Validation Through Simulations of a Cn2 Profiler for the ESO/VLT Adaptive Optics Facility

The Adaptive Optics Facility (AOF) project envisages transforming one of the VLT units into an adaptive telescope and providing its ESO (European Southern Observatory) second generation instruments with turbulence corrected wavefronts. For MUSE and HAWK-I this correction will be achieved through the GALACSI and GRAAL AO modules working in conjunction with a 1170 actuators Deformable Secondary Mirror (DSM) and the new Laser Guide Star Facility (4LGSF). Multiple wavefront sensors will enable GLAO and LTAO capabilities, whose performance can greatly benefit from a knowledge about the stratification of the turbulence in the atmosphere. This work, totally based on end-to-end simulations, describes the validation tests conducted on a Cn2 profiler adapted for the AOF specifications. Because an absolute profile calibration is strongly dependent on a reliable knowledge of turbulence parameters r0 and L0, the tests presented here refer only to normalized output profiles. Uncertainties in the input parameters inherent to the code are tested as well as the profiler response to different turbulence distributions. It adopts a correction for the unseen turbulence, critical for the GRAAL mode, and highlights the effects of masking out parts of the corrected wavefront on the results. Simulations of data with typical turbulence profiles from Paranal were input to the profiler, showing that it is possible to identify reliably the input features for all the AOF modes.Comment: 15 pages, 12 figures, accepted for publication in the MNRAS Accepted 2015 January 22. Received 2015 January 21; in original form 2014 December

The AGN properties of the starburst galaxy NGC 7582

NGC 7582 was identified as a Starburst galaxy in the optical \cite[(Veron et al. 1981)]{Veron et al.(1981)} but its X-Ray emission is typical of a Seyfert 1 galaxy \cite[(Ward et al. 1978)]{Ward et al.(1978)}. We analyzed a datacube of this object obtained with the GMOS-IFU on the Gemini-South telescope. After a subtraction of the stellar component using the {\sc starlight} code \cite[(Cid Fernandes et al. 2005)]{Cid Fernandes et al. (2005)}, we looked for optical signatures of the AGN. We detected a broad $H\alpha$ component (figure \ref{fig1}) in the source where \cite[Bianchi et al.(2007)]{Bianchi et al.(2007)} identified the AGN in an HST optical image. We also found a broad $H\beta$ feature (figure \ref{fig2}), but its emission reveals a extended source. We suggest that it is the light of the AGN scattered in the ionization cone. We propose that NGC 7582 is a Seyfert 1 galaxy. A number of other "hot-spots" and Wolf-Rayet features were also identified.Comment: 1 page, 2 figures, to be published in the Proceedings of the IAU Symposium no. 26

An atlas of Calcium triplet spectra of active galaxies

We present a spectroscopic atlas of active galactic nuclei covering the region around the 8498, 8542, 8662 Calcium triplet (CaT) lines. The sample comprises 78 objects, divided into 43 Seyfert 2s, 26 Seyfert 1s, 3 Starburst and 6 normal galaxies. The spectra pertain to the inner ~300 pc in radius, and thus sample the central kinematics and stellar populations of active galaxies. The data are used to measure stellar velocity dispersions (sigma_star) both with cross-correlation and direct fitting methods. These measurements are found to be in good agreement with each-other and with those in previous studies for objects in common. The CaT equivalent width is also measured. We find average values and sample dispersions of W_CaT of 4.6+/-2.0, 7.0 and 7.7+/-1.0 angstrons for Seyfert 1s, Seyfert 2s and normal galaxies, respectively. We further present an atlas of [SIII]\lambda 9069 emission line profiles for a subset of 40 galaxies. These data are analyzed in a companion paper which addresses the connection between stellar and Narrow Line Region kinematics, the behaviour of the CaT equivalent width as a function of sigma_star, activity type and stellar population properties.Comment: 18 pages, 10 figures, accepted for publication in MNRA

A Near-Infrared Template Derived from I Zw 1 for the FeII Emission in Active Galaxies

In AGN spectra, a series of FeII multiplets form a pseudo-continuum that extends from the ultraviolet to the near-infrared (NIR). This emission is believed to originate in the Broad Line Region (BLR), and it has been known for a long time that pure photoionization fails to reproduce it in the most extreme cases, as does the collisional-excitation alone. The most recent models by Sigut & Pradhan (2003) include details of the FeII ion microphysics and cover a wide range in ionization parameter log U_ion= (-3.0 -> -1.3) and density log n_H = (9.6 -> 12.6). With the aid of such models and a spectral synthesis approach, we study for the first time in detail the NIR emission of I Zw 1. The main goals are to confirm the role played by Ly\alpha-fluorescence mechanisms in the production of the FeII spectrum and to construct the first semi-empirical NIR FeII template that best represents this emission and can be used to subtract it in other sources. A good overall match between the observed FeII+MgII features with those predicted by the best fitted model is obtained, corroborating the Ly\alpha-fluorescence as a key process to understand the FeII spectrum. The best model is then adjusted by applying a deconvolution method on the observed FeII+MgII spectrum. The derived semi-empirical template is then fitted to the spectrum of Ark 564, suitably reproducing its observed FeII+MgII emission. Our approach extends the current set of available FeII templates into the NIR region.Comment: 47 pages, 5 tables, 12 figures. Accepted for publication in The Astrophysical Journa

The impact of CYP2C19 genotype on phenoconversion by concomitant medication

Introduction: Pharmacogenetics-informed drug prescribing is increasingly applied in clinical practice. Typically, drug metabolizing phenotypes are determined based on genetic test results, whereupon dosage or drugs are adjusted. Drug-drug-interactions (DDIs) caused by concomitant medication can however cause mismatches between predicted and observed phenotypes (phenoconversion). Here we investigated the impact of CYP2C19 genotype on the outcome of CYP2C19-dependent DDIs in human liver microsomes.Methods: Liver samples from 40 patients were included, and genotyped for CYP2C19*2, *3 and *17 variants. S-mephenytoin metabolism in microsomal fractions was used as proxy for CYP2C19 activity, and concordance between genotype-predicted and observed CYP2C19 phenotype was examined. Individual microsomes were subsequently co-exposed to fluvoxamine, voriconazole, omeprazole or pantoprazole to simulate DDIs.Results: Maximal CYP2C19 activity (Vmax) in genotype-predicted intermediate metabolizers (IMs; *1/*2 or *2/*17), rapid metabolizers (RMs; *1/*17) and ultrarapid metabolizers (UMs; *17/*17) was not different from Vmax of predicted normal metabolizers (NMs; *1/*1). Conversely, CYP2C19*2/*2 genotyped-donors exhibited Vmax rates ∼9% of NMs, confirming the genotype-predicted poor metabolizer (PM) phenotype. Categorizing CYP2C19 activity, we found a 40% concordance between genetically-predicted CYP2C19 phenotypes and measured phenotypes, indicating substantial phenoconversion. Eight patients (20%) exhibited CYP2C19 IM/PM phenotypes that were not predicted by their CYP2C19 genotype, of which six could be linked to the presence of diabetes or liver disease. In subsequent DDI experiments, CYP2C19 activity was inhibited by omeprazole (−37% ± 8%), voriconazole (−59% ± 4%) and fluvoxamine (−85% ± 2%), but not by pantoprazole (−2 ± 4%). The strength of CYP2C19 inhibitors remained unaffected by CYP2C19 genotype, as similar percental declines in CYP2C19 activity and comparable metabolism-dependent inhibitory constants (Kinact/KI) of omeprazole were observed between CYP2C19 genotypes. However, the consequences of CYP2C19 inhibitor-mediated phenoconversion were different between CYP2C19 genotypes. In example, voriconazole converted 50% of *1/*1 donors to a IM/PM phenotype, but only 14% of *1/*17 donors. Fluvoxamine converted all donors to phenotypic IMs/PMs, but *1/*17 (14%) were less likely to become PMs than *1/*1 (50%) or *1/*2 and *2/*17 (57%).Conclusion: This study suggests that the differential outcome of CYP2C19-mediated DDIs between genotypes are primarily dictated by basal CYP2C19 activity, that may in part be predicted by CYP2C19 genotype but likely also depends on disease-related factors

The CaT strength in Seyfert nuclei revisited: analyzing young stars and non-stellar light contributions to the spectra

In a former paper (Garcia-Rissmann et al. 2005; hereafter Paper I), we have presented spectra of 64 active, 9 normal and 5 Starburst galaxies in the region around the near-IR Calcium triplet absorption lines and the [SIII]9069 line. In the present paper we analyze the CaT strength (WCaT), and kinematical products derived in that study, namely stellar and ionized gas velocity dispersions. Our main results may be summarized as follows: (1) Seyfert 2s show no sign of dilution in WCaT with respect to the values spanned by normal galaxies, even when optical absorption lines such as the CaII K band at 3933 A are much weaker than in old, bulge-like stellar populations. (2) The location of Seyfert 2s in the WCaT-WCaK plane is consistent with evolutionary synthesis models. The implication is that the source responsible for the dilution of optical lines in these AGN is a young stellar population, rather than an AGN featureless continuum, confirming the conclusion of the pioneer study of Terlevich, Diaz & Terlevich. (3) In Seyfert 1s, both W[SIII] and WCaT tend to be diluted due to the presence of a non-stellar component, in agreement with the unification paradigm. (4) A comparison of stellar and gas velocity dispersions confirms the existence of a correlation between the typical velocities of stars and clouds of the Narrow Line Region. The strength and scatter around this correlation are similar to those previously obtained from the [OIII]5007 line width.Comment: 14 pages, 15 figures. Paper accepted for publication in MNRA

Gender differences in clinical registration trials: is there a real problem?

AimsSeveral studies have reported the under-representation of women in clinical trials, thereby challenging the external validity of the benefit/risk assessments of launched drugs. Our aim was to determine the extent to which women have been included in clinical trials used for drug registration and to analyse the fraction of women participating in phases I, II and III.MethodsWe conducted cross-sectional, structured research into publicly available registration dossiers of Food and Drug Administration (FDA)-approved drugs that are prescribed frequently. Furthermore, we analysed compounds with high hepatic clearance and a known gender-related difference in drug response. In a sensitivity analysis, we compared figures with US disease prevalence data.ResultsFor 38 of the initial 137 drugs (28%), sufficient data were reported and publicly available. For these drugs, 185479 trial participants were included, of whom 47% were female and 44% were male; gender was not reported for 9% of participants. However, the number of female participants varied with the phase of the trial, with 22% females in phase I trials vs. 48% and 49%, respectively, in phase II and III trials. When compared with US disease prevalence data, 10 drugs (26%) had a greater than 20% difference between the proportion of females affected with the disease compared with representation in clinical trials.ConclusionsFrom these publicly available data, there was no evidence of any systematic under-representation of women in clinical trials.Drug Delivery Technolog