| 2. |
- Venkatesan, Meera, et al.
(author)
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Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes : parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.
- 2014
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In: The American journal of tropical medicine and hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 91:4, s. 833-43
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Journal article (peer-reviewed)abstract
- Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.
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| 3. |
- Bolhar, Robert, et al.
(author)
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Atmospheric S and lithospheric Pb in sulphides from the 2.06 Ga Phalaborwa phoscorite-carbonatite Complex, South Africa
- 2020
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In: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 530
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Journal article (peer-reviewed)abstract
- Lead and multiple sulphur isotope compositions were measured in-situ by SIMS on sulphide minerals from phoscorites and carbonatites of the ca. 2.06 Ga Phalaborwa Complex in South Africa. Additionally, sulphide mineral separates and bulk-rock samples were analyzed with IRMS methods to confirm SIMS data. Lead isotope ratios define a trend stretching from unradiogenic to highly radiogenic ratios corresponding to a Pb–Pb regression date of 2054 ± 99 Ma. This apparent date is consistent with the timing of emplacement and thus provides an age estimate for the sulphide mineralization. The least radiogenic Pb isotope compositions overlap, and the regression line intersects, a hypothetical mixing line between MORB mantle and an upper crustal reservoir at ca. 2.1 Ga, suggesting that either a significant quantity of crustal Pb contributed to sulphide mineralization, or that sulphidic xenomelts were derived from an isotopically enriched mantle source. Sulphur isotope ratios of individual sulphide minerals obtained by SIMS are highly variable (δ34S: −15 to +15‰ V-CDT) and, importantly, reveal the contribution of pre-Great Oxidation Event (GOE) atmospheric sulphur with mass-independent isotope fractionation (Δ33S = δ33S–[(1+δ34S)0.515-1]×1000 ≠0.0‰). Mass-independent sulphur isotope fractionation is also revealed by sulphur isotope ratios measured on sulphide mineral separates (Δ33S: 0.2 to 0.7‰) and bulk rock samples (Δ33S: 0.2 to 0.4‰). Generally, the range of sulphur isotope ratios obtained with SIMS is much larger than that observed in non-SIMS data, possibly reflecting isotopic variability at the μm scale, resolvable only with microbeam measurements. Various sources and mechanisms by which supracrustal material may have been incorporated into mantle-derived carbonatite-phoscorite magmas are assessed, taking into account that geological evidence for the presence of sedimentary material available for assimilation during shallow-level magma emplacement is lacking. Given the variability in S and Pb isotopic compositions, it is inferred that pre-GOE surficial Pb and S were not derived from asthenospheric mantle contaminated with supracrustal materials. Instead, whole rock trace element compositions, in concert with published geochemical and petrological evidence, are consistent with interaction of asthenospheric, plume-derived melt with compositionally heterogeneous lithospheric mantle that was metasomatically modified by fluids and melts released from a subducting slab. Despite geochemical and geochronological similarities with the 2055 Ma Busvheld Complex, lead and sulphur isotope data for both complexes are resolvably different, pointing to distinct lithospheric mantle sources involved in sulphide mineralization.
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