| 1. |
- Mansoor, Rashid, et al.
(author)
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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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In: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
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Journal article (peer-reviewed)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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| 2. |
- Abdulla, Salim, et al.
(author)
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Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative : an individual patient data meta-analysis
- 2015
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14
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Journal article (peer-reviewed)abstract
- Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up. Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive. Results: PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28-63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 > 5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2-12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95-4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44-3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC1/2 since 2007. Conclusions: Several factors affect PC1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC1/2 data. Studies with frequent parasite count measurements to characterize PC1/2 should be encouraged. In western Cambodia, where PC1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.
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| 3. |
- Simonov, K. A., et al.
(author)
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Synthesis of armchair graphene nanoribbons from the 10,10′-dibromo-9,9′-bianthracene molecules on Ag(111) : The role of organometallic intermediates
- 2018
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Journal article (peer-reviewed)abstract
- We investigate the bottom-up growth of N = 7 armchair graphene nanoribbons (7-AGNRs) from the 10,10′-dibromo-9,9′-bianthracene (DBBA) molecules on Ag(111) with the focus on the role of the organometallic (OM) intermediates. It is demonstrated that DBBA molecules on Ag(111) are partially debrominated at room temperature and lose all bromine atoms at elevated temperatures. Similar to DBBA on Cu(111), debrominated molecules form OM chains on Ag(111). Nevertheless, in contrast with the Cu(111) substrate, formation of polyanthracene chains from OM intermediates via an Ullmann-type reaction is feasible on Ag(111). Cleavage of C-Ag bonds occurs before the thermal threshold for the surface-catalyzed activation of C-H bonds on Ag(111) is reached, while on Cu(111) activation of C-H bonds occurs in parallel with the cleavage of the stronger C-Cu bonds. Consequently, while OM intermediates obstruct the Ullmann reaction between DBBA molecules on the Cu(111) substrate, they are required for the formation of polyanthracene chains on Ag(111). If the Ullmann-type reaction on Ag(111) is inhibited, heating of the OM chains produces nanographenes instead. Heating of the polyanthracene chains produces 7-AGNRs, while heating of nanographenes causes the formation of the disordered structures with the possible admixture of short GNRs.
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| 4. |
- Blanco, A., et al.
(author)
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Performance of timing resistive plate chambers with relativistic neutrons from 300 to 1500 MeV
- 2015
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In: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 10:2
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Journal article (peer-reviewed)abstract
- A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic neutrons produced from a deuteron beam of varying energy (300 to 1500 AMeV) in experiment S406 at GSI, Darmstad, Germany. Each layer, with an active area of about 2000 × 500 mm2, is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C2H2F4 and 10% SF6. The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Measurements of the time of flight jitter of neutrons, in the mentioned energy range, point to a contribution of the resistive plate chamber in the order of 150 ps, independent of the neutron energy.
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| 5. |
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| 6. |
- Machado, J., et al.
(author)
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Performance of timing Resistive Plate Chambers with protons from 200 to 800 MeV
- 2015
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In: Journal of Instrumentation. - 1748-0221. ; 10:1, s. C01043-
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Journal article (peer-reviewed)abstract
- A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic protons produced from a deuteron beam of varying energy (200 to 800 AMeV) in experiment S406 at GSI, Darmstadt, Germany. The aim of the experiment is to characterize the response of the prototype to protons in this energy range, which deposit from 1.75 to 6 times more energy than minimum ionizing particles. Each layer, with an active area of about 2000 × 500 mm 2 , is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C 2 H 2 F 4 and 10% SF 6 . The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Results show an uniform efficiency close to 100% along with a timing resolution of around 60 ps on the entire 2000 × 500 mm 2 area.
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| 7. |
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| 8. |
- Morris, U., et al.
(author)
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Characterising temporal trends in asymptomatic Plasmodium infections and transporter polymorphisms during transition from high to low transmission in Zanzibar, 2005-2013
- 2015
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In: Infection Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 33, s. 110-117
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Journal article (peer-reviewed)abstract
- Background: Improved understanding of the asymptomatic malaria parasite reservoir is a prerequisite to pursue malaria elimination efforts. We therefore characterised temporal trends and transporter polymorphisms in asymptomatic Plasmodium infections during the transition from high to low transmission in Zanzibar. Methods: Healthy individuals participating in cross-sectional surveys conducted 2005-2013 were screened for asymptomatic malaria by PCR. Complexity/diversity of infection and transporter polymorphisms were assessed in Plasmodium falciparum positive samples. Symptomatic samples were included for comparison of polymorphisms in 2013. Results: PCR-determined parasite prevalence declined from 21.1% (CI95% 17.4-24.9) to 2.3% (CI95% 1.7-2.9) from 2005 to 2013. P. falciparum remained the predominant species; prevalence was highest in children and young adults aged 5-25 years. Parasite densities and complexity of infection, but not population genetic diversity of P. falciparum, decreased from 2005-2009. pfcrt 761 (99.2-64.7%, p < 0.001) and pfmdr1 86Y frequencies (89.4-66.7%, p = 0.03) decreased over time. Pfmdr1 (a.a.86,184,1246) YYY and YYD haplotypes were more frequent in asymptomatic than symptomatic infections in 2013 (p < 0.001). Conclusions: There is a declining, albeit persistent, reservoir of parasites present at low-densities in asymptomatic individuals in Zanzibar. This study revealed important characteristics of the remaining parasite population, including intriguing temporal trends in molecular markers associated with antimalarial resistance, which need to be further investigated. (C) 2015 Elsevier B.V. All rights reserved.
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| 9. |
- Vinogradov, N. A., et al.
(author)
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The structural evolution of graphene/Fe(110) systems upon annealing
- 2017
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In: Carbon. - : Elsevier BV. - 0008-6223 .- 1873-3891. ; 111, s. 113-120
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Journal article (peer-reviewed)abstract
- The thermal stability and the structural evolution of graphene grown on Fe(110) has been studied upon annealing in ultra-high vacuum conditions (UHV, P <= 10(-9) mbar) and in the presence of gaseous ethylene at a pressure of similar to 10(-6) mbar by grazing incidence X-ray diffraction. It was observed that upon annealing at temperatures below 630 degrees C, graphene on Fe is thermally stable. Exposure to ethylene at these temperatures promotes the formation of graphene while inhibiting its deterioration. Annealing graphene/Fe(110) at temperatures above 630 degrees C results in a fast degradation of graphene followed by carburization of the sample, that is the irreversible formation of various iron carbides, with the most common phases being Fe3C (cementite) and Fe7C3 (Eckstrom-Adcock carbide). Annealing of the carburized sample does not result in the formation of a detectable graphitic structure.
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