Context. The origin of the observed diversity of planetary system architectures is one of the main topics of exoplanetary research. The detection of a statistically significant sample of planets ...around young stars allows us to study the early stages of planet formation and evolution, but only a handful are known so far. In this regard a considerable contribution is expected from the NASA TESS satellite, which is now performing a survey of ~85% of the sky to search for short-period transiting planets. Aims. In its first month of operation TESS found a planet candidate with an orbital period of 8.14 days around a member of the Tuc-Hor young association (~40 Myr), the G6V main component of the binary system DS Tuc. If confirmed, it would be the first transiting planet around a young star suitable for radial velocity and/or atmospheric characterisation. Our aim is to validate the planetary nature of this companion and to measure its orbital and physical parameters. Methods. We obtained accurate planet parameters by coupling an independent reprocessing of the TESS light curve with improved stellar parameters and the dilution caused by the binary companion; we analysed high-precision archival radial velocities to impose an upper limit of about 0.1 MJup on the planet mass; we finally ruled out the presence of external companions beyond 40 au with adaptive optics images. Results. We confirm the presence of a young giant (R = 0.50 RJup) planet having a non-negligible possibility to be inflated (theoretical mass ≲ 20 M⊕) around DS Tuc A. We discuss the feasibility of mass determination, Rossiter-McLaughlin analysis, and atmosphere characterisation allowed by the brightness of the star.
Introduction
Chronic venous disease (CVD) is a common condition associated with valvular dysfunction, venous hypertension and endothelial inflammation. Sulodexide facilitates the healing of venous ...ulcers and is frequently used in patients with CVD without ulcer. This review assessed the efficacy and safety of sulodexide for treatment of signs and symptoms of lower extremity CVD.
Methods
We searched MEDLINE, EMBASE, CINAHL and AMED as well as the Cochrane Central Register of Controlled Trials and the World Health Organisation (WHO) International Clinical Trials Registry Platform Search Portal. We also manually searched potentially relevant journals, conference proceedings and journal supplements. Any study monitoring any effect of sulodexide in patients with CVD at any stage of the disease, classified or non-classified, was considered. Treatment effects were estimated using standardised mean differences (SMDs), mean differences (MDs) and risk ratios (RRs), as appropriate. We calculated 95% confidence intervals (CIs) and heterogeneity (
Q
, tau and
I
2
).
Results
The search found 64 studies, but only 23 provided data on 7153 participants (mean age 55 years; 68% female). The 13 studies providing extractable quantitative information included 1901 participants (mean age 55.2 years; 65% female). Sulodexide decreased the intensity of pain, cramps, heaviness, oedema and total symptom score and reduced inflammatory mediators in patients with CVD. The risk of adverse events (AEs) was not different between sulodexide and placebo or heparan sulphate (RR 1.31, 95% CI 0.74–2.32;
I
2
= 0%; 270 participants). The overall risk of AEs with sulodexide was low: 3% (95% CI 1–4%) estimated from 3656 participants.
Conclusion
Sulodexide was found to have a beneficial venoactive effect on the major signs and symptoms of CVD such as pain, cramps, heaviness and oedema without increasing the risk of AEs. It is also likely to exert a systemic effect on the course of CVD by interfering with inflammatory chemokines.
We consider stochastic reaction-diffusion equations with colored noise on the space of real-valued and continuous functions on a compact subset of ℝ
d
for
d
=
1
,
2
,
3
. We prove Schauder-type ...estimates, which will depend on the color of the noise, for the stationary and evolution problems associated with the corresponding transition semigroup.
Abstract
Atmospheric mass loss plays a major role in the evolution of exoplanets. This process is driven by the stellar high-energy irradiation, especially in the first hundreds of millions of years ...after dissipation of the proto-planetary disk. A major source of uncertainty in modeling atmospheric photoevaporation and photochemistry is due to the lack of direct measurements of the stellar flux at extreme-UV (EUV) wavelengths. Several empirical relationships have been proposed in the past to link EUV fluxes to emission levels in X-rays, but the stellar samples employed for this aim are heterogeneous, and the available scaling laws provide significantly different predictions, especially for very active stars. We present new far-UV and X-ray observations of V1298 Tau with Hubble Space Telescope/Cosmic Origins Spectrograph and XMM-Newton, aimed to determine more accurately the high-energy emission of this solar-mass pre-main-sequence star, which hosts four exoplanets. Spectroscopic data were employed to derive the plasma emission measure distribution versus temperature, from the chromosphere to the corona, and the possible variability of this irradiation on short and year-long timescales, due to magnetic activity. As a side result, we have also measured the chemical abundances of several elements in the outer atmosphere of V1298 Tau. We employ our results as a new benchmark point for the calibration of the X-ray to EUV scaling laws, and hence to predict the time evolution of the irradiation in the EUV band, and its effect on the evaporation of exo-atmospheres.
Aims. We investigate the detection of Cool Cores (CCs) in the distant galaxy cluster population with the purpose of measuring the CC fraction out to redshift $0.7\le z<1.4$. Using a sample of nearby ...clusters spanning a wide range of morphologies, we define criteria to characterize cool cores, which are applicable to the high-redshift sample. Methods. We analyzed azimuthally-averaged surface brightness (SB) profiles with the known scaling relations, and we fitted single/double β models to the data. Additionally, we measured a surface brightness concentration, cSB, as the ratio of the peak over the ambient SB. To verify that this is an unbiased parameter as a function of redshift, we developed a model independent “cloning” technique to simulate the nearby clusters as they would appear at the same redshifts and luminosities as those in the distant sample. This method is based on the application of the cosmological surface brightness dimming to high-resolution Chandra images, assuming no intrinsic cluster evolution. We obtained a more physical parameterization of the CC presence by computing the cooling time at a radius of 20 kpc from the cluster center. Results. The distribution of the SB concentration and the stacked radial profiles of the low-z sample, combined with published information on the CC properties of these clusters, show 3 degrees of SB cuspiness: non-CC, moderate, and strong CC. The same analysis applied to the high-z clusters reveals two regimes: non-CC and moderate CC. The cooling time distribution corroborates this result by showing a strong negative correlation with cSB. Conclusions. Our analysis indicates a significant fraction of distant clusters harboring a moderate CC out to $z=1.4$, similar to those found in the local sample. The absence of strong cooling is likely linked with a higher merger rate expected at redshift $z > 0.7$, and should also be related to the shorter age of distant clusters, implying less time to develop a cool core.
Context. Low-mass stars have been recognised as promising targets in the search for rocky, small planets with the potential of supporting life. As a consequence, Doppler search programmes using ...high-resolution spectrographs like HARPS or HARPS-N are providing huge quantities of optical spectra of M dwarfs. However, determining the stellar parameters of M dwarfs using optical spectra has proven to be challenging. Aims. We aim to calibrate empirical relationships to determine accurate stellar parameters for early-M dwarfs (spectral types M0-M4.5) using the same spectra as those that are used for radial velocity determinations, without the necessity of acquiring IR spectra or relying on atmospheric models and/or photometric calibrations. Methods. Our methodology consists of using ratios of pseudo-equivalent widths of spectral features as a temperature diagnostic, a technique frequently used in solar-type stars. Stars with effective temperatures obtained from interferometric estimates of their radii are used as calibrators. Empirical calibrations for the spectral type are also provided. Combinations of features and ratios of features are used to derive calibrations for the stellar metallicity. Our methods are then applied to a large sample of M dwarfs that are currently being observed in the framework of the HARPS GTO search for extrasolar planets. The derived temperatures and metallicities are used together with photometric estimates of mass, radius, and surface gravity to calibrate empirical relationships for these parameters. Results. A long list of spectral features in the optical spectra of early-M dwarfs was identified. This list shows that the pseudo-equivalent width of roughly 43% of the features is strongly anticorrelated with the effective temperature. The correlation with the stellar metallicity is weaker. A total of 112 temperature sensitive ratios were identified and calibrated over the range 3100−3950 K, providing effective temperatures with typical uncertainties of about 70 K. Eighty-two ratios of pseudo-equivalent widths of features were calibrated to derive spectral types within 0.5 subtypes for stars with spectral types between K7V and M4.5V. We calibrated 696 combinations of the pseudo-equivalent widths of individual features and temperature-sensitive ratios for the stellar metallicity over a metallicity range from −0.54 to +0.24 dex, with estimated uncertainties in the range of 0.07−0.10 dex. We provide our own empirical calibrations for stellar mass, radius, and surface gravity. These parameters depend on the stellar metallicity. For a given effective temperature, lower metallicities predict lower masses and radii as well as higher gravities.
An effective host immune response, critical for successful control of Cytomegalovirus (CMV) disease in solid organ transplant recipients, is affected by intensity and type of immunosuppressive ...therapy. We used information prospectively captured in the VICTOR‐trial to investigate the impact of immunosuppressive therapy on short‐ and long‐term outcomes of CMV treatment in organ transplant recipients. Dual, as compared to triple, immunosuppressive therapy (odds ratios OR of 2.55; 95% CI: 1.51–4.60; p = 0.002), lower blood concentrations of calcineurin inhibitors (OR of 5.53; CI: 1.04–29.35; p = 0.045), and longer time since transplantation (OR of 1.70; CI: 1.01–2.87; p = 0.047) all showed better early (Day 21) CMV DNAemia eradication. We observed no effect of the intensity of the immunosuppressive therapy on overall rates of viral eradication or recurrence. The type of calcineurin inhibitor (tacrolimus/cyclosporine) or use of mycophenolate did not affect treatment efficacy, although both tacrolimus and mycophenolate treated patients showed a lower rate of virological recurrence OR 0.51 (95% CI: 0.26–0.98; p = 0.044) and OR 0.45 (95% CI: 0.22–0.93; p = 0.031), respectively. Lower total intensity of immunosuppressive therapy was associated with more effective early, but not overall, CMV DNAemia eradication by valganciclovir/ganciclovir therapy. Both mycophenolate and tacrolimus (rather than cyclosporine) therapy seem to be associated with reduced risk of recurrence.
Lower total intensity of immunosuppressive therapy is associated with more effective early, but not overall, CMV DNAemia eradication by valganciclovir/ganciclovir therapy in organ transplant recipients with CMV disease. See Editorial by Avery and Kaplan on page 1727.
Background. It is unknown whether specific viral polymorphisms affect in vivo therapeutic response in patients with cytomegalovirus (CMV) disease. Polymorphisms in the CMV glycoprotein B (gB) gene ...allow discrimination of 4 distinct genotypes (gB1-gB4). We assessed the influence of gB genotypes on the clinical and virologic outcome of CMV disease. Methods. Solid-organ transplant recipients enrolled in a multicenter trial of CMV disease treatment (VICTOR study) were included in this study. CMV gB genotyping was performed using quantitative real-time polymerase chain reaction at day 0 (start of antiviral therapy). Results. Among 239 patients with CMV disease, the prevalence of gB strain types was 26% for gB1, 10% for gB2, 10% for gB3, and 5% for gB4, whereas mixed infections were present in 49%. Donor-seropositive/recipient-seropositive patients were more likely to have mixed gB infection than donor-seropositive/recipient-seronegative patients (40% vs. 12%; P<.001). Median baseline viral loads were higher and time to viral eradication was longer (P=.005 and P=.026, respectively) for mixed infection versus infection with a single genotype. In a multivariate model, mixed gB infection was a significant predictor of failure to eradicate virus by day 21 (mixed vs single genotype; odds ratio, 2.66; 95% confidence interval, 1.31–5.38; P=.007) after controlling for baseline viral load, CMV serostatus at baseline, ganciclovir resistance, and antiviral treatment. No effect of gB genotype was seen on virologic or clinical CMV recurrence. Conclusions. No specific gB genotype appears to confer a specific CMV virulence advantage. However, mixed gB genotype infections are associated with higher viral loads and delayed viral clearance.
Human cytomegalovirus (CMV) infection is a substantial cause of morbidity and mortality in immunocompromised hosts and globally is one of the most important congenital infections. The nucleoside ...analogue ganciclovir (GCV), which requires initial phosphorylation by the viral UL97 kinase, is the mainstay for treatment. To date, CMV decay kinetics during GCV therapy have not been extensively investigated and its clinical implications not fully appreciated. We measured CMV DNA levels in the blood of 92 solid organ transplant recipients with CMV disease over the initial 21 days of ganciclovir therapy and identified four distinct decay patterns, including a new pattern exhibiting a transient viral rebound (Hump) following initial decline. Since current viral dynamics models were unable to account for this Hump profile, we developed a novel multi-level model, which includes the intracellular role of UL97 in the continued activation of ganciclovir, that successfully described all the decline patterns observed. Fitting the data allowed us to estimate ganciclovir effectiveness in vivo (mean 92%), infected cell half-life (mean 0.7 days), and other viral dynamics parameters that determine which of the four kinetic patterns will ensue. An important clinical implication of our results is that the virological efficacy of GCV operates over a broad dose range. The model also raises the possibility that GCV can drive replication to a new lower steady state but ultimately cannot fully eradicate it. This model is likely to be generalizable to other anti-CMV nucleoside analogs that require activation by viral enzymes such as UL97 or its homologues.
Though an important cause of morbidity and mortality in solid organ transplantation (SOT), the long‐term outcomes of cytomegalovirus (CMV) disease treatment have not been well studied. In a ...randomized trial, 321 SOT recipients with CMV disease were followed 1 year after treatment with either twice daily intravenous ganciclovir or oral valganciclovir (for 21 days) followed by once daily valganciclovir until day 49 in all patients. Clinical and viral eradication of CMV disease was similar between groups. Clinical recurrence beyond day 49 was found in 15.1% and virological recurrence in 30.0%, no difference between groups (p > 0.77). In a multivariable logistic regression analysis, the only independent predictor for recurrence was failure to eradicate DNAemia by day 21 (clinical: OR 3.9 1.3–11.3, p = 0.012; virological: OR 5.6 2.5–12.6, p < 0.0001). Eight patients developed ganciclovir resistance, with no difference between groups (p = 0.62). Twenty patients (valganciclovir: 11, ganciclovir: 9, p = 0.82) died, 12 due to infections, two involving CMV disease. There were no differences in long‐term outcomes between treatment arms, further supporting the use of oral valganciclovir for treatment of CMV disease. Persistent DNAemia at day 21, CMV IgG serostatus and development of resistance may be relevant factors for further individualization of treatment.
In transplanted patients treated for CMV disease with GCV/VGCV, there was no difference in long‐term outcomes while persistent DNAemi at Day 21, CMV IGG serostatus at start of treatment, and development of resistance are relevant factors for individualization of treatment.
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