| 1. |
- Feroci, M., et al.
(författare)
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The large observatory for x-ray timing
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
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Konferensbidrag (refereegranskat)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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| 2. |
- Feroci, M., et al.
(författare)
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LOFT - The large observatory for x-ray timing
- 2012
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
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Konferensbidrag (refereegranskat)abstract
- The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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| 3. |
- Feroci, M., et al.
(författare)
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The Large Observatory for X-ray Timing (LOFT)
- 2012
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 415-444
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Tidskriftsartikel (refereegranskat)abstract
- High-time-resolution X-ray observations of compact objects provide direct access to strong-field gravity, to the equation of state of ultradense matter and to black hole masses and spins. A 10 m(2)-class instrument in combination with good spectral resolution is required to exploit the relevant diagnostics and answer two of the fundamental questions of the European Space Agency (ESA) Cosmic Vision Theme "Matter under extreme conditions", namely: does matter orbiting close to the event horizon follow the predictions of general relativity? What is the equation of state of matter in neutron stars? The Large Observatory For X-ray Timing (LOFT), selected by ESA as one of the four Cosmic Vision M3 candidate missions to undergo an assessment phase, will revolutionise the study of collapsed objects in our galaxy and of the brightest supermassive black holes in active galactic nuclei. Thanks to an innovative design and the development of large-area monolithic silicon drift detectors, the Large Area Detector (LAD) on board LOFT will achieve an effective area of similar to 12 m(2) (more than an order of magnitude larger than any spaceborne predecessor) in the 2-30 keV range (up to 50 keV in expanded mode), yet still fits a conventional platform and small/medium-class launcher. With this large area and a spectral resolution of < 260 eV, LOFT will yield unprecedented information on strongly curved spacetimes and matter under extreme conditions of pressure and magnetic field strength.
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| 4. |
- Boisgontier, MP, et al.
(författare)
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Adverse Childhood Experiences, Depressive Symptoms, Functional Dependence, and Physical Activity: A Moderated Mediation Model
- 2020
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Ingår i: Journal of physical activity & health. - : Human Kinetics. - 1543-5474 .- 1543-3080. ; 17:8, s. 790-799
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adverse childhood experiences, depressive symptoms, and functional dependence are interrelated. However, the mechanisms underlying these associations remain unclear. The authors investigated the potential of depressive symptoms to mediate the effect of adverse childhood experiences on functional dependence in older age and whether physical activity moderated this mediation. Method: Data from 25,775 adults aged 62 (9) years from the Survey of Health Ageing and Retirement in Europe were used in adjusted linear mixed-effects models to test whether depressive symptoms mediated the associations between adverse childhood experiences and functional dependence in activities of daily living (ADL) and instrumental ADL (IADL) and whether physical activity moderated these mediations. Results: The results showed a graded association between the number of adverse childhood experiences (0 vs 1 and 0 vs ≥2) and the number of functional limitations in both ADL (bs = 0.040 and 0.067) and IADL (bs = 0.046 and 0.076). These associations were mediated by depressive symptoms. Physical activity reduced the effect of adverse childhood experiences on depressive symptoms (bs = −0.179 and −0.515) and tempered the effect of depressive symptoms on functional dependence both in ADL (b = −0.073) and IADL (b = −0.100). As a result of these reductions, the effect of adverse childhood experiences and depressive symptoms on functional dependence in ADL (Ps > .081) and IADL (Ps > .528) was nonsignificant in physically active participants. Conclusions: These findings suggest that, after age 50, engaging in physical activity more than once a week protects functional independence from the detrimental effects of adverse childhood experiences and depression. In inactive individuals, the detrimental effects of adverse childhood experiences on functional dependence are mediated by depressive symptoms.
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| 5. |
- Courvoisier, D. S., et al.
(författare)
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Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent : Trajectories of Disease Activity in a Large Multinational Cohort Study
- 2016
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 11, s. 302-306
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Tidskriftsartikel (refereegranskat)abstract
- Background Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). Methods Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients’ characteristics and effectiveness outcomes. Findings We identified three types of treatment response trajectories: ‘gradual responders’ (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; ‘rapid responders’ (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; ‘inadequate responders’ (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (p = 0.03), and EULAR good or moderate responses at 1 year was much higher among ‘rapid responders’ (p < 0.001). Interpretation Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.
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| 6. |
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| 7. |
- Courvoisier, D, et al.
(författare)
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POINTS TO CONSIDER WHEN ANALYSING AND REPORTING COMPARATIVE EFFECTIVENESS RESEARCH WITH OBSERVATIONAL DATA IN RHEUMATOLOGY
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 124-125
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Comparing drug effectiveness in observational settings is hampered by several major threats, among them confounding and attrition bias bias (patients who stop treatment no longer contribute information, which may overestimate true drug effectiveness).Objectives:To present points to consider (PtC) when analysing and reporting comparative effectiveness with observational data in rheumatology (EULAR-funded taskforce).Methods:The task force comprises 18 experts: epidemiologists, statisticians, rheumatologists, patients, and health professionals.Results:A systematic literature review of methods currently used for comparative effectiveness research in rheumatology and a statistical simulation study were used to inform the PtC (table). Overarching principles focused on defining treatment effectiveness and promoting robust and transparent epidemiological and statistical methods increase the trustworthiness of the results.Points to considerReporting of comparative effectiveness observational studies must follow the STROBE guidelinesAuthors should prepare a statistical analysis plan in advanceTo provide a more complete picture of effectiveness, several outcomes across multiple health domains should be comparedLost to follow-up from the study sample must be reported by the exposure of interestThe proportion of patients who stop and/or change therapy over time, as well as the reasons for treatment discontinuation must be reportedCovariates should be chosen based on subject matter knowledge and model selection should be justifiedThe study baseline should be at treatment initiation and a description of how covariate measurements relate to baseline should be includedThe analysis should be based on all patients starting a treatment and not limited to patients remaining on treatment at a certain time pointWhen treatment discontinuation occurs before the time of outcome assessment, this attrition should be taken into account in the analysis.Sensitivity analyses should be undertaken to explore the influence of assumptions related to missingness, particularly in case of attritionConclusion:The increased use of real-world comparative effectiveness studies makes it imperative to reduce divergent or contradictory results due to biases. Having clear recommendations for the analysis and reporting of these studies should promote agreement of observational studies, and improve studies’ trustworthiness, which may also facilitate meta-analysis of observational data.Disclosure of Interests:Delphine Courvoisier: None declared, Kim Lauper: None declared, Sytske Anne Bergstra: None declared, Maarten de Wit Grant/research support from: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Consultant of: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Speakers bureau: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Thomas Frisell: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Joanna KEDRA: None declared, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Maria Jose Santos Speakers bureau: Novartis and Pfizer, Tanja Stamm Grant/research support from: AbbVie, Roche, Consultant of: AbbVie, Sanofi Genzyme, Speakers bureau: AbbVie, Roche, Sanofi, Simon Stones Consultant of: I have been a paid consultant for Envision Pharma Group and Parexel. This does not relate to this abstract., Speakers bureau: I have been a paid speaker for Actelion and Janssen. These do not relate to this abstract., Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific
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| 8. |
- Gottenberg, J. E., et al.
(författare)
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Brief Report : Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity with Better Effectiveness of Abatacept: Results from the Pan-European Registry Analysis
- 2016
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191. ; 68:6, s. 1346-1352
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the role of rheumatoid factor (RF) status and anti-citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA). Methods We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR-DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM-RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated. Results We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease- and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69-0.90], P <0.001 and HR 0.78 [95% CI 0.68-0.90], P <0.001, respectively), compared to RF-negative and ACPA-negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P <0.001). Conclusion Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.
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| 9. |
- Lauper, K, et al.
(författare)
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A SYSTEMATIC REVIEW TO INFORM THE EULAR POINTS TO CONSIDER WHEN ANALYSING AND REPORTING COMPARATIVE EFFECTIVENESS RESEARCH WITH OBSERVATIONAL DATA IN RHEUMATOLOGY
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 123-124
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Comparative effectiveness studies using observational data are increasingly used. Despite their high potential for bias, there are no detailed recommendations on how these studies should best be analysed and reported in rheumatology.Objectives:To conduct a systematic literature review of comparative effectiveness research in rheumatology to inform the EULAR task force developing points to consider when analysing and reporting comparative effectiveness research with observational data.Methods:All original articles comparing drug effectiveness in longitudinal observational studies of ≥100 patients published in key rheumatology journals (Scientific Citation Index > 2) between 1.01.2008 and 25.03.2019 available in Ovid MEDLINE® were included. Titles and abstracts were screened by two reviewers for the first 1000 abstracts and independently checked to ensure sufficient agreement has been reached. The main information extracted included the types of outcomes used to assess effectiveness, and the types of analyses performed, focusing particularly on confounding and attrition.Results:9969 abstracts were screened, with 218 articles proceeding to full-text extraction (Figure 1), representing a number of rheumatic and musculoskeletal diseases. Agreement between the two reviewers for the first 1000 abstracts was 92.7% with a kappa of 0.6. The majority of the studies used several outcomes to evaluate effectiveness (Figure 2A). Most of the studies did not explain how they addressed missing data on the covariates (70%) (Figure 2B). When addressed (30%), 44% used complete case analysis and 10% last observation carried forward (LOCF). 25% of studies did not adjust for confounding factors and there was no clear correlation between the number of factors used to adjust and the number of participants in the studies. An important number of studies selected covariates using bivariate screening and/or stepwise selection. 86% of the studies did not acknowledge attrition (Figure 2C). When trying to correct for attrition (14%), 38% used non-responder (NR) imputation, 24% used LUNDEX1, a form of NR imputation, and 21% LOCF.Conclusion:Most of studies used multiple outcomes. However, the vast majority did not acknowledge missing data and attrition, and a quarter did not adjust for any confounding factors. Moreover, when attempting to account for attrition, several studies used methods which potentially increase bias (LOCF, complete case analysis, bivariate screening…). This systematic review confirms the need for the development of recommendations for the assessment and reporting of comparative drug effectiveness in observational data in rheumatology.References:[1]Kristensen et al. A&R. 2006 Feb;54(2):600-6.Acknowledgments:Support of the Standing Committee on Epidemiology and Health Services ResearchDisclosure of Interests:Kim Lauper: None declared, Joanna KEDRA: None declared, Maarten de Wit Grant/research support from: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Consultant of: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Speakers bureau: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Thomas Frisell: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Maria Jose Santos Speakers bureau: Novartis and Pfizer, Tanja Stamm Grant/research support from: AbbVie, Roche, Consultant of: AbbVie, Sanofi Genzyme, Speakers bureau: AbbVie, Roche, Sanofi, Simon Stones Consultant of: I have been a paid consultant for Envision Pharma Group and Parexel. This does not relate to this abstract., Speakers bureau: I have been a paid speaker for Actelion and Janssen. These do not relate to this abstract., Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific, Sytske Anne Bergstra: None declared, Delphine Courvoisier: None declared
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