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  • Collaboration, The PANDA, et al. (författare)
  • Feasibility studies of time-like proton electromagnetic form factors at PANDA at FAIR
  • 2016
  • Ingår i: European Physical Journal A. - : Springer Publishing Company. - 1434-6001 .- 1434-601X. ; 52:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Simulation results for future measurements of electromagnetic proton form factors at P ¯ ANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision with which the proton form factors can be determined is estimated. The signal channel p¯ p→ e+e- is studied on the basis of two different but consistent procedures. The suppression of the main background channel, i.e.p¯ p→ π+π-, is studied. Furthermore, the background versus signal efficiency, statistical and systematical uncertainties on the extracted proton form factors are evaluated using two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. However, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam conditions and detector performance.
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4.
  • Singh, B., et al. (författare)
  • Feasibility study for the measurement of pi N transition distribution amplitudes at (P)over-barANDA in (P)over-barp -> J/psi pi(0)
  • 2017
  • Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 95:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The exclusive charmonium production process in (P) over barp annihilation with an associated pi 0 meson (p) over barp -> J/psi pi(0) is studied in the framework of QCD collinear factorization. The feasibility of measuring this reaction through the J/psi -> e(+) e(-) decay channel with the AntiProton ANnihilation at DArmstadt ((P) over bar ANDA) experiment is investigated. Simulations on signal reconstruction efficiency as well as the background rejection from various sources including the (P) over barp -> pi(+)pi(-)pi(0) and (p) over barp -> J/psi pi(0)pi(0) reactions are performed with PANDAROOT, the simulation and analysis software framework of the (P) over bar ANDA experiment. It is shown that the measurement can be done at (P) over bar ANDA with significant constraining power under the assumption of an integrated luminosity attainable in four to five months of data taking at the maximum design luminosity.
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5.
  • Singh, B., et al. (författare)
  • Study of doubly strange systems using stored antiprotons
  • 2016
  • Ingår i: Nuclear Physics A. - : Elsevier. - 0375-9474 .- 1873-1554. ; 954, s. 323-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Bound nuclear systems with two units of strangeness are still poorly known despite their importance for many strong interaction phenomena. Stored antiprotons beams in the GeV range represent an unparalleled factory for various hyperon-antihyperon pairs. Their outstanding large production probability in antiproton collisions will open the floodgates for a series of new studies of systems which contain two or even more units of strangeness at the PANDA experiment at FAIR. For the first time, high resolution gamma-spectroscopy of doubly strange Lambda Lambda-hypernuclei will be performed, thus complementing measurements of ground state decays of Lambda Lambda-hypernuclei at J-PARC or possible decays of particle unstable hypernuclei in heavy ion reactions. High resolution spectroscopy of multistrange Xi(-) -atoms will be feasible and even the production of Omega(-) -atoms will be within reach. The latter might open the door to the vertical bar S vertical bar = 3 world in strangeness nuclear physics, by the study of the hadronic Omega(-) -nucleus interaction. For the first time it will be possible to study the behavior of Xi(+) in nuclear systems under well controlled conditions.
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6.
  • Erni, W., et al. (författare)
  • Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
  • 2013
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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7.
  • Singh, B. P., et al. (författare)
  • Experimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR
  • 2015
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (pi N) TDAs from (p) over barp -> e(+)e(-)pi(0) reaction with the future PANDA detector at the FAIR facility. At high center-of-mass energy and high invariant mass squared of the lepton pair q(2), the amplitude of the signal channel (p) over barp -> e(+)e(-)pi(0) admits a QCD factorized description in terms of pi N TDAs and nucleon Distribution Amplitudes (DAs) in the forward aid backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring (p) over barp -> e(+)e(-)pi(0) with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. (p) over barp -> pi(+)pi(-)pi(0) were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 < q(2) < 4.3 GeV2 and 5 < q(2) < 9 GeV2, respectively, with a neutral pion scattered in the forward or backward cone vertical bar cos theta(pi 0)vertical bar > 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 . 10(7) (1 . 10(7)) at low (high) q(2) for s = 5 GeV2, and of 1 . 10(8) (6 . 10(6)) at low (high) q(2) for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing pi N TDAs.
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8.
  • Bursill, D., et al. (författare)
  • Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout
  • 2019
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 78:11, s. 1592-1600
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. Methods A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. Results The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). Conclusion Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.
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  • Okada, S., et al. (författare)
  • First application of superconducting transition-edge sensor microcalorimeters to hadronic atom X-ray spectroscopy
  • 2016
  • Ingår i: Progress of Theoretical and Experimental Physics. - : Oxford University Press (OUP). - 2050-3911. ; 2016:9
  • Tidskriftsartikel (refereegranskat)abstract
    • High-resolution pionic atom X-ray spectroscopy was performed with an X-ray spectrometer based on a 240 pixel array of superconducting transition-edge sensor (TES) microcalorimeters at the φM1 beam line of the Paul Scherrer Institute. X-rays emitted by pionic carbon via the 4f → 3d transition and the parallel 4d → 3p transition were observed with a full width at half maximum energy resolution of 6.8 eV at 6.4 keV. The measured X-ray energies are consistent with calculated electromagnetic values which considered the strong interaction effect assessed via the Seki-Masutani potential for the 3p energy level, and favor the electronic population of two filled 1s electrons in the K-shell. Absolute energy calibration with an uncertainty of 0.1 eV was demonstrated under a high-rate hadron beam condition of 1.45 MHz. This is the first application of a TES spectrometer to hadronic atom X-ray spectroscopy and is an important milestone towards next-generation high-resolution kaonic atom X-ray spectroscopy.
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  • Doriese, W B, et al. (författare)
  • A practical superconducting-microcalorimeter X-ray spectrometer for beamline and laboratory science
  • 2017
  • Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 88:5
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe a series of microcalorimeter X-ray spectrometers designed for a broad suite of measurement applications. The chief advantage of this type of spectrometer is that it can be orders of magnitude more efficient at collecting X-rays than more traditional high-resolution spectrometers that rely on wavelength-dispersive techniques. This advantage is most useful in applications that are traditionally photon-starved and/or involve radiation-sensitive samples. Each energy-dispersive spectrometer is built around an array of several hundred transition-edge sensors (TESs). TESs are superconducting thin films that are biased into their superconducting-to-normal-metal transitions. The spectrometers share a common readout architecture and many design elements, such as a compact, 65 mK detector package, 8-column time-division-multiplexed superconducting quantum-interference device readout, and a liquid-cryogen-free cryogenic system that is a two-stage adiabatic-demagnetization refrigerator backed by a pulse-tube cryocooler. We have adapted this flexible architecture to mate to a variety of sample chambers and measurement systems that encompass a range of observing geometries. There are two different types of TES pixels employed. The first, designed for X-ray energies below 10 keV, has a best demonstrated energy resolution of 2.1 eV (full-width-at-half-maximum or FWHM) at 5.9 keV. The second, designed for X-ray energies below 2 keV, has a best demonstrated resolution of 1.0 eV (FWHM) at 500 eV. Our team has now deployed seven of these X-ray spectrometers to a variety of light sources, accelerator facilities, and laboratory-scale experiments; these seven spectrometers have already performed measurements related to their applications. Another five of these spectrometers will come online in the near future. We have applied our TES spectrometers to the following measurement applications: synchrotron-based absorption and emission spectroscopy and energy-resolved scattering; accelerator-based spectroscopy of hadronic atoms and particle-induced-emission spectroscopy; laboratory-based time-resolved absorption and emission spectroscopy with a tabletop, broadband source; and laboratory-based metrology of X-ray-emission lines. Here, we discuss the design, construction, and operation of our TES spectrometers and show first-light measurements from the various systems. Finally, because X-ray-TES technology continues to mature, we discuss improvements to array size, energy resolution, and counting speed that we anticipate in our next generation of TES-X-ray spectrometers and beyond.
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  • Hashimoto, T., et al. (författare)
  • Beamline test of a transition-edge-sensor spectrometer in preparation for kaonic-atom measurements
  • 2017
  • Ingår i: IEEE Transactions on Applied Superconductivity. - 1051-8223. ; 27:4
  • Tidskriftsartikel (refereegranskat)abstract
    • We are developing a new technique to apply transition-edge sensors (TESs) to X-ray spectroscopy of exotic atoms, especially of kaonic atoms. To demonstrate the feasibility of this pioneering project, performance of a TES-based X-ray detector was evaluated in pion- and kaon-beam environments at particle accelerators.We successfully observed X-rays from pionic-carbon atoms with a resolution as good as 7 eV FWHM at 6 keV. Also at a kaon beamline, we confirmed that the TES spectrometer will be able to achieve our resolution goal, 6 eV, in our first scientific campaign to measure X-rays from kaonic-helium atoms.
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  • Hashimoto, T., et al. (författare)
  • Kaonic-Atom X-ray Spectroscopy with Superconducting Microcalorimeters
  • 2017
  • Ingår i: Proceedings of the 12th International Conference on Hypernuclear and Strange Particle Physics (HYP2015). - 9784890271221 ; 17
  • Konferensbidrag (refereegranskat)abstract
    • We will measure kaonic helium X-rays using transition-edge-sensor microcalorimeters, TES, in the J-PARC hadron experimental facility. To demonstrate the feasibility of the experiment, we performed a measurement of pionic carbon X-rays at PSI, where an excellent FWHM energy resolution of 7 eV at 6.4 keV was achieved. We also evaluated the expected TES performance in the kaon beam at J-PARC. The simulation results show that the TES spectrometer would work with a good energy resolution, and clear peaks of kaonic helium X-rays would be observed on a reasonably suppressed background.
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  • Sumpter, N. A., et al. (författare)
  • Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout
  • 2023
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:5, s. 816-825
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. Methods. A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. Results. The PRS was associated with earlier age at gout onset in men (beta = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; beta = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; beta = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (beta = 0.07 [95% CI -2.32, 2.45] in European women; beta = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; beta -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (beta = -2.42 [95% CI -3.37, -1.46] and beta = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (beta = -1.79 [95% CI -4.74, 1.16]). Conclusion. Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.
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  • Bursill, D., et al. (författare)
  • Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout
  • 2019
  • Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X. ; 71:3, s. 427-434
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. Methods Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. Results There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (>= 80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. Conclusion Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.
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  • Hetland, M. L., et al. (författare)
  • Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
  • 2020
  • Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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  • Kern, Jan, et al. (författare)
  • Taking snapshots of photosynthetic water oxidation using femtosecond X-ray diffraction and spectroscopy
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4371-
  • Tidskriftsartikel (refereegranskat)abstract
    • The dioxygen we breathe is formed by light-induced oxidation of water in photosystem II. O-2 formation takes place at a catalytic manganese cluster within milliseconds after the photosystem II reaction centre is excited by three single-turnover flashes. Here we present combined X-ray emission spectra and diffraction data of 2-flash (2F) and 3-flash (3F) photosystem II samples, and of a transient 3F' state (250 mu s after the third flash), collected under functional conditions using an X-ray free electron laser. The spectra show that the initial O-O bond formation, coupled to Mn reduction, does not yet occur within 250 mu s after the third flash. Diffraction data of all states studied exhibit an anomalous scattering signal from Mn but show no significant structural changes at the present resolution of 4.5 angstrom. This study represents the initial frames in a molecular movie of the structural changes during the catalytic reaction in photosystem II.
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20.
  • Uhlig, Jens, et al. (författare)
  • Table-Top Ultrafast X-Ray Microcalorimeter Spectrometry for Molecular Structure
  • 2013
  • Ingår i: Physical Review Letters. - 1079-7114. ; 110:13
  • Tidskriftsartikel (refereegranskat)abstract
    • This work presents an x-ray absorption measurement by use of ionizing radiation generated by a femtosecond pulsed laser source. The spectrometer was a microcalorimetric array whose pixels are capable of accurately measuring energies of individual radiation quanta. An isotropic continuum x-ray spectrum in the few-keV range was generated from a laser plasma source with a water-jet target. X rays were transmitted through a ferrocene powder sample to the detector, whose pixels have average photon energy resolution Delta E = 3.14 eV full-width-at-half-maximum at 5.9 keV. The bond distance of ferrocene was retrieved from this first hard-x-ray absorption fine-structure spectrum collected with an energy-dispersive detector. This technique will be broadly enabling for time-resolved observations of structural dynamics in photoactive systems. DOI: 10.1103/PhysRevLett.110.138302
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21.
  • Ullom, J. N., et al. (författare)
  • X-ray absorption spectroscopy of iron tris (bipyridine) using superconducting microcalorimeters
  • 2014
  • Ingår i: 2014 Conference on Lasers and Electro-Optics (CLEO) : Laser Science to Photonic Applications - Laser Science to Photonic Applications. - 9781557529992 ; , s. 1-2
  • Konferensbidrag (refereegranskat)abstract
    • We are developing a tabletop apparatus for time-resolved X-ray absorption spectroscopy. Short X-ray pulses are generated by focusing a pulsed 800 nm laser onto a water jet target. X-rays that pass through a sample of interest are detected using energy-resolving superconducting microcalorimeter detectors. We have successfully observed EXAFS features from iron tris(bipyridine) in a water solution. We discuss details of the microcalorimeter spectra and describe the steps that remain before the intrinsic sub-picosecond sensitivity of the apparatus can be realized.
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22.
  • Albusoda, A., et al. (författare)
  • A fresh look at IBS-opportunities for systems medicine approaches
  • 2017
  • Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 29:3
  • Tidskriftsartikel (refereegranskat)abstract
    • NeuroGUT is a EU-funded initial training network (ITN) of 14 research projects in neurogastroenterology that have employed an equal number of early-stage researchers. Neurogut trainees haveamong other activitiesattended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and were asked to critically review and evaluate the current knowledge on IBS for their respective research activities, and to state what they were missing. Most appreciated were the topics brain imaging of gut activity, the role of the gut microbiota, the pharmacology of gut functions, the IBS-IBD interrelation, the new Rome IV criteria, the role of gas, and the placebo response in functional disorders. Missed were more detailed coverage of high-resolution manometry, functional brain imaging, advanced systems medicine approaches and bioinformatics technology, better sub-classification of IBS patients, and the development of disease biomarkers, extended at the molecular (genetic/epigenetic, proteonomic) level. They summarize that despite excellent specialized research, there is a gap open that should be filled with systems medicine. For this, it would be necessary that medical research learns even more from the data sciences and other basic disciplines, for example, information technology and system biology, and also welcomes a change in paradigm that enhances open sharing of data, information, and resources.
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23.
  • Dures, E., et al. (författare)
  • 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - 0003-4967 .- 1468-2060.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs.Methods A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs.Results Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making.Conclusions These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.
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24.
  • Fullagar, Wilfred K., et al. (författare)
  • Beating Darwin-Bragg losses in lab-based ultrafast X-ray experiments
  • 2017
  • Ingår i: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 4:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of low temperature thermal detectors for avoiding Darwin-Bragg losses in lab-based ultrafast experiments has begun. An outline of the background of this new development is offered, showing the relevant history and initiative taken by this work.
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26.
  • Hashimoto, T., et al. (författare)
  • Measurements of Strong-Interaction Effects in Kaonic-Helium Isotopes at Sub-eV Precision with X-Ray Microcalorimeters
  • 2022
  • Ingår i: Physical Review Letters. - 1079-7114. ; 128:11
  • Tidskriftsartikel (refereegranskat)abstract
    • We have measured the 3d→2p transition x rays of kaonic 3He and 4He atoms using superconducting transition-edge-sensor microcalorimeters with an energy resolution better than 6 eV (FWHM). We determined the energies to be 6224.5±0.4(stat)±0.2(syst) eV and 6463.7±0.3(stat)±0.1(syst) eV, and widths to be 2.5±1.0(stat)±0.4(syst) eV and 1.0±0.6(stat)±0.3(stat) eV, for kaonic 3He and 4He, respectively. These values are nearly 10 times more precise than in previous measurements. Our results exclude the large strong-interaction shifts and widths that are suggested by a coupled-channel approach and agree with calculations based on optical-potential models.
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27.
  • Kunnus, Kristjan, et al. (författare)
  • Quantifying the Steric Effect on Metal-Ligand Bonding in Fe Carbene Photosensitizers with Fe 2p3d Resonant Inelastic X-ray Scattering
  • 2022
  • Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 61:4, s. 1961-1972
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the electronic structure and chemical bonding of transition metal complexes is important for improving the function of molecular photosensitizers and catalysts. We have utilized X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS) at the Fe L3 edge to investigate the electronic structure of two Fe N-heterocyclic carbene complexes with similar chemical structures but different steric effects and contrasting excited-state dynamics: [Fe(bmip)2]2+ and [Fe(btbip)2]2+, bmip = 2,6-bis(3-methyl-imidazole-1-ylidine)pyridine and btbip = 2,6-bis(3-tert-butyl-imidazole-1-ylidene)pyridine. In combination with charge transfer multiplet and ab initio calculations, we quantified how changes in Fe-carbene bond length due to steric effects modify the metal-ligand bonding, including σ/πdonation and πback-donation. We find that σ donation is significantly stronger in [Fe(bmip)2]2+, whereas the πback-donation is similar in both complexes. The resulting stronger ligand field and nephelauxetic effect in [Fe(bmip)2]2+ lead to approximately 1 eV destabilization of the quintet metal-centered 5T2g excited state compared to [Fe(btbip)2]2+, providing an explanation for the absence of a photoinduced 5T2g population and a longer metal-to-ligand charge-transfer excited-state lifetime in [Fe(bmip)2]2+. This work demonstrates how combined modeling of XAS and RIXS spectra can be utilized to understand the electronic structure of transition metal complexes governed by correlated electrons and donation/back-donation interactions.
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28.
  • Lend, K., et al. (författare)
  • Sex differences in remission rates over 24 weeks among three different biological treatments compared to conventional therapy in patients with early rheumatoid arthritis (NORD-STAR): a post-hoc analysis of a randomised controlled trial
  • 2023
  • Ingår i: The Lancet Rheumatology. - 2665-9913. ; 4:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Rheumatoid arthritis is a chronic inflammatory disease with a well-recognised female preponderance. In this post-hoc analysis of the NORD-STAR trial, we aimed to examine sex differences in remission rates with three different biological treatments combined with methotrexate versus active conventional treatment over 24 weeks, in patients with early rheumatoid arthritis. Methods: NORD-STAR was a multicentre, investigator-initiated, assessor-blinded, phase 4, randomised, controlled trial of early rheumatoid arthritis, done in Denmark, Finland, Iceland, Norway, Sweden, and the Netherlands. Newly diagnosed patients, naive to disease-modifying antirheumatic drugs, aged 18 years or older with early rheumatoid arthritis and with a symptom duration less than 24 months were randomly assigned (1:1:1:1) to receive active conventional treatment, certolizumab-pegol, abatacept, or tocilizumab. Sex was reported in case report forms by study physicians or by study nurses. Data on gender were not collected. Remission outcomes were analysed with logistic generalised estimating equations (GEE), using a logit link and exchangeable correlation matrix. The model included treatment, time, sex, and the relevant interactions. For this post-hoc analysis, the co-primary outcomes were differences in Clinical Disease Activity Index (CDAI) remission (CDAI score ≤2·8) between sexes over time and at week 24, assessed with interaction terms (men vs women within each treatment comparison) and using active conventional treatment as the reference. We present adjusted average marginal differences in remission rates (risk differences) with 95% CIs. Findings: Between Dec 14, 2012, and Dec 11, 2018, 812 patients were enrolled and randomly assigned; 217 received active conventional treatment, 203 received certolizumab-pegol, 204 received abatacept, and 188 received tocilizumab. All 812 patients were included in this analysis; 561 (69%) were women and 251 (31%) were men. Observed CDAI remission rates at 24 weeks were numerically higher among men than among women despite comparable disease activity at baseline (55% vs 50% with active conventional treatment, 57% vs 52% with certolizumab-pegol, 65% vs 51% with abatacept, and 61% vs 40% with tocilizumab). In the adjusted analysis, with active conventional treatment as the reference, the only significant difference between men and women was in the tocilizumab group (pinteraction=0·015); men in the tocilizumab group had a higher probability of CDAI remission, on average over time, than did men in the active conventional treatment group (0·12; 95% CI 0·00 to 0·23), whereas women in the tocilizumab group had a lower probability of remission than did women in the active conventional treatment group (–0·05, 95% CI –0·13 to 0·02). Interpretation: Numerically higher remission rates were observed in men than in women in all four treatment groups at week 24, suggesting that this generalised sex difference is not related to the treatment. The difference between men and women was significantly greater with tocilizumab, an interleukin (IL)-6 inhibitor, than with active conventional treatment, suggesting a possible additional sex-based effect specific for IL-6 blockade. Funding: None. © 2022 Elsevier Ltd
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31.
  • Pfeffer, M. G., et al. (författare)
  • Palladium versus Platinum: The Metal in the Catalytic Center of a Molecular Photocatalyst Determines the Mechanism of the Hydrogen Production with Visible Light
  • 2015
  • Ingår i: Angewandte Chemie-International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 54:17, s. 5044-5048
  • Tidskriftsartikel (refereegranskat)abstract
    • To develop highly efficient molecular photocatalysts for visible light-driven hydrogen production, a thorough understanding of the photophysical and chemical processes in the photocatalyst is of vital importance. In this context, in situ X-ray absorption spectroscopic (XAS) investigations show that the nature of the catalytically active metal center in a (N boolean AND N)MCl2 (M=Pd or Pt) coordination sphere has a significant impact on the mechanism of the hydrogen formation. Pd as the catalytic center showed a substantially altered chemical environment and a formation of metal colloids during catalysis, whereas no changes of the coordination sphere were observed for Pt as catalytic center. The high stability of the Pt center was confirmed by chloride addition and mercury poisoning experiments. Thus, for Pt a fundamentally different catalytic mechanism without the involvement of colloids is confirmed.
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33.
  • Uhlig, Jens, et al. (författare)
  • High-resolution X-ray emission spectroscopy with transition-edge sensors: present performance and future potential.
  • 2015
  • Ingår i: Journal of Synchrotron Radiation. - 1600-5775. ; 22:Pt 3, s. 766-775
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray emission spectroscopy (XES) is a powerful element-selective tool to analyze the oxidation states of atoms in complex compounds, determine their electronic configuration, and identify unknown compounds in challenging environments. Until now the low efficiency of wavelength-dispersive X-ray spectrometer technology has limited the use of XES, especially in combination with weaker laboratory X-ray sources. More efficient energy-dispersive detectors have either insufficient energy resolution because of the statistical limits described by Fano or too low counting rates to be of practical use. This paper updates an approach to high-resolution X-ray emission spectroscopy that uses a microcalorimeter detector array of superconducting transition-edge sensors (TESs). TES arrays are discussed and compared with conventional methods, and shown under which circumstances they are superior. It is also shown that a TES array can be integrated into a table-top time-resolved X-ray source and a soft X-ray synchrotron beamline to perform emission spectroscopy with good chemical sensitivity over a very wide range of energies.
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34.
  • Ullom, J N (creator_code:cre_t)
  • X-ray Spectrometer
  • 2019
  • Patent (övrigt vetenskapligt/konstnärligt)abstract
    • An x-ray spectrometer includes: an x-ray plasma source that produces first x-rays; an x-ray optic in optical communication with the x-ray plasma source and that: receives the first x-rays from the x-ray plasma source; focuses the first x-rays to produce second x-rays; and communicates the second x-rays to a sample that produces product x-rays in response to receipt of the second x-rays and second light; and a microcalorimeter array detector in optical communication with the sample and that receives the product x-rays from the sample.
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37.
  • Bauer, K., et al. (författare)
  • Welcome message from the PADE chairs
  • 2013
  • Ingår i: Welcome message from the PADE chairs  (Editorial). - : IEEE Computer Society. - 9781479905379 ; , s. lxi-lxii
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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38.
  • Biasin, Elisa, et al. (författare)
  • Femtosecond X-Ray Scattering Study of Ultrafast Photoinduced Structural Dynamics in Solvated[Co(terpy)2]2$
  • 2016
  • Ingår i: Physical Review Letters. - : American Physical Society (APS). - 1079-7114 .- 0031-9007. ; 117:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the structural dynamics of photoexcited [Co(terpy)2]2+ in an aqueous solution with ultrafast x-ray diffuse scattering experiments conducted at the Linac Coherent Light Source. Through direct comparisons with density functional theory calculations, our analysis shows that the photoexcitation event leads to elongation of the Co-N bonds, followed by coherent Co-N bond length oscillations arising from the impulsive excitation of a vibrational mode dominated by the symmetrical stretch of all six Co-N bonds. This mode has a period of 0.33 ps and decays on a subpicosecond time scale. We find that the equilibrium bond-elongated structure of the high spin state is established on a single-picosecond time scale and that this state has a lifetime of ∼7 ps.
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39.
  • Dijkshoorn, B, et al. (författare)
  • PROFOUND ANTICOAGULANT EFFECTS OF INITIAL ANTIRHEUMATIC TREATMENTS IN EARLY RHEUMATOID ARTHRITIS PATIENTS: A NORD-STAR SPIN-OFF STUDY
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 40-41
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Patients with rheumatoid arthritis (RA) are at an increased risk of venous thromboembolism. Thus far, there have not been any comparative studies investigating the effects of initial antirheumatic treatments in (very) early RA patients.ObjectivesTo assess the effects of different initial treatments on hemostatic parameters in patients with early RA.MethodsNORD-STAR is an international, multicentre, open-label, assessor-blinded, phase 4 study where patients with newly diagnosed RA started methotrexate (MTX) and were randomised 1:1:1:1 to a) conventional treatment (either prednisolone tapered to 5mg/day, or sulfasalazine combined with hydroxychloroquine and intra-articular corticosteroids), b) certolizumab pegol, c) abatacept, d) tocilizumab1. This study is a spin-off from the main NORD-STAR study extensively investigating hemostatic system in 24 per protocol consecutive Dutch participants at baseline, 12 weeks and 24 weeks after the start of the treatment. Statistical analysis was done using paired samples t-test in SPSS version 28.ResultsThe mean age of investigated patients was 51.8 (± 12.7) years and 58.3% were female. At baseline patients had an average DAS28 score of 4.6 (± 0.9) and had elevated levels of investigated coagulation biomarkers: Factor 1 + 2, fibrinogen, D-dimer and parameters of the two global hemostatic assays, i.e. endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). These biomarkers decreased significantly at 12 and 24 weeks in patients in all groups (Table 1). Overall fibrinolytic potential (OFP) was decreased and clot lysis time (CLT) was prolonged at baseline, demonstrating impaired fibrinolytic activity in early RA. The reduction of coagulation parameters was significantly higher in biological treatment arms in comparison to the standard MTX treatment arm. In addition, tocilizumab was more effective compared to certolizumab and abatacept, (Figure 1), which was expected considering the direct inhibitory effect of this drug on the IL-6 synthesis and consequently the coagulation activation as well. After 24 weeks of treatment with methotrexate and tocilizumab, the average fibrinogen of patients was reduced by 63% vs 31% and 36% in the certolizumab and abatacept groups, respectively. The changes in DAS-28 and the changes in fibrinogen had a correlation of 0.385 which did not reach statistical significance.Table 1.Measurements are marked with * if p<0.05, ** if p<0.01 and *** if p<0.001BaselineW12W24Factor 1 + 2 (pmol/L)270.25 (149.4)190.36 (108.6)**179.52 (85.3)***Fibrinogen (g/L)4.64 (1.5)3.61 (1.6)**2.63 (1.2)***D-dimer (mg/L)2.17 (3.0)0.33 (0.23)**0.29 (0.2)**OHP (Abs-sum)157.38 (64.9)120.62 (68.7)*100.49 (53.8)***OCP (Abs-sum)369.52 (58.8)305.04 (101.7)*275.91 (83.1)***OFP (%)57.97 (13.1)63.20 (12.7)*65.25 (11.4)***Lag time (s)304.5 (71.1)306.8 (71.8)312.7 (65.4)Slope0.07 (0.02)0.066 (0.03)0.094 (0.12)Max Abs1.17 (0.3)1.00 (0.4)*0.91 (0.3)**CLT (s)1405 (356)1317 (377)1231 (320)**ETP (nM*min)1480 (471)1395 (395)*1337 (429)*Peak (nM)231 (78)223 (68)223 (74)Lagtime (min)4.06 (2.1)3.28 (1.2)**2.87 (1.0)***ttPeak (min)7.40 (2.2)6.61 (1.5)*6.13 (1.4)**Figure 1.ConclusionOur results indicate an enhanced coagulation and fibrinolytic impairment in newly diagnosed RA patients. Effective antirheumatic treatments reduce this hemostatic imbalance, with significantly more pronounced effects of biologic drugs compared to conventional (MTX+glucocorticoids) treatment.References[1]Hetland M et al. BMJ. 2020Disclosure of InterestsBas Dijkshoorn: None declared, Aleksandra Antovic: None declared, Daisy Vedder: None declared, Anna Rudin: None declared, Dan Nordström Speakers bureau: Novartis, UCB, Consultant of: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, UCB, Björn Gudbjornsson Speakers bureau: Amgen and Novartis - not related to this work, Consultant of: Novartis - not related to this work, Kristina Lend: None declared, Till Uhlig Speakers bureau: Grünenthal, Novartis, Consultant of: Grünenthal, Novartis, Grant/research support from: NORDFORSK, Espen A Haavardsholm Consultant of: Pfizer, AbbVie, Celgene, Novartis, Janssen, Gilead, Eli-Lilly, UCB, Grant/research support from: NORDFORSK, Norwegian Regional Health Authorities, South-Eastern Norway Regional Health Authority, Gerdur Gröndal: None declared, Merete Lund Hetland Consultant of: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Marte Heiberg: None declared, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Orion, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, Amgen, BMS, Merck, Celgene and Novartis, Kim Hørslev-Petersen: None declared, Jon Lampa Speakers bureau: Pfizer, Janssen, Novartis, Ronald van Vollenhoven Speakers bureau: Abbvie, Galapagos, GSK, Janssen, Pfizer, R-Pharma, UCB, Consultant of: Abbvie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pifzer, UCB, Grant/research support from: BMS, GSK, UCB, Michael Nurmohamed Speakers bureau: Abbvie, Janssen, Celgene, Consultant of: Abbvie, Grant/research support from: Abbvie, Amgen, Pfizer, Galapagos, BMS.
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45.
  • Haldrup, K., et al. (författare)
  • Guest-Host Interactions Investigated by Time-Resolved X-ray Spectroscopies and Scattering at MHz Rates: Solvation Dynamics and Photoinduced Spin Transition in Aqueous Fe(bipy)(3)(2+)
  • 2012
  • Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 116:40, s. 9878-9887
  • Tidskriftsartikel (refereegranskat)abstract
    • We have studied the photoinduced low spin (LS) to high spin (HS) conversion of [Fe(bipy)(3)](2+) in aqueous solution. In a laser pump/X-ray probe synchrotron setup permitting simultaneous, time-resolved X-ray diffuse scattering (XDS) and X-ray spectroscopic measurements at a 3.26 MHz repetition rate, we observed the interplay between intramolecular dynamics and the intermolecular caging solvent response with better than 100 ps time resolution. On this time scale, the initial ultrafast spin transition and the associated intramolecular geometric structure changes are long completed, as is the solvent heating due to the initial energy dissipation from the excited HS molecule. Combining information from X-ray emission spectroscopy and scattering, the excitation fraction as well as the temperature and density changes of the solvent can be closely followed on the subnanosecond time scale of the HS lifetime, allowing the detection of an ultrafast change in bulk solvent density. An analysis approach directly utilizing the spectroscopic data in the XDS analysis effectively reduces the number of free parameters, and both combined permit extraction of information about the ultrafast structural dynamics of the caging solvent, in particular, a decrease in the number of water molecules in the first solvation shell is inferred, as predicted by recent theoretical work.
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  • Hifinger, M, et al. (författare)
  • Economic considerations and patients' preferences affect treatment selection for patients with rheumatoid arthritis: a discrete choice experiment among European rheumatologists
  • 2017
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:1, s. 126-132
  • Tidskriftsartikel (refereegranskat)abstract
    • To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis.MethodsIn a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists.ResultsResponses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients’ preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK.ConclusionsOverall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals.
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