heidelberg, Bioquant, Applied Biomathematics [New York], SimCYP Ltd, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Utah School of Medicine [Salt Lake City], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Mizuho Information and Research Institute, Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Oxford, Computer Science (North Carolina State University), North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of California [Irvine] (UC Irvine), Indian Institute of Technology Madras (IIT Madras), California State University [Northridge] (CSUN), Biotechnology and Biological Sciences Research Council (BBSRC), IBM Research [Melbourne], Benaroya Research Institute [Seattle] (BRI), Okinawa Institute of Science and Technology Graduate University, Keio University, Department of Computing and Mathematical sciences, members, SBML Level 3 Community, Université de Lausanne (UNIL), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of California, Universiteit Leiden [Leiden], Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Inria Grenoble - Rhône-Alpes, Humboldt University of Berlin, Universität Heidelberg [Heidelberg], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Humboldt-Universität zu Berlin, University of California-University of California, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], University of California [Irvine] (UCI), Biotechnology and Biological Sciences Research Council, Computer Science, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)
- Subjects
computational modeling ,Medicine (General) ,Markup language ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,INFORMATION ,Interoperability ,interoperability ,Review ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,ANNOTATION ,0302 clinical medicine ,Software ,file forma ,Models ,Biology (General) ,0303 health sciences ,Computational model ,Applied Mathematics ,Systems Biology ,systems biology ,File format ,3. Good health ,Networking and Information Technology R&D ,Networking and Information Technology R&D (NITRD) ,Computational Theory and Mathematics ,SIMULATION ,General Agricultural and Biological Sciences ,STANDARDS ,REPOSITORY ,Information Systems ,QH301-705.5 ,Bioinformatics ,Systems biology ,Software ecosystem ,Reviews ,Bioengineering ,Methods & Resources ,Biology ,MARKUP LANGUAGE ,Models, Biological ,SBML Level 3 Community members ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,R5-920 ,Animals ,Humans ,SBML ,reproducibility ,030304 developmental biology ,ENVIRONMENT ,General Immunology and Microbiology ,file format ,business.industry ,Computational Biology ,Biological ,ONTOLOGY ,Metabolism ,Logistic Models ,Biochemistry and Cell Biology ,Other Biological Sciences ,Software engineering ,business ,030217 neurology & neurosurgery - Abstract
Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution., Over the past two decades, scientists from different fields have been developing SBML, a standard format for encoding computational models in biology and medicine. This article summarizes recent progress and gives perspectives on emerging challenges.
- Published
- 2020
41. Comparison of Lesser Toe Proximal Interphalangeal Joint Arthrodesis Versus Resection Arthroplasty: A Randomized Controlled Study.
- Author
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Scheidt S, Nowak V, Mittag F, Götze M, Wülker N, and Hofmann UK
- Subjects
- Arthroplasty methods, Humans, Prospective Studies, Retrospective Studies, Toes surgery, Treatment Outcome, Arthrodesis methods, Metatarsophalangeal Joint surgery
- Abstract
The goal of this study was to compare operative outcomes after lesser toe deformity correction with either proximal interphalangeal (PIP) joint arthrodesis or PIP joint resection arthroplasty. A prospective randomized controlled trial was performed with 37 patients (48 toes) operated on with one of these two procedures. Evaluation of the numeric rating scale score, the American Orthopedic Foot and Ankle Society score, osseous consolidation, and clinical outcome was performed preoperatively and at 6 weeks and 6 months postoperatively. Both study groups showed significant improvement at 6 months postoperatively. Although osseous consolidation was significantly higher for the arthrodesis group ( P =.001), this difference did not affect clinical outcomes, and at 6 months postoperatively, pain on the numeric rating scale was 0 (range, 0-7) for the arthroplasty group and 0 (range, 0-5) for the arthrodesis group ( P =.669). The American Orthopedic Foot and Ankle Society score was 83 (range, 39-95) and 80 (range, 59-95), respectively ( P =.879). No difference was observed for signs of inflammation or axis correction. Even a direct comparison of toes with radiologically osseous fusion (n=16) with those without fusion (n=32) did not show any clinical differences. This randomized controlled study showed no clinical differences in outcome between PIP joint arthrodesis and PIP joint resection arthroplasty for correction of lesser toe deformities, with good to excellent outcomes for both groups. [ Orthopedics . 2022;45(2):86-90.].
- Published
- 2022
- Full Text
- View/download PDF
42. Interobserver Reliability When Classifying MR Imaging of the Lumbar Spine: Written Instructions Alone Do Not Suffice.
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Hofmann UK, Keller RL, Gesicki M, Walter C, and Mittag F
- Subjects
- Humans, Observer Variation, Reproducibility of Results, Low Back Pain diagnostic imaging, Lumbar Vertebrae diagnostic imaging, Magnetic Resonance Imaging classification, Magnetic Resonance Imaging methods
- Abstract
Purpose: Numerous classification systems have been proposed to analyze lumbar spine MRI scans. When evaluating these systems, most studies draw their conclusions from measurements of experienced clinicians. The aim of this study was to evaluate the impact of specific measurement training on interobserver reliability in MRI classification of the lumbar spine., Methods: Various measurement and classification systems were assessed for their interobserver reliability in 30 MRIs from patients with chronic lumbar back and sciatic pain. Two observers were experienced spine surgeons. The third observer was an inexperienced medical student who, prior to the study measurements, in addition to being given the detailed written instructions also given to the surgeons, obtained a list of 20 reference measurements in MRI scans from other patients to practice with., Results: Excellent agreement was observed between the medical student and the spine surgeon who had also created the reference measurements. Between the two spine surgeons, agreement was markedly lower in all systems investigated (e.g., antero-posterior spinal canal diameter intraclass correlation coefficient [ICC] [3.1] = 0.979 vs. ICC [3.1] = 0.857)., Conclusion: These data warrant the creation of publicly available standardised measurement examples of accepted classification systems to increase reliability of the interpretation of MR images.
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- 2020
- Full Text
- View/download PDF
43. Predictability of the effects of epidural injection in lumbar spinal stenosis by assessment of lumbar MRI scans.
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Hofmann UK, Keller RL, von Bernstorff M, Walter C, and Mittag F
- Subjects
- Adult, Aged, Bupivacaine administration & dosage, Female, Glucocorticoids administration & dosage, Humans, Injections, Epidural, Male, Middle Aged, Pain Management methods, Retrospective Studies, Sciatica drug therapy, Spinal Stenosis drug therapy, Triamcinolone administration & dosage, Anti-Inflammatory Agents administration & dosage, Lumbar Vertebrae diagnostic imaging, Magnetic Resonance Imaging methods, Sciatica diagnostic imaging, Spinal Stenosis diagnostic imaging
- Abstract
Background: Numerous classification systems have been proposed to interpret lumbar MRI scans. The clinical impact of the measured parameters remains unclear. To evaluate the clinical significance of imaging results in patients with multisegmental degenerative pathologies, treating specialists can perform image-guided local injections to target defined areas such as the epidural space., Objective: The aim of this retrospective study was to evaluate the correlation between lumbar spinal stenosis measurements obtained by MRI and improvement obtained through local epidural injection., Methods: In this retrospective study various measurement and classification systems for lumbar spinal stenosis were applied to MRI scans of 100 patients with this pathological condition. The reported effect of epidural bupivacaine/triamcinolone injections at the site was recorded in these patients and a comparative analysis performed., Results: MRI features assessed in this study did not show any relevant correlation with reported pain relief after epidural injection in patients with chronic lumbar stenosis, with the exception of posterior disc height with a weak Kendall's tau of -0.187 (p= 0.009)., Conclusions: Although MRI is crucial for evaluating lumbar spinal stenosis, it cannot replace but is rather complementary to a good patient history and clinical examination or the results of local diagnostic injections.
- Published
- 2020
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44. Transfer of plantar pressure from the medial to the central forefoot in patients with hallux valgus.
- Author
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Hofmann UK, Götze M, Wiesenreiter K, Müller O, Wünschel M, and Mittag F
- Subjects
- Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Exercise Test methods, Female, Foot surgery, Hallux Valgus diagnosis, Hallux Valgus surgery, Humans, Male, Metatarsal Bones physiopathology, Metatarsal Bones surgery, Middle Aged, Young Adult, Foot physiopathology, Gait physiology, Hallux Valgus physiopathology, Pressure, Weight-Bearing physiology
- Abstract
Background: The aim of the study was to evaluate changes in plantar pressure distribution in feet affected by hallux valgus compared with their contralateral non-affected feet and with the feet of healthy control subjects., Methods: Thirty-six patients with unilateral hallux valgus who were indicated for surgery and 30 healthy subjects were assessed on a pedobarographic instrumented treadmill for step length and width, mean stance phase, and plantar foot pressure distribution. Plantar pressure distribution was divided into eight regions., Results: Significantly higher plantar pressures were observed in hallux valgus feet under the second and third metatarsal heads (p = .033) and the fourth and fifth toes (p < .001) than in the healthy control feet. Although decreased pressures were measured under the hallux in affected feet (197 [82-467] kPa) in contrast to the contralateral side (221 [89-514] kPa), this difference failed to reach statistical significance (p = .055). The gait parameters step width, step length, and single-limb support did not show any differences between hallux valgus and control feet., Conclusion: Although the literature on changes in plantar pressures in hallux valgus remains divided, our findings on transferring load from the painful medial to the central and lateral forefoot region are consistent with the development of transfer metatarsalgia in patients with hallux valgus.
- Published
- 2019
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45. Evaluation of Patients' Posture and Gait Profile After Lumbar Fusion Surgery by Video Rasterstereography and Treadmill Gait Analysis.
- Author
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Scheidt S, Hofmann UK, and Mittag F
- Subjects
- Biomechanical Phenomena, Female, Humans, Male, Reproducibility of Results, Rotation, Exercise Test, Gait Analysis methods, Lumbar Vertebrae surgery, Posture, Spinal Fusion
- Abstract
This protocol provides guidance on how to perform high resolution video rasterstereography and treadmill gait analysis on patients after lumbar fusion surgery to obtain results about altered variables of gait and posture. These observed changes can then be correlated with the patient-reported outcome measure of pain relief. The rasterstereographic device projects lines of parallel light onto the surface of the tested subject's back. The deformation of these lines is recognized by the device. From these data, a special software then generates a 3-D profile based on the principle of triangulation. With an inaccuracy of only 0.2 mm it can measure changes in posture at very high precision. Gait and stance parameters are recorded using a treadmill equipped with an electric sensor mat that contains 10,200 miniature force sensors in the registering zone under the belt. Initial walking speed on the treadmill is 0.5 km/h. Speed is then gradually increased by increments of 0.1 km/h until each subject reaches his or her individual maximum well tolerable walking speed. At this speed, parameters are recorded during a 20 s measurement interval. Subjects are tested barefoot and without holding a handrail. Among various other parameters, stride width, step length, stance phase and foot rotation are measured. Both methods used reportedly have a high intra- and inter-observer reliability. The advantage of these highly accurate techniques is that they offer an objective and very detailed perspective on changes in the patient's posture and gait. Due to the amount of data generated, these techniques are, however, not so much suitable for everyday routine use, but rather interesting to scientifically evaluate long term alterations in posture and gait in patients like for example after lumbar fusion surgery.
- Published
- 2019
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46. PREOPERATIVE ANALYSIS OF RADIOGRAPHIC FINDINGS IN 516 PATIENTS WITH HALLUX VALGUS DEFORMITY.
- Author
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Götze M, Hasmann SE, Hofmann UK, Walter C, and Mittag F
- Abstract
Objective: This is a descriptive study to report our method of operative correction for patients with hallux valgus deformities., Methods: From 2006 to 2012, 516 consecutive patients (601 feet) with hallux valgus deformities were treated surgically in our department after conservative treatments were exhausted. The hallux valgus angle, intermetatarsal angle, distal metatarsal articular angle, and degree of osteoarthritis in the first metatarsophalangeal joint were measured on preoperative plain radiographs of the weight-bearing forefoot., Results: Young patients with severe intermetatarsal deviation received a combined proximal and distal osteotomy of the first metatarsal (n = 21). Patients with low intermetatarsal deviation received a distal metatarsal chevron osteotomy (n = 196), whereas patients with severe intermetatarsal deviation and less flexible deformities without osteoarthritis received a basal metatarsal osteotomy with a distal soft tissue procedure (n = 173). Elderly active patients with osteoarthritis in the first metatarsophalangeal joint received an arthrodesis (n = 100) or resection arthroplasty (n = 58)., Conclusion: Determining a few simple angles on plain radiographs of the weight-bearing forefoot in combination with the age and level of activity of patients can help simplify the operative correction method by using the schema we developed. Level of evidence IV, case series ., Competing Interests: All authors declare no potential conflict of interest related to this article.
- Published
- 2019
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47. Expanding the clinical phenotype of IARS2-related mitochondrial disease.
- Author
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Vona B, Maroofian R, Bellacchio E, Najafi M, Thompson K, Alahmad A, He L, Ahangari N, Rad A, Shahrokhzadeh S, Bahena P, Mittag F, Traub F, Movaffagh J, Amiri N, Doosti M, Boostani R, Shirzadeh E, Haaf T, Diodato D, Schmidts M, Taylor RW, and Karimiani EG
- Subjects
- Adult, Amino Acid Sequence, Bone Diseases, Developmental diagnosis, Bone Diseases, Developmental pathology, Cataract diagnosis, Cataract pathology, Consanguinity, Female, Gene Expression, Hearing Loss, Sensorineural diagnosis, Hearing Loss, Sensorineural pathology, Hereditary Sensory and Autonomic Neuropathies diagnosis, Hereditary Sensory and Autonomic Neuropathies pathology, Homozygote, Humans, Leigh Disease diagnosis, Leigh Disease pathology, Male, Mitochondrial Diseases diagnosis, Mitochondrial Diseases pathology, Models, Molecular, Mutation, Missense, Pedigree, Protein Conformation, Protein Subunits genetics, Syndrome, Exome Sequencing, Bone Diseases, Developmental genetics, Cataract genetics, Hearing Loss, Sensorineural genetics, Hereditary Sensory and Autonomic Neuropathies genetics, Isoleucine-tRNA Ligase genetics, Leigh Disease genetics, Mitochondrial Diseases genetics
- Abstract
Background: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies., Methods: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis., Results: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein., Conclusions: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia.
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- 2018
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48. Influence of spine surgery on the ability to perform an emergency stop while driving a car.
- Author
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Hofmann UK, Wittmann S, Fischer AN, Jordan M, Feierabend MM, Rondak IC, Ipach I, and Mittag F
- Subjects
- Adult, Aged, Cross-Sectional Studies, Female, Humans, Low Back Pain physiopathology, Low Back Pain surgery, Male, Middle Aged, Postoperative Period, Risk Factors, Automobile Driving, Low Back Pain rehabilitation, Lumbar Vertebrae surgery, Orthopedic Procedures rehabilitation, Reaction Time physiology
- Abstract
Background: Spinal surgeries have strongly increased in number over the past decade. The question of when it is safe to resume driving is thereby one the most frequently asked questions that patients ask of their treating physician., Objective: The aim of this study was to assess braking performance before and after spine surgery., Methods: Reaction time, foot transfer time (together brake response time [BRT]), and brake force (BF) were evaluated in a drive simulator. A longitudinal patient cohort (n= 27) was tested preoperatively and at the first follow-up. A cross-sectional cohort (n= 27) was tested at > 1 year postoperatively. The values from these groups were compared with a healthy age-matched control group of 24 volunteers., Results: No significant improvement in BRT was seen in lumbar fusion three months postoperatively (p= 0.597); BF was even weaker than it was preoperatively (p= 0.044). In comparison to the control group (median BRT 479 ms), preoperative BRT was already impaired in lumbar fusion patients (median 560 ms), representing an increased braking distance of 2.25 m at 100 km/h., Conclusion: Although most patients performed adequately, about one third presented critical braking performance. Risk factors for impaired braking may include scheduled multisegmental fusion surgery, female sex, and pain.
- Published
- 2018
- Full Text
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49. Predictability of the effects of facet joint infiltration in the degenerate lumbar spine when assessing MRI scans.
- Author
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Hofmann UK, Keller RL, Walter C, and Mittag F
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Injections, Intra-Articular, Low Back Pain drug therapy, Male, Middle Aged, Retrospective Studies, Low Back Pain diagnostic imaging, Lumbar Vertebrae diagnostic imaging, Magnetic Resonance Imaging methods, Spinal Stenosis diagnostic imaging, Zygapophyseal Joint diagnostic imaging
- Abstract
Background: Imaging results are frequently considered as hallmarks of disease by spine surgeons to plan their future treatment strategy. Numerous classification systems have been proposed to quantify or grade lumbar magnetic resonance imaging (MRI) scans and thus objectify imaging findings. The clinical impact of the measured parameters remains, however, unclear. To evaluate the pathological significance of imaging findings in patients with multisegmental degenerative findings, clinicians can perform image-guided local infiltrations to target defined areas such as the facet joints. The aim of the present retrospective study was to evaluate the correlation of MRI facet joint degeneration and spinal stenosis measurements with improvement obtained by image-guided intraarticular facet joint infiltration., Methods: Fifty MRI scans of patients with chronic lumbar back pain were graded radiologically using a wide range of classification and measurement systems. The reported effect of facet joint injections at the site was recorded, and a comparative analysis performed., Results: When we allocated patients according to their reported pain relief, 27 showed no improvement (0-30%), 16 reported good improvement (31-75%) and 7 reported excellent improvement (> 75%). MRI features assessed in this study did, however, not show any relevant correlation with reported pain after facet joint infiltration: Values for Kendall's tau ranged from τ = - 0.190 for neuroforaminal stenosis grading as suggested by Lee, to τ = 0.133 for posterior disc height as proposed by Hasegawa., Conclusion: Despite the trend in evidence-based medicine to provide medical algorithms, our findings underline the continuing need for individualised spine care that, along with imaging techniques or targeted infiltrations, includes diagnostic dimensions such as good patient history and clinical examination to formulate a diagnosis., Trial Registration: ClinicalTrials.gov , NCT03308149 , retrospectively registered October 2017.
- Published
- 2017
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50. INFLUENCE OF AGE ON PARAMETERS FOR FEMOROACETABULAR IMPINGEMENT AND HIP DYSPLASIA IN X-RAYS.
- Author
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Hofmann UK, Ipach I, Rondak IC, Syha R, Götze M, and Mittag F
- Abstract
Objective: While several radiographic parameters have been established to describe the geometry and pathology of the hip, their reference values and clinical significance remain a matter of dispute. The present study tests the hypothesis that age has a relevant impact on radiographic hip parameters., Method: Pelvic antero-posterior views were measured for CE angle, Sharp's angle, acetabular depth-to-width ratio, femoral head extrusion index, roof obliquity, caput-collum-diaphyseal (CCD) angle, and Murray's femoral head ratio, and the values obtained were correlated with age., Results: Significant weak and moderate linear correlations (all Ps<0.001) were observed between age and CE angle (ρ=0.31), Sharp's angle (ρ=-0.38), extrusion index (ρ=-0.22), CCD angle (ρ=-0.15), depth-to-width ratio (ρ=-0.38), and roof obliquity (ρ=-0.19), while Murray's femoral head ratio (ρ=0.05; P=0.274) was not associated with age. Interestingly, the parameters describing the acetabulum all showed a relevant increase in coverage with age, leading to CE-angles well beyond 40° and a Sharp's angle below 35° in a large portion of asymptomatic older adults., Conclusion: While a decrease in CCD angle with age is described in most orthopedic textbooks, the changes observed with age in acetabular geometry far exceed those measured at the femoral head-neck junction. We recommend considering these alterations that may be attributable to age when formulating a radiographic diagnosis. Level of Evidence III, Diagnostic Studies - Investigating a Diagnostic Test., Competing Interests: All authors declare no potential conflict of interest related to this article.
- Published
- 2017
- Full Text
- View/download PDF
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