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- bazargan, mohsen, et al.
(författare)
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Crystal rotations and alignment in spatially varying magma flows: Two-dimensional examples of common subvolcanic flow geometries
- 2019
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Konferensbidrag (refereegranskat)abstract
- Elongate inclusions immersed in a viscous flow generally rotate at a rate that is different from the local angular velocity of the fluid. As a result, the inclusions tend to orient themselves into a coherent pattern commonly referred to as shape-preferred orientation (SPO). The SPO of the particles can be used as a strain marker that allows the reconstruction of the fluid's velocity field. Moreover, the SPO of elongate crystals is one of the main mechanisms that lead to the anisotropy of magnetic susceptibility (AMS), which allows rapid measurement of average crystal orientations. A robust model is therefore highly desirable that can link the AMS measurements of the exposed flow to the complete velocity field when the flow was active. Much of the previous work on the dynamics of flow-induced particle rotations has been focused on spatially homogenous flows with large-scale tectonic deformations as the main application. Here, we show how the method can be extended to cover flows that vary in space as well as time, such as magma with embedded crystals moving through the volcanic plumbing system. Additionally, we introduce an evolution equation for the probability density function (PDF) of crystal orientations. The PDF evolution is coupled with the Navier-Stokes equation governing the flow, thus yielding a PDF of crystal orientations at every position. The overall correctness of the evolution equation as well as the accuracy of the numerical method are demonstrated by rigorous testing. We then apply this new theory to a number of simple, two-dimensional flow geometries commonly encountered in magmatic intrusions, such as flow from a dike into a reservoir and from a reservoir into a dike, isothermal flow inside an inflating or deflating reservoir, and thermal convection in a magma chamber. We confirm some of the previous general findings. For example, near channel walls, the flow is often parallel to the bonding surface, and the resulting simple shear flow causes preferred crystal orientations that parallel the boundary. On the other hand, where pure shear deformation dominates, there is a tendency for crystals to orient themselves in the direction of the most tensile strain rate. This occurs not only near the centre of certain flows but also along the boundaries of a deflating magma chamber and in thermal convection where the convective currents turn away from the chamber walls, thus leading to crystal orientations perpendicular to the bounding surface. Flows impinging on a boundary are instead characterizing by a most tensile strain rate that is parallel to the surface, thus leading to boundary-parallel crystal orientations. In the field, this local pattern due to an impinging flow may be difficult to distinguish from that due to simple shear flow along the wall. In other words, while a given flow will always result in a unique pattern of crystal orientations, it is generally impossible to infer the local flow field from only a local observation of the crystal PDF. Overall, we find that the crystal orientation patterns agree well with results from analogue experiments where similar geometries are available.
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| 2. |
- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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