The primordial power spectrum describes the initial perturbations in the Universe which eventually grew into the large-scale structure we observe today, and thereby provides an indirect probe of ...inflation or other structure-formation mechanisms. Here, we introduce a new method to estimate this spectrum from the empirical power spectrum of cosmic microwave background (CMB) maps. A sparsity-based linear inversion method, coined \textbf{PRISM}, is presented. This technique leverages a sparsity prior on features in the primordial power spectrum in a wavelet basis to regularise the inverse problem. This non-parametric approach does not assume a strong prior on the shape of the primordial power spectrum, yet is able to correctly reconstruct its global shape as well as localised features. These advantages make this method robust for detecting deviations from the currently favoured scale-invariant spectrum. We investigate the strength of this method on a set of WMAP 9-year simulated data for three types of primordial power spectra: a nearly scale-invariant spectrum, a spectrum with a small running of the spectral index, and a spectrum with a localised feature. This technique proves to easily detect deviations from a pure scale-invariant power spectrum and is suitable for distinguishing between simple models of the inflation. We process the WMAP 9-year data and find no significant departure from a nearly scale-invariant power spectrum with the spectral index \(n_s = 0.972\). A high resolution primordial power spectrum can be reconstructed with this technique, where any strong local deviations or small global deviations from a pure scale-invariant spectrum can easily be detected.
Future cosmological surveys will provide 3D large scale structure maps with large sky coverage, for which a 3D Spherical Fourier-Bessel (SFB) analysis in spherical coordinates is natural. Wavelets ...are particularly well-suited to the analysis and denoising of cosmological data, but a spherical 3D isotropic wavelet transform does not currently exist to analyse spherical 3D data. The aim of this paper is to present a new formalism for a spherical 3D isotropic wavelet, i.e. one based on the SFB decomposition of a 3D field and accompany the formalism with a public code to perform wavelet transforms. We describe a new 3D isotropic spherical wavelet decomposition based on the undecimated wavelet transform (UWT) described in Starck et al. 2006. We also present a new fast Discrete Spherical Fourier-Bessel Transform (DSFBT) based on both a discrete Bessel Transform and the HEALPIX angular pixelisation scheme. We test the 3D wavelet transform and as a toy-application, apply a denoising algorithm in wavelet space to the Virgo large box cosmological simulations and find we can successfully remove noise without much loss to the large scale structure. We have described a new spherical 3D isotropic wavelet transform, ideally suited to analyse and denoise future 3D spherical cosmological surveys, which uses a novel Discrete Spherical Fourier-Bessel Transform. We illustrate its potential use for denoising using a toy model. All the algorithms presented in this paper are available for download as a public code called MRS3D at http://jstarck.free.fr/mrs3d.html
Mapping the underlying density field, including non-visible dark matter, using weak gravitational lensing measurements is now a standard tool in cosmology. Due to its importance to the science ...results of current and upcoming surveys, the quality of the convergence reconstruction methods should be well understood. We compare three methods: Kaiser-Squires (KS), Wiener filter, and GLIMPSE. KS is a direct inversion, not accounting for survey masks or noise. The Wiener filter is well-motivated for Gaussian density fields in a Bayesian framework. GLIMPSE uses sparsity, aiming to reconstruct non-linearities in the density field. We compare these methods with several tests using public Dark Energy Survey (DES) Science Verification (SV) data and realistic DES simulations. The Wiener filter and GLIMPSE offer substantial improvements over smoothed KS with a range of metrics. Both the Wiener filter and GLIMPSE convergence reconstructions show a 12 per cent improvement in Pearson correlation with the underlying truth from simulations. To compare the mapping methods' abilities to find mass peaks, we measure the difference between peak counts from simulated {\Lambda}CDM shear catalogues and catalogues with no mass fluctuations (a standard data vector when inferring cosmology from peak statistics); the maximum signal-to-noise of these peak statistics is increased by a factor of 3.5 for the Wiener filter and 9 for GLIMPSE. With simulations we measure the reconstruction of the harmonic phases; the phase residuals' concentration is improved 17 per cent by GLIMPSE and 18 per cent by the Wiener filter. The correlation between reconstructions from data and foreground redMaPPer clusters is increased 18 per cent by the Wiener filter and 32 per cent by GLIMPSE.
There are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against ...SARS-CoV-2 in vitro. This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma.
Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0·6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884.
45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59–77) versus untreated controls (42% IQR 31–73) (p = 0·004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0·47, p = 0·02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed.
A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19.
This work was supported by grant IP-COVID-19-625, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina and Laboratorio ELEA/Phoenix, Argentina.
In human and mice ATP-binding cassette efflux transporter ABCG2 represents the main route for active drug transport into milk. However, there is no detailed information on the role of ABCG2 in drug ...secretion and accumulation in milk of dairy animals. We therefore examined ABCG2-mediated drug transport in the bovine mammary gland by parallel pharmacokinetic studies in lactating Jersey cows and in vitro flux studies using the anthelmintic drug monepantel (MNP) as representative bovine ABCG2 (bABCG2) drug substrate. Animals received MNP (Zolvix, Novartis Animal Health Inc.) once (2.5 mg/kg per os) and the concentrations of MNP and the active MNP metabolite MNPSO2 were assessed by high-performance liquid chromatography. Compared with the parent drug MNP, we detected higher MNPSO2 plasma concentrations (expressed as area under the concentration-versus-time curve). Moreover, we observed MNPSO2 excretion into milk of dairy cows with a high milk-to-plasma ratio of 6.75. In mechanistic flux assays, we determined a preferential time-dependent basolateral-to-apical (B > A) MNPSO2 transport across polarized Madin-Darby canine kidney II cells-bABCG2 monolayers using liquid chromatography coupled with tandem mass spectrometry analysis. The B > A MNPSO2 transport was significantly inhibited by the ABCG2 inhibitor fumitremorgin C in bABCG2- but not in mock-transduced MDCKII cells. Additionally, the antibiotic drug enrofloxacin, the benzimidazole anthelmintic oxfendazole and the macrocyclic lactone anthelmintic moxidectin caused a reduction in the MNPSO2(B > A) net efflux. Altogether, this study indicated that therapeutically relevant drugs like the anthelmintic MNP represent substrates of the bovine mammary ABCG2 transporter and may thereby be actively concentrated in dairy milk.
•Eprinomectin concentrations in ticks were related to the administered dose rate.•There was a correlation between plasma and ticks eprinomectin concentrations.•High efficacy against ticks was ...obtained after eprinomectin administration•Eprinomectin is a useful treatment to control ticks in cattle.
Eprinomectin (EPM) is a macrocyclic lactone used against endo-ectoparasites without withdrawal time in milk and meat after its pour-on administration at 0.5mg/kg. Previous experiments evaluated the efficacy of EPM against Rhipicephalus (Boophilus) microplus in cattle. This study assessed EPM efficacy against R. (B.) microplus after topical administration at two dose rates and investigated the relationship between EPM systemic exposure in the host and drug concentrations accumulated in ticks recovered from treated animals. A standardized pharmaco-parasitological study was performed in two phases. In phase 1 eighteen Braford cattle naturally infected with R. (B.) microplus were divided into three experimental groups with a similar level of infestation (Kruskal–Wallis test, P>0.05): control group and treated groups with EPM pour-on (1 and 1.5mg/kg). Samples of heparinized blood and ticks at different life stages were taken between 0 and 21 days (d) post-administration to measure EPM concentrations by HPLC. The efficacy trial (phase 2) included eighteen Braford calves naturally infected with R. (B.) microplus divided into control group and 1mg/kg and 1.5mg/kg EPM treated groups. Female ticks (4.5–8mm) on cattle were counted between 1 and 23 days post-treatment to evaluate the efficacy of EPM. The reproductive efficiency index (REI) and the fertility efficiency index (FEI) were evaluated. Plasma concentrations of EPM showed a linear relationship with the level of dose rate administered. Peak plasma concentrations were within a range between 13.8 and 90ng/ml, which guarantee milk drug concentrations below the maximum residues level. High EPM concentrations were detected in ticks. EPM concentrations in R. (B.) microplus were correlated to plasma concentrations between 1.25 days and 21 days post-administration (r 0.84; P<0.05). EPM efficacy calculated using the Henderson–Tilton formula was 98.9% and 99.1% (7 days post-administration) and 100% (23 days post-administration) after EPM treatment at 1 and 1.5mg/kg, respectively. EPM administered at 1.5mg/kg also showed a significantly higher deleterious effect on tick fertility as measured by FEI (P<0.01). Therefore, treatment with EPM may be useful for controlling ticks in cattle, particularly in dairy production systems.
The LSST DESC DC2 Simulated Sky Survey Abolfathi, Bela; Alonso, David; Armstrong, Robert ...
The Astrophysical journal. Supplement series,
03/2021, Volume:
253, Issue:
1
Journal Article
Peer reviewed
Open access
Abstract
We describe the simulated sky survey underlying the second data challenge (DC2) carried out in preparation for analysis of the Vera C. Rubin Observatory Legacy Survey of Space and Time ...(LSST) by the LSST Dark Energy Science Collaboration (LSST DESC). Significant connections across multiple science domains will be a hallmark of LSST; the DC2 program represents a unique modeling effort that stresses this interconnectivity in a way that has not been attempted before. This effort encompasses a full end-to-end approach: starting from a large
N
-body simulation, through setting up LSST-like observations including realistic cadences, through image simulations, and finally processing with Rubin’s LSST Science Pipelines. This last step ensures that we generate data products resembling those to be delivered by the Rubin Observatory as closely as is currently possible. The simulated DC2 sky survey covers six optical bands in a wide-fast-deep area of approximately 300 deg
2
, as well as a deep drilling field of approximately 1 deg
2
. We simulate 5 yr of the planned 10 yr survey. The DC2 sky survey has multiple purposes. First, the LSST DESC working groups can use the data set to develop a range of DESC analysis pipelines to prepare for the advent of actual data. Second, it serves as a realistic test bed for the image processing software under development for LSST by the Rubin Observatory. In particular, simulated data provide a controlled way to investigate certain image-level systematic effects. Finally, the DC2 sky survey enables the exploration of new scientific ideas in both static and time domain cosmology.
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Quality control analysis of nanomaterials has been identified as a major issue to pursue their development in different industrial fields including nanomedicine. One difficulty is the ...lack of standardized and validated protocols suitable to achieve their characterization. In a previous work, we have developed standardized protocols for the evaluation of the size and zeta potential of nanomaterials based on methods described in the ISO standard and have performed validation of each one. The present work was aimed to transfer these protocols in three independent receiving laboratories. No official guideline was described in the literature to achieve such a transfer. A comparative study for receiving laboratories equipped with the same instrument as the sending laboratory was designed based on the Code of Federal Regulation edited by the Food and Drug Administration. For the receiving laboratory equipped with an instrument working at a different wavelength, a new validation was designed and applied. Corresponding statistical methods were used for the analysis of the results. A successful transfer of the protocols in all receiving laboratories was achieved. All laboratories recorded consistent results applying in blind the protocol of size measurements on two samples of nanomaterials from which included one reference.
Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite ...monepantel sulphone (MNPSO2) into milk. The goal of this study was to evaluate the presence of potential in vivo drug‐drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO2 was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO2 into milk was observed. The milk‐to‐plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO2 were not modified in the presence of OFZ. The pattern of MNPSO2 excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO2) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO2) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO2.
The main goal of the current work was to develop and validate an in vitro fluke egg hatch test, as a method for the detection of albendazole (ABZ) resistance in the liver fluke, Fasciola hepatica. ...Fluke eggs (200/ml, n= 5) from six different isolates were used in the current experimental work. They were obtained from different geographical locations and named Cullompton (UK), CEDIVE (Chascomus, Argentina), INTA-Bariloche (Bariloche, Argentina), Rubino (Uruguay), Cajamarca (Perú) and Río Chico (Catamarca, Argentina). The fluke eggs were incubated (25 °C) for a 12-h period in the presence of either ABZ or its sulphoxide metabolite (ABZ.SO) (5, 0.5 or 0.05 nmol/ml). Untreated eggs were incubated as a control. Incubated eggs (with or without drug present) were kept in darkness at 25 °C for 15 days. Afterwards, the trematode eggs were exposed to daylight over a 2-h period. Hatched and unhatched eggs were evaluated using an optical microscope, and the ovicidal activity was assessed for each fluke isolate. A very low ovicidal activity ( ≤ 13.4%) was observed in the ABZ-resistant CEDIVE isolate for both ABZ and ABZ.SO. Conversely, in the INTA-Bariloche and Río Chico isolates, which are suspected to be susceptible to ABZ, ovicidal activities ≥ 70.3% were observed after incubation with ABZ at the lowest concentration tested (0.05 nmol/ml). This finding correlates with that previously described for the ABZ-susceptible Cullompton. Finally, the Cajamarca and Rubino isolates behaved as ABZ resistant, since no ovicidal activity was observed after eggs were incubated with ABZ at 0.5 nmol/ml. Considering the specific results obtained for each isolate under assessment, the egg hatch test described here may be a suitable method for detection of ABZ resistance in F. hepatica.
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