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- Kloprogge, F., et al.
(författare)
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Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis
- 2018
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Background The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. A search in PubMed, Embase, ClinicalTrials. gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing < 15 kg and 15-25 kg, respectively, and 20.2% lower in pregnant women compared with non-pregnant adults. Lumefantrine exposure decreased with increasing pre-treatment parasitaemia, and the dose limitation on absorption of lumefantrine was substantial. Simulations using the lumefantrine pharmacokinetic model suggest that, in young children and pregnant women beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (twice daily for 3 days). The model was developed using venous plasma data from patients receiving intact tablets with fat, and evaluations of alternative dosing regimens were consequently only representative for venous plasma after administration of intact tablets with fat. The absence of artemether-dihydroartemisinin data limited the prediction of parasite killing rates and recrudescent infections. Thus, the suggested optimised dosing schedule was based on the pharmacokinetic endpoint of lumefantrine plasma exposure at day 7. Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment.
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- Palmroth, M., et al.
(författare)
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Magnetosheath jet properties and evolution as determined by a global hybrid-Vlasov simulation
- 2018
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 36:5, s. 1171-1182
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Tidskriftsartikel (refereegranskat)abstract
- We use a global hybrid-Vlasov simulation for the magnetosphere, Vlasiator, to investigate magnetosheath high-speed jets. Unlike many other hybrid-kinetic simulations, Vlasiator includes an unscaled geomagnetic dipole, indicating that the simulation spatial and temporal dimensions can be given in SI units without scaling. Thus, for the first time, this allows investigating the magnetosheath jet properties and comparing them directly with the observed jets within the Earth's magnetosheath. In the run shown in this paper, the interplanetary magnetic field (IMF) cone angle is 30°, and a foreshock develops upstream of the quasi-parallel magnetosheath. We visually detect a structure with high dynamic pressure propagating from the bow shock through the magnetosheath. The structure is confirmed as a jet using three different criteria, which have been adopted in previous observational studies. We compare these criteria against the simulation results. We find that the magnetosheath jet is an elongated structure extending earthward from the bow shock by ∼ 2.6 RE, while its size perpendicular to the direction of propagation is ∼ 0.5R/E. We also investigate the jet evolution and find that the jet originates due to the interaction of the bow shock with a high-dynamic-pressure structure that reproduces observational features associated with a short, large-amplitude magnetic structure (SLAMS). The simulation shows that magnetosheath jets can develop also under steady IMF, as inferred by observational studies. To our knowledge, this paper therefore shows the first global kinetic simulation of a magnetosheath jet, which is in accordance with three observational jet criteria and is caused by a SLAMS advecting towards the bow shock.
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- Hietala, H., et al.
(författare)
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In Situ Observations of a Magnetosheath High-Speed Jet Triggering Magnetopause Reconnection
- 2018
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 45:4, s. 1732-1740
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Tidskriftsartikel (refereegranskat)abstract
- Magnetosheath high-speed jets-localized dynamic pressure enhancements typically of similar to 1 Earth radius in size-impact the dayside magnetopause several times per hour. Here we present the first in situ measurements suggesting that such an impact triggered magnetopause reconnection. We use observations from the five Time History of Events and Macroscale Interactions during Substorms spacecraft in a string-of-pearls configuration on 7 August 2007. The spacecraft recorded magnetopause in-and-out motion during an impact of a magnetosheath jet (V-N similar to -300km/s along the magnetopause normal direction). There was no evidence for reconnection for the preimpact crossing, yet three probes observed reconnection after the impact. We infer that the jet impact compressed the originally thick (60-70 d(i)), high magnetic shear (140-160 degrees magnetopause until it was thin enough for reconnection to occur. Magnetosheath high-speed jets could therefore act as a driver for bursty dayside reconnection.
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- Eriksson, Louise, 1973-, et al.
(författare)
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Invasive forest pathogens in Europe : Cross-country variationin public awareness but consistency in policy acceptability
- 2019
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Ingår i: Ambio. - : Springer Netherlands. - 0044-7447 .- 1654-7209. ; 48:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Political action can reduce introductions of diseases caused by invasive forest pathogens (IPs) and public support is important for effective prevention. The public’s awareness of IP problems and the acceptability of policies aiming to combat these pathogens were surveyed in nine European countries (N = 3469). Although awareness of specific diseases (e.g., ash dieback) varied, problem awareness and policy acceptability were similar across countries. The public was positive towards policies for informational measures and stricter standards for plant production, but less positive towards restricting public access to protected areas. Multilevel models, including individual and country level variables, revealed that media exposure was positively associated with awareness of IP problems, and strengthened the link between problem awareness and policy acceptability. Results suggest that learning about IPs through the media and recognizing the associated problems increase policy acceptability. Overall, the study elaborates on the anthropogenic dimension of diseases caused by IPs.
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- Hietala, M., et al.
(författare)
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Moisture stability and mechanical durability of peat biocomposites
- 2017
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Ingår i: ICCM21 Proceedings. - : ICCM, International Committee on Composite Materials.
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Konferensbidrag (refereegranskat)abstract
- Peat, the organic matter formed from incomplete degradation of vegetation in peatlands, was studied as lignocellulosic raw material in manufacture of biocomposites. Peat mosses with varying degree of decomposition, namely slightly decomposed peat (H2) and moderately decomposed peat (H6), were ground into different particle size fractions which were used to prepare peat-polypropylene (PP) composites with 50 wt% peat content using extrusion compounding. The moisture absorption and dimensional stability as well as the mechanical properties and microstructure before and after cyclic freeze-thaw conditioning of the peat-PP composites were analysed and compared to reference wood-plastic composite (WPC). The mechanical properties of peat-PP composites were better than the properties of reference WPC before the freeze-thaw conditioning, and the mechanical permanence of peat-PP composites was better after the cyclic conditioning. Especially when peat with higher decomposition degree was used (H6), the mechanical permanence of peat-PP composites was improved. Likewise, the moisture absorption and the dimensional stability properties were improved the more decomposed the used peat was. The particle size did not affect the composite properties as much as the decomposition degree of peat, though the dimensional stability of peat-PP composite with moderately decomposed peat was better with smaller particle size peat.
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- Plaschke, F., et al.
(författare)
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Magnetosheath High-Speed Jets : Internal Structure and InteractionWith Ambient Plasma
- 2017
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 122:10, s. 10157-10175
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Tidskriftsartikel (refereegranskat)abstract
- For the first time, we have studied the rich internal structure of a magnetosheath high-speed jet. Measurements by the Magnetospheric Multiscale (MMS) spacecraft reveal large-amplitude density, temperature, and magnetic field variations inside the jet. The propagation velocity and normal direction of planar magnetic field structures (i.e., current sheets and waves) are investigated via four-spacecraft timing. We find structures to mainly convect with the jet plasma. There are indications of the presence of a tangential discontinuity. At other times, there are small cross-structure flows. Where this is the case, current sheets and waves overtake the plasma in the jet's core region; ahead and behind that core region, along the jet's path, current sheets are overtaken by the plasma; that is, they move in opposite direction to the jet in the plasma rest frame. Jet structures are found to be mainly thermal and magnetic pressure balance structures, notwithstanding that the dynamic pressure dominates by far. Although the jet is supermagnetosonic in the Earth's frame of reference, it is submagnetosonic with respect to the plasma ahead. Consequently, we find no fast shock. Instead, we find some evidence for (a series of) jets pushing ambient plasma out of their way, thereby stirring the magnetosheath and causing anomalous sunward flows in the subsolar magnetosheath. Furthermore, we find that jets modify the magnetic field in the magnetosheath, aligning it with their propagation direction.
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