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- Karis, O., et al.
(författare)
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Observation of short- and long-range hybridization of a buried Cu monolayer in Ni
- 2000
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 62:24, s. R16239-R16242
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of a Cu monolayer buried in Ni fcc(100) is studied by means of x-ray emission and absorption spectroscopies in combination with first principles calculations. The local character of the x-ray probes allows us to investigate changes in the chemical interaction for these ultrathin film systems. In comparison to bulk Cu, the occupied d states of a buried Cu monolayer, as mapped in the x-ray emission spectrum, remain mostly unaltered. The absorption spectrum on the other hand shows that the empty states of the buried Cu monolayer are modified, and instead resemble the unoccupied electronic density of bulk Ni. These findings agree well with our first principle electronic structure calculations and the results are interpreted in terms of short- and long-range hybridization.
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2. |
- 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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- Mansoor, Rashid, et al.
(författare)
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Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
- 2022
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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5. |
- Wassdahl, N., et al.
(författare)
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Soft x-ray emission studies of adsorbates
- 1992
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Ingår i: Physical Review Letters. - 0031-9007. ; 69:5, s. 812-815
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Tidskriftsartikel (refereegranskat)abstract
- Soft x-ray emission spectroscopy is for the first time applied to surfaces and adsorbates. Surface sensitivity is achieved by employing synchrotron radiation in grazing incidence for the excitation. We present O K emission from adsorbed atomic oxygen on Ni(100) and Cu(100) and molecular CO on Ni(100). The observed spectral features correspond to the occupied 2p partial density of states of the adsorbates.
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- Aldred, M. A., et al.
(författare)
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BMPR2 gene rearrangements account for a significant proportion of mutations in familial and idiopathic pulmonary arterial hypertension
- 2006
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Ingår i: Hum Mutat.. ; 27:2
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Tidskriftsartikel (refereegranskat)abstract
- Mutations of the BMPR2 gene predispose to pulmonary arterial hypertension (PAH), a serious, progressive disease of the pulmonary vascular system. However, despite the fact that most PAH families are consistent with linkage to the BMPR2 locus, sequencing only identifies mutations in some 55% of familial cases and between 10% and 40% of cases without a family history (idiopathic or IPAH). We therefore conducted a systematic analysis for larger gene rearrangements in panels of both familial and idiopathic PAH cases that were negative on sequencing of coding regions. Analysis of exon dosage across the entire gene using Multiplex Ligation-dependent Probe Amplification identified nine novel rearrangements and enabled full characterization at the exon level of previously reported deletions. Overall, BMPR2 rearrangements were identified in 7 of 58 families and 6 of 126 IPAH cases, suggesting that gross rearrangements underlie around 12% of all FPAH cases and 5% of IPAH. Importantly, two deletions encompassed all functional protein domains and are predicted to result in null mutations, providing the strongest support yet that the predominant molecular mechanism for disease predisposition is haploinsufficiency. Dosage analysis should now be considered an integral of part of the molecular work-up of PAH patients. (c) 2006 Wiley-Liss, Inc.
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- Andersen, Jesper N, et al.
(författare)
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Photoemission Spectroscopy At Max-Lab
- 1991
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Ingår i: Synchrotron Radiation News. - : Informa UK Limited. - 0894-0886 .- 1931-7344. ; 4:4, s. 15-19
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Tidskriftsartikel (refereegranskat)
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- Denecke, R., et al.
(författare)
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Beamline 1511 at MAX II, capabilities and performance
- 1999
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - 0368-2048. ; 101-103, s. 971-977
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Tidskriftsartikel (refereegranskat)abstract
- The new undulator beamline 1511 at MAX-lab, now under commissioning, has been optimized for X-ray emission and photoelectron spectroscopies. Using an SX-700 high flux monochromator the accessible photon energy range is from 90 eV to about 1500 eV. The performance of the undulator agrees very well with the specifications, as shown by measurements using a photodiode. The energy resolution of the monochromator has been checked using absorption measurements in a gas cell. It was found to meet the expectations and exceeds a resolving power of 10 000 at 244 eV. The photon flux as a function of energy has been recorded as well and gives a maximum flux of 3×1013 photons/s/100 mA/0.1% BW. Beamlines 1511 and 1411 will be the first synchrotron beamlines making use of a so-called beam waist phenomenon, known from laser physics. We show results of ray-tracing calculations to determine the ultimate spot size on the sample location. The endstations to be used at this new beamline and their capabilities will be discussed as an example of the future use of this facility.
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- J. Schnadt, J. N. O`Shea, L. Patthey, J. Schiessling, M. Shi, J. Krempasky, J. Åhlund, N. Mårtensson, and P. A, Brühwiler
(författare)
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Structural study of adsorption of isonicotinic acid and related molecules on rutile TiO2(110) II.: XPS
- 2003
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Ingår i: Surf. Sci.. ; :544, s. 74-
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Tidskriftsartikel (refereegranskat)
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