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| 2. |
- Harrison, J.R., et al.
(författare)
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Overview of new MAST physics in anticipation of first results from MAST Upgrade
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- The mega amp spherical tokamak (MAST) was a low aspect ratio device (R/a = 0.85/0.65 ∼ 1.3) with similar poloidal cross-section to other medium-size tokamaks. The physics programme concentrates on addressing key physics issues for the operation of ITER, design of DEMO and future spherical tokamaks by utilising high resolution diagnostic measurements closely coupled with theory and modelling to significantly advance our understanding. An empirical scaling of the energy confinement time that favours higher power, lower collisionality devices is consistent with gyrokinetic modelling of electron scale turbulence. Measurements of ion scale turbulence with beam emission spectroscopy and gyrokinetic modelling in up-down symmetric plasmas find that the symmetry of the turbulence is broken by flow shear. Near the non-linear stability threshold, flow shear tilts the density fluctuation correlation function and skews the fluctuation amplitude distribution. Results from fast particle physics studies include the observation that sawteeth are found to redistribute passing and trapped fast particles injected from neutral beam injectors in equal measure, suggesting that resonances between the m = 1 perturbation and the fast ion orbits may be playing a dominant role in the fast ion transport. Measured D-D fusion products from a neutron camera and a charged fusion product detector are 40% lower than predictions from TRANSP/NUBEAM, highlighting possible deficiencies in the guiding centre approximation. Modelling of fast ion losses in the presence of resonant magnetic perturbations (RMPs) can reproduce trends observed in experiments when the plasma response and charge-exchange losses are accounted for. Measurements with a neutral particle analyser during merging-compression start-up indicate the acceleration of ions and electrons. Transport at the plasma edge has been improved through reciprocating probe measurements that have characterised a geodesic acoustic mode at the edge of an ohmic L-mode plasma and particle-in-cell modelling has improved the interpretation of plasma potential estimates from ball-pen probes. The application of RMPs leads to a reduction in particle confinement in L-mode and H-mode and an increase in the core ionization source. The ejection of secondary filaments following type-I ELMs correlates with interactions with surfaces near the X-point. Simulations of the interaction between pairs of filaments in the scrape-off layer suggest this results in modest changes to their velocity, and in most cases can be treated as moving independently. A stochastic model of scrape-off layer profile formation based on the superposition of non-interacting filaments is in good agreement with measured time-average profiles. Transport in the divertor has been improved through fast camera imaging, indicating the presence of a quiescent region devoid of filament near the X-point, extending from the separatrix to ψ n ∼ 1.02. Simulations of turbulent transport in the divertor show that the angle between the divertor leg on the curvature vector strongly influences transport into the private flux region via the interchange mechanism. Coherence imaging measurements show counter-streaming flows of impurities due to gas puffing increasing the pressure on field lines where the gas is ionised. MAST Upgrade is based on the original MAST device, with substantially improved capabilities to operate with a Super-X divertor to test extended divertor leg concepts. SOLPS-ITER modelling predicts the detachment threshold will be reduced by more than a factor of 2, in terms of upstream density, in the Super-X compared with a conventional configuration and that the radiation front movement is passively stabilised before it reaches the X-point. 1D fluid modelling reveals the key role of momentum and power loss mechanisms in governing detachment onset and evolution. Analytic modelling indicates that long legs placed at large major radius, or equivalently low at the target compared with the X-point are more amenable to external control. With MAST Upgrade experiments expected in 2019, a thorough characterisation of the sources of the intrinsic error field has been carried out and a mitigation strategy developed.
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| 4. |
- Glinatsi, D., et al.
(författare)
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Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: Study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study
- 2017
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. Methods/design: In a pragmatic, 80-160-week, multicenter, randomized, open-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1:1:1:1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i.a. glucocorticoids (arm 1A) or methotrexate + prednisolone p.o. (arm 1B), (2) methotrexate + certolizumab-pegol, (3) methotrexate + abatacept, or (4) methotrexate + tocilizumab. The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index (CDAI) remission at week 24. Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks. Patients not achieving sustained CDAI remission over 24 consecutive weeks, exit the study after 80 weeks. In part 2, patients are re-randomized to two different de-escalation strategies, either immediate or delayed (after 24 weeks) tapering, followed by cessation of study medication. All patients remain on stable doses of methotrexate. The primary clinical endpoint in part 2 is the proportion of patients in remission (CDAI ≤2.8) 24 weeks after initiating treatment de-escalation. Radiographic assessment will be performed regularly throughout the trial, and blood and urine samples will be stored in a biobank for later biomarker analyses. Discussion: NORD-STAR is the first investigator-initiated, randomized, early RA trial to compare (1) csDMARD and three different bDMARD therapies head to head and (2) two different de-escalation strategies. The trial has the potential to identify which treatment strategy to apply in early RA to achieve the best possible outcomes for both patients and society. Trial registration:NCT01491815and NCT02466581. Registered on 8 December 2011 and May 2015, respectively. EudraCT: 2011-004720-35 © 2017 The Author(s).
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| 5. |
- Kopic, S., et al.
(författare)
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Isolated pulmonary regurgitation causes decreased right ventricular longitudinal function and compensatory increased septal pumping in a porcine model
- 2017
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 221:3, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Longitudinal ventricular contraction is a parameter of cardiac performance with predictive power. Right ventricular (RV) longitudinal function is impaired in patients with free pulmonary regurgitation (PR) following corrective surgery for Tetralogy of Fallot (TOF). It remains unclear whether this is a consequence of the surgical repair, or whether it is inherent to PR. The aim of this study was to assess the relationship between longitudinal, lateral and septal pumping in a porcine model of isolated PR. Methods: Piglets were divided into a control (n = 8) group and a treatment (n = 12) group, which received a stent in the pulmonary valve orifice, inducing PR. After 2-3 months, animals were subjected to cardiac magnetic resonance imaging. A subset of animals (n = 6) then underwent percutaneous pulmonary valve replacement (PPVR) with follow-up 1 month later. Longitudinal, lateral and septal contributions to stroke volume (SV) were quantified by measuring volumetric displacements from end-diastole to end-systole in the cardiac short axis and long axis. Results: PR resulted in a lower longitudinal contribution to RV stroke volume, compared to controls (60.0 ± 2.6% vs. 73.6 ± 3.8%; P = 0.012). Furthermore, a compensatory increase in septal contribution to RVSV was observed (11.0 ± 1.6% vs. -3.1 ± 1.5%; P < 0.0001). The left ventricle (LV) showed counter-regulation with an increased longitudinal LVSV. Changes in RV longitudinal function were reversed by PPVR. Conclusion: These findings suggest that PR contributes to decreased RV longitudinal function in the absence of scarring from cardiac surgery. Measurement of longitudinal RVSV may aid risk stratification and timing for interventional correction of PR in TOF patients.
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| 7. |
- Arvidsson, Per M., et al.
(författare)
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Hemodynamic forces using four-dimensional flow MRI : An independent biomarker of cardiac function in heart failure with left ventricular dyssynchrony?
- 2018
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 315:6, s. 1627-1639
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Tidskriftsartikel (refereegranskat)abstract
- Patients with heart failure with left ventricular (LV) dyssynchrony often do not respond to cardiac resynchronization therapy (CRT), indicating that the pathophysiology is insufficiently understood. Intracardiac hemodynamic forces computed from four-dimensional (4-D) flow MRI have been proposed as a new measure of cardiac function. We therefore aimed to investigate how hemodynamic forces are altered in LV dyssynchrony. Thirty-one patients with heart failure and LV dyssynchrony and 39 control subjects underwent cardiac MRI with the acquisition of 4-D flow. Hemodynamic forces were computed using Navier-Stokes equations and integrated over the manually delineated LV volume. The ratio between transverse (lateral-septal and inferior-anterior) and longitudinal (apical-basal) forces was calculated for systole and diastole separately and compared with QRS duration, aortic valve opening delay, global longitudinal strain, and ejection fraction (EF). Patients exhibited hemodynamic force patterns that were significantly altered compared with control subjects, including loss of longitudinal forces in diastole (force ratio, control subjects vs. patients: 0.32 vs. 0.90, P < 0.0001) and increased transverse force magnitudes. The systolic force ratio was correlated with global longitudinal strain and EF (P < 0.01). The diastolic force ratio separated patients from control subjects (area under the curve: 0.98, P < 0.0001) but was not correlated to other dyssynchrony measures (P > 0.05 for all). Hemodynamic forces by 4-D flow represent a new approach to the quantification of LV dyssynchrony. Diastolic force patterns separate healthy from diseased ventricles. Different force patterns in patients indicate the possible use of force analysis for risk stratification and CRT implantation guidance. NEW & NOTEWORTHY In this report, we demonstrate that patients with heart failure with left ventricular dyssynchrony exhibit significantly altered hemodynamic forces compared with normal. Force patterns in patients mechanistically reflect left ventricular dysfunction on the organ level, largely independent of traditional dyssynchrony measures. Force analysis may help clinical decision making and could potentially be used to improve therapy outcomes.
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| 8. |
- Arvidsson, Per M., et al.
(författare)
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Left and right ventricular hemodynamic forces in healthy volunteers and elite athletes assessed with 4D flow magnetic resonance imaging
- 2017
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 312:2, s. 314-328
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Tidskriftsartikel (refereegranskat)abstract
- Intracardiac blood flow is driven by hemodynamic forces that are exchanged between the blood and myocardium. Previous studies have been limited to 2D measurements or investigated only left ventricular (LV) forces. Right ventricular (RV) forces and their mechanistic contribution to asymmetric redirection of flow in the RV have not been measured. We therefore aimed to quantify 3D hemodynamic forces in both ventricles in a cohort of healthy subjects, using magnetic resonance imaging 4D flow measurements. Twenty five controls, 14 elite endurance athletes, and 2 patients with LV dyssynchrony were included. 4D flow data were used as input for the Navier-Stokes equations to compute hemodynamic forces over the entire cardiac cycle. Hemodynamic forces were found in a qualitatively consistent pattern in all healthy subjects, with variations in amplitude. LV forces were mainly aligned along the apical-basal longitudinal axis, with an additional component aimed toward the aortic valve during systole. Conversely, RV forces were found in both longitudinal and short-axis planes, with a systolic force component driving a slingshot-like acceleration that explains the mechanism behind the redirection of blood flow toward the pulmonary valve. No differences were found between controls and athletes when indexing forces to ventricular volumes, indicating that cardiac force expenditures are tuned to accelerate blood similarly in small and large hearts. Patients’ forces differed from controls in both timing and amplitude. Normal cardiac pumping is associated with specific force patterns for both ventricles, and deviation from these forces may be a sensitive marker of ventricular dysfunction. Reference values are provided for future studies. New & Noteworthy Biventricular hemodynamic forces were quantified for the first time in healthy controls and elite athletes (n = 39). Hemodynamic forces constitute a slingshot-like mechanism in the right ventricle, redirecting blood flow toward the pulmonary circulation. Force patterns were similar between healthy subjects and athletes, indicating potential utility as a cardiac function biomarker.
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