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- Telloni, D., et al.
(author)
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Study of two interacting interplanetary coronal mass ejections encountered by Solar Orbiter during its first perihelion passage Observations and modeling
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Journal article (peer-reviewed)abstract
- Context. Solar Orbiter, the new-generation mission dedicated to solar and heliospheric exploration, was successfully launched on February 10, 2020, 04:03 UTC from Cape Canaveral. During its first perihelion passage in June 2020, two successive interplanetary coronal mass ejections (ICMEs), propagating along the heliospheric current sheet (HCS), impacted the spacecraft.Aims. This paper addresses the investigation of the ICMEs encountered by Solar Orbiter on June 7-8, 2020, from both an observational and a modeling perspective. The aim is to provide a full description of those events, their mutual interaction, and their coupling with the ambient solar wind and the HCS.Methods. Data acquired by the MAG magnetometer, the Energetic Particle Detector suite, and the Radio and Plasma Waves instrument are used to provide information on the ICMEs' magnetic topology configuration, their magnetic connectivity to the Sun, and insights into the heliospheric plasma environment where they travel, respectively. On the modeling side, the Heliospheric Upwind eXtrapolation model, the 3D COronal Rope Ejection technique, and the EUropean Heliospheric FORecasting Information Asset (EUHFORIA) tool are used to complement Solar Orbiter observations of the ambient solar wind and ICMEs, and to simulate the evolution and interaction of the ejecta in the inner heliosphere, respectively.Results. Both data analysis and numerical simulations indicate that the passage of two distinct, dynamically and magnetically interacting (via magnetic reconnection processes) ICMEs at Solar Orbiter is a possible scenario, supported by the numerous similarities between EUHFORIA time series at Solar Orbiter and Solar Orbiter data.Conclusions. The combination of in situ measurements and numerical simulations (together with remote sensing observations of the corona and inner heliosphere) will significantly lead to a deeper understanding of the physical processes occurring during the CME-CME interaction.
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| 4. |
- Brasseur, Z., et al.
(author)
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Measurement report: Introduction to the HyICE-2018 campaign for measurements of ice-nucleating particles and instrument inter-comparison in the Hyytiala boreal forest
- 2022
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:8, s. 5117-5145
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Journal article (peer-reviewed)abstract
- The formation of ice particles in Earth's atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice-nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the low and mid latitudes. Although less is known about the sources of ice nucleation at high latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high-latitude boreal forests in the mixed-phase cloud regime. We introduce the HyICE-2018 measurement campaign conducted in the boreal forest of Hyytiala, Finland, between February and June 2018. The campaign utilized the infrastructure of the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR) II, with additional INP instruments, including the Portable Ice Nucleation Chamber I and II (PINC and PINCii), the SPectrometer for Ice Nuclei (SPIN), the Portable Ice Nucleation Experiment (PINE), the Ice Nucleation SpEctrometer of the Karlsruhe Institute of Technology (INSEKT) and the Microlitre Nucleation by Immersed Particle Instrument (mu L-NIPI), used to quantify the INP concentrations and sources in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018, and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare measured INP concentrations to INP parameterizations, and we observe good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA.
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- Kloprogge, F., et al.
(author)
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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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In: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:6
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Journal article (peer-reviewed)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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| 10. |
- Sandholm, Niina, et al.
(author)
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New susceptibility loci associated with kidney disease in type 1 diabetes
- 2012
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In: PLOS Genetics. - San Francisco, USA : Public Library of Science, PLOS. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002921-
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Journal article (peer-reviewed)abstract
- Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
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| 11. |
- Stephen, D, et al.
(author)
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Continental-scale patterns of nutrient and fish effects on shallow lakes: introduction to a pan-European mesocosm experiment
- 2004
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In: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 49:12, s. 1517-1524
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Journal article (peer-reviewed)abstract
- 1. Shallow lake ecosystems are normally dominated by submerged and emergent plants. Biological stabilising mechanisms help preserve this dominance. The systems may switch to dominance by phytoplankton, however, with loss of submerged plants. This process usually takes place against a background of increasing nutrient loadings but also requires additional switch mechanisms, which damage the plants or interfere with their stabilising mechanisms. 2. The extent to which the details or even major features of this general model may change with geographical location are not clear. Manipulation of the fish community (biomanipulation) has often been used to clear the water of algae and restore the aquatic plants in northerly locations, but it is again not clear whether this is equally appropriate at lower latitudes. 3. Eleven parallel experiments (collectively the International Mesocosm Experiment, IME) were carried out in six lakes in Finland, Sweden, England, the Netherlands and Spain in 1998 and 1999 to investigate the between-year and large-scale spatial variation in relationships between nutrient loading and zooplanktivorous fish on submerged plant and plankton communities in shallow lakes. 4. Comparability of experiments in different locations was achieved to a high degree. Cross-laboratory comparisons of chemical analyses revealed some systematic differences between laboratories. These are unlikely to lead to major misinterpretations. 5. Nutrient addition, overall, had its greatest effect on water chemistry then substantial effects on phytoplankton and zooplankton. Fish addition had its major effect on zooplankton and did not systematically change the water chemistry. There was no trend in the relative importance of fish effects with latitude, but nutrient addition affected more variables with decreasing latitude. 6. The relative importance of top-down and bottom-up influences on the plankton differed in different locations and between years at the same location. The outcome of the experiments in different years was more predictable with decreasing latitude and this was attributed to more variable weather at higher latitudes that created more variable starting conditions for the experiments.
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| 12. |
- Hakkinen, K, et al.
(author)
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Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder
- 2022
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In: The pharmacogenomics journal. - : Springer Science and Business Media LLC. - 1473-1150 .- 1470-269X. ; 22:3, s. 166-172
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Journal article (peer-reviewed)abstract
- We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.
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| 13. |
- Palmroth, M., et al.
(author)
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Magnetosheath jet properties and evolution as determined by a global hybrid-Vlasov simulation
- 2018
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In: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 36:5, s. 1171-1182
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Journal article (peer-reviewed)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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| 16. |
- Autti, Taina, et al.
(author)
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Bone marrow transplantation in aspartylglucosaminuria : histopathological and MRI study
- 1999
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In: Neuropediatrics. - : Georg Thieme Verlag KG. - 0174-304X .- 1439-1899. ; 30:6, s. 283-8
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Journal article (peer-reviewed)abstract
- This study comprised two patients with aspartylglucosaminuria (AGU), who were followed up for 4 and 7 years. The patients underwent allogeneic bone marrow transplantation (BMT) at the ages of 2 and 2.6 years. Both patients had abnormal speech development and gross motor clumsiness. At the time of the BMT, they were mentally retarded. We report on follow-up data of these patients obtained by MRI, in addition to the histopathological, biochemical and clinical investigations. MR images of six non-transplanted patients and seven healthy children served as controls. In the non-transplanted patients, MRI revealed evident delay of myelination in contrast to the two transplanted patients showing fair or evident grey- vs. white matter differentiation on T2-weighted images. The aspartylglucosaminidase (AGA) activity in blood leukocytes reached a heterozygous level. Urinary excretion of aspartylglucosamine and glycoasparagines slowly decreased but remained about a third of the pre-BMT level 5 years after BMT. Storage lysosomes in electron microscopic investigations were not decreased 6 months after BMT, but after 1.5-2 years, rectal mucosa samples showed a decrease in the storage vacuoles of different cells. Three years after BMT, no cells with storage vacuoles were present. Allogeneic BMT slowly normalises the pathological, biochemical and MRI findings in patients with AGU.
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| 22. |
- Hietala, H., et al.
(author)
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In Situ Observations of a Magnetosheath High-Speed Jet Triggering Magnetopause Reconnection
- 2018
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In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 45:4, s. 1732-1740
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Journal article (peer-reviewed)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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| 24. |
- Moss, B, et al.
(author)
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Continental-scale patterns of nutrient and fish effects on shallow lakes: synthesis of a pan-European mesocosm experiment
- 2004
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In: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 49:12, s. 1633-1649
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Journal article (peer-reviewed)abstract
- 1. Results are analysed from 11 experiments in which effects of fish addition and nutrient loading on shallow lakes were studied in mesocosms. The experiments, five in 1998, six in 1999, were carried out in six lakes, distributed from Finland to southern Spain, according to a standard protocol. 2. Effects of the treatments on 29 standard chemical, phytoplankton and zooplankton variables are examined to assess the relative importance of bottom-up (nutrient enrichment) and top-down (fish predation) effects. For each year, the experiments in different locations are treated as replicates in a meta-analysis. Results of individual experiments are then compared in terms of the patterns of significant influences of nutrient addition and fish predation with these overall results (the baseline), and between years in the same location. 3. The overall meta-analysis gave consistent results across the 2 years, with nutrient loading influencing all of the chemical variables, and on average 31% of primary producer and 39% of zooplankton variables. In contrast, fish influenced none of the chemical variables, 11% of the primary producer and 44% of the zooplankton variables. Nutrient effects on the system were thus about three times greater than fish effects, although fish effects were not inconsiderable. 4. The relative importance of nutrients and fish in individual experiments often differed between years at the same location and effects deviated to varying degrees from the baseline. These deviations were treated as measures of consistency (predictability) of conclusions in repeat experiments. Consistency increased southwards and this is interpreted as a consequence of more variable annual weather northwards. 5. The influence of nutrient loading was greater southwards and this was probably manifested through naturally greater annual macrophyte abundance in warmer locations in consequence of the longer plant growing-season. There was no trend in the relative importance of fish effects with latitude but this may partly be an artefact of the simple fish community used. These findings suggest that nutrient control should be a greater priority than biomanipulation in the restoration of eutrophicated shallow lakes in warm temperate regions. 6. Starting conditions affected the outcome of experiments. High initial concentrations of total phosphorus and planktonic chlorophyll a concentration (created by local conditions prior to the experiment) led to de-emphasis of the importance of nutrient loading in the experiment.
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