337 results on '"Dahle, C."'
Search Results
2. The Effect of Pseudo-Stochastic Orbit Parameters on GRACE Monthly Gravity Fields: Insights from Lumped Coefficients
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Meyer, U., Dahle, C., Sneeuw, N., Jäggi, A., Beutler, G., Bock, H., Rizos, Chris, Series editor, Sneeuw, Nico, editor, Novák, Pavel, editor, Crespi, Mattia, editor, and Sansò, Fernando, editor
- Published
- 2016
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3. Impact of tracking loop settings of the Swarm GPS receiver on gravity field recovery
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Dahle, C., Arnold, D., and Jäggi, A.
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- 2017
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4. Combined monthly GRACE-FO gravity fields for a Global Gravity-based Groundwater Product.
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Meyer, U, Lasser, M, Dahle, C, Förste, C, Behzadpour, S, Koch, I, and Jäggi, A
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GRAVITY ,GROUNDWATER ,OCEAN circulation ,SIGNAL-to-noise ratio ,WATERSHEDS ,TIME series analysis - Abstract
The Combination Service for Time-variable Gravity fields (COST-G) operationally provides combinations of monthly Earth gravity field models derived from observations of the microwave ranging instrument of the GRACE Follow-on (GRACE-FO) satellite mission, applying the quality control and combination methodology originally developed by the Horizon 2020 project European Gravity Service for Improved Emergency Management for the data of the GRACE satellites. In the frame of the follow-up Horizon 2020 project Global Gravity-based Groundwater Product (G3P), the GRACE-FO combination is used to derive global grids of groundwater storage anomalies. To meet the user requirements and achieve optimal signal-to-noise ratio, the combination has been further developed and extended to incorporate: • new time-series based on the alternative accelerometer transplant product generated in the frame of the project by the Institute of Geodesy at the Graz University of Technology, which specifically improves the estimation of the C
30 coefficient and also reduces the noise at medium to short wavelengths, and • the new time-series AIUB–GRACE-FO–RL02 of monthly GRACE-FO gravity fields, which is derived at the Astronomical Institute of the University of Bern by applying empirical noise modelling techniques. The COST-G quality control confirms the consistency of the contributing GRACE-FO time-series concerning the signal amplitude of seasonal hydrology in large river basins and the secular mass change in polar regions, but it also indicates rather diverse noise characteristics. The difference in the noise levels is taken into account in the combination process by relative weights derived by variance component estimation on the solution level. The weights are expected to be inverse proportional to the noise levels of the individual gravity field solutions. However, this expectation is violated when applying the weighting scheme as developed for the GRACE combination. The reason is found in the high-order coefficients of the gravity field, which are poorly determined from the low–low range-rate observations due to the observation geometry and suffer from aliasing due to the malfunctioning accelerometer onboard one of the GRACE-FO satellites. Hence, for the final G3P-combination a revised weighting scheme is applied where the gravity field coefficients beyond order 60 are excluded from the determination of the weights. The quality of the combined gravity fields is assessed by comparison of the noise content and the signal-to-noise ratio with the individual time-series. Independent validation is provided by the COST-G validation centre at the GFZ German Research Centre for Geosciences, where orbit fits of the low-flying Gravity and steady-state Ocean Circulation Explorer satellite are performed that confirm the high quality of the combined GRACE-FO gravity fields. By the end of the G3P project, the new combination scheme is implemented by COST-G as the new COST-G–GRACE-FO–RL02 and continued to be used for the operational GRACE-FO combination. [ABSTRACT FROM AUTHOR]- Published
- 2024
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5. Swarm kinematic orbits and gravity fields from 18 months of GPS data
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Jäggi, A., Dahle, C., Arnold, D., Bock, H., Meyer, U., Beutler, G., and van den IJssel, J.
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- 2016
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- View/download PDF
6. Combined monthly GRACE-FO gravity fields for a Global Gravity-based Groundwater Product
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Meyer, U, primary, Lasser, M, additional, Dahle, C, additional, Förste, C, additional, Behzadpour, S, additional, Koch, I, additional, and Jäggi, A, additional
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- 2023
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7. Temporal gravity changes over nine years as observed by the Swarm satellites
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Encarnação, J., Arnold, D., Bezdek, A., Dahle, C., Guo, J., van den Ijssel, J., Jäggi, A., Klokocnik, J., Krauss, S., Mayer-Gürr, T., Meyer, U., Sebera, J., Shum, C., Pieter, V., and Yu, Z.
- Abstract
The Swarm satellites, designed for observing Earth's magnetic field, also gather GPS data with enough precision to study Earth's time-varying gravity field with a resolution of approximately 1500 km. The models, which span from 2014 to the present and don't require any additional gravimetric data or prior information, are updated monthly. These data fill in the gaps between the GRACE and GRACE-FO missions, as well as any other short interruptions in their series. After more than 9 years of successful operation, the Swarm satellites are still in good health. The planned future mission profile allows for many more years of operation, such that Swarm helps to guarantee continuous observation of Earth’s time variable gravity field.A consortium of international research institutes supported by theEuropean Space Agency and the International Combination Service for Time-variable Gravity Fields (COST-G), publishes the gravity field models every 3 months at the Swarm Data Access server(https://swarm-diss.eo.esa.int)and the International Centre for Global Earth Models(http://icgem.gfz-potsdam.de/series/02_COST-G/Swarm). These models are based on “individual” gravity field models estimated by each institute using different gravity inversion strategies, which are combined using Variance Component Estimation to produce the published models.We showcase the geophysical signals represented in our models across large hydrological basins, compare them with GRACE and GRACE-FO results and the discrepancies over deep oceans areas. Our analysis encompasses the time frame of the GRACE/GRACE-FO gap and highlights the significant importance of the Swarm satellites in bridging the gap caused by the absence of low-low satellite-to-satellite tracking data., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)
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- 2023
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8. PO.2.45 Autoantibodies associated with systemic sclerosis (SSC) in three diseases characterized by type I interferons: a comparison between SLE, primary Sjögren’s syndrome, SSC and healthy blood donors
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Andraos, R, primary, Ahmad, A, additional, Eriksson, P, additional, Dahlström, Ö, additional, Wirestam, L, additional, Dahle, C, additional, Hesselstrand, R, additional, Andréasson, K, additional, and Sjöwall, C, additional
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- 2022
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9. Estimating Sub-Monthly Global Mass Transport Signals Using GRACE, GPS and OBP Data Sets
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Jansen, M.J.F., Gunter, B.C., Rietbroek, R., Dahle, C., Kusche, J., Flechtner, F., Brunnabend, S.-E., Schröter, J., and Mertikas, Stelios P., editor
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- 2010
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10. POS0536 REFINING THE SEROLOGICAL SCORES OF THE ACR/EULAR 2010 RHEUMATOID ARTHRITIS CLASSIFICATION CRITERIA: AN INTERNATIONAL STUDY
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Van Hoovels, L., primary, Vander Cruyssen, B., additional, Sieghart, D., additional, Bonroy, C., additional, Nagy, E., additional, Pullerits, R., additional, Čučnik, S., additional, Dahle, C., additional, Heijnen, I., additional, Bernasconi, L., additional, Benkhadra, F., additional, Bogaert, L., additional, Van Den Bremt, S., additional, Vanliedekerke, A., additional, Vanheule, G., additional, Robbrecht, J., additional, Studholme, L., additional, Claudine, W., additional, Müller, R., additional, Kyburz, D., additional, Sjowall, C., additional, Kastbom, A., additional, Jese, R., additional, Jovancevic, B., additional, Kiss, E. V., additional, Jacques, P., additional, Steiner, G., additional, Verschueren, P., additional, and Bossuyt, X., additional
- Published
- 2022
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11. Clinical effectiveness and safety of dimethyl fumarate for patients treated at least 6 years in the swedish post-market surveillance study 'immunomodulation and multiple sclerosis epidemiology 5' (IMSE 5)
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Forsberg, L., Ekström, E., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Lantblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Forsberg, L., Ekström, E., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Lantblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Introduction: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE). Objectives/Aims: To assess the effectiveness and safety of DMF with focus on patients treated at least 72 months. Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS), Adverse Events (AEs) and Serious AEs (SAEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve. Results: 2565 DMF-treated patients were included between March 2014 and March 2022 with an overall drug survival rate of 38.7% and a mean treatment duration of 37 months. The main reasons for discontinuation were AEs (47%) and lack of effect (30%). 199 AEs were reported of which 63 were serious. For both serious and non-serious AEs reported, gastrointestinal disorders were the most common (19% and 27%, respectively).509 patients had continuous treatment for at least 72 months. This cohort had a mean age of 42 years and a mean treatment duration of 84 months. The majority (51%) had switched from interferon or glatiramer acetate and 24% were treatment naïve.Significant improvements in mean values at 72 months of treatment compared to baseline were noted for MSSS, MSIS-29 Psychological, and EQ-5D (p<0.05). All other tests remained stable after 6 years of treatment. Number of relapses per 1000 patient years were improved from 199.6 before DMF treatment start to 23.0 during treatment with DMF.49 patients (10%) have discontinued DMF treatment in the 72 month cohort with a mean treatment duration of 84 months (range 70-97 months). The
- Published
- 2022
12. Improved clinical outcomes in patients treated with natalizumab for at least 11 years - real-world data from a swedish national post-marketing surveillance study (IMSE 1)
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Forsberg, L., Ekström, E., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Forsberg, L., Ekström, E., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Introduction: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006). Objectives/Aims: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting. Methods: Adverse events (AEs), Serious AEs (SAEs), John Cunningham virus status (JCV) and clinical effectiveness measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT) and Multiple Sclerosis Impact Scale (MSIS-29) data is collected from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test. Results: A total of 3622 NTZ patients were included in the IMSE 1 study from August 2006 until March 2022 (72% female; mean age 36 years; 80% RRMS; mean treatment duration 49 months) and 186 had been treated for at east 132 months. Of the 132-month cohort, 73% were female, the mean age was 36 years, 88% had RRMS, and the mean treatment duration was 155 months. The majority were treated with interferons and glatiramer acetate prior NTZ (64%). 25% (47/186) discontinued NTZ treatment of which 47% (n=22) discontinued due to JCV positive (JCV+). In total, 30% (55/186) of these patients were JCV+ with a mean JCV index of 1.2±1.0 (2% missing data). Relapses before treatment were reduced from 380/1000 patient years to 43/1000 during treatment, 71% were relapse-free and 18% had 1 relapse during the entire treatment period (15% missing data). Most clinical effectiveness measures, MSSS, MSIS-29 and SDMT showed statistically significant improvement between baseline and 132
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- 2022
13. Clinical effectiveness and safety of cladribine tablets for patients treated at least 12 months in the Swedish post-market surveillance study 'immunomodulation and multiple sclerosis epidemiology 10' (IMSE 10)
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Rosengren, V., Forsberg, L., Ekström, E., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Rosengren, V., Forsberg, L., Ekström, E., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Introduction: Cladribine is a deoxyadenosine analogue prodrug that selectively induces immune reconstitution by targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). CladT are included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology”(IMSE). Objectives: To assess the safety and effectiveness of CladT with focus on patients treated at least 12 months. Methods: Data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS), relapses and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using Wilcoxon Signed Rank Test and relapse rates were tested using paired samples T-test. Results: 208 patients were included in the IMSE 10 study since the Swedish market launch in April 2018 with an overall drug survival rate of 94.2%. 12 patients discontinued treatment, of which 1 later restarted. The most common reason for discontinuation was lack of effect (83%). 21 AEs were reported of which 7 were serious. The most common AE reported were infection and infestation (8 reports).139 patients were treated for at least 12 months. 29 % of the patients was treated with CladT as their first MS drug. 19 % were treated with natalizumab and 10 % with dimethyl fumarate prior to CladT. The number of relapses decreased significantly from 249 per 1,000 patient years before treatment start to 73 during treatment. 12 patients in this cohort have experienced a relapse during treatment. Significant improvements in mean values at 12 months of tre
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- 2022
14. Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab‐treated multiple sclerosis
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Mellergård, J., Tisell, A., Blystad, I., Grönqvist, A., Blennow, K., Olsson, B., Dahle, C., Vrethem, M., Lundberg, P., and Ernerudh, J.
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- 2017
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15. The Effect of Pseudo-Stochastic Orbit Parameters on GRACE Monthly Gravity Fields: Insights from Lumped Coefficients
- Author
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Meyer, U., primary, Dahle, C., additional, Sneeuw, N., additional, Jäggi, A., additional, Beutler, G., additional, and Bock, H., additional
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- 2015
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16. Combination Service for Time-variable Gravity Fields (COST-G): operations and new developments
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Meyer, U., Peter, H., Encarnacao, J., Lasser, M., Jäggi, A., Flechtner, F., Dahle, C., Boergens, E., Förste, C., Mayer-Gürr, T., Kvas, A., Behzadpour, S., Lemoine, J. M., Bourgogne, S., Koch, I., Flury, J., Groh, A., Eicker, A., Meyssignac, B., Zhou, H., Yan, Z., Chen, Q., Guo, X., Wang, C., and Feng, W.
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520 Astronomy - Abstract
Since its start of operations in July 2019, IAGâ?Ts Combination Service for Time-variable Gravity fields (COST-G) is providing a complete time-series of combined monthly GRACE gravity fields and a regularly updated time-series of monthly gravity fields derived from kinematic Swarm orbits. Starting from October 2020, the COST-G product line is complemented by a time-series of operationally combined and monthly updated GRACE-FO gravity fields. All these combinations are performed by variance component estimation on the solution level. We report on new developments, i.e., a planned extension of COST-G to include Chinese analysis centers of GRACE and GRACE-FO data, a re-consideration of the combination strategy to better focus on the range of spherical harmonic coefficients most relevant for the users, and the potential application of COST-G products for orbit determination of altimeter satellites.
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- 2021
17. Combination Service for Time-variable Gravity Fields (COST-G): operational GRACE-FO combination and validation of Chinese GRACE time-series
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Meyer, U., Lasser, M., Jäggi, A., Dahle, C., Flechtner, F., Kvas, A., Behzadpour, S., Mayer-Gürr, T., Lemoine, J., Koch, I., Flury, J., Bourgogne, S., Groh, A., Eicker, A., Förste, C., Luo, Z., Ran, J., Shen, Y., Zhao, Q., Feng, W., and COST-G Team
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Series (stratigraphy) ,Gravity (chemistry) ,Meteorology ,Computer science ,Quality assessment ,Service (economics) ,media_common.quotation_subject ,Mode (statistics) ,Time variable ,media_common - Abstract
The Combination Service for Time-variable Gravity Fields (COST-G) of the International Association of Geodesy (IAG) provides combined monthly gravity fields of its associated and partner Analysis Centers (ACs). In November 2020, the combination of monthly GRACE-FO gravity fields started its operational mode, providing consolidated L2 (spherical harmonics) and L3 (gridded and post- processed) products with a latency of currently 3 months. We present an overview and quality assessment of the available products.COST-G aims at the extension of its service to include further GRACE and GRACE-FO analysis centers. In January 2020 a collaboration with representatives of five Chinese ACs was initiated, who provided GRACE time-series according to the COST-G requirements. We present the results of a test combination with the Chinese AC models, including comparison and quality assessment of all contributing time-series and validation of the combined gravity fields.
- Published
- 2021
18. Regional brain shrinkage over two years: Individual differences and effects of pro-inflammatory genetic polymorphisms
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Persson, N., Ghisletta, P., Dahle, C. L., Bender, A. R., Yang, Y., Yuan, P., Daugherty, A. M., and Raz, N.
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- 2014
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19. Combination Service for Time-variable Gravity Fields: operational GRACE-FO combination and validation of Chinese GRACE time-series
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Meyer, U., Lasser, M., Jäggi, A., Flechtner, F., Dahle, C., Boergens, E., Förster, C., Mayer-Gürr, T., Kvas, A., Behzadpour, S., Lemoine, J. M., Bourgogne, S., Koch, I., Flury, J., Groh, A., Eicker, A., Meyssignac, B., Zhou, H., Yan, Z., Chen, Q., Guo, X., Wang, C., and Feng, W.
- Subjects
520 Astronomy - Abstract
The Combination Service for Time-variable Gravity Fields (COST-G) of the International Association of Geodesy (IAG) provides combined monthly gravity fields of its associated and partner Analysis Centers (ACs). In November 2020, the combination of monthly GRACE-FO gravity fields started its operational mode, providing consolidated L2 (spherical harmonics) and L3 (gridded and post-processed) products with a latency of currently 3 months. We present an overview and quality assessment of the available products. COST-G aims at the extension of its service to include further GRACE and GRACE-FO analysis centers. In January 2020 a collaboration with representatives of five Chinese ACs was initiated, who provided GRACE time-series according to the COST-G requirements. We present the results of a test combination with the Chinese AC models, including comparison and quality assessment of all contributing time-series and validation of the combined gravity fields.
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- 2021
- Full Text
- View/download PDF
20. Clinical effectiveness and safety of teriflunomide for patients treated at least 48 months in the Swedish post-market surveillance study 'Immunomodulation and Multiple Sclerosis Epidemiology 4' (IMSE 4)
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Rosengren, V., Ekström, E., Forsberg, L., Kågström, S., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Rosengren, V., Ekström, E., Forsberg, L., Kågström, S., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Teriflunomide (TFM) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS) included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE). Objectives: To assess the safety and effectiveness of TFM with focus on patients treated at least 48 months. Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using Wilcoxon Signed Rank Test and drug survival using Kaplan-Meier curve. Results: 645 patients were included in the IMSE 4 study from March 2014 to April 2021, 70% were female, mean age at treatment start was 46 years and mean treatment duration was 31 months. The most common prior treatment was interferon beta or glatiramer acetate (34%) and 17% were treatment naïve. One- two- and three- year drug survival rates were 74%, 59% and 49% respectively. 340 patients (53%) have discontinued treatment with main reasons for discontinuation being AEs (41%) and lack of effect (40%). Of 68 reported AEs, 20 were serious. For both serious and non-serious AEs, skin and subcutaneous tissue disorders were the most common (25% and 21%, respectively). At the cut-off date, 168 patients had been treated for at least 48 months. This cohort had a mean age of 48 years at treatment start and a mean treatment duration of 65 months. The majority (64%) had switched from interferon or glatiramer acetate and 12% were treatment naïve. Significant improvement in mean values at 48 months of treatment compared to baseline were noted for SDMT in the 48-month cohort (49.1 ± 8.2 to 50.5 ± 10.0, n=35, p=0.049) while a minor worsening were noted for EDSS (2.2 ± 1.7 to 2.6 ± 2.0, n=37
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- 2021
21. Clinical effectiveness and safety of dimethyl fumarate for patients treated at least 5 years in the Swedish post-market surveillance study 'Immunomodulation and Multiple Sclerosis Epidemiology 5' (IMSE 5)
- Author
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Rosengren, V., Ekström, E., Forsberg, L., Kågström, S., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Rosengren, V., Ekström, E., Forsberg, L., Kågström, S., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE). Objectives: To assess the effectiveness and safety of DMF with focus on patients treated at least 60 months. Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.Results: 2466 DMF-treated patients were included between March 2014 and April 2021 with an overall drug survival rate of 41.2% and a mean treatment duration of 34 months. The main reasons for discontinuation were AEs (49%) and lack of effect (30%). 198 AEs were reported of which 62 were serious. For both serious and non-serious AEs reported, gastrointestinal disorders were the most common (19% and 27%, respectively). 588 patients had continuous treatment for at least 60 months. This cohort had a mean age of 42.1 years and a mean treatment duration of 72.4 months. The majority (63%) had switched from interferon or glatiramer acetate and 22% were treatment naïve. Significant improvements in mean values at 60 months of treatment compared to baseline were noted for MSSS in the 60-month cohort (p<0.001). MSIS-29 Psychological showed a tendency for improvement while all other tests remained stable after 5 years of treatment. Number of relapses per 1000 patients years were improved from 198.9 before DMF treatment start to 27.9 during treatment with DMF. 69 patients (12%) have discontinued DMF treatment in the 60 month cohort with a mean treatment duration of 67
- Published
- 2021
22. Real-world longitudinal data of peginterferon beta-1a from the Swedish national post-marketing surveillance study (IMSE 6) - effectiveness and safety profile
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Ekström, E., Rosengren, V., Kågström, S., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Ekström, E., Rosengren, V., Kågström, S., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Subcutaneous peginterferon beta-1a (PegIFN) was approved for relapsing-remitting multiple sclerosis (RRMS) in Europe 2014. Phase II and III studies have shown that PegIFN reduces relapse rate and disability progression. PegIFN were included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 6) due to the importance of studying the long-term safety and effectiveness. Objectives: To follow-up the long-term safety and effectiveness of PegIFN in a real-world setting. Methods: Data was obtained from the Swedish Neuro Registry (NeuroReg). All clinical measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve. Results: 393 patients (78% female; 86% RRMS) were included in IMSE 6 between June 2015 and April 2021. Mean age at treatment start was 42 years, mean treatment duration was 23 months. 25% were treatment naïve and 47% switched from other injectables prior PegIFN. The one- and two-year drug survival rate was 58% and 41% respectively, and 31% overall. In total, 271 patients discontinued their PegIFN treatment at some time point, mainly due to adverse events (51%) and lack of effect (26%). Most patients switched to rituximab (37%). During the entire treatment period 54% were relapse-free and 8% had only one relapse (36% missing data). In patients treated at least 24 months tendencies of improve-ments were seen for SDMT and EQ-5D. MSIS-PSYCH showed significantly worsened results (21.2 ± 18.6 to 24.3 ± 19.3, n=46). EDSS, MSSS, MSIS-PHYS and VAS scores remained stable. 25 adverse events (AEs) have been reported to Swedish Medical Product Agency (MPA). 6 of these were classified as serious where general disorders and administration site, and skin
- Published
- 2021
23. The long-term safety and effectiveness of natalizumab (IMSE 1) - Real-world data from a Swedish nationwide pharmaco-epidemiological study
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Ekström, E., Rosengren, V., Kågström, S., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Ekström, E., Rosengren, V., Kågström, S., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. The “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (August 2006). Objective: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting. Methods: IMSE 1 includes patients starting NTZ treatment. Data is collected from the nationwide Swedish Neuroregistry. Adverse events (AEs), JC-virus status (JCV) and clinical effectiveness measures Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT) are registered prospectively. Results: 3476 patients (75% female; 81% RRMS) were included from August 2006 until April 2021. Mean age at treatment start was 36 years and mean treatment duration was 51.3 months. 1190 patients were currently treated with NTZ at cut-off and 13% of these were JCV positive (JCV+) with a mean JCV index at 1.07 ± 0.97. 2470 patients (71%) discontinued their NTZ treatment at some time point where the main reason was JCV+ (40%). Most of these patients switched to rituximab (39%). The number of relapses per 1,000 patient years were reduced from 380 before treatment start to 73 during treatment (25% missing data). 61% were relapse-free and 12% had only one relapse during the entire treatment period. All clinical measures showed improvement in mean between baseline and 132 months. Improvements on MSSS, MSIS-29 and SDMT were statistically significant. 117 Serious AEs had been reported to the Swedish Medical Product Agency and included nine cases (2 fatal) of progressive multifocal leukoencephalopathy (PML). Eight of these nine cases had been reported between year 2008 and 2012, and one in 2018. 17 patients died within 6 mo
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- 2021
24. A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)
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Ekström, E., Rosengren, V., Kågström, S., Forsberg, L., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Ekström, E., Rosengren, V., Kågström, S., Forsberg, L., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Alemtuzumab (ALZ) is a modulatory drug for patients with relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long-term safety and effectiveness in a real-world setting where ALZ was included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study 3” (IMSE 3) upon launch in Sweden (March 2014). Objective: To follow up the effectiveness and long-term safety of ALZ in a real-world setting. Methods: Swedish MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg). IMSE 3 includes patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life – 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS). The Wilcoxon signed-rank test was used to assess changes in effectiveness. Results: 118 patients (59% female; 95% RRMS) have been included in IMSE 3 between March 2014 and April 2021. Mean age at treatment start was 34 years. At cut-off date 85 patients had been treated with ALZ with at least 48 months of follow-up. Mean values at baseline compared to 48 months showed significant improvements for MSSS and SDMT while EQ-5D, EDSS, MSIS-29 and VAS scores showed tendencies of improvement. The largest proportion of the entire cohort switched from natalizumab (39%) or were treatment naïve (14%) prior ALZ. The number of relapses per 1,000 patient years decreased from 441 before ALZ initiation to 84 during ALZ treatment (16% missing data). 36 adverse events (AEs) were reported to the Swedish Medical Products Agency. 23 were classified as serious and the most common AEs categories were infections and infestations and blood and lymphatic system disorders (23% respectively). For non-serious events endocrine disorders (43%) was the most common c
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- 2021
25. Clinical effectiveness and safety of cladribine tablets for patients treated at least 12 months in the swedish post-market surveillance study 'immunomodulation and multiple sclerosis epidemiology 10' (IMSE 10)
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Rosengren, V., Ekström, E., Forsberg, L., Kågström, S., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Rosengren, V., Ekström, E., Forsberg, L., Kågström, S., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Cladribine is a deoxyadenosine analogue prodrug that selectively induces immune reconstitution by targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). CladT are included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE). Objective: To assess the safety and effectiveness of CladT with focus on patients treated at least 12 months. Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life-5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS), relapses and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and relapse rates were tested using the paired samples T-test. Results: 140 patients were included in the IMSE 10 study since the Swedish market launch in April 2018 with a one year drug survival rate of 96.5%. 6 patients discontinued treatment, of which 2 later restarted. 18 AEs were reported of which 5 were serious. The most common AE reported were infection and infestation (8 reports). 22% of the patients was treated with CladT as their first MS drug. 18% were treated with natalizumab and 11% with dimethyl fumarate prior to CladT. 83 patients were treated for at least 12 months. Relapse data was available for 47 of 83 patients in the 12-month cohort. The number of relapses decreased significantly from 249.6 per 1,000 patient years before treatment start to 53.5 during treatment. Only 5 patients in this cohort experienced a relapse during treatment.Significant improvements in mean values at 12 months of treatment compared to baseline were noted for MSSS (p=0.007) and VAS (p=0.029) for the 12-month cohort. All other tests remai
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- 2021
26. Combination Service for Time-variable Gravity Fields (COST-G) – operations
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Meyer, U., Jäggi, A., Flechtner, F., Dahle, C., Mayer-Gürr, T., Kvas, A., Lemoine, J., Bourgogne, S., Groh, A., Eicker, A., and Meyssignac, B.
- Abstract
With the release of the combined GRACE monthly gravity field time-series COST-G RL01 the Combination Service for Time-variable Gravity fields (COST-G) of the International Association of Geodesy (IAG) became operational in July 2019. We present the COST-G RL01 time-series and provide validation in terms of orbit fit, ice mass trends, lake altimetry and sea level budget. We identify weak points in the combined monthly gravity fields and discuss possible improvements of the combination strategy for future combinations. While COST-G RL01 is based on sets of re-processed GRACE monthly gravity fields, COST-G also provides combinations of monthly Swarm high-low satellite-to-satellite tracking (hl-SST) gravity fields on an operational basis with a latency of 3 months. Combinations of GRACE-FO monthly gravity fields are in the process of operationalization. We provide a status report and first results of GRACE-FO combinations. Combined GRACE, Swarm and GRACE-FO gravity fields complement each other to provide a long-term time-series of mass variation in the system Earth.
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- 2020
27. Uncertainties of Terrestrial Water Storage Anomalies for Global Basins – A Comparison Between Modelled and Formal Covariances
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Boergens, E., Kvas, A., Dobslaw, H., Eicker, A., Dahle, C., and Flechtner, F.
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The application of GRACE and GRACE-FO observed gridded terrestrial water storage data (TWS) often requires realistic assumptions of the data variances and covariances. Such covariances are, e.g., needed for data assimilation in various models or combinations with other data sets. The formal variance-covariance matrices now provided with the Stokes coefficients can yield such spatial variances and covariances after variance propagating them through the various post-processing steps, including the filtering, and spherical harmonic synthesis. However, a rigorous variance propagation to the TWS grids is beyond the capabilities of most non-geodetic users. That is why we developed a new spatial covariance model for global TWS grids. This covariance model is non-stationary (time-depending), non-homogeneous (location-depending), and anisotropic (direction-depending). Additionally, it allows latitudinal wave-like correlations caused by residual striping errors. The model is tested for both GFZ RL06 Level-3 TWS data as provided via the GravIS portal (gravis.gfz-potsdam.de) and ITSG-Grace2018 GravIS-like processed Level-3 TWS data. The model parameters are fitted to empirical correlations derived from both TWS fields. Both data sets yield the same model parameters within the uncertainty of the parameter estimation. Now, the covariance model derived thereof can be used to estimate uncertainties of mean TWS time series of arbitrary regions such as river basins. Here, we use a global basin segmentation covering all continents. At the same time, such regional uncertainties can be derived from formal variance-covariance matrices as well. To this end, the formal ITSG-Grace2018 variance-covariance matrices of the spherical harmonic coefficients are used. Thus, the modelled and formal basin uncertainties can be compared against each other globally, both spatially and temporally. Further, external validation investigates the usefulness of the basin uncertainties for applications such as data assimilation into hydrological models. Our results show a high agreement between the modelled and the formal basin uncertainties proving our approach of modelled covariance to be a suitable surrogate for the formal variance-covariance matrices.
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- 2020
28. Combination Service for Time-variable Gravity Field Solutions (COST-G) – GRACE-FO operational combination
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Meyer, U., Lasser, M., Jäggi, A., Flechtner, F., Dahle, C., Mayer-Gürr, T., Kvas, A., Behzadpour, S., Lemoine, J., Bourgogne, S., Koch, I., Groh, A., Förste, C., Eicker, A., and Meyssignac, B.
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- 2020
29. Globale Massenverteilungen aus Satellitengravimetrie: Das interaktive Datenportal GravIS
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Boergens, E., Dahle, C., Dobslaw, H., Sasgen, I., Reißland, S., and Flechtner, F.
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Über das vom GFZ Potsdam betriebene Datenportal »Gravity Information Service« (GravIS, gravis.gfz-potsdam.de) werden vorprozessierte Daten der Satellitenmissionen GRACE und GRACE Follow-On (GRACE-FO) bereitgestellt. Die verfügbaren Datensätze umfassen Massenanomalien der Eisschilde Grönlands und der Antarktis, terrestrische Wasserspeicheränderungen sowie ozeanische Bodendruckvariationen, aus denen der masseninduzierte Meeresspiegelanstieg abgeleitet werden kann. Dabei werden die Daten dem Nutzer sowohl regelmäßig gegittert als auch für ausgewählte Regionen als Gebietsmittelwerte zur Verfügung gestellt. Der Nutzer kann sich räumliche und zeitliche Veränderungen sowohl global als auch regional interaktiv anzeigen lassen. Das Portal richtet sich an Anwender aus der Hydrologie, Ozeanographie und Kryosphäre, aber auch an die populärwissenschaftlich interessierte Öffentlichkeit. Alle zugrunde liegenden Daten stehen dem Nutzer auch zum Download für weitere Auswertungen zur Verfügung.
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- 2020
30. V. 0002
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Dahle, C. and Murböck, M.
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Post-processed GRACE/GRACE-FO spherical harmonic coefficients of COST-G RL01 Level-2 GSM products representing an estimate of Earth's gravity field variations during the specified timespan. Post-processing steps comprise: (1) subtraction of a long-term mean field; (2) optionally, decorrelation and smoothing with VDK filter (anisotropic filter taking the actual error covariance information of the underlying GSM coefficients into account, see Horvath et al. (2018)); (3) replacement of coefficients C20, C30 (only for the months starting from 2016/11 and later), C21 and S21 and its formal standard deviations by values estimated from a combination of GRACE/GRACE-FO and Satellite Laser Ranging (SLR); (4) subtraction of linear trend caused by Glacial Isostatic Adjustment (GIA) as provided by a numerical model; (5) insertion of geocenter coefficients (C10, C11, S11); and (6) removal of estimated aliased signal of the S2 tide (161 days period). These coefficients represent signals caused by water mass redistribution over the continents and in the oceans.
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- 2020
31. Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus : a prospective study of Swedish cases with recent-onset disease
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Frodlund, M., Wetterö, J., Dahle, C., Dahlström, Ö., Skogh, T., Rönnelid, Johan, Sjöwall, C., Frodlund, M., Wetterö, J., Dahle, C., Dahlström, Ö., Skogh, T., Rönnelid, Johan, and Sjöwall, C.
- Abstract
Serum immunoglobulin (Ig)G anti-nuclear antibodies (ANA) detected by indirect immunofluorescence (IF) microscopy remains a hallmark of systemic lupus erythematosus (SLE). Whether or not IF-ANA status varies over time is controversial. We therefore designed a prospective study with longitudinal follow-up of patients with recent-onset SLE. The study population consisted of 54 recently diagnosed SLE cases, all meeting the 1982 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Clinical follow-up data, including disease activity, organ damage and sera, were collected from clinical onset of SLE and onwards, in most cases yearly (0-96 months). IF-ANA was analysed on human epithelial cells-2 (HEp-2) cells and categorized regarding staining patterns. Using an addressable laser bead assay (FIDIS (TM) Connective profile), we measured IgG-ANA fine specificities against Ro52/SSA, Ro60/SSA, Sjogren's syndrome type B antigen (La/SSB), Smith antigen (Sm), Smith antigen/ribonucleoprotein (Sm/RNP), U1 RNP (U1RNP), dsDNA, ribosomal-P protein and histone. At baseline, all patients were judged ANA-positive at an abnormal titre corresponding to the 95th percentile of healthy blood donors, but seven of 54 patients (13%) lost ANA-positivity over time. Homogeneous (AC-1; 46%) and speckled (AC-4 or 5; 31%) were the most frequently observed patterns at inclusion, whereas 7% switched pattern at least once during follow-up. Established associations between ANA fine specificities and clinical data were confirmed. Levels of anti-Sm/RNP, but not of anti-dsDNA, correlated with clinical disease activity [modified SLE disease activity 2000 (mSLEDAI-2K)]. Our data indicate that a considerable proportion of Swedish patients with SLE lose ANA-positivity over time, whereas consistent staining patterns were frequent. The clinical and mechanistic relevance of ANA seroconversion remains uncertain. Further prospective evaluations in la
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- 2020
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32. A swedish post-market surveillance study of the long-term effectiveness and safety of alemtuzumab (imse 3) for patients treated for at least 36 months
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Leandersson, Å., Kågström, S., Forsberg, L., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Leandersson, Å., Kågström, S., Forsberg, L., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Alemtuzumab (ALZ) is an approved disease-modi-fying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long-term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) upon launch in Sweden (March 2014). Objectives: To track effectiveness and long-term safety of ALZ in a real-world setting, with focus on patients treated with ALZ for at least 36 months. Methods: Swedish MS patients are registered into the nationwide Swedish MS Registry (NeuroReg). IMSE 3 includes all patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life – 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS). Results: A total of 118 patients (59% female; 95% RRMS) were included in IMSE 3 between March 2014 and June 2020. Out of 118 patients, 93 had been treated for at least 36 months (62% female), of which 10 patients had switched to another DMT. Mean age at treatment start for patients treated ⩾ 36 months was 34 years and mean treatment duration was 54 months. Mean number of drugs prior ALZ initiation was 2.4. Most of the patients (40%, n=37) switched to ALZ from natalizumab or were treatment naïve (13%, n=12) prior ALZ. The mean num-ber of relapses was reduced from 0.72 one year before ALZ initiation to 0.10 during the first treatment year, followed by 0.08 the second treatment year and 0.06 the third year of ALZ treatment (n=79, 15% missing data). In patients treated ⩾ 36 months significant improvements in mean baseline compared to 36 months were seen for MSSS (3.3 ± 2.7 to 2.3 ± 2.3, n=44) and EQ-5D (0.7 ± 0.3 to 0.8 ± 0.3, n=50), while SDMT showed signific
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- 2020
33. A swedish post-market surveillance study of the long-term effectiveness and safety of teriflunomid (IMSE 4) for patients treated at least 36 months
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Forsberg, L., Kågström, S., Leandersson, Å., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Gunnarsson, Martin, Piehl, F., Olsson, T., Forsberg, L., Kågström, S., Leandersson, Å., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Teriflunomid (TFM) is an oral therapy for relaps-ing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE). Objectives: To assess the long-term safety and effectiveness of TFM for patients treated in a real-world setting over time. Methods: A large majority of MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). The IMSE 4 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve. Results: 609 TFM-treated patients had been included in the IMSE 4 study from March 2014 to June 2020, 70% were female and mean age at treatment start was 46 years. Mean treatment duration was 27 months and 89% of the patients had RRMS. The most common prior treatment was interferon beta or glatiramer acetate (39%) and 17% of the patients were treatment naïve. The overall one- two- and three- year drug survival rates were 73%, 59% and 48% respectively. 307 (50%) patients had discontinued treatment at some point, of which 34% started rituximab treatment (36% had no new treatment registered). The most common rea-sons for discontinuation were AEs (42%) and lack of effect (40%). 204 patients had been continuously treated with TFM for ⩾36 months and significant changes in mean baseline values compared to values at 36 months were noted only for EDSS (2.0 ± 1.6 to 2.3 ± 1.8, n=49). All other clinical measures were stable. A total of 68 AEs were reported of which 20 events were classified as serious (S). The most common AE category was skin and subcutaneous tissue disord
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- 2020
34. A swedish post-market surveillance study : long-term effectiveness and safety of cladribine tablets (IMSE 10) for patients treated at least 12 months
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Forsberg, L., Kågström, S., Leandersson, Å., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Forsberg, L., Kågström, S., Leandersson, Å., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Cladribine is a deoxyadenosine analogue prodrug. Cladribine tablets (CT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). CT are included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE). Objectives: To assess the safety and effectiveness of CT in a real-world setting with focus on patients treated at least 12 months. Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS), relapses and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and relapse rates were tested using the paired samples T-test. Results: 85 patients were included in the IMSE 10 study since CT were introduced on the Swedish market in April 2018. 42 patients were treated for at least 12 months. Five AEs were reported since the study start, four were classified as infections and infestations. 25 % of the entire cohort was treated with CT as their first MS drug. 13 % were treated with natalizumab and 12 % with dimethyl fumarate prior to CT. Five AEs were reported since the study start, four were classified as infections and infestations. Relapse data was available for 27/42 patients in the 12-month cohort. The number of reported relapses decreased significantly from 208.6 per 1,000 patient years before treatment start to 83.6 during treatment. Only three patients in this cohort experienced a relapse during treatment of which two were during the first treatment year. Significant improvements in mean values at 12 months of treatment compared to baseline were noted for MSSS for the 12-month cohort (n=17). All other tests remained stable but significantly uncha
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- 2020
35. Real-world data of peginterferon beta-1a from a swedish national post-marketing surveillance study (IMSE 6) - effectiveness and safety profile
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Kågström, S., Leandersson, Å., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Kågström, S., Leandersson, Å., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Subcutaneous peginterferon beta-1a (PegIFN) was approved for relapsing-remitting multiple sclerosis (RRMS) in Europe 2014. The clinical trial program showed that PegIFN reduced the relapse rate and proportion with disability progression compared to placebo. At its launch in Sweden, PegIFN was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 6), providing possibilities to track long-term effectiveness and safety in a population-based setting. Objectives: To follow-up the long-term effectiveness and safety of PegIFN treatment in Swedish patients in a real-world context. Methods: Data was obtained from the nationwide Swedish Neuro Registry (NeuroReg) between June 2015 and May 2020. Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve. Results: A total of 364 patients (78% female; 87% RRMS; mean age at treatments start 43 years) were followed up to 57 months (mean 20 months), of which 200 (55%) patients had been treated for at least 12 months. The majority of the patients had switched from other injectables (164 patients, 45%) or were treatment naïve (90 patients, 25%) prior to treatment with PegIFN. Over the dura-tion of the follow-up, 68% (247/364) patients discontinued their PegIFN treatment for various reasons (60% adverse events, 24% lack of effect) and switched mainly to rituximab (105 patients, 43%). The overall drug survival was 32%, 40% for men and 30% for women. The one- and two-year drug survival rate was 57% and 40%, respectively. The mean number of relapses were reduced from 0.35 one year before treatment start to 0.11 one year after (35% missing data). All clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life – 5-Dimension test (EQ-5D), Visual Analogue Score (VAS) and Symbol Digit Modalities Test (SDMT)) remai
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- 2020
36. A swedish post-market surveillance study : long-term effectiveness and safety of dimethyl fumarate (imse 5) for patients treated at least 36 months: on-demand eposters p0001-p0286
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Forsberg, L., Kågström, S., Leandersson, Å., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Forsberg, L., Kågström, S., Leandersson, Å., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE). Objectives: To assess the effectiveness and safety of DMF with focus on patients treated at least 36 months in the IMSE study. Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve. Results: 2349 DMF-treated patients were included between March 2014 and June 2020 with an overall drug survival rate of 45%. The main reasons for discontinuation were AEs (50%) and lack of effect (30%). 186 AEs were reported to the Swedish Medical Products Agency, of which 59 were serious. A total of 8 patients have died during DMF treatment or within 6 months of treatment discontinuation. 36 month cohort: 940 patients had con-tinuous treatment for at least 36 months. This cohort had a mean age of 42 years and a mean treatment duration of 56 months. The majority (50%) had switched from interferon or glatiramer ace-tate, and (24%) were treatment naïve (TN). Significant improve-ments in mean values at 36 months of treatment compared to baseline for the 36-month cohort were noted for MSSS, SDMT, MSIS-29 Psychological, EQ-5D and VAS. When TN patients were solely assessed (n=230) improvements were noted for all above mentioned measures as well as MSIS-29 Psychological. The remaining patients in the cohort; treatment experienced patients (n=710) displayed significant improvements only for MSSS, MSIS-29 Psychological and EQ-5D. TN patients had a
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- 2020
37. Efficacy and safety in patients treated with natalizumab for at least 10 years - real-world data from a swedish national surveillance study (IMSE 1)
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Kågström, S., Leandersson, Å., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Sundström, P., Martin, C., Gunnarsson, Martin, Piehl, F., Olsson, T., Kågström, S., Leandersson, Å., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Sundström, P., Martin, C., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evalua-tion of long-term safety and effectiveness in a real-world setting. To this end, the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (August 2006). Objectives: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting, with focus on patients treated at least 10 years. Methods: IMSE 1 includes patients starting NTZ treatment and data is collected from the nationwide Swedish Neuro Registry (NeuroReg). Adverse events (AEs), JC-virus status (JCV) and clinical effectiveness measures are registered in NeuroReg pro-spectively. Effectiveness measures were assessed using the Wilcoxon Signed Rank Test. Results: A total of 3291 patients were included in the IMSE 1 study from August 2006 until June 2020 (72% female; mean age 36 years; 80% RRMS; mean treatment duration 50 months). 171/3291 patients (5%) had been treated for at least 120 months (73% female; men age 36 years; 87% RRMS; mean treatment duration 139 months). A total of 64% (110/171) were treated with interferons or glatiramer acetate prior to NTZ treatment. Over the duration of follow-up discontinued 21% (35/171) their NTZ treat-ment of which 46% (16/35) discontinued due to JCV positive (JCV+). In total, 27% (46/171) of these patients were JCV+ with a mean JCV index of 1.2±1.0 (4% missing data). The mean num-ber of relapses were reduced from 0.84 one year before NTZ treat-ment start to 0.00 during the first treatment year (12% missing data). All clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT)) showed improvement in mean between baseline and 120 months. However, only MSSS, MSIS-29 psy-chological and SDMT
- Published
- 2020
38. Relation of edss to patient-reported outcome measurements in ms : real-world data from a swedish nationwide study of fingolimod (imse 2)
- Author
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Leandersson, Å., Kågström, S., Forsberg, L., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., Olsson, T., Leandersson, Å., Kågström, S., Forsberg, L., Hillert, J., Nilsson, P., Dahle, C., Svenningsson, A., Lycke, J., Landtblom, A. -M, Burman, J., Martin, C., Sundström, P., Gunnarsson, Martin, Piehl, F., and Olsson, T.
- Abstract
Background: Fingolimod (FGL) is an oral disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis, introduced in Sweden 2011. Already from launch, FGL was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) in order to enable long-term surveillance of effectiveness and safety aspects in a large population-based cohort. Objectives: To assess the relation between Expanded Disability Status Scale (EDSS) and patient-reported outcome measurements (PROMS) in patients treated with FGL. Methods: Swedish MS patients are registered into the nation-wide Swedish MS Registry. Demographic data, EDSS and the Multiple Sclerosis Impact Scale (MSIS-29), Symbol Digit Modalities Test (SDMT), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) were collected for FGL patients who agreed to participate in the IMSE 2 study. Spearman rank correlation were used to determine associations between EDSS and PROMS. Results: From September 2011 until June 2020, 1670 MS patients (68% female) were included in IMSE 2. Mean age at treatment start was 39 years and mean treatment duration in the entire cohort was 44 months (M). Out of 1670 patients, 560 (63% female) had been treated with FGL for at least 60 M. Mean age was 40 years and mean treatment duration 81 M. Significant (p<0.05) correla-tions was found between EDSS and all PROMs. The strongest correlation was found between the physical component of MSIS-29 for both baseline (r=0.60, n=778) and 60 M (r=0.64, n=109). Also, for both EQ-5D and VAS, Spearman coefficient indicates a moderate correlation for baseline (EQ-5D; r=-0.48, n=744 and VAS; -0.43, n=706) and 60 M (EQ-5D; r=-0.47, n=102 and VAS; -0.48, n=102) respectively. The correlation between EDSS and SDMT and the psychological component of MSIS-29, both indi-cated a weak correlation for baseline (SDMT; r=-0.28, n=771 and MSIS-29 psychological; r=0.28, n=778). For 60 M the correla-tions were
- Published
- 2020
39. IgA antibodies against tissue transglutaminase, endomysium and gliadin in idiopathic polyneuropathy
- Author
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Vrethem, M., Lindh, J., Tondel, M., Persson, B., and Dahle, C.
- Published
- 2013
- Full Text
- View/download PDF
40. Estimating Sub-Monthly Global Mass Transport Signals Using GRACE, GPS and OBP Data Sets
- Author
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Jansen, M.J.F., primary, Gunter, B.C., additional, Rietbroek, R., additional, Dahle, C., additional, Kusche, J., additional, Flechtner, F., additional, Brunnabend, S.-E., additional, and Schröter, J., additional
- Published
- 2010
- Full Text
- View/download PDF
41. Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes
- Author
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Ahmad, A, primary, Heijke, R, additional, Eriksson, P, additional, Wirestam, L, additional, Kechagias, S, additional, Dahle, C, additional, and Sjöwall, C, additional
- Published
- 2020
- Full Text
- View/download PDF
42. Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease
- Author
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Frodlund, M, primary, Wetterö, J, additional, Dahle, C, additional, Dahlström, Ö, additional, Skogh, T, additional, Rönnelid, J, additional, and Sjöwall, C, additional
- Published
- 2019
- Full Text
- View/download PDF
43. Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase
- Author
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Dahle, C., Hagman, A., Ignatova, S., and Ström, M.
- Published
- 2010
- Full Text
- View/download PDF
44. Assessment of the first gravity and mass change fields from the GRACE Follow-On Science Data System
- Author
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Landerer, F., Dahle, C., Webb, F., Flechtner, F., Save, H., Wiese , D., McCullough, C., Yuan, D., Bettadpur, S., and Murböck, M.
- Published
- 2019
45. Impact of inter-satellite links and ultra-stable clocks within future GNSS constellations on gravity field parameters
- Author
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Murböck, M., Dahle, C., Michalak, G., Neumayer, K., König, R., and Flechtner, F.
- Published
- 2019
46. GRACE-FO geopotential GSM coefficients GFZ RL06
- Author
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Dahle, C., Flechtner, F., Murböck, M., Michalak, G., Neumayer, K., Abrykosov, O., Reinhold, A., and König, R.
- Subjects
Physics::Space Physics ,Astrophysics::Earth and Planetary Astrophysics ,Physics::Atmospheric and Oceanic Physics ,Physics::Geophysics - Abstract
Spherical harmonic coefficients representing an estimate of Earth's mean gravity field during the specified timespan derived from GRACE-FO mission measurements. These coefficients represent the full magnitude of land hydrology, ice, and solid Earth processes. Further, they represent atmospheric and oceanic processes not captured in the accompanying GAC product.
- Published
- 2019
47. Combination Service for Time-Variable Gravity Models (COST-G) - current status
- Author
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Jäggi, A., Meyer, U., Lasser, M., Lopez, T., Flechtner, F., Dahle, C., Mayer-Dürr, T., Kvas, A., Lemoine, J.-M., Förste, C., Bourgogne, S., Weigelt, M., and Groh, A.
- Subjects
520 Astronomy - Published
- 2019
- Full Text
- View/download PDF
48. GRACE Follow-On: First Mass Change Observations and Mission Status
- Author
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Landerer, F., Flechtner, F., Webb, F., Dahle, C., Save, H., Watkins, M., Bettadpur, S., and Morton, P.
- Published
- 2019
49. GRACE-FO geopotential GAD coefficients GFZ RL06
- Author
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Dobslaw, H., Dill, R., and Dahle, C.
- Subjects
Physics::Atmospheric and Oceanic Physics ,Physics::Geophysics - Abstract
Spherical harmonic coefficients that are zero over the continents, and provide the anomalous simulated ocean bottom pressure that includes non-tidal air and water contributions elsewhere during the specified timespan. These coefficients differ from GLO (or GAC) coefficients over the ocean domain by disregarding upper air density anomalies. The anomalous signals are relative to the mean field from 2003-2014.
- Published
- 2019
50. V. 0001
- Author
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Dahle, C. and Murböck, M.
- Abstract
Post-processed GRACE/GRACE-FO spherical harmonic coefficients of GFZ RL06 Level-2 GSM products representing an estimate of Earth's gravity field variations during the specified timespan. Post-processing steps comprise: (1) subtraction of a long-term mean field; (2) optionally, decorrelation and smoothing with VDK filter (anisotropic filter taking the actual error covariance information of the underlying GSM coefficients into account, see Horvath et al. (2018)); (3) replacement of coefficient C20 and its uncertainty by values estimated from Satellite Laser Ranging (SLR); (4) subtraction of linear trend caused by Glacial Isostatic Adjustment (GIA) as provided by a numerical model; (5) insertion of coefficients of degree 1; and (6) removal of estimated signal with 161 days period. These coefficients represent signals caused by water mass redistribution over the continents and in the oceans. These post-processed GRACE/GRACE-FO GSM products are denoted as Level-2B products.
- Published
- 2019
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