Gallium (Ga) is under study for the treatment of osteolytic disorders in equines. Previous studies indicate that oral gallium maltolate (GaM) would provide a higher bioavailability than oral Ga ...salts. However, oral administration to adult horses of 2 mg/kg of GaM, in the form of a solution mixed with food, did not lead to detectable Ga levels in plasma. Therefore, a study was performed to model the chemical behaviour of GaM in the digestive tract. The equilibrium formation constants for Ga(III) and maltol were calculated by means of UV–visible measurements and validated by 1H‐NMR measurements at selected pH values. Data indicate that the dissociation of GaM in aqueous solutions is very rapid, while the re‐association is slower. Based on these results, poor Ga absorption seems to be due to the equilibrium dissociation of GaM in the stomach and to its slow formation rate in the intestine. The concomitant presence of high concentrations of phytates (strong charged metal chelating agents, which represent about 1% of dry matter in vegetables) might also explain the low absorption of GaM by the gastrointestinal tract. Methods of optimizing Ga absorption after oral administration of GaM require further investigation.
Pollina, G. F., Zagotto, G., Maritan, P., Iacopetti, I., Busetto, R Pharmacokinetics of gallium nitrate after oral administration in adult horses – pilot study. J. vet. Pharmacol. Therap. 35, ...489–494.
Gallium (Ga), a metal in group IIIA of the periodic table, has shown a remarkable activity against bone resorption and could therefore possibly prove useful in the treatment of certain diseases in sport horses, for example navicular disease. The aim of this study was to gain more information concerning the kinetics of Ga after oral administration of gallium nitrate (GaN) in adult horses. Six horses received a single dose of 10 mg/kg of GaN mixed with the food ration. Absorption was slow (Tmax = 10 ± 3 h, T½abs = 2 ± 0.8 h), and a Cmax of 26 ± 11 μg/L was achieved. Excretion followed a one‐phase elimination model, with a long half‐life (T½el = 52 ± 14 h). By means of a mathematical model, we estimated that the plasmatic levels should reach 93 μg/L (1.33 μm) at steady state, following the repeated daily administration of 10 mg/kg of GaN. A three times lower concentration has been demonstrated as effective in inhibiting the osteolytic activity of osteoclasts in vitro. The results of this study suggest that the administration of oral GaN at a rate of 10 mg/kg per day may be considered for future clinical studies.
The
Euclid
mission – with its spectroscopic galaxy survey covering a sky area over 15 000 deg
2
in the redshift range 0.9 <
z
< 1.8 – will provide a sample of tens of thousands of cosmic voids. ...This paper thoroughly explores for the first time the constraining power of the void size function on the properties of dark energy (DE) from a survey mock catalogue, the official
Euclid
Flagship simulation. We identified voids in the Flagship light-cone, which closely matches the features of the upcoming
Euclid
spectroscopic data set. We modelled the void size function considering a state-of-the art methodology: we relied on the volume-conserving (Vdn) model, a modification of the popular Sheth & van de Weygaert model for void number counts, extended by means of a linear function of the large-scale galaxy bias. We found an excellent agreement between model predictions and measured mock void number counts. We computed updated forecasts for the
Euclid
mission on DE from the void size function and provided reliable void number estimates to serve as a basis for further forecasts of cosmological applications using voids. We analysed two different cosmological models for DE: the first described by a constant DE equation of state parameter,
w
, and the second by a dynamic equation of state with coefficients
w
0
and
w
a
. We forecast 1
σ
errors on
w
lower than 10% and we estimated an expected figure of merit (FoM) for the dynamical DE scenario FoM
w
0
,
w
a
= 17 when considering only the neutrino mass as additional free parameter of the model. The analysis is based on conservative assumptions to ensure full robustness, and is a pathfinder for future enhancements of the technique. Our results showcase the impressive constraining power of the void size function from the
Euclid
spectroscopic sample, both as a stand-alone probe, and to be combined with other
Euclid
cosmological probes.
ABSTRACT
The CMB lensing signal from cosmic voids and superclusters probes the growth of structure in the low-redshift cosmic web. In this analysis, we cross-correlated the Planck CMB lensing map ...with voids detected in the Dark Energy Survey Year 3 (Y3) data set (∼5000 deg2), expanding on previous measurements that used Y1 catalogues (∼1300 deg2). Given the increased statistical power compared to Y1 data, we report a 6.6σ detection of negative CMB convergence (κ) imprints using approximately 3600 voids detected from a redMaGiC luminous red galaxy sample. However, the measured signal is lower than expected from the MICE N-body simulation that is based on the ΛCDM model (parameters Ωm = 0.25, σ8 = 0.8), and the discrepancy is associated mostly with the void centre region. Considering the full void lensing profile, we fit an amplitude $A_{\kappa }=\kappa _{{\rm DES}}/\kappa _{{\rm MICE}}$ to a simulation-based template with fixed shape and found a moderate 2σ deviation in the signal with Aκ ≈ 0.79 ± 0.12. We also examined the WebSky simulation that is based on a Planck 2018 ΛCDM cosmology, but the results were even less consistent given the slightly higher matter density fluctuations than in MICE. We then identified superclusters in the DES and the MICE catalogues, and detected their imprints at the 8.4σ level; again with a lower-than-expected Aκ = 0.84 ± 0.10 amplitude. The combination of voids and superclusters yields a 10.3σ detection with an Aκ = 0.82 ± 0.08 constraint on the CMB lensing amplitude, thus the overall signal is 2.3σ weaker than expected from MICE.
Luminous tracers of large-scale structure are not entirely representative of the distribution of mass in our Universe. As they arise from the highest peaks in the matter density field, the spatial ...distribution of luminous objects is biased towards those peaks. On large scales, where density fluctuations are mild, this bias simply amounts to a constant offset in the clustering amplitude of the tracer, known as linear bias. In this work we focus on the relative bias between galaxies and galaxy clusters that are located inside and in the vicinity of cosmic voids, extended regions of relatively low density in the large-scale structure of the Universe. With the help of mock data we verify that the relation between galaxy and cluster overdensity around voids remains linear. Hence, the void-centric density profiles of different tracers can be linked by a single multiplicative constant. This amounts to the same value as the relative linear bias between tracers for the largest voids in the sample. For voids of small sizes, which typically arise in higher density regions, this constant has a higher value, possibly showing an environmental dependence similar to that observed for the linear bias itself. We confirm our findings by analysing data obtained during the first year of observations by the Dark Energy Survey. As a side product, we present the first catalogue of three-dimensional voids extracted from a photometric survey with a controlled photo-z uncertainty. Finally, our results will be relevant in forthcoming analyses that attempt to use voids as cosmological probes.
What are the mass and galaxy profiles of cosmic voids? In this paper, we use two methods to extract voids in the Dark Energy Survey (DES) Year 1 redMaGiC galaxy sample to address this question. We ...use either 2D slices in projection, or the 3D distribution of galaxies based on photometric redshifts to identify voids. For the mass profile, we measure the tangential shear profiles of background galaxies to infer the excess surface mass density. The signal-to-noise ratio for our lensing measurement ranges between 10.7 and 14.0 for the two void samples. We infer their 3D density profiles by fitting models based on N-body simulations and find good agreement for void radii in the range 15–85 Mpc. Comparison with their galaxy profiles then allows us to test the relation between mass and light at the 10 per cent level, the most stringent test to date. We find very similar shapes for the two profiles, consistent with a linear relationship between mass and light both within and outside the void radius. We validate our analysis with the help of simulated mock catalogues and estimate the impact of photometric redshift uncertainties on the measurement. Our methodology can be used for cosmological applications, including tests of gravity with voids. Finally, this is especially promising when the lensing profiles are combined with spectroscopic measurements of void dynamics via redshift-space distortions.
Summary
objectives Some histological features may suggest the malignant nature of a parathyroid tumour. However, the diagnosis of parathyroid cancer can only be definitively established in the ...presence of local invasion or metastases.
design We further investigated the role of the retinoblastoma gene (Rb1) and the breast cancer susceptibility gene (BRCA2) in the differential diagnosis between benign and malignant parathyroid tumours by evaluating loss of heterozygosity (LOH) at these loci and Rb protein (pRb) immunohistochemistry.
patients and measurements Fifty‐three parathyroid adenomas from patients with sporadic primary hyperparathyroidism (PHPT) and 10 parathyroid cancer specimens were studied. Microsatellite polymorphisms at the Rb1 and BRCA2 loci were polymerase chain reaction (PCR) amplified from each patient's paired tumour and leucocyte DNA samples, using oligonucleotide primers flanking the repeat sequence. Immunohistochemical staining of pRb was carried out using a monoclonal antibody.
results All but one of the 53 tumour–leucocyte pairs was informative for at least one of the three polymorphic markers of the Rb1 gene. Fifteen adenomas (28·8%) showed LOH. Regarding the BRCA2 gene, 46 tumour–leucocyte pairs were informative and LOH was present in eight (17·4%). All six carcinomas had LOH for at least one marker at the Rb1 locus. LOH for the BRCA2 microsatellite was found in three of the five informative primary tumour samples. Immunohistochemical analysis revealed that all adenomas were positive and the number of pRb‐positive cells varied significantly among different samples. The mean percentage of stained cells was 15·7%. Eleven of the 30 (36·7%) adenomas showed sparse positive staining, 13 (43·3%) intermediate staining and six (20%) extensive staining. All parathyroid cancers were entirely negative for pRb immunostaining.
conclusions Inactivation of the Rb1 gene is a common event in parathyroid tumorigenesis. Retention of heterozygosity seems to exclude parathyroid malignancy, which is suggested by the combined finding of LOH and lack of protein expression.
The Euclid mission \(-\) with its spectroscopic galaxy survey covering a sky area over \(15\,000 \ \mathrm{deg}^2\) in the redshift range \(0.9<z<1.8\ -\) will provide a sample of tens of thousands ...of cosmic voids. This paper explores for the first time the constraining power of the void size function on the properties of dark energy (DE) from a survey mock catalogue, the official Euclid Flagship simulation. We identify voids in the Flagship light-cone, which closely matches the features of the upcoming Euclid spectroscopic data set. We model the void size function considering a state-of-the art methodology: we rely on the volume conserving (Vdn) model, a modification of the popular Sheth & van de Weygaert model for void number counts, extended by means of a linear function of the large-scale galaxy bias. We find an excellent agreement between model predictions and measured mock void number counts. We compute updated forecasts for the Euclid mission on DE from the void size function and provide reliable void number estimates to serve as a basis for further forecasts of cosmological applications using voids. We analyse two different cosmological models for DE: the first described by a constant DE equation of state parameter, \(w\), and the second by a dynamic equation of state with coefficients \(w_0\) and \(w_a\). We forecast \(1\sigma\) errors on \(w\) lower than \(10\%\), and we estimate an expected figure of merit (FoM) for the dynamical DE scenario \(\mathrm{FoM}_{w_0,w_a} = 17\) when considering only the neutrino mass as additional free parameter of the model. The analysis is based on conservative assumptions to ensure full robustness, and is a pathfinder for future enhancements of the technique. Our results showcase the impressive constraining power of the void size function from the Euclid spectroscopic sample, both as a stand-alone probe, and to be combined with other Euclid cosmological probes.
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