| 1. |
- Hieronymus, F., et al.
(författare)
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Determining maximal achievable effect sizes of antidepressant therapies in placebo-controlled trials
- 2021
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 144:3, s. 300-309
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Tidskriftsartikel (refereegranskat)abstract
- Objective Antidepressants outperform placebo with an effect size of around 0.30. It has been suggested that effect sizes as high as 0.875 are necessary for a minimal clinically important difference. Whether such effect sizes are achievable in placebo-controlled trials is unknown. Therefore, we aimed to assess what effect sizes are theoretically achievable in placebo-controlled trials of antidepressants. Methods Patient-level analyses comparing Hamilton Depression Rating Scale (HDRS-17) outcomes for simulated antidepressant therapies to placebo-treated participants (n = 2201) from clinical trials of selective serotonin reuptake inhibitors. Results An optimally effective antidepressant, where all treated participants achieve HDRS-17 scores comparable to those displayed by healthy volunteers (remission-type model), had a maximum effect size of 1.75, with a mean difference of 11.6 points on the HDRS-17. In simulations where patients received an additional 50% symptom reduction over that obtained with placebo (improvement-type model), the maximum effect size was 1.08 with a mean HDRS-17 difference of 7.2. When adjusting for normal rates of treatment discontinuation, maximum effect sizes were 1.10 (remission-type model) and 0.76 (improvement-type model) with HDRS-17 mean differences of 8.8 and 5.6, respectively. Conclusions Three methodological issues (i) a large and variable placebo response, (ii) a high rate of dropout and (iii) HDRS-17-ratings significantly larger than zero in healthy volunteers, reduce the degree of treatment-placebo separation achievable in depression trials. Assuming that those who discontinue treatment have only partial response, even a highly effective antidepressant would have difficulties surpassing such effect size cut-offs as have been suggested to signify a minimal clinically important difference.
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| 2. |
- Bazargan, Mohsen, et al.
(författare)
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Elastic Wave Propagation in a Stainless-Steel Standard and Verification of a COMSOL Multiphysics Numerical Elastic Wave Toolbox
- 2022
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Ingår i: Resources. - : MDPI AG. - 2079-9276. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory-based elastic wave measurements are commonly used to quantify the seismic properties of Earth’s crust and upper mantle. Different types of laboratory apparatuses are available for such measurements, simulating seismic properties at different pressure and temperature. To complement such laboratory measurements, we present a numerical toolbox to investigate the seismic properties of rock samples. The numerical model is benchmarked against experimental results from a multi-anvil apparatus, using measurements of a stainless steel calibration standard. Measured values of the mean compressional- and shear-wave velocities at room conditions of the steel block were 6.03 km/s and 3.26 km/s, respectively. Calculated numerical results predicted 6.12 km/s and 3.30 km/s for compressional and shear-wave velocities. Subsequently, we measured Vp and Vs up to 600 MPa hydrostatic confining pressure and 600 °C. These measurements, at pressure and temperature, were then used as the basis to predict numerical wave speeds. There is, in general, good agreement between measurement and predicted numerical results. The numerical method presented in this study serves as a flexible toolbox, allowing for the easy setup of different model geometries and composite materials.
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| 3. |
- Bazargan, Mohsen, et al.
(författare)
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Evolution of the statistical distribution of crystal orientations in time- and space-varying viscous flows
- 2019
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Ingår i: Geophysical Journal International. - : Oxford University Press (OUP). - 0956-540X .- 1365-246X. ; 218:2, s. 773-786
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Tidskriftsartikel (refereegranskat)abstract
- Magmas and other viscously deforming fluids in the Earth frequently contain embedded crystals or other solid inclusions. These inclusions generally rotate about their own axis and, under certain conditions, align themselves in a direction dictated by the details of the flow. This rotational behaviour has been studied extensively for homogeneous flows. Here, we couple the crystal rotation dynamics with the fluid mechanical Navier-Stokes equations for the large-scale flow, thus allowing the analysis of crystal rotations in settings that are variable in both space and time. The solution is valid provided that the intercrystal spacing is sufficiently large to preclude interaction between crystals. Additionally, we derive an evolution equation for the probability density function (PDF) of crystal orientations based on the fundamental concept of conservation of generic properties in continuum mechanics. The resulting system of equations is extensively tested against previous analytical and numerical solutions. Given the focus on method validation, we limit the fluid mechanics to simple systems with analytical solutions for the velocity field. Even for the simple examples computed, all of which are characterized by fluid flow that is constant in time, the crystal orientation patterns are spatially complex and change in time. Pressure-driven flow in a channel results in coherent bands of crystal orientations with band thickness decreasing towards the channel walls. In corner flow constrained by two mutually perpendicular walls, the pattern of crystal orientations does not exhibit any significant similarity with the flow field. Given that there is no local one-to-one correspondence between the flow and the PDF pattern, a combined and larger-scale solution of the two systems is generally required. The simple flow examples shown demonstrate the viability of this new approach. Application to more complex flow geometries which may commonly occur in nature is deferred to future studies.
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| 4. |
- Bazargan, Mohsen, et al.
(författare)
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Joint pressure and temperature effects on seismic properties of gneisses and amphibolite
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Pressure and temperature change simultaneously in the Earth’s crust from surface to depth. Joint pressure and temperature changes influence many different physical properties. There are many studies on samples at elevated pressure, where the influence of open cracks, fractures, voids and pores have been studied. Applying confining pressure has a direct influence on crack closure, and this influence on dynamic properties (density and elastic modulus, bulk, shear and young’s) of rocks above 200 MPa is assumed linear with the linear increase in wave speed. This is because it is generally assumed that most cracks are closed above 200 MPa, which in nature would correspond to a depth of ~7-8 km. However, from the KTB deep drilling well in Germany, it is known that fluid-filled fractures and pores can remain open until 8 to 9 km depth. Applying temperature can affect the dynamic properties of rock by thermal expansion, possibly reopening cracks that were closed at pressures >200 MPa, and thermally expanding grains. This influence is also assumed to be linear at a temperature below partial melting, and in the absence of phase transitions. A similar effect has been observed by a number of research groups during laboratory experiments and calculating seismic velocity results under 600 MPa confining pressure and 600oC temperature. In this work, an effort has been made to mathematically investigate the influence of temperature and pressure on the seismic properties (velocity of pressure and shear waves, density and Poisson’s ratio) of crystalline rocks, measured during laboratory experiments. Elastic wave speeds, moduli and density are increasing as a function of pressure and decreasing as a function of temperature. However, these pressure and temperature-related changes are shown to be nonlinear from room conditions up to 600oC and 600 MPa. In this presentation, we focus on non-linear changes mainly in the high-pressure portion of the velocity as a function of pressure (>200 MPa). When confining pressure is applied, measured P- and S- waves show an increase in velocity and decrease in anisotropy. However, the effect of temperature on measured P- and S- waves show a decrease in velocity and increases in anisotropy. These changes are not very different from linear, but it is not possible to fit velocity as a function of pressure or temperature with linear mathematical functions. The implications of non-linear relationships between pressure, temperature and elastic wave speeds are discussed in this presentation.
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| 5. |
- Bazargan, Mohsen, et al.
(författare)
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Numerical, predictive and experimental study on elastic wave propagation in crystalline rocks
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Calculating anisotropy and better understanding this physical effect is one of the main challenges in geophysics, whether in the size of the field or micro scale. one of the very common methods of calculating seismic anisotropy is to take into account the bulk properties of the material, in a micro-scale, this is based on the average value of Crystallographic preferred orientation measurements by using, for example, Scanning Electron Microscopy to operate - Electron backscatter diffraction method.
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| 6. |
- Bergbauer, S., et al.
(författare)
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Thermal stress evolution in cooling pluton environments of different geometries
- 1998
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 25:5, s. 707-71-
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Tidskriftsartikel (refereegranskat)abstract
- Thermoelastic displacement potentials and fast Fourier transforms can be combined to rapidly calculate the thermal stresses in 2-D for plutons that cool by conduction. First, temperature distributions over time are computed by solving the diffusion equation. Thermal stresses are then obtained using thermoelastic stress potentials. This method can be applied to a broad range of pluton geometries and initial conditions, and requires far less computation time than finite difference or finite element analyses. Results of 2-D analyses show that pluton geometry strongly influences the thermal stresses that occur in a cooling pluton. Thermal stresses of several tens of MPa arise during cooling and are highest at the corners or where the intrusion is thin. The most tensile stress is greater inside a pluton than in the host rock. Moreover, the orientation of the most tensile stress in a cooling pluton generally changes over time. This could result in multiple fracture sets, which would significantly affect the mechanical and hydraulic behavior of a pluton.
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| 7. |
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| 8. |
- Eken, Tuna, 1978-, et al.
(författare)
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S and P velocity heterogeneities within the upper mantle below the Baltic Shield
- 2008
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Ingår i: Tectonophysics. - : Elsevier BV. - 0040-1951 .- 1879-3266. ; 462:1-4, s. 109-124
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Tidskriftsartikel (refereegranskat)abstract
- Upper mantle structure beneath the Baltic (Fennoscandian) Shield is investigated using non-linear tomographic inversion of relative arrival-time residuals. 52 selected teleseismic earthquakes recorded by 45 broadband stations of the Swedish National Seismological Network (SNSN) provide 1532 good quality S-wave relative arrival times. SV and SH arrival-time residuals were initially analyzed independently, providing two separate models. These reveal several consistent major features, many of which are also consistent with P-wave results. Lateral velocity variations of ± 3–4% are observed to depths of at least 470 km. The correlation between the SH and SV models is investigated and shows a pattern of minor but significant differences down to around 150–200 km depth, below which the models are essentially similar. Direct cell by cell comparison of the model velocities reveals a similar pattern, with velocity differences between the models of up to 4%. Numerical tests show that differences in the two S-wave models can only be partially attributed to noise and limited resolution, and some features are attributed to the effect of large scale anisotropy. One of the significant and sharp discrepancies between the S models coincides with a presumed boundary between Archean and Proterozic domains, suggesting different anisotropic characteristics in the two regions.
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| 9. |
- Hieronymus, C. F., et al.
(författare)
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A dynamical model for generating Eurasian lithospheric stress and strain rate fields : Effect of rheology and cratons
- 2008
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:B7, s. B07404-
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Tidskriftsartikel (refereegranskat)abstract
- For most continents, stress models driven by plate boundary forces have successfully reproduced the main characteristics of the stress field. However, Eurasia has remained a challenge due to its large areas of intraplate deformation. We present a set of three-dimensional models of the upper mantle lithosphere system for a simplified geometry of the Eurasian plate where we try to match the first-order characteristics of the stress and strain rate fields simultaneously. For typical elastic, viscous, or plastic rheologies, high stress levels are required in order to produce realistic convergence rates between India and Asia. Our models show robustly that such stresses are transmitted throughout most of the plate, dominating locally generated stresses even in distal regions such as Europe in a manner that is not compatible with observations. Cratons with roots that extend deep into the mantle are unable to provide a significant stress-shielding effect unless the viscosity contrast between the asthenosphere and the underlying mantle is around 100 or greater. A damage rheology for the lithosphere with history-dependent behavior and material softening by a viscosity reduction of several orders of magnitude is shown to eliminate this conundrum. Continental convergence at high velocity but low stress is facilitated by the formation of long-lived shear zones similar to those observed north of the Himalayas. The low stress associated with the collision, together with the decoupling effect of the shear zones, causes the distal stress field in Europe to be controlled by the effects of the neighboring boundaries in agreement with observations.
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| 10. |
- Hieronymus, Christoph F., et al.
(författare)
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A dynamical model for generating sharp seismic velocity contrasts underneath continents : Application to the Sorgenfrei-Tornquist Zone
- 2007
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Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 262:1-2, s. 77-91
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Tidskriftsartikel (refereegranskat)abstract
- New seismic velocity models based on teleseismic traveltime tomography show a sharp lithospheric boundary at the Sorgenfrei–Tornquist Zone (STZ) between 100 and 250 km depth with P-waves about 4% faster and S-waves 6% faster within the cratonic lithosphere to the north. Experiments and thermodynamic calculations indicate that seismic velocity differences in the shallow mantle down to the transition zone must be mostly of thermal origin as typical mantle rocks are characterized by similar velocities based on composition alone. We propose a dynamical model of convection in the upper mantle that is consistent with rheological data and that satisfies the seismic observations by maintaining an abrupt lateral temperature contrast over hundreds of Myrs. A step-like increase in lithospheric thickness from 100 to 250 km is assumed to have formed in a Triassic rifting event at the STZ (around 220 Ma) and is subsequently exposed to active convection below. A lithosphere that is distinct from the mantle in terms of temperature and composition remains stable against convective erosion. Heat advection to different depth beneath the thin and the thick lithosphere leads to a maximum horizontal contrast of 500 °C at 150 km depth over a lateral transition distance of 100 km, sufficient to generate 5% and 8% in maximum P- and S-wave velocity perturbation, respectively. A purely conductive model under the same conditions yields only Δvp ≈ 1% and Δvs ≈ 2%, while a lithospheric evolution simulation without a compositional effect on the rheology leads to significant thermo-mechanical erosion of the lithosphere giving Δvp ≈ 2% and Δvs ≈ 4%.
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