Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects

BACKGROUND\ud \ud Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact).\ud \ud METHODS\ud \ud Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective).\ud \ud RESULTS\ud \ud Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether, 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h x μg/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (Cmax) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and Cmax values of artemether and DHA were 20-35% lower.\ud \ud CONCLUSIONS\ud \ud Considering that cherry was the preferred flavour, and that the novel A-L dispersible tablet demonstrated similar pharmacokinetic performances to the tablet administered crushed, a cherry-flavoured A-L dispersible tablet formulation was selected for further development and testing in a large efficacy and safety study in African children with malaria

Impact of cross-section uncertainties on supernova neutrino spectral parameter fitting in the Deep Underground Neutrino Experiment

A primary goal of the upcoming Deep Underground Neutrino Experiment (DUNE) is to measure the $\mathcal{O}(10)$ MeV neutrinos produced by a Galactic core-collapse supernova if one should occur during the lifetime of the experiment. The liquid-argon-based detectors planned for DUNE are expected to be uniquely sensitive to the $\nu_e$ component of the supernova flux, enabling a wide variety of physics and astrophysics measurements. A key requirement for a correct interpretation of these measurements is a good understanding of the energy-dependent total cross section $\sigma(E_\nu)$ for charged-current $\nu_e$ absorption on argon. In the context of a simulated extraction of supernova $\nu_e$ spectral parameters from a toy analysis, we investigate the impact of $\sigma(E_\nu)$ modeling uncertainties on DUNE's supernova neutrino physics sensitivity for the first time. We find that the currently large theoretical uncertainties on $\sigma(E_\nu)$ must be substantially reduced before the $\nu_e$ flux parameters can be extracted reliably: in the absence of external constraints, a measurement of the integrated neutrino luminosity with less than 10\% bias with DUNE requires $\sigma(E_\nu)$ to be known to about 5%. The neutrino spectral shape parameters can be known to better than 10% for a 20% uncertainty on the cross-section scale, although they will be sensitive to uncertainties on the shape of $\sigma(E_\nu)$. A direct measurement of low-energy $\nu_e$-argon scattering would be invaluable for improving the theoretical precision to the needed level.Comment: 25 pages, 21 figure

Urban Biotopes of Aotearoa New Zealand (URBANZ) II: Floristics, biodiversity and conservation values of urban residential and public woodlands, Christchurch

Urban forests are increasingly valued for multiple benefits such as amenity, cultural values, native biodiversity, ecosystem services, and carbon sequestration. Urban biodiversity in particular, is the new focus although global homogenisation is undermining regional differentiation. In the northern hemisphere (e.g., Canada and USA) and in the southern hemisphere, particularly in countries like South Africa, Australia, South America and New Zealand, local biodiversity is further impacted by historical colonisation from Europe. After several centuries, urban forests are now composed of synthetic and spontaneous mixtures of native species, and exotic species from around the temperate world (e.g., Europe, North and South America, South Africa, Asia). As far as we are aware no-one has carried out in-depth study of these synthetic forests in any Southern Hemisphere city. Here we describe the composition, structure, and biodiversity conservation imperatives of urban temperate forests at 90 random locations in Christchurch city, New Zealand. We document considerable plant diversity; the total number of species encountered in the 253 sampled urban forest patches was 486. Despite this incredibly variable data set, our ability to explain variation in species richness was surprisingly good and clearly indicates that total species richness was higher in larger patches with greater litter and vegetation cover, and taller canopy height. Species richness was also higher in patches surrounded by higher population densities and closer to very large native forest patches. Native species richness was higher in patches with higher soil pH, lower canopy height, and greater litter cover and in patches closer to very large native forest patches indicating dispersal out of native areas and into gardens. Eight distinct forest communities were identified by Two-Way INdicator SPecies ANalysis (TWINSPAN) using the occurrence of 241 species that occurred in more than two out of all 253 forest patches. Christchurch urban forest canopies were dominated by exotic tree species in parklands and in street tree plantings (linear parkland). Native tree and shrub species were not as common in public spaces but their overall density high in residential gardens. There was some explanatory power in our data, since less deprivation resulted in greater diversity and density, and more native species, which in turn is associated with private ownership. We hypothesise that a number of other factors, which were not well reflected in our measured environmental variables, are responsible for much of the remaining variation in the plant community structure, e.g., advertising, peoples choice. For a more sustainable asset base of native trees in New Zealand cities we need more, longer-lived native species, in large public spaces, including a greater proportion of species that bear fruit and nectar suitable for native wildlife. We may then achieve cities with ecological integrity that present multiple historical dimensions, and sequester carbon in legible landscapes. © 2009 Elsevier GmbH. All rights reserved

RF conditioning of high power input coulpers for XFEL superconducting cavities

SCK-CEN (2014) - ISBN: 978-1-62993-828-8International audienc

POWER COUPLERS FOR XFEL

The LAL contribution to the XFEL project will be the delivery of 800 power couplers to equip 100 Crymodules. The LAL’s tasks consist on the industrial monitoring and coupler quality control at two different production sites, in addition to the RF conditioning at LAL of the 800 produced couplers. The RF conditioning and all the coupler preparation process will be held in a 70 m 2 ISO5 clean room. An RF power station delivering 5 MW, allow 8 couplers conditioning in the same time. Being in production control side and also RF conditioning one, the aim of LAL is to reach the rate of 8 couplers delivery per week, after a rump up phase. Starting of coupler mass production is scheduled for beginning 2013

2,2-difluorovinyl benzoates for diverse synthesis of gem-difluoroenol ethers by Ni-catalyzed cross-coupling reactions

202109 bcvcVersion of RecordPublishe