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1. Update of the fracture risk prediction tool FRAX:a systematic review of potential cohorts and analysis plan

Author

Vandenput, L, Johansson, H, McCloskey, E V, Liu, E, Åkesson, K E, Anderson, F A, Azagra, R, Bager, C L, Beaudart, C, Bischoff-Ferrari, H A, Biver, E, Bruyère, O, Cauley, J A, Center, J R, Chapurlat, R, Christiansen, C, Cooper, C, Crandall, C J, Cummings, S R, da Silva, J A P, Dawson-Hughes, B, Diez-Perez, A, Dufour, A B, Eisman, J A, Elders, P J M, Ferrari, S, Fujita, Y, Fujiwara, S, Glüer, C-C, Goldshtein, I, Goltzman, D, Gudnason, V, Hall, J, Hans, D, Hoff, M, Hollick, R J, Huisman, M, Iki, M, Ish-Shalom, S, Jones, G, Karlsson, M K, Khosla, S, Kiel, D P, Koh, W-P, Koromani, F, Kotowicz, M A, Kröger, H, Kwok, T, Lamy, O, Langhammer, A, Larijani, B, Lippuner, K, Mellström, D, Merlijn, T, Nordström, A, Nordström, P, O'Neill, T W, Obermayer-Pietsch, B, Ohlsson, C, Orwoll, E S, Pasco, J A, Rivadeneira, F, Schei, B, Schott, A-M, Shiroma, E J, Siggeirsdottir, K, Simonsick, E M, Sornay-Rendu, E, Sund, R, Swart, K M A, Szulc, P, Tamaki, J, Torgerson, D J, van Schoor, N M, van Staa, T P, Vila, J, Wareham, N J, Wright, N C, Yoshimura, N, Zillikens, M C, Zwart, M, Harvey, N C, Lorentzon, M, Leslie, W D, and Kanis, J A

Subjects
SDG 3 - Good Health and Well-being, Bone Density, Hip Fractures, Risk Factors, Endocrinology, Diabetes and Metabolism, Humans, Osteoporosis, Prospective Studies, 610 Medicine & health, Risk Assessment, Osteoporotic Fractures
Abstract

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Published
2022
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2. Update of the fracture risk prediction tool FRAX: A systematic review of potential cohorts and analysis plan

Author

Vandenput, Lisbeth, Johansson, H., McCloskey, E. V., Liu, E., Akesson, Kristina E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, Charlotte, Bischoff-Ferrari, H.A., Biver, E., Bruyère, Olivier, Cauley, J.A., Center, J.R., Chapulat, R., Christiansen, C., Cooper, Cyrus, Crandall, Carolyn J., Cummings, Steven, da Silva, J.A.P., Dawson-Hughes, Bess, Diez-Pérez, A., Dufour, Alyssa B., Eisman, J.A., Elders, Petra J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.C., Goldstein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, Rosemary J., Huisman, Martijn, Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, Sundeep, Kiel, D.P., Koh, W-P, Koromani, F., Kotowicz, M.A., Kroger, H., Kwok, T., Lamy, Olivier, Langhammer, Arnulf, Larijani, Bagher, Lippuner, Kurt, Mellström, D, Merlijn, Thomas, Nordstrom, A., Nordstrom, P., O'Neill, T.W., Obermayer-Piestch, B., Harvey, Nicholas, Kanis, J A., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schei, B., Schott, A.M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., Van Schoor, N.M., van Staa, T.P., Vilas, J.C., Wareham, N.J, Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Lorentzon, M., and Leslie, W.D.

Abstract

Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Published
2022

3. Novel Approach to Estimate Osteoarthritis Progression: Use of the Reliable Change Index in the Evaluation of Joint Space Loss

Author

Parsons, Camille M., Judge, Andrew, Leyland, Kirsten, Bruyere, Olivier, Dop, Florence Petit, Chapurlat, Roland, Reginster, Jean-yves, Edwards, Mark H., Dennison, Elaine M., Cooper, Cyrus, Inskip, Hazel, Reginster, J. -y., Christiansen, C., Delmas, P., Genant, H., Zacher, J., Bellamy, N., Speirs, C., Breart, G., Meyer, O., Gensburger, D., Arlot, M., Roux, J. -P., Deroisy, R., Sambrook, P., Leeb, B., Verbruggen, A., Bensen, W. G., Hala, T., Holm−bentzen, M., Valter, I., Chevalier, X., Swoboda, B., Adami, S., Kloppenburg, M., Grazuleviciute, E., Badurski, J., Branco, J., Nasonov, E., Navarro, F., Spector, T., Barnsley, L., Hall, S., Jones, G., Klestov, A., March, L., Nash, P., Romas, E., Will, R., Erlacher, L., Leeb, F. B., Resch, H., Rainer, F., Zamani, O., Appelboom, T., Devogelaer, J. P., Kvasz, A., Raeman, F., Beaulieu, A. D., Brown, J., Cividino, A. A., Morin, F., Olszynski, W. P., Raynauld, J. P., Thorne, J. C., Pavelka, K., Alexandersen, P., Hoeck, H. C., Holm-Bentzen, M., Lundqvist, P., Aim, L., Audouy, P., Beaunier, P., Benhamou, C. L., Berenbaum, F., Chabaud, E., Cohen-Solal, M., Delbecq, D., Euller-Ziegler, L., Fardellone, Patrice, Hilliquin, P., Jacquety, E., Jude, N., Lechevalier, D., Mouchet, J. C., Richette, P., Sainte Lorette, E., Schaeverbeke, T., Sebbah, A., Vignot, E., Brabant, T., Burm-Ester, G. R., Grifka, J., Mueller, P. E. M., Bianchi, G., Grassi, W., Di Matteo, L., Modena, V., Di Munno, O., Orto-Lani, S., Punzi, L., Zangari, M., Roorda, L. D., van Riel, P. L. C. M., Czerwinski, E., Gorecki, A., Tlustochowicz, W., da Silva, J. Canas, Gomes, J. A. Melo, Miranda, L. M., Radulescu, F., Alexeeva, L. I., Orlov-Morozov, A. V., Pikhlak, E. G., Pilyaev, V. G., Shostak, N. A., Shmidt, E. I., Zagorodniy, N. V., Rodriguez, L. Arboleya, Ruiz, P. Benito, Carmona, E. Chamizo, Estevez, E. Collantes, Herrero-Beaumont, G., Mola, E. Martin, Moreno, A., Hernandez, A. Naranjo, Sarabia, F. Navarro, Padrino, J. M., Palacios, C., Serna, A. Rodriguez, Ivorra, J. A. Roman, Torrijos, A., Abdulhakim, E., Arden, N., Birrell, F., Donnachie, H., Fraser, W., Keen, R., Sarmiento, R., Stone, M. D., Grp, Sekoia Study, Department of public health, Université de Liège, Service de Rhumatologie et Pathologie Osseuse [Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), World Health Organization (WHO), World Health Organization, University of Southampton, University of Bristol [Bristol], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Department of Public Health, Epidemiology and Health Economics, Center for Permafrost (CENPERM), Department of Geosciences and Natural Resource Management [Copenhagen] (IGN), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Queen's University [Kingston, Canada], Department of Computer Science [Auckland], University of Auckland [Auckland], Institut de Recherche sur la Fusion par confinement Magnétique (IRFM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Antwerp (UA), Arkema (Arkema), Hutchinson SA, Chair of Aerodynamics and Fluid Mechanics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Leiden University Medical Center (LUMC), Universiteit Leiden, CEDOC - Department of Rheumatology, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), CHLO/Hospital Egas Moniz, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Radio and Space Plasma Physics Group [Leicester] (RSPP), University of Leicester, School of Environmental Sciences, University of Greenwich, Johns Hopkins University (JHU), University of Queensland [Brisbane], Université Laval [Québec] (ULaval), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Institute of Rheumatology, University Prague, Oskar Klein Centre [Stockholm], Stockholm University, Laboratoire de Réactivité de Surface (LRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de rhumatologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Département de Rhumatologie, CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Sud Francilien, Laboratoire d'Electronique, d'Informatique et d'Image [EA 7508] (Le2i), Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Aquitaine’s Care and Research organisation for inflammatory and Immune-Mediated diseases [CHU Bordeaux] (FHU ACRONIM), CHU Bordeaux [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Department of Bone and Joint Diseases, Faculty of Medicine and Health Sciences, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Departamento de Construcción y Agronomía, Facultad de Ciencias Agrarias y Ambientales, University of Oxford, The University of Sydney, IUMEA, University of Las Palmas de Gran Canaria (ULPGC), the SEKOIA management team, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, Royaume-Uni], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], APH - Aging & Later Life, and Rehabilitation medicine

Subjects
Male, medicine.medical_specialty, Knee Joint, [SDV]Life Sciences [q-bio], Radiography, Osteoarthritis, Thiophenes, Placebo, Severity of Illness Index, Article, law.invention, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Rheumatology, Randomized controlled trial, Strontium ranelate, law, Internal medicine, Severity of illness, Medicine, Humans, skin and connective tissue diseases, Aged, Bone Density Conservation Agents, business.industry, Reproducibility of Results, Middle Aged, Osteoarthritis, Knee, medicine.disease, Multicenter study, Physical therapy, Disease Progression, Female, sense organs, business, medicine.drug
Abstract

Contains fulltext : 202254.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression. METHODS: Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. RESULTS: Between consecutive years, 57-69% of participants had an apparent decrease (change

Published
2019
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5. Additional file 3 of Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects

Author

Christiansen, C., J. E. Castillo-Fernandez, A. Domingo-Relloso, W. Zhao, J. S. El-Sayed Moustafa, P.-C. Tsai, J. Maddock, K. Haack, S. A. Cole, S. L. R. Kardia, M. Molokhia, M. Suderman, C. Power, C. Relton, A. Wong, D. Kuh, A. Goodman, K. S. Small, J. A. Smith, M. Tellez-Plaza, A. Navas-Acien, G. B. Ploubidis, R. Hardy, and J. T. Bell

Abstract

Additional file 3: Figure S1. Receiver operating characteristic (ROC) curves predicting current smokers and smoke exposure. a Top 5 CpG from 450 k only predicting smoke exposure and b Top 5 CpG from EPIC predicting smoke exposure.

Published
2021
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6. Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures (Nature Communications, (2019), 10, 1, (2054), 10.1038/s41467-019-09860-0)

Author

Styrkarsdottir, U, Stefansson, OA, Gunnarsdottir, K, Thorleifsson, G, Lund, SH, Stefansdottir, L, Juliusson, K, Agustsdottir, AB, Zink, F, Halldorsson, GH, Ivarsdottir, EV, Benonisdottir, S, Jonsson, H, Gylfason, A, Norland, K, Trajanoska, K, Boer, CG, Southam, L, Leung, JCS, Tang, NLS, Kwok, TCY, Lee, JSW, Ho, SC, Byrjalsen, I, Center, JR, Lee, SH, Koh, JM, Lohmander, LS, Ho-Pham, LT, Nguyen, TV, Eisman, JA, Woo, J, Leung, PC, Loughlin, J, Zeggini, E, Christiansen, C, Rivadeneira, F, van Meurs, J, Uitterlinden, AG, Mogensen, B, Ingvarsson, T, Sigurdsson, G, Benediktsson, R, Sulem, P, Jonsdottir, I, Masson, G, Holm, H, Norddahl, GL, Thorsteinsdottir, U, Gudbjartsson, DF, and Stefansson, K

Abstract

© 2019, The Author(s). The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file. In addition, affiliations 16 and 17 incorrectly read ‘School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia’ and ‘St Vincent’s Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.’ This has now been corrected in both the PDF and HTML versions of the Article.

Published
2019

8. Cavitation estimates by orbit prediction of a journal bearing – Finite element modelling and experimental studies

Author

Christiansen, C K, Klit, P, Walther, J H, and Vølund, A

Subjects
Cavitation, test rig, journal bearing, Finite Element, journal orbit
Abstract

The paper presents a two-sided approach to establish understanding of the cavitation phenomenon in dynamically loaded journal bearings, more specifically the engine bearings of large two-stroke marine diesel engines. One disadvantage of the journal bearing is the converging-diverging geometry making it prone to cavitation which again affects the load carrying capacity of the bearing. In combustion engines the journal bearing plays a vital role especially as main and crosshead bearings transmitting the combustion forces. Those forces vary highly during one combustion cycle which is further influencing the load carrying capacity and ultimately the chances of fatal shaft-sleeve contact. By solving Reynolds equation numerically using finite elements and incorporating a cavitation algorithm, the dynamic coefficients can be used to establish the journal orbit for a given bearing and load pattern. Validation of the results is done against the Ruston and Hornsby 6VEB-X Mk III engine. Besides the numerical investigations a cavitation test rig has been developed. With this rig it is possible to generate cavitation under controlled conditions in terms of load/eccentricity and rotational speed. The development of cavitation in time in terms of position and distribution can be visually recorded.

Published
2015

12. Management of hypersensitivity reactions to iodinated contrast media

Author

Brockow, Knut, Christiansen, C., Kanny, G., Clément, O., Barbaud, A., Bircher, A., Dewachter, P., Guéant, J. L., Rodriguez Guéant, R. M., Mouton Faivre, C., Ring, J., Romano, A., Sainte Laudy, J., Demoly, P., Pichler, W. J., Aberer, W., Ballmer Weber, B. K., Bilo, M. B., Birnbaum, J., Blanca, M., Blõmecke, B., Campi, P., De Weck, A., Drouet, M., Dzviga, C., Fernandez, J., Gomez, E., Kapp, A., Kidon, M., Kowalski, M., Laroche, D., Mertès, M., Merk, H., Moneret Vautrin, D. A., Pascual Marcos, C., Rebelo Gomes, E., Rueff, F., Sanz, M. L., Torres, M. J., Vervloet, D., Wedi, B., MARONE, GIANNI, Brockow, Knut, Christiansen, C., Kanny, G., Clément, O., Barbaud, A., Bircher, A., Dewachter, P., Guéant, J. L., Rodriguez Guéant, R. M., Mouton Faivre, C., Ring, J., Romano, A., Sainte Laudy, J., Demoly, P., Pichler, W. J., Aberer, W., Ballmer Weber, B. K., Bilo, M. B., Birnbaum, J., Blanca, M., Blõmecke, B., Campi, P., De Weck, A., Drouet, M., Dzviga, C., Fernandez, J., Gomez, E., Kapp, A., Kidon, M., Kowalski, M., Laroche, D., Marone, Gianni, Mertès, M., Merk, H., Moneret Vautrin, D. A., Pascual Marcos, C., Rebelo Gomes, E., Rueff, F., Sanz, M. L., Torres, M. J., Vervloet, D., and Wedi, B.

Subjects
medicine.medical_specialty, Allergy, Premedication, Immunology, Drug Hypersensitivity, Iodinated contrast media, Skin test, Immediate reaction, Prevalence, Immunology and Allergy, Medicine, In patient, Iodine Compound, business.industry, Contrast media, Risk Factor, ALLERGIC/HYPERSENSITIVITY, Nonimmediate reaction, Diagnostic test, medicine.disease, Dermatology, Surgery, Skin reaction, business, Diagnosi, Human
Abstract

All iodinated contrast media (CM) are known to cause both immediate (≤1 h) and nonimmediate (>1 h) hypersensitivity reactions. Although for most immediate reactions an allergic hypersensitivity cannot be demonstrated, recent studies indicate that the severe immediate reactions may be IgE-mediated, while most of the nonimmediate exanthematous skin reactions, appear to be T-cell mediated. Patients who experience such hypersensitivity reactions are therefore advised to undergo an allergologic evaluation. Several investigators have found skin testing to be useful in confirming a CM allergy, especially in patients with nonimmediate skin eruptions. If a patient with confirmed allergy to a CM needs a new CM exposure, a skin test negative CM should be chosen and premedication may be tried. However, none of these precautional measures is a guarantee against a repeat reaction. More research focusing on pathomechanisms, diagnostic testing and premedication is therefore clearly needed in order to prevent CM-induced hypersensitivity reactions in the future.

Published
2005
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13. Genome-wide Association Study for Radiographic Vertebral Fractures: A Potential Role for the 16q24 BMD Locus versus Lessons Learned from Challenging Phenotype Definition

Author

Oei, L, Estrada, K, Duncan, E, Christiansen, C, Liu, C, Langdahl, B, Obermayer-Pietsch, B, Riancho, J, Prince, R, van Schoor, N, McCloskey, E, Hsu, Y, Evangelou, E, Ntzani, E, Evans, D, Alonso, N, Husted, L, Valero, C, Hernandez, J, Lewis, JR, Kaptoge, S, Zhu, K, Cupples, L, Medina-Gómez, C, and Vandenput, L

Abstract

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2,666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at P 1.25) may still be consistent with an effect size

Published
2016

15. Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures

Author

Austin, M, Yang, Yc, Vittinghoff, E, Adami, Silvano, Boonen, S, Bauer, Dc, Bianchi, G, Bolognese, Ma, Christiansen, C, Eastell, R, Grauer, A, Hawkins, F, Kendler, Dl, Oliveri, B, Mcclung, Mr, Reid, Ir, Siris, Es, Zanchetta, J, Zerbini, Ca, Libanati, C, Cummings, Sr, and Freedom, Trial

Subjects
PERCENT OF TREATMENT EFFECT EXPLAINED, SURROGATE, Bone density, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medicina Clínica, law.invention, Placebos, Fractures, Bone, Absorptiometry, Photon, Randomized controlled trial, Bone Density, law, Monoclonal, purl.org/becyt/ford/3.2 [https], 80 and over, Medicine, Orthopedics and Sports Medicine, Humanized, Aged, 80 and over, Bone mineral, Bone Density Conservation Agents, musculoskeletal, neural, and ocular physiology, Antibodies, Monoclonal, Middle Aged, musculoskeletal system, Photon, FRACTURE, bone mineral density, denosumab, Denosumab, Spinal Fractures, purl.org/becyt/ford/3 [https], Female, Medicina Critica y de Emergencia, medicine.drug, musculoskeletal diseases, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Bone pathology, Urology, Antibodies, Monoclonal, Humanized, Placebo, Antibodies, Double-Blind Method, Humans, Absorptiometry, Bone, Reduction (orthopedic surgery), Aged, DENOSUMAB, business.industry, Original Articles, Surgery, business, Fractures, Risk Reduction Behavior, BONE MINERAL DENSITY
Abstract

Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < -4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab. Copyright © 2012 American Society for Bone and Mineral Research. Fil: Austin, Matthew. Amgen Incorporated; Estados Unidos Fil: Yang, Yu Ching. Amgen Incorporated; Estados Unidos Fil: Vittinghoff, Eric. University of California; Estados Unidos Fil: Adami, Silvano. Universita di Verona; Italia Fil: Boonen, Steven. Katholikie Universiteit Leuven; Bélgica Fil: Bauer, Douglas C. University of California; Estados Unidos Fil: Bianchi, Gerolamo. Azienda Sanitaria Genovese; Italia Fil: Bolognese, Michael A.. Bethesda Health Research Center; Estados Unidos Fil: Christiansen, Claus Bohn. Center For Clinical And Basic Research As; Estados Unidos Fil: Eastell, Richard. University Of Sheffield; Reino Unido Fil: Grauer, Andreas. Amgen Incorporated; Estados Unidos Fil: Hawkins, Federico. Hospital Universitario 12 de Octubre; España Fil: Kendler, David L.. University of British Columbia; Canadá Fil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: McClung, Michael R.. Oregon Osteoporosis Center; Estados Unidos Fil: Reid, Ian R.. The University of Auckland; Nueva Zelanda Fil: Siris, Ethel S.. Columbia University; Estados Unidos Fil: Zanchetta, Jose. Universidad del Salvador; Argentina Fil: Zerbini, Cristiano A.F.. Centro Paulista de Investigação Clinica; Brasil Fil: Libanati, Cesar. Amgen Incorporated; Estados Unidos Fil: Cummings, Steven R.. University of California; Estados Unidos

Published
2012
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16. Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis

Author

Cummings, Sr, San Martin, J, Mcclung, Mr, Siris, Es, Eastell, R, Reid, Ir, Delmas, P, Zoog, Hb, Austin, M, Wang, A, Kutilek, S, Adami, S, Zanchetta, J, Libanati, C, Siddhanti, S, Christiansen, C, Freedom, Trial, and Nuti, R

Subjects
Risk, medicine.medical_specialty, Bone density, denosumab, prevention, postmenopausal, osteoporosis, Osteoporosis, Urology, Antibodies, Monoclonal, Humanized, Placebo, Bone densitometry, Bone remodeling, Fractures, Bone, Clinical trials, Bone Density, medicine, Humans, Cumulative incidence, Osteoporosis, Postmenopausal, Aged, Aged, 80 and over, Practice, Hip fracture, Bone Density Conservation Agents, Hip Fractures, business.industry, Incidence, RANK Ligand, Hazard ratio, Obstetrics and Gynecology, Antibodies, Monoclonal, Bone QCT, Bisphosphonates, General Medicine, Middle Aged, medicine.disease, Surgery, Denosumab, Relative risk, Spinal Fractures, Female, Bone Remodeling, Osteonecrosis of the jaw, business, medicine.drug
Abstract

Denosumab is a fully human monoclonal antibody against the receptor activator of the cytokine, nuclear factor-κB ligand, which is of critical importance for the formation, function, and survival of osteoclasts. This antibody binds nuclear factor-κB ligand and reversibly inhibits osteoclast-mediated bone resorption in osteoclasts and osteoclast precursors. Earlier studies reported that subcutaneous administration of denosumab every 6 months reduced bone turnover and increased bone mineral density. This international, randomized, placebo-controlled trial evaluated the effect of denosumab on the risk of fracture in 7808 postmenopausal women with osteoporosis. Participants had a bone mineral density T score less than -2.5 at the lumbar spine or total hip. Women with T scores less than -4.0 were excluded. Their ages ranged from 60 to 90 years. The study subjects used in the final analysis had been randomized to receive subcutaneous injections of 60 mg of denosumab (n = 3902) or placebo (n = 3906) every 6 months for 36 months. A new vertebral fracture was the primary outcome. The occurrence of nonvertebral fracture and hip fracture were the secondary end points. At 36-months, the cumulative incidence of new radiographic vertebral fracture was reduced by 68% in the denosumab group compared to the placebo group (denosumab: 2.3% vs. placebo: 7.2%); the risk ratio was 0.32, with a 95% confidence interval [CI] of 0.26-0.41; P < 0.001). The risk of hip fracture was reduced by 40% with the drug compared to the placebo group (cumulative incidence of denosumab: 0.7% vs. placebo: 1.2%); the hazard ratio was 0.60, with a 95% CI of 0.37-0.97; P = 0.04. Similarly, denosumab reduced the cumulative incidence of nonvertebral fracture from 8.0% in the placebo group to 6.5% in the denosumab group (hazard ratio, 0.80; 95% CI, 0.67-0.95; P = 0.01)-a 20% relative reduction in risk. During the 36-months of the study, denosumab was not associated with a significant increase in the incidence of infection, cancer, or cardiovascular events. No increase was found in the occurrence of delayed fracture healing or hypocalcemia and other adverse effects associated with potent antiresorptive agents. Osteonecrosis of the jaw was not observed in either group. These findings show that subcutaneous injections of denosumab every 6 months for 36 months is associated with a significant reduction in the risk of vertebral, hip, and nonvertebral fractures among postmenopausal women with osteoporosis.

Published
2009
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17. Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland

Author

Styrkarsdottir, U, Thorleifsson, G, Eiriksdottir, B, Gudjonsson, SA, Ingvarsson, T, Center, JR, Nguyen, TV, Eisman, JA, Christiansen, C, Thorsteinsdottir, U, Sigurdsson, G, and Stefansson, K

Subjects
musculoskeletal diseases, Aged, 80 and over, Male, Iceland, Middle Aged, Anatomy & Morphology, Polymorphism, Single Nucleotide, Collagen Type I, Fractures, Bone, INDEL Mutation, Bone Density, Humans, Female, Aged
Abstract

© 2015 American Society for Bone and Mineral Research. We conducted a genome-wide association study of low bone mineral density (BMD) at the hip and spine utilizing sequence variants found through whole-genome sequencing of 2636 Icelanders. We found two rare missense mutations, p.Gly496Ala and p.Gly703Ser, in the COL1A2 gene that associate with measures of osteoporosis in Icelanders. Mutations in COL1A2 are known to cause the autosomal dominant disorder osteogenesis imperfecta. Both variants associate with low BMD and with osteoporotic fractures. p.Gly496Ala (frequency of 0.105%) shows the strongest association with low BMD at the spine (p = 1.8 × 10-7, odds ratio [OR] = 4.61 [95% confidence interval (CI) 2.59, 8.18]), whereas p.Gly703Ser (frequency of 0.050%) is most strongly associated with low BMD at the hip (p = 1.9 × 10-8, OR = 9.34 [95% CI 4.28, 20.3]). Association with fractures was p = 2.2 × 10-5, OR = 3.75 (95% CI 2.03, 6.93) and p = 0.0023, OR = 4.32 (95% CI 1.69, 11.1), respectively. The carriers of these variants do not have signs of osteogenesis imperfecta other than low BMD, demonstrating that similar mutations in COL1A2 can affect skeletal phenotypes in more than one way.

Published
2015

18. Elliptic flow of identified hadrons in Pb-Pb collisions at √s_NN = 2.76 TeV

Author

Abelev, A., Adam, B., Adamová, J., Aggarwal, D., Agnello, M. M., Agostinelli, M., Agrawal, A., Ahammed, N., Ahmad, Z., Ahmed, N., Ahn, I., Ahn, S. U., Aimo, S. A., Aiola, I., Ajaz, S., Akindinov, M., Alam, A., Aleksandrov, S. N., Alessandro, D., Alexandre, B., Alici, D., Alkin, A., Alme, A., Alt, J., Altinpinar, T., Altsybeev, S., Alves Garcia Prado, I., Andrei, C., Andronic, C., Anguelov, A., Anielski, V., Antičić, J., Antinori, T., Antonioli, F., Aphecetche, P., Appelshäuser, L., Arcelli, H., Armesto, S., Arnaldi, N., Aronsson, R., Arsene, T., Arslandok, I. C., Augustinus, M., Averbeck, A., Awes, R., Azmi, T. C., Bach, M. D., Badalà, M., Baek, A., Bagnasco, Y. W., Bailhache, S., Bala, R., Baldisseri, R., Baltasar Dos Santos Pedrosa, A., Baral, F., Barbera, R. C., Barile, R., Barnaföldi, F., Barnby, G. G., Barret, L. S., Bartke, V., Basile, J., Bastid, M., Basu, N., Bathen, S., Batigne, B., Batista Camejo, G., Batyunya, A., Batzing, B., Baumann, P. C., Bearden, C., Beck, I. G., Bedda, H., Behera, C., Belikov, N. K., Bellini, I., Bellwied, F., Belmont-Moreno, R., Belmont, E., Belyaev, R., Bencedi, V., Beole, G., Berceanu, S., Bercuci, I., Berdnikov, A., Berenyi, Y., Berger, D., Bertens, M. E., Berzano, R. A., Betev, D., Bhasin, L., Bhat, A., Bhati, I. R., Bhattacharjee, A. K., Bhom, B., Bianchi, J., Bianchi, L., Bianchin, N., Bielčík, C., Bielčíková, J., Bilandzic, J., Bjelogrlic, A., Blanco, S., Blau, F., Blume, D., Bock, C., Bogdanov, F., Bøggild, A., Bogolyubsky, H., Böhmer, M., Boldizsár, F. V., Bombara, L., Book, M., Borel, J., Borissov, H., Bossú, A., Botje, F., Botta, M., Böttger, E., Braun-Munzinger, S., Bregant, P., Breitner, M., Broker, T., Browning, T. A., Broz, T. A., Bruna, M., Bruno, E., Budnikov, G. E., Buesching, D., Bufalino, H., Buncic, S., Busch, P., Buthelezi, O., Caffarri, Z., Cai, D., Caines, X., Calero Diaz, H., Caliva, L., Calvo Villar, A., Camerini, E., Carena, P., Carena, F., Castillo Castellanos, W., Casula, J., Catanescu, E. A. R., Cavicchioli, V., Ceballos Sanchez, C., Cepila, C., Cerello, J., Chang, P., Chapeland, B., Charvet, S., Chattopadhyay, J. L., Chattopadhyay, S., Chelnokov, S., Cherney, V., Cheshkov, M., Cheynis, C., Chibante Barroso, B., Chinellato, V., Chochula, D. D., Chojnacki, P., Choudhury, M., Christakoglou, S., Christensen, P., Christiansen, C. H., Chujo, P., Chung, T., Cicalo, S. U., Cifarelli, C., Cindolo, L., Cleymans, F., Colamaria, J., Colella, F., Collu, D., Colocci, A., Conesa Balbastre, M., Conesa del Valle, G., Connors, Z., Contreras, M. E., Cormier, J. G., Corrales Morales, T. M., Cortese, Y., Cortés Maldonado, P., Cosentino, I., Costa, M. R., Crochet, F., Cruz Albino, P., Cuautle, R., Cunqueiro, E., Dainese, L., Dang, A., Danu, R., Das, A., Das, D., Das, I., Das, K., Dash, S., Dash, A., De, S., Delagrange, S., Deloff, H., Dénes, A., D’Erasmo, E., De Caro, G., de Cataldo, A., de Cuveland, G., De Falco, J., De Gruttola, A., De Marco, D., De Pasquale, N., de Rooij, S., Diaz Corchero, R., Dietel, M. A., Dillenseger, T., Divià, P., Di Bari, R., Di Liberto, D., Di Mauro, S., Di Nezza, A., Djuvsland, P., Dobrin, Ø., Dobrowolski, A., Domenicis Gimenez, T., Dönigus, D., Dordic, B., Dørheim, O., Dubey, S., Dubla, A. K., Ducroux, A., Dupieux, L., Dutta Majumdar, P., Hilden, A. K., Ehlers, T. E., Elia, R. J., Engel, D., Erazmus, H., Erdal, B., Eschweiler, H. A., Espagnon, D., Esposito, B., Estienne, M., Esumi, M., Evans, S., Evdokimov, D., Fabris, S., Faivre, D., Falchieri, J., Fantoni, D., Fasel, A., Fehlker, M., Feldkamp, D., Felea, L., Feliciello, D., Feofilov, A., Ferencei, G., Fernández Téllez, J., Ferreiro, A., Ferretti, E. G., Festanti, A., Figiel, A., Figueredo, J., Filchagin, M. A. S., Finogeev, S., Fionda, D., Fiore, F. M., Floratos, E. M., Floris, E., Foertsch, M., Foka, S., Fokin, P., Fragiacomo, S., Francescon, E., Frankenfeld, A., Fuchs, U., Furget, U., Fusco Girard, C., Gaardhøje, M., Gagliardi, J. J., Gago, M., Gallio, A. M., Gangadharan, M., Ganoti, D. R., Garabatos, P., Garcia-Solis, C., Gargiulo, E., Garishvili, C., Gerhard, I., Germain, J., Gheata, M., Gheata, A., Ghidini, M., Ghosh, B., Ghosh, P., Gianotti, S. K., Giubellino, P., Gladysz-Dziadus, P., Glässel, E., Gomez Ramirez, P., González-Zamora, A., Gorbunov, P., Görlich, S., Gotovac, L., Graczykowski, S., Grelli, L. K., Grigoras, A., Grigoriev, C., Grigoryan, V., Grigoryan, A., Grinyov, S., Grion, B., Grosse-Oetringhaus, N., Grossiord, J. F., Grosso, J. -Y., Guber, R., Guernane, F., Guerzoni, R., Guilbaud, B., Gulbrandsen, M., Gulkanyan, K., Gumbo, H., Gunji, M., Gupta, T., Gupta, A., Khan, R., Haake, K. H., Haaland, R., Hadjidakis, Ø., Haiduc, C., Hamagaki, M., Hamar, H., Hanratty, G., Hansen, L. D., Harris, A., Hartmann, J. W., Harton, H., Hatzifotiadou, A., Hayashi, D., Heckel, S., Heide, S. T., Helstrup, M., Herghelegiu, H., Herrera Corral, A., Hess, G., Hetland, B. A., Hippolyte, K. F., Hladky, B., Hristov, J., Huang, P., Humanic, M., Hussain, T. J., Hutter, N., Hwang, D., Ilkaev, D. S., Ilkiv, R., Inaba, I., Innocenti, M., Ionita, G. M., Ippolitov, C., Irfan, M., Ivanov, M., Jacholkowski, V., Jacobs, A., Jahnke, P. M., Jang, C., Janik, H. J., Jayarathna, M. A., Jena, P. H. S. Y., Jena, C., Jimenez Bustamante, S., Jones, R. T., Jung, P. G., Jusko, H., Kadyshevskiy, A., Kalcher, V., Kalinak, S., Kalweit, P., Kamin, A., Kang, J., Kaplin, J. H., Kar, V., Karasu Uysal, S., Karavichev, A., Karavicheva, O., Karpechev, T., Kebschull, E., Keidel, U., Keijdener, R., Keil SVN, D. L. D., Khan, M., Khan, M. M., Khan, P., Khanzadeev, S. A., Kharlov, A., Kileng, Y., Kim, B., Kim, D. W., Kim, D. J., Kim, J. S., Kim, M., Kim, S., Kirsch, T., Kisel, S., Kiselev, I., Kisiel, S., Kiss, A., Klay, G., Klein, J. L., Klein-Bösing, J., Kluge, C., Knichel, A., Knospe, M. L., Kobdaj, A. G., Kofarago, C., Köhler, M., Kollegger, M. K., Kolojvari, T., Kondratiev, A., Kondratyeva, V., Konevskikh, N., Kovalenko, A., Kowalski, V., Kox, M., Koyithatta Meethaleveedu, S., Kral, G., Králik, J., Kramer, I., Kravčáková, F., Krelina, A., Kretz, M., Krivda, M., Krizek, M., Kryshen, F., Krzewicki, E., Kučera, M., Kucheriaev, V., Kugathasan, Y., Kuhn, T., Kuijer, C., Kulakov, P. G., Kumar, I., Kurashvili, J., Kurepin, P., Kurepin, A., Kuryakin, A. B., Kushpil, A., Kweon, S., Kwon, M. J., Ladron de Guevara, Y., Lagana Fernandes, P., Lakomov, C., Langoy, I., Lara, R., Lardeux, C., Lattuca, A., La Pointe, A., La Rocca, S. L., Lea, P., Leardini, R., Lee, L., Legrand, G. R., Lehnert, I., Lemmon, J., Lenti, R. C., Leogrande, V., Leoncino, E., León Monzón, M., Lévai, I., Li, P., Lien, S., Lietava, J., Lindal, R., Lindenstruth, S., Lippmann, V., Lisa, C., Ljunggren, M. A., Lodato, H. M., Loenne, D. F., Loggins, P. I., Loginov, V. R., Lohner, V., Loizides, D., Lopez, C., López Torres, X., Lu, E., Luettig, X. -G., Lunardon, P., Luparello, M., Ma, G., Maevskaya, R., Mager, A., Mahapatra, M., Mahmood, D. P., Maire, S. M., Majka, A., Malaev, R. D., Maldonado Cervantes, M., Malinina, I., Mal’Kevich, L., Malzacher, D., Mamonov, P., Manceau, A., Manko, L., Manso, V., Manzari, F., Marchisone, V., Mareš, M., Margagliotti, J., Margotti, G. V., Marín, A., Markert, A., Marquard, C., Martashvili, M., Martin, I., Martinengo, N. A., Martínez, P., Martínez García, M. I., Martin Blanco, G., Martynov, J., Mas, Y., Masciocchi, A., Masera, S., Masoni, M., Massacrier, A., Mastroserio, L., Matyja, A., Mayer, A., Mazer, C., Mazzoni, J., Meddi, M. A., Menchaca-Rocha, F., Mercado Pérez, A., Meres, J., Miake, M., Mikhaylov, Y., Milano, K., Milosevic, L., Mischke, J., Mishra, A., Miskowiec, A. N., Mitra, D., Mitu, J., Mlynarz, C. M., Mohammadi, J., Mohanty, N., Molnar, B., Montaño Zetina, L., Montes, L., Morando, E., Moreira De Godoy, M., Moretto, D. A., Morsch, S., Muccifora, A., Mudnic, V., Mühlheim, E., Muhuri, D., Mukherjee, S., Müller, M., Munhoz, H., Murray, M. G., Musa, S., Musinsky, L., Nandi, J., Nania, B. K., Nappi, R., Nattrass, E., Nayak, C., Nayak, K., Nazarenko, T. K., Nedosekin, S., Nicassio, A., Niculescu, M., Nielsen, M., Nikolaev, B. S., Nikulin, S., Nilsen, V., Noferini, B. S., Nomokonov, F., Nooren, P., Norman, G., Nyanin, J., Nystrand, A., Oeschler, J., Oh, H., Oh, S., Okatan, S. K., Olah, A., Oleniacz, L., Oliveira Da Silva, J., Onderwaater, A. C., Oppedisano, J., Ortiz Velasquez, C., Oskarsson, A., Otwinowski, A., Oyama, J., Sahoo, K., Pachmayer, P., Pachr, Y., Pagano, M., Paić, P., Painke, G., Pajares, F., Pal, C., Palmeri, S. K., Pant, A., Papikyan, D., Pappalardo, V., Pareek, G. S., Park, P., Parmar, W. J., Passfeld, S., Patalakha, A., Paticchio, D. I., Paul, V., Pawlak, B., Peitzmann, T., Pereira Da Costa, T., Pereira De Oliveira Filho, H., Peresunko, E., Pérez Lara, D., Pesci, C. E., Peskov, A., Pestov, V., Petráček, Y., Petran, V., Petris, M., Petrovici, M., Petta, M., Piano, C., Pikna, S., Pillot, M., Pinazza, P., Pinsky, O., Piyarathna, L., Ploskon, D. B., Planinic, M., Pluta, M., Pochybova, J., Podesta-Lerma, S., Poghosyan, P. L. M., Pohjoisaho, M. G., Polichtchouk, E. H. O., Poljak, B., Pop, N., Porteboeuf-Houssais, A., Porter, S., Potukuchi, J., Prasad, B., Preghenella, S. K., Prino, R., Pruneau, F., Pshenichnov, C. A., Puddu, I., Pujahari, G., Punin, P., Putschke, V., Qvigstad, J., Rachevski, H., Raha, A., Rak, S., Rakotozafindrabe, J., Ramello, A., Raniwala, L., Raniwala, R., Räsänen, S., Rascanu, S. S., Rathee, B. T., Rauf, D., Razazi, A. W., Read, V., Real, K. F., Redlich, J. S., Reed, K., Rehman, R. J., Reichelt, A., Reicher, P., Reidt, M., Renfordt, F., Reolon, R., Reshetin, A. R., Rettig, A., Revol, F., Reygers, J. -P., Riabov, K., Ricci, V., Richert, R. A., Richter, T., Riedler, M., Riegler, P., Riggi, W., Rivetti, F., Rocco, A., Rodríguez Cahuantzi, E., Rodriguez Manso, M., Røed, A., Rogochaya, K., Rohni, E., Rohr, S., Röhrich, D., Romita, D., Ronchetti, R., Ronflette, F., Rosnet, L., Rossi, P., Roukoutakis, A., Roy, F., Roy, A., Roy, C., Rubio Montero, P., Rui, A. J., Russo, R., Ryabinkin, R., Ryabov, E., Rybicki, Y., Sadovsky, A., Šafařík, S., Sahlmuller, K., Sahoo, B., Sahu, R., Saini, P. K., Sakai, J., Salgado, S., Salzwedel, C. A., Sambyal, J., Samsonov, S., Sanchez Castro, V., Sánchez Rodríguez, X., Šándor, F. J., Sandoval, L., Sano, A., Santagati, M., Sarkar, G., Scapparone, D., Scarlassara, E., Scharenberg, F., Schiaua, R. P., Schicker, C., Schmidt, R., Schmidt, C., Schuchmann, H. R., Schukraft, S., Schulc, J., Schuster, M., Schutz, T., Schwarz, Y., Schweda, K., Scioli, K., Scomparin, G., Scott, E., Segato, R., Seger, G., Sekiguchi, J. E., Selyuzhenkov, Y., Seo, I., Serradilla, J., Sevcenco, E., Shabetai, A., Shabratova, A., Shahoyan, G., Shangaraev, R., Sharma, A., Sharma, N., Shigaki, S., Shtejer, K., Sibiriak, K., Siddhanta, Y., Siemiarczuk, S., Silvermyr, T., Silvestre, D., Simatovic, C., Singaraju, G., Singh, R., Singha, R., Singhal, S., Sinha, V., Sinha, B. C., Sitar, T., Sitta, B., Skaali, M., Skjerdal, T. B., Slupecki, K., Smirnov, M., Snellings, N., Søgaard, R. J. M., Soltz, C., Song, R., Song, J., Soramel, M., Sorensen, F., Spacek, S., Spiriti, M., Sputowska, E., Spyropoulou-Stassinaki, I., Srivastava, M., Stachel, B. K., Stan, J., Stefanek, I., Steinpreis, G., Stenlund, M., Steyn, E., Stiller, G., Stocco, J. H., Stolpovskiy, D., Strmen, M., Suaide, P., Sugitate, A. A. P., Suire, T., Suleymanov, C., Sultanov, M., Šumbera, R., Susa, M., Symons, T., Szabo, T. J. M., Szanto de Toledo, A., Szarka, A., Szczepankiewicz, I., Szymanski, A., Takahashi, M., Tangaro, J., Tapia Takaki, M. A., Tarantola Peloni, J. D., Tarazona Martinez, A., Tarzila, A., Tauro, M. G., Tejeda Muñoz, A., Telesca, G., Terrevoli, A., Thäder, C., Thomas, J., Tieulent, D., Timmins, R., Toia, A. R., Trubnikov, A., Trzaska, V., Tsuji, W. H., Tumkin, T., Turrisi, A., Tveter, R., Ullaland, T. S., Uras, K., Usai, A., Vajzer, G. L., Vala, M., Valencia Palomo, M., Vallero, L., Vande Vyvre, S., Van Der Maarel, P., Van Hoorne, J., van Leeuwen, J. W., Vargas, M., Vargyas, A., Varma, M., Vasileiou, R., Vasiliev, M., Vechernin, A., Veldhoen, V., Velure, M., Venaruzzo, A., Vercellin, M., Vergara Limón, E., Vernet, S., Verweij, R., Vickovic, M., Viesti, L., Viinikainen, G., Vilakazi, J., Villalobos Baillie, Z., Vinogradov, O., Vinogradov, A., Vinogradov, L., Virgili, Y., Viyogi, T., Vodopyanov, Y. P., Völkl, A., Voloshin, M. A., Voloshin, K., Volpe, S. A., von Haller, G., Vorobyev, B., Vranic, I., Vrláková, D., Vulpescu, J., Vyushin, B., Wagner, A., Wagner, B., Wagner, J., Wang, V., Wang, M., Watanabe, Y., Weber, D., Wessels, M., Westerhoff, J. P., Wiechula, U., Wikne, J., Wilde, J., Wilk, M., Wilkinson, G., Williams, J., Windelband, M. C. S., Winn, B., Yaldo, M., Yamaguchi, C. G., Yang, Y., Yang, H., Yang, P., Yano, S., Yasnopolskiy, S., Yi, S., Yin, J., Yoo, Z., Yushmanov, I. -K., Zaccolo, I., Zach, V., Zaman, C., Zampolli, A., Zaporozhets, C., Zarochentsev, S., Závada, A., Zaviyalov, P., Zbroszczyk, N., Zgura, H., Zhalov, I. S., Zhang, M., Zhang, H., Zhang, X., Zhao, Y., Zhigareva, C., Zhou, N., Zhou, D., Zhou, F., Zhou, Y., Zhu, Z., Zhu, H., Zhu, J., Zichichi, X., Zimmermann, A., Zinovjev, M. B., Zoccarato, G., and Zyzak, Y.

Subjects
Collective flow, Heavy Ions, Particle correlations and fluctuations, High Energy Physics::Experiment, Nuclear Experiment
Published
2015

19. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

Author

Reppe, S. Wang, Y. Thompson, W.K. McEvoy, L.K. Schork, A.J. Zuber, V. LeBlanc, M. Bettella, F. Mills, I.G. Desikan, R.S. Djurovic, S. Gautvik, K.M. Dale, A.M. Andreassen, O.A. Estrada, K. Styrkarsdottir, U. Evangelou, E. Hsu, Y.-H. Duncan, E.L. Ntzani, E.E. Oei, L. Albagha, O.M.E. Amin, N. Kemp, J.P. Koller, D.L. Li, G. Liu, C.-T. Minster, R.L. Moayyeri, A. Vandenput, L. Willner, D. Xiao, S.-M. Yerges-Armstrong, L.M. Zheng, H.-F. Alonso, N. Eriksson, J. Kammerer, C.M. Kaptoge, S.K. Leo, P.J. Thorleifsson, G. Wilson, S.G. Wilson, J.F. Aalto, V. Alen, M. Aragaki, A.K. Aspelund, T. Center, J.R. Dailiana, Z. Duggan, D.J. Garcia, M. Garcia-Giralt, N. Giroux, S. Hallmans, G. Hocking, L.J. Husted, L.B. Jameson, K.A. Khusainova, R. Kim, G.S. Kooperberg, C. Koromila, T. Kruk, M. Laaksonen, M. Lacroix, A.Z. Lee, S.H. Leung, P.C. Lewis, J.R. Masi, L. Mencej-Bedrac, S. Nguyen, T.V. Nogues, X. Patel, M.S. Prezelj, J. Rose, L.M. Scollen, S. Siggeirsdottir, K. Smith, A.V. Svensson, O. Trompet, S. Trummer, O. Van Schoor, N.M. Woo, J. Zhu, K. Balcells, S. Brandi, M.L. Buckley, B.M. Cheng, S. Christiansen, C. Cooper, C. Dedoussis, G. Ford, I. Frost, M. Goltzman, D. González-Macías, J. Kähönen, M. Karlsson, M. Khusnutdinova, E. Koh, J.-M. Kollia, P. Langdahl, B.L. Leslie, W.D. Lips, P. Ljunggren, Ö. Lorenc, R.S. Marc, J. Mellström, D. Obermayer-Pietsch, B. Olmos, J.M. Pettersson-Kymmer, U. Reid, D.M. Riancho, J.A. Ridker, P.M. Rousseau, F. Slagboom, P.E. Tang, N.L.S. Urreizti, R. Van Hul, W. Viikari, J. Zarrabeitia, M.T. Aulchenko, Y.S. Castano-Betancourt, M. Grundberg, E. Herrera, L. Ingvarsson, T. Johannsdottir, H. Kwan, T. Li, R. Luben, R. Medina-Gómez, C. Palsson, S.Th. Rotter, J.I. Sigurdsson, G. Van Meurs, J.B.J. Verlaan, D. Williams, F.M.K. Wood, A.R. Zhou, Y. Pastinen, T. Raychaudhuri, S. Cauley, J.A. Chasman, D.I. Clark, G.R. Cummings, S.R. Danoy, P. Dennison, E.M. Eastell, R. Eisman, J.A. Gudnason, V. Hofman, A. Jackson, R.D. Jones, G. Jukema, J.W. Khaw, K.-T. Lehtimäki, T. Liu, Y. Lorentzon, M. McCloskey, E. Mitchell, B.D. Nandakumar, K. Nicholson, G.C. Oostra, B.A. Peacock, M. Pols, H.A.P. Prince, R.L. Raitakari, O. Reid, I.R. Robbins, J. Sambrook, P.N. Sham, P.C. Shuldiner, A.R. Tylavsky, F.A. Van Duijn, C.M. Wareham, N.J. Cupples, L.A. Econs, M.J. Evans, D.M. Harris, T.B. Kung, A.W.C. Psaty, B.M. Reeve, J. Spector, T.D. Streeten, E.A. Zillikens, M.C. Thorsteinsdottir, U. Ohlsson, C. Karasik, D. Richards, J.B. Brown, M.A. Stefansson, K. Uitterlinden, A.G. Ralston, S.H. Ioannidis, J.P.A. Kiel, D.P. Rivadeneira, F. GEFOS Consortium

Subjects
musculoskeletal diseases
Abstract

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity. © 2015 Reppe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Published
2015

22. Common variant at 16p11.2 conferring risk of psychosis

Author

Steinberg, S., de Jong, S., Sigurdsson, E., Murray, R., Corvin, A., Gill, M., Morris, D., O'Neill, F. A., Kendler, K., Riley, B., 2, Wellcome Trust Case Control Consortium, Craddock, N., Owen, M. J., Vassos, E., O'Donovan, M. C., Thorsteinsdottir, U., Kong, A., Ehrenreich, H., Carracedo, A., Golimbet, V., Andreassen, O. A., Børglum, A. D., Mors, O., Mortensen, P. B., Giegling, I., Werge, T., Ophoff, R. A., Nöthen, M. M., Rietschel, M., Cichon, S., Ruggeri, M., Tosato, S., Palotie, A., St Clair, D., Rujescu, D., Breuer, R., Collier, D. A., Stefansson, H., Stefansson, K., Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Fraser, G., Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Walker, N., Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris C A, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Melle, I., Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Djurovic, S., Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Agartz, I., Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Tuulio-Henriksson, A., Mattheisen, M., Suvisaari, J., Lönnqvist, J., Paunio, T., Olsen, L., Hansen, T., Ingason, A., Pirinen, M., Strengman, E., GROUP, Hougaard, D. M., Costas, J., Orntoft, T., Didriksen, M., Hollegaard, M. V., Nordentoft, M., Abramova, L., Kaleda, V., Arrojo, M., Sanjuán, J., Arango, C., Etain, B., Demontis, D., Bellivier, F., Méary, A., Schürhoff, F., Szoke, A., Ribolsi, M., Magni, V., Siracusano, A., Sperling, S., Rossner, M., Christiansen, C., Jamain, S., Kiemeney, L. A., Franke, B., van den Berg, L. H., Veldink, J., Curran, S., Bolton, P., Poot, M., Staal, W., Rehnstrom, K., Kilpinen, H., Pietiläinen, O. P. H., Freitag, C. M., Meyer, J., Magnusson, P., Saemundsen, E., Martsenkovsky, I., Bikshaieva, I., Martsenkovska, I., Vashchenko, O., Raleva, M., Paketchieva, K., Lin, K., Stefanovski, B., Durmishi, N., Pejovic Milovancevic, M., Lecic Tosevski, D., Silagadze, T., Naneishvili, N., Mikeladze, N., Surguladze, S., Vincent, J. B., Farmer, A., Papiol, S., Mitchell, P. B., Wright, A., Schofield, P. R., Fullerton, J. M., Montgomery, G. W., Martin, N. G., Rubino, I. A., van Winkel, R., Kenis, G., De Hert, M., Huttenlocher, J., Réthelyi, J. M., Bitter, I., Terenius, L., Jönsson, E. G., Bakker, S., van Os, J., Jablensky, A., Leboyer, M., Bramon, E., Powell, J., deCODE Genet, IS-101 Reykjavik, Iceland Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA Univ Bonn, Inst Genom Math, Bonn, Germany Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany CHUS, Galician Fdn Genom Med SERGAS, Santiago De Compostela, Spain Aarhus Univ, Dept Biomed, Aarhus, Denmark Aarhus Univ, iSEQ, Ctr Integrat Sequencing, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark Fdn FondaMental, Creteil, France Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland Wellcome Trust Sanger Inst, Cambridge, England South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, Dept Neurosci, London, England Kings Coll London, London, England DFG Res Ctr Mol Physiol Brain CMPB, Gottingen, Germany Max Planck Inst Expt Med, Div Clin Neurosci, D-37075 Gottingen, Germany Univ Tubingen, Inst Human Genet, Dept Med Genet, Tubingen, Germany Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland Univ Iceland, Sch Med, Reykjavik, Iceland Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, London, England Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-80539 Munich, Germany Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany Univ Aberdeen, Dept Mental Hlth, Royal Cornhill Hosp, Aberdeen, Scotland Ravenscraig Hosp, Greenock, Scotland [Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict,Oslo Univ Hosp, Oslo, Norway Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland Univ Helsinki, Cent Hosp, Helsinki, Finland Natl Inst Hlth & Welf THL, Publ Hlth Genom Unit, Helsinki, Finland Univ Copenhagen, Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, Roskilde, Denmark Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands Statens Serum Inst, Dept Clin Biochem Immunol & Genet, Sect Neonatal Screening & Hormones, DK-2300 Copenhagen, Denmark Aarhus Univ Hosp, Dept Mol Med, DK-8000 Aarhus, Denmark H Lundbeck & Co AS, Synapt Transmiss, Copenhagen, Denmark Copenhagen Univ Hosp, Psychiat Ctr Copenhagen, Copenhagen, Denmark Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia CHUS, Serv Psychiat, Santiago De Compostela, Spain Univ Valencia, Network Ctr Biomed Res Mental Hlth CIBERSAM, Unit Psychiat, Fac Med, Valencia, Spain Univ Complutense, Hosp Gen Univ Gregorio Maranon, IiSGM, CIBERSAM, E-28040 Madrid, Spain Hop H Mondor A Chenevier, AP HP, Creteil, France Univ Paris Est, Fac Med, Creteil, France Univ Roma Tor Vergata, Dept Neurosci, Sect Psychiat, Rome, Italy Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany Nord Biosci, Herlev, Denmark Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London, England Radboud Univ Nijmegen, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60054 Frankfurt, Germany Univ Trier, Dept Neurobehav Genet, Trier, Germany Natl Univ Hosp Reykjavik, Dept Child & Adolescent Psychiat, Reykjavik, Iceland State Diagnost & Counseling Ctr, Kopavogur, Iceland Ukrainian Res Inst Social Forens Psychiat & Drug, Dept Child Adolescent Psychiat & Med Social Rehab, Kiev, Ukraine Univ Skopje, Dept Child & Adolescent Psychiat, Skopje, Macedonia Inst Mental Hlth, Belgrade, Serbia Univ Belgrade, Fac Med, Belgrade, Serbia Tbilisi State Med Univ TSMU, Dept Psychiat & Drug Addict, Tbilisi, Rep of Georgia Ilia State Univ, Social & Affect Neurosci Lab, Tbilisi, Rep of Georgia Ctr Addict & Mental Hlth CAMH, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada Prince Wales Hosp, Black Dog Inst, Randwick, NSW 2031, Australia Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia Neurosci Res Australia, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Queensland Inst Med Res, Brisbane, Qld 4006, Australia Catholic Univ Louvain, Univ Psychiat Ctr, Kortenberg, Belgium Maastricht Univ, European Grad Sch Neurosci EURON,Med Ctr, Sch Mental Hlth & Neurosci,Dept Psychiat & Psycho, South Limburg Mental Hlth Res & Teaching Network, Maastricht, Netherlands Semmelweis Univ, Dept Psychiat & Psychotherapy, H-1085 Budapest, Hungary Karolinska Hosp & Inst, HUBIN Project, Dept Clin Neurosci, Stockholm, Sweden Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands Maastricht Univ, Dept Psychiat, Med Ctr, Maastricht, Netherlands Univ Western Australia, Graylands Hosp, CCRN, Perth, WA 6009, Australia UCL, Mental Hlth Sci Unit, London, England UCL, Inst Cognit Neurosci, London, England South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, Dept Psychosis Studies, London, England Trinity Coll Dublin, Sch Med, Neuropsychiat Genet Res Grp, Dublin, Ireland Queens Univ Belfast, Dept Psychiat, Belfast, Antrim, North Ireland Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales Univ Santiago de Compostela, Biomed Network Res Ctr Rare Dis CIBERER, Galician Fdn Genom Med, Genom Med Grp, Santiago De Compostela, Spain Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark German Ctr Neurodegenerat Disorders DZNE, Bonn, Germany Univ Bonn, Inst Human Genet, Bonn, Germany Inst Neurosci & Med INM 1, Julich, Germany Univ Verona, Sect Psychiat, I-37100 Verona, Italy Broad Inst MIT & Harvard, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA USA Univ Helsinki, Dept Med Genet, Helsinki, Finland Univ Cent Hosp, Helsinki, Finland Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany Eli Lilly & Co Ltd, Erl Wood Manor, Windlesham, Surrey, England, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and RS: MHeNs - R2 - Mental Health

Subjects
Oncology, Male, association, Bipolar disorder, cross-disorder, schizophrenia, 1p11.2, Bipolar Disorder, International Cooperation, Genome-wide association study, Disease, 0302 clinical medicine, Risk Factors, Epidemiology, Odds Ratio, Medicine, genetics [Schizophrenia], Oligonucleotide Array Sequence Analysis, Genetics, Aged, 80 and over, bipolar disorder, 0303 health sciences, Middle Aged, 16p11.2, 3. Good health, Europe, Psychiatry and Mental health, genetics [Chromosomes, Human, Pair 16], epidemiology [Bipolar Disorder], Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], genetics [Polymorphism, Single Nucleotide], Female, Adult, medicine.medical_specialty, Psychosis, Genotype, complications [Bipolar Disorder], epidemiology [Schizophrenia], Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, complications [Schizophrenia], Internal medicine, mental disorders, Humans, Genetic Predisposition to Disease, ddc:610, Molecular Biology, Settore MED/25 - Psichiatria, 030304 developmental biology, Aged, Chromosome Aberrations, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Gene Expression Profiling, Odds ratio, medicine.disease, Schizophrenia, Autism, business, Body mass index, genetics [Bipolar Disorder], 030217 neurology & neurosurgery, Chromosomes, Human, Pair 16, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders). National Institute of Mental Health N01 MH900001 MH074027 1U24MH081810 R01 MH078075 Eli Lilly and Company Pritzker Neuropsychiatric Disorders Research Fund L.L.C. Massachusetts General Hospital in Boston, MA (NIMH) 2N01MH080001-001 Wellcome Trust 076113 085475 075491/Z/04 085475/B/08/Z 085475/Z/08/Z Medical Research Council G0601030 Anthony P Monaco, PI, University of Oxford National Genome Research Network of the German Federal Ministry of Education and Research (BMBF) 01GS08144 01GS08147 Centre of Excellence for Complex Disease Genetics of the Academy of Finland 213506 129680 Biocentrum Helsinki Foundation Research Program for Molecular Medicine, Faculty of Medicine, University of Helsinki Stanley Medical Research Institute Danish Council for Strategic Research 2101-07-0059 H Lundbeck A/S; the Research Council of Norway 163070/V50 Danish Medical Research Council South-East Norway Health Authority 2004-123 Medical Research Council Ministerio de Sanidad y Consumo, Spain PI081522 Xunta de Galicia 08CSA005208PR Swedish Research Council Wellcome Trust Case Control Consortium 2 Max Planck Society; Saarland University T6 03 10 00-45 Netherlands Foundation for Brain Research (Hersenstichting) 2008(1).34 2006-037761 PIAP-GA-2008-218251 HEALTH-F2-2009-223423 HEALTH-F4-2009-242257 info:eu-repo/grantAgreement/EC/FP7/218251

Published
2014
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23. Mortality in elderly ICU patients:a cohort study

Author

Nielsson, Malene Schou, Christiansen, C F, Johansen, M B, Rasmussen, Bodil Steen, Tønnesen, E, and Nørgaard, Mette

Subjects
health care facilities, manpower, and services, sense organs
Abstract

The population is aging. We examined changes in the proportion of elderly (≥ 80 years) intensive care unit (ICU) patients during 2005-2011 and the association between age and mortality controlling for preexisting morbidity.

Published
2014
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25. Comparison of the effects of a monounsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects

Author

Eva Pedersen, Kjeld Hermansen, Jørgen Ingerslev, O. W. Rasmussen, Christiansen C, M Vesterlund, C Thomsen, and H Storm

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, Diet therapy, Cardiovascular risk factors, Medicine (miscellaneous), chemistry.chemical_compound, Dietary Fats, Unsaturated, Risk Factors, Internal medicine, Diabetes mellitus, von Willebrand Factor, Dietary Carbohydrates, medicine, Humans, Insulin, First-degree relatives, Risk factor, Triglycerides, Apolipoproteins B, Nutrition and Dietetics, Apolipoprotein A-I, Cholesterol, business.industry, Cholesterol, HDL, Cholesterol, LDL, Carbohydrate, medicine.disease, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Fat diet, Cardiovascular Diseases, Female, business
Abstract

Recent studies have demonstrated beneficial metabolic effects of dietary monounsaturated fatty acids (MUFA) in Type-2 diabetes mellitus (Type-2 DM). The question arises if dietary MUFA also has desirable effects on risk markers in subjects with high risk of developing Type-2 DM.University department of endocrinology.Sixteen healthy, first-degree relatives (six men, 10 women, age (mean+/-s.d.): 35+/-2 years) with normal oral glucose tolerance tests.Randomised study with two 4-week treatment periods with either a carbohydrate-rich (CHO) diet (55 E% carbohydrate, 30 E% fat, 15 E% protein) or a diet rich in olive oil [MUFA 40 E% fat (25 E% as MUFA), 45 E% carbohydrate, 15 E% protein]. The periods were divided by a 4-week wash-out period.Similar lowering effects on total cholesterol, low density lipoprotein (LDL)-cholesterol, triglyceride and apoB levels were seen after the two diets. Slightly higher levels of high-density lipoprotein (HDL)-cholesterol (1.4+/-0.4 vs 1.3+/-0.4 mmol/l, P0. 0001) and apoA-1 (1.2+/-0.3 vs 1.1+/-0.3 mmol/l, P0.05) were found in the MUFA-diet. Furthermore, the insulin sensitivity, as assessed by Bergman's minimal model, and the first response insulin areas were similar, as were the 24-h blood pressures and the von Willebrand Factor (vWF) levels.Isocaloric diets rich in MUFA or rich in carbohydrate, respectively, seem to have similar effects on cardiovascular risk factors in persons at high risk of developing Type-2 DM. A potential risk, however, on body weight of high-fat diets should be kept in mind.This study was supported by grants from the Danish Diabetes Association, Institute of Clinical Experimental Research, Aarhus University, The Danish Heart Foundation, The Danish Medical Research Council, Velux Foundation, Poul and Erna Sehested Hansens Foundation, Mogens Svarre Mogensens Foundation.

Published
1999
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26. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene

Author

Ettinger, B., Black, D.M., Mitlak, B.H., Knickerbocker, R.K., Nickelsen, T., Genant, H.K., Christiansen, C., Delmas, P.D., Zanchetta, J.R., Stakkestad, J., Gluer, C.C., Krueger, B.P., Cohen, F.J., Eckert, S., Ensrud, K.E., Avioli, L.V., Lips, P.T.A.M., Cummings, S.R., and EMGO+ - Musculoskeletal Health

Subjects
SDG 3 - Good Health and Well-being
Abstract

Context: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. Objective: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. Design: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. Setting and Participants: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. Interventions: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. Main Outcome Measures: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. Results: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4- 0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1% (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P

Published
1999
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27. Evidence against molecular aggregates in concentrated solutions of X-ray contrast media

Author

Per C. Sontum, Christiansen C, Tore Skotland, and Vera Kasparkova

Subjects
Molecular diffusion, Osmotic concentration, business.industry, Scattering, Chemistry, Diffusion, Pharmaceutical Science, Iodixanol, Light scattering, Contrast medium, Optics, Dynamic light scattering, Chemical physics, medicine, business, medicine.drug
Abstract

In order to evaluate the possible existence of large molecular aggregates in concentrated solutions of X-ray contrast media used for medical imaging, a comprehensive study of the effect of the contrast medium concentration on the osmolarity, light scattering and molecular diffusion has been performed for the two X-ray contrast media, Omnipaque (iohexol) and Visipaque (iodixanol). The measured change in osmolarity and light scattering with increasing concentration of contrast medium was well explained by solvent–solute and solute–solute interactions. Minima were observed for both the concentration-normalized osmolarity and the inverse of the concentration-normalized Rayleigh ratio, observations which are incompatible with the hypothesis of aggregation at higher concentrations. From the observed minima, dynamic clusters containing at maximum two to three molecules were demonstrated. The apparent molecular diameter measured with dynamic light scattering, was found to be well predicted from the thermodynamic expression of the concentration dependency of the mutual diffusion coefficient. The observed scattering intensity was incompatible with an actual increase in the geometric size of the scatterers (i.e. aggregation) with increasing concentration. Contrary to the conclusions made by other investigators, the results presented clearly demonstrate the absence of `large colloidal-like structures or molecular aggregates' in the X-ray contrast media investigated.

Published
1998
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28. Photon correlation spectroscopy applied to characterisation of denaturation and thermal stability of human albumin

Author

Christiansen C and Per Christian Sontum

Subjects
Protein Denaturation, Chemistry, Fatty Acids, Clinical Biochemistry, Kinetics, Temperature, Analytical chemistry, Albumin, Pharmaceutical Science, Hydrogen-Ion Concentration, Analytical Chemistry, Metal, Dynamic light scattering, Spectrophotometry, Albumins, visual_art, Drug Discovery, visual_art.visual_art_medium, Humans, Molecule, Denaturation (biochemistry), Thermal stability, Quantitative analysis (chemistry), Spectroscopy
Abstract

Photon correlation spectroscopy and light absorption measurements have been applied for characterisation of denaturation kinetics and thermal stability of human albumin in solution. The hydrodynamic size of the molecules has been studied as a function of pH, and the denaturation rate of ten different lots of 5% (w/v) human albumin solution has been measured at various temperatures. In the native (pH 7) state, the hydrodynamic molecular diameter was found to 6.3 nm. The molecular size was relatively stable between pH 10 and 5, but increased with decreasing pH to approximately 20 nm at pH 3. The denaturation rate, measured as change in hydrodynamic diameter per min, was strongly dependent on temperature and increased 3-fold per degree in the 73-75 degrees C range. The investigated lots of albumin solution showed large variations in stability at 74 degrees C, with denaturation rates ranging from 10 to 100 nm min-1. The observed thermal stability for the lots investigated was ranked identically with both the employed techniques. In an effort to explain the observed lot to lot variations in denaturation rate, a broad chemical characterisation including determination of free SH content, fatty acid content and composition and metal content, was performed. However, lot to lot variations in these parameters was not found to fully elucidate the observed variations in thermal stability.

Published
1997
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29. Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits

Author

Styrkarsdottir, U, Thorleifsson, G, Sulem, P, Gudbjartsson, DF, Sigurdsson, A, Jonasdottir, A, Oddsson, A, Helgason, A, Magnusson, OT, Walters, GB, Frigge, ML, Helgadottir, HT, Johannsdottir, H, Bergsteinsdottir, K, Ogmundsdottir, MH, Center, JR, Nguyen, TV, Eisman, JA, Christiansen, C, Steingrimsson, E, Jonasson, JG, Tryggvadottir, L, Eyjolfsson, GI, Theodors, A, Jonsson, T, Ingvarsson, T, Olafsson, I, Rafnar, T, Kong, A, Sigurdsson, G, Masson, G, Thorsteinsdottir, U, and Stefansson, K

Subjects
musculoskeletal diseases, Mice, Knockout, Menarche, Male, Heterozygote, Skin Neoplasms, General Science & Technology, Denmark, Water-Electrolyte Imbalance, Australia, Iceland, Down-Regulation, Receptors, G-Protein-Coupled, Mice, Biliary Tract Neoplasms, Phenotype, Codon, Nonsense, Bone Density, Carcinoma, Squamous Cell, Animals, Humans, Testosterone, Female, Osteoporotic Fractures
Abstract

Low bone mineral density (BMD) is used as a parameter of osteoporosis. Genome-wide association studies of BMD have hitherto focused on BMD as a quantitative trait, yielding common variants of small effects that contribute to the population diversity in BMD. Here we use BMD as a dichotomous trait, searching for variants that may have a direct effect on the risk of pathologically low BMD rather than on the regulation of BMD in the healthy population. Through whole-genome sequencing of Icelandic individuals, we found a rare nonsense mutation within the leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) gene (c.376C>T) that is strongly associated with low BMD, and with osteoporotic fractures. This mutation leads to termination of LGR4 at position 126 and fully disrupts its function. The c.376C>T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer. Interestingly, the phenotype of carriers of the c.376C>T mutation overlaps that of Lgr4 mutant mice. © 2013 Macmillan Publishers Limited. All rights reserved.

Published
2013

36. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Author

Estrada, K, Styrkarsdottir, U, Evangelou, E, Hsu, YH, Duncan, EL, Ntzani, EE, Oei, L, Albagha, OME, Amin, N, Kemp, JP, Koller, DL, Li, G, Liu, CT, Minster, RL, Moayyeri, A, Vandenput, L, Willner, D, Xiao, SM, Yerges-Armstrong, LM, Zheng, HF, Alonso, N, Eriksson, J, Kammerer, CM, Kaptoge, SK, Leo, PJ, Thorleifsson, G, Wilson, SG, Wilson, JF, Aalto, V, Alen, M, Aragaki, AK, Aspelund, T, Center, JR, Dailiana, Z, Duggan, DJ, Garcia, M, Garcia-Giralt, N, Giroux, S, Hallmans, G, Hocking, LJ, Husted, LB, Jameson, KA, Khusainova, R, Kim, GS, Kooperberg, C, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, AZ, Lee, SH, Leung, PC, Lewis, JR, Masi, L, Mencej-Bedrac, S, Nguyen, TV, Nogues, X, Patel, MS, Prezelj, J, Rose, LM, Scollen, S, Siggeirsdottir, K, Smith, AV, Svensson, O, Trompet, S, Trummer, O, Van Schoor, NM, Woo, J, Zhu, K, Balcells, S, Brandi, ML, Buckley, BM, Cheng, S, Christiansen, C, Cooper, C, Dedoussis, G, Ford, I, Frost, M, Goltzman, D, González-Macías, J, Kähönen, M, Karlsson, M, Khusnutdinova, E, Koh, JM, Kollia, P, Langdahl, BL, Leslie, WD, Lips, P, Ljunggren, Ø, Lorenc, RS, Marc, J, Mellström, D, Obermayer-Pietsch, B, Olmos, JM, Pettersson-Kymmer, U, Reid, DM, Riancho, JA, Ridker, PM, Rousseau, F, Lagboom, PES, and Tang, NLS

Subjects
musculoskeletal diseases, Male, Genotype, Quantitative Trait Loci, European Continental Ancestry Group, Mitochondrial Membrane Transport Proteins, Polymorphism, Single Nucleotide, Fractures, Bone, Risk Factors, Bone Density, Humans, Genetic Predisposition to Disease, Glycoproteins, Extracellular Matrix Proteins, Lumbar Vertebrae, Femur Neck, Gene Expression Profiling, Spectrin, Computational Biology, Phosphoproteins, Low Density Lipoprotein Receptor-Related Protein-5, Osteoporosis, Intercellular Signaling Peptides and Proteins, Female, Developmental Biology, Genome-Wide Association Study
Abstract

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10 -4, Bonferroni corrected), of which six reached P < 5 × 10 -8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. © 2012 Nature America, Inc. All rights reserved.

Published
2012

38. Youth Religiosity and Moral Critique: God, Government and Generations in a Time of AIDS in Uganda

Author

Christiansen, C

Abstract

This article stresses the centrality of youth questions in Uganda, whereby HIV, religious and political issues are contributing to changes in the societal landscape. The ‘youth question’ has become a very important focus in developmental aids, but its conceptualization still remains ambiguous. It is this ambiguity in the conceptualization of young people, as victims and agents, which informs efforts to involve youth in the work towards preventing the spread of HIV and mitigating the negative impact of AIDS. The article demonstrates that young people largely consent to the lower social positioning of youth as they regard themselves as persons still in the making, and they find this positioning a comfortable zone from which to criticise the older generations for not maintaining family solidarity and providing sufficiently for the younger generation. Based on a drama developed by a Catholic youth group, it shows how youth combine cultural values, child rights and Christian morality to present the selfishness and low morals of the older generations, and themselves, as keepers of morality in the interest of the society as a whole. Drawing on the human rights framework, development agencies refer to young people’s rights to partake in matters regarding their own lives and entitlement, to grow up in safe spaces of socialization and develop skill. The concept used in this article tends to define ‘youth’ as a category of social being and social becoming where sexuality is becoming part of political discourse.

Published
2012

39. Recommendations on the management of fragility fracture risk in women younger than 70 years

Author

Palacios, S. Christiansen, C. Sánchez Borrego, R. Gambacciani, M. Hadji, P. Karsdal, M. Lambrinoudaki, I. Lello, S. O'beirne, B. Romao, F. Rozenberg, S. Stevenson, J.C. Ben-Rafael, Z.

Abstract

The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for fracture. There are precise diagnostic methods, including a tool to diagnose the risk for fracture. Yet there continues to be an under-diagnosis, with the unrecoverable delay in instituting preventive measures. Women under the age of 70 years, being much more numerous than those older, and having risk factors, are a group in which it is essential to avoid that first fragility fracture. Today it is usual not to differentiate between the treatment and the prevention of osteoporosis since the common aim is to prevent fragility fractures. Included in this are women with osteoporosis or with low bone mass and increased risk for fracture, for whom risk factors play a primary role. There is clearly controversy over the type of treatment and its duration, especially given the possible adverse effects of long-term use. This justifies the concept of sequential treatment, even more so in women under the age of 70, since they presumably will need treatment for many years. Bone metabolism is age-dependent. In postmenopausal women under 70 years of age, the increase in bone resorption is clearly predominant, related to a sharp drop in estrogens. Thus a logical treatment is the prevention of fragility fractures by hormone replacement therapy (HRT) and, in asymptomatic women, selective estradiol receptor modulators (SERMs). Afterwards, there is a period of greater resorption, albeit less intense but continuous, when one could utilise anti-resorptive treatments such as bisphosphonates or denosumab or a dual agent like strontium ranelate. Bone formation treatment, such as parathyroid hormone (PTH), in women under 70 years will be uncommon. That is because it should be used in cases where the formation is greatly diminished and there is a high risk for fracture, something found in much older women. © 2012 Informa UK, Ltd.

Published
2012

40. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Author

Estrada, K. Styrkarsdottir, U. Evangelou, E. Hsu, Y.-H. Duncan, E.L. Ntzani, E.E. Oei, L. Albagha, O.M.E. Amin, N. Kemp, J.P. Koller, D.L. Li, G. Liu, C.-T. Minster, R.L. Moayyeri, A. Vandenput, L. Willner, D. Xiao, S.-M. Yerges-Armstrong, L.M. Zheng, H.-F. Alonso, N. Eriksson, J. Kammerer, C.M. Kaptoge, S.K. Leo, P.J. Thorleifsson, G. Wilson, S.G. Wilson, J.F. Aalto, V. Alen, M. Aragaki, A.K. Aspelund, T. Center, J.R. Dailiana, Z. Duggan, D.J. Garcia, M. Garcia-Giralt, N. Giroux, S. Hallmans, G. Hocking, L.J. Husted, L.B. Jameson, K.A. Khusainova, R. Kim, G.S. Kooperberg, C. Koromila, T. Kruk, M. Laaksonen, M. Lacroix, A.Z. Lee, S.H. Leung, P.C. Lewis, J.R. Masi, L. Mencej-Bedrac, S. Nguyen, T.V. Nogues, X. Patel, M.S. Prezelj, J. Rose, L.M. Scollen, S. Siggeirsdottir, K. Smith, A.V. Svensson, O. Trompet, S. Trummer, O. Van Schoor, N.M. Woo, J. Zhu, K. Balcells, S. Brandi, M.L. Buckley, B.M. Cheng, S. Christiansen, C. Cooper, C. Dedoussis, G. Ford, I. Frost, M. Goltzman, D. González-Macías, J. Kähönen, M. Karlsson, M. Khusnutdinova, E. Koh, J.-M. Kollia, P. Langdahl, B.L. Leslie, W.D. Lips, P. Ljunggren, O. Lorenc, R.S. Marc, J. Mellström, D. Obermayer-Pietsch, B. Olmos, J.M. Pettersson-Kymmer, U. Reid, D.M. Riancho, J.A. Ridker, P.M. Rousseau, F. Lagboom, P.E.S. Tang, N.L.S. Urreizti, R. Van Hul, W. Viikari, J. Zarrabeitia, M.T. Aulchenko, Y.S. Castano-Betancourt, M. Grundberg, E. Herrera, L. Ingvarsson, T. Johannsdottir, H. Kwan, T. Li, R. Luben, R. Medina-Gómez, C. Th Palsson, S. Reppe, S. Rotter, J.I. Sigurdsson, G. Van Meurs, J.B.J. Verlaan, D. Williams, F.M.K. Wood, A.R. Zhou, Y. Gautvik, K.M. Pastinen, T. Raychaudhuri, S. Cauley, J.A. Chasman, D.I. Clark, G.R. Cummings, S.R. Danoy, P. Dennison, E.M. Eastell, R. Eisman, J.A. Gudnason, V. Hofman, A. Jackson, R.D. Jones, G. Jukema, J.W. Khaw, K.-T. Lehtimäki, T. Liu, Y. Lorentzon, M. Mccloskey, E. Mitchell, B.D. Nandakumar, K. Nicholson, G.C. Oostra, B.A. Peacock, M. Pols, H.A.P. Prince, R.L. Raitakari, O. Reid, I.R. Robbins, J. Sambrook, P.N. Sham, P.C. Shuldiner, A.R. Tylavsky, F.A. Van Duijn, C.M. Wareham, N.J. Cupples, L.A. Econs, M.J. Evans, D.M. Harris, T.B. Kung, A.W.C. Psaty, B.M. Reeve, J. Spector, T.D. Streeten, E.A. Zillikens, M.C. Thorsteinsdottir, U. Ohlsson, C. Karasik, D. Richards, J.B. Brown, M.A. Stefansson, K. Uitterlinden, A.G. Ralston, S.H. Ioannidis, J.P.A. Kiel, D.P. Rivadeneira, F.

Subjects
musculoskeletal diseases
Abstract

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10 -4, Bonferroni corrected), of which six reached P < 5 × 10 -8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. © 2012 Nature America, Inc. All rights reserved.

Published
2012

41. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

Author

Vassiliadis, E., Oliveira, C. P., Alvares-da-Silva, M. R., Zhang, C., Carrilho, F. J., Stefano, J. T., Rabelo, F., Pereira, L., Kappel, C. R., Henriksen, K., Veidal, S. S., Vainer, B., Duffin, K. L., Christiansen, C., Leeming, D. J., and Karsdal, M.

Abstract

Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCl4-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P

Published
2012

42. Investigation of two novel biochemical markers of inflammation, matrix metalloproteinase and cathepsin generated fragments of C-reactive protein, in patients with ankylosing spondylitis

Author

Skjøt-Arkil, H., Schett, G., Zhang, C., Larsen, D. V., Wang, Y., Zheng, Q., Larsen, M. R., Nawrocki, A., Anne C Bay-Jensen, Henriksen, K., Christiansen, C., Alexandersen, P., Leeming, D. J., and Karsdal, M. A.

Subjects
Inflammation, Male, Mice, Inbred BALB C, Enzyme-Linked Immunosorbent Assay, Middle Aged, Cathepsins, Matrix Metalloproteinases, Peptide Fragments, Diagnosis, Differential, Epitopes, Mice, C-Reactive Protein, ROC Curve, Animals, Humans, Female, Spondylitis, Ankylosing, Amino Acid Sequence, Biomarkers, Aged
Abstract

Ankylosing spondylitis (AS) is a chronic inflammation of the spine and the sacroiliac joints. Current markers of inflammation, such as C-reactive protein (CRP), are reflecting the production of an acute phase reactant rather than tissue specific inflammation, but the use of CRP as a diagnostic and prognostic marker for AS has not provided the sought accuracy and specificity. We hypothesized that local enzymatic activity in the disease-affected tissue, which is associated with extensive tissue turnover may, by cleavage, modify the CRP produced in the liver. These cleavage products may provide additional information on systemic inflammation as compared to that of full-length CRP. We investigated whether these CRP degradation products would provide additional diagnostic value in AS patients compared to full-length CRP.CRP fragments were identified by mass-spectrometry. Two fragments were selected for ELISA development. One assay exclusively identified a matrix metalloproteinase (MMP) generated fragment, CRP-MMP, whereas the other assay identified a cathepsin generated fragment, CRP-CAT. Full-length CRP, CRP-MMP and CRP-CAT were measured in serum samples from 40 AS patients and 40 sex- and age-matched controls.Full-length CRP was not elevated in AS patients compared to controls, whereas CRP-MMP was elevated by 25% (p0.001) and CRP-CAT by 50% (p0.0001). The Area Under Curve of the Receiver-Operator Characteristic curve of CRP-CAT was the highest with 77%.MMP and cathepsin degraded CRP provided more discriminative diagnostic potential compared to that of full-length CRP in this current study. These data suggest that different pools of CRP may provide insight into the inflammation processes in AS.

Published
2012

43. Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats

Author

Feigh, M, Andreassen, KV, Neutzsky-Wulff, AV, Petersen, ST, Hansen, C, Bay-Jensen, AC, Henriksen, JE, Beck-Nielsen, H, Christiansen, C, Henriksen, K, and Karsdal, MA

Subjects
Blood Glucose, Calcitonin, Glycated Hemoglobin, Male, endocrine system, endocrine system diseases, Administration, Oral, Gastric Inhibitory Polypeptide, Glucose Tolerance Test, Research Papers, Rats, Rats, Zucker, Diabetes Mellitus, Type 2, Glucagon-Like Peptide 1, Hyperglycemia, Insulin-Secreting Cells, Animals, Hypoglycemic Agents, hormones, hormone substitutes, and hormone antagonists
Abstract

Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes.Male ZDF rats were treated with oral sCT (0.5, 1.0 or 2 mg·kg(-1) ) or oral vehicle twice daily from age 8 to 18 weeks. Zucker lean rats served as control group. Fasting and non-fasted blood glucose, glycosylated haemoglobin (HbA1c) and levels of pancreas and incretin hormones were determined. Oral glucose tolerance test and i.p. glucose tolerance test were compared, and beta-cell area and function were evaluated.Oral sCT treatment dose-dependently attenuated fasting and non-fasted hyperglycaemia during the intervention period. At the end of the study period, oral sCT treatment by dose decreased diabetic hyperglycaemia by ∼9 mM and reduced HbA1c levels by 1.7%. Furthermore, a pronounced reduction in glucose excursions was dose-dependently observed for oral sCT treatment during oral glucose tolerance test. In addition, oral sCT treatment sustained hyperinsulinaemia and attenuated hyperglucagonaemia and hypersecretion of total glucagon-like peptide-1 predominantly in the basal state. Lastly, oral sCT treatment dose-dependently improved pancreatic beta-cell function and beta-cell area at study end.Oral sCT attenuated diabetic hyperglycaemia in male ZDF rats by improving postprandial glycaemic control, exerting an insulinotropic and glucagonostatic action in the basal state and by preserving pancreatic beta-cell function and beta-cell area.

Published
2012
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45. Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health

Author

Sturdee, Dw, Pines, A, International Menopause Society Writing Group, Archer, Df, Baber, Rj, Barlow, D, Birkhäuser, Mh, Brincat, M, Cardozo, L, de Villiers TJ, Gambacciani, M, Gompel, Aa, Henderson, Vw, Kluft, C, Lobo, Ra, Maclennan, Ah, Marsden, J, Nappi, Re, Panay, N, Pickar, Jh, Robinson, D, Simon, J, Sitruk Ware RL, Albertazzi P, Stevenson J. C., Berry, E, Böcker, W, Burger, H, Christiansen, C, Foidart, Jm, Gambaccian, M, Genazzani, Andrea, Huang, Ke, Huber, J, Limpaphayom, K, Lumsden, Ma, Maclennan, A, Murphy, A, Naftolin, F, Nappi, Ra, Palacios, S, Rizzoli, R, Rosano, G, Russo, J, Samsioe, G, Schneider, Hp, Shapiro, S, Sitruk Ware, R, Skouby, S, Stevenson, Jc, and Sturdee, D. W.

Subjects
Gerontology, medicine.medical_specialty, Genital Neoplasms, Female, medicine.medical_treatment, Health Behavior, Osteoporosis, Alternative medicine, Breast Neoplasms, Health Promotion, Risk Assessment, Quality of life, Humans, Postmenopausal Hormone Replacement Therapy, Medicine, Drug Dosage Calculations, Osteoporosis, Postmenopausal, Ovarian Neoplasms, business.industry, Estrogen Replacement Therapy, Obstetrics and Gynecology, General Medicine, Middle Aged, medicine.disease, Postmenopause, Menopause, Health promotion, Cardiovascular Diseases, Critical Pathways, Quality of Life, Physical therapy, Women's Health, Female, Hormone therapy, business, Risk assessment
Abstract

The past decade has seen marked fluctuations in opinions concerning the merits and risks of postmenopausal hormone replacement therapy (HRT). In July 2002, menopause management faced a major turnin...

Published
2011

46. The impact of pre-admission morbidity level on 3-year mortality after intensive care: a Danish cohort study

Author

Christiansen, C F, Christensen, S, Johansen, M B, Larsen, K M, Tønnesen, Else Kirstine, and Sørensen, H T

Subjects
health care facilities, manpower, and services
Abstract

Chronic diseases are common among intensive care unit (ICU) patients and may worsen their prognosis. We examined the prevalence and impact of pre-admission/index morbidity among ICU patients compared with a general population cohort.

Published
2011
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48. Common variants at VRK2 and TCF4 conferring risk of schizophrenia

Author

Steinberg, S., Jong, S. d., Genomics, I. S., Andreassen, O. A., Werge, T., Børglum, A. D., Mors, O., Mortensen, P. B., Gustafsson, O., Costas, J., O. P. H., Demontis, D., Papiol, S., Huttenlocher, J., Mattheisen, M., Breuer, R., Vassos, E., Giegling, I., Fraser, G., Walker, N., Tuulio Henriksson, A., Suvisaari, J., Lönnqvist, J., Paunio, T., Agartz, I., Melle, I., Djurovic, S., Strengman, E., G. R. O., Jürgens, G., Glenthøj, B., Terenius, L., Hougaard, D. M., Orntoft, T., Wiuf, C., Didriksen, M., Hollegaard, M. V., Nordentoft, M., Winkel, R. v., Kenis, G., Abramova, L., Kaleda, V., Arrojo, M., Sanjuán, J., Arango, C., Sperling, S., Rossner, M., Ribolsi, M., Magni, V., Siracusano, A., Christiansen, C., Kiemeney, L. A., Veldink, J., Den, L. v., Ingason, A., Muglia, P., Murray, R., Nöthen, M. M., Sigurdsson, E., Petursson, H., Thorsteinsdottir, U., Kong, A., Rubino, I. A., Hert, M. D., Réthelyi, J. M., Bitter, I., Jönsson, E. G., Golimbet, V., Carracedo, A., Ehrenreich, H., Craddock, N., Owen, M. J., O'Donovan, M. C., Case, W. T., Ruggeri, Mirella, Tosato, Sarah, Peltonen, L., Ophoff, R. A., Collier, D. A., Clair, D. S., Rietschel, M., Cichon, S., Stefansson, H., Rujescu, D., Stefansson, K., Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Amsterdam Neuroscience, Adult Psychiatry, and deCODE Genetics, IS-101 Reykjavik, Iceland.

Subjects
schizophrenia, sequence variants, TCF4, Genome-wide association study, Transcription Factor 4, 0302 clinical medicine, VRK2 protein, human, Polymorphism (computer science), Genotype, genetics [Schizophrenia], Neurogranin, Genetics (clinical), Schizophrenia, Risk, Alleles, Polymorphism, Single Nucleotide, Transcription Factors, Humans, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Genetic Predisposition to Disease, Protein-Serine-Threonine Kinases, Genome-Wide Association Study, Genetics, 0303 health sciences, Association Studies Articles, Single Nucleotide, General Medicine, genetics [Transcription Factors], 3. Good health, Protein Serine-Threonine Kinases, Biology, genetics [Protein-Serine-Threonine Kinases], Molecular epidemiology [NCEBP 1], 03 medical and health sciences, ddc:570, Polymorphism, Allele, genetics [Basic Helix-Loop-Helix Leucine Zipper Transcription Factors], Settore MED/25 - Psichiatria, Molecular Biology, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 030304 developmental biology, Intron, Odds ratio, Molecular biology, TCF4 protein, human, 030217 neurology & neurosurgery
Abstract

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10(-9)] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10(-9)). European Union LSHM-CT-2006-037761 PIAP-GA-2008-218251 HEALTH-F2-2009-223423 National Genome Research Network of the German Federal Ministry of Education and Research (BMBF) 01GS08144 01GS08147 National Institute of Mental Health R01 MH078075 N01 MH900001 MH074027 Centre of Excellence for Complex Disease Genetics of the Academy of Finland 213506 129680 Biocentrum Helsinki Foundation Faculty of Medicine, University of Helsinki Stanley Medical Research Institute Danish Council for Strategic Research 2101-07-0059 H. Lundbeck A/S Research Council of Norway 163070/V50 South-East Norway Health Authority 2004-123 Medical Research Council Ministerio de Sanidad y Consumo, Spain PI081522 Xunta de Galicia 08CSA005208PR Swedish Research Council Wellcome Trust 083948/Z/07/Z Max Planck Society Eli Lilly and Company info:eu-repo/grantAgreement/EC/FP7/218251

Published
2011
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50. Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study

Author

Brockow, K, Romano, A, Aberer, W, Bircher, AJ, Barbaud, A, Bonadonna, P, Faria, E, Kanny, G, Lerch, M, Pichler, WJ, Ring, J, Rodrigues Cernadas, J, Tomaz, E, Demoly, P, Christiansen, C, and European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity

Subjects
Hipersensibilidade a Medicamentos, Testes Cutâneos, Meios de Contraste
Abstract

BACKGROUND: Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. METHODS: Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. RESULTS: Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. CONCLUSIONS: These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.

Published
2009

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