Scientific Objectives of Einstein Telescope

The advanced interferometer network will herald a new era in observational astronomy. There is a very strong science case to go beyond the advanced detector network and build detectors that operate in a frequency range from 1 Hz-10 kHz, with sensitivity a factor ten better in amplitude. Such detectors will be able to probe a range of topics in nuclear physics, astronomy, cosmology and fundamental physics, providing insights into many unsolved problems in these areas.Comment: 18 pages, 4 figures, Plenary talk given at Amaldi Meeting, July 201

A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant interpopulation pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/ or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective

A European spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant interpopulation pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective

A nebular analysis of the central Orion nebula with MUSE

A nebular analysis of the central Orion Nebula and its main structures is presented. We exploit MUSE integral field observations in the wavelength range 4595-9366 \r{A} to produce the first O, S and N ionic and total abundance maps of a region spanning 6' x 5' with a spatial resolution of 0.2". We use the S$_{23}$ ( = ([SII]$\lambda$6717,31+[SIII]$\lambda$9068)/H$\beta$) parameter, together with [OII]/[OIII] as an indicator of the degree of ionisation, to distinguish between the various small-scale structures. The only Orion Bullet covered by MUSE is HH 201, which shows a double component in the [FeII]$\lambda$8617 line throughout indicating an expansion, and we discuss a scenario in which this object is undergoing a disruptive event. We separate the proplyds located south of the Bright Bar into four categories depending on their S$_{23}$ values, propose the utility of the S$_{23}$ parameter as an indicator of the shock-contribution to the excitation of line-emitting atoms, and show that the MUSE data is able to identify the proplyds associated with disks and microjets. We compute the second order structure function for the H$\alpha$, [OIII]$\lambda$5007, [SII]$\lambda$6731 and [OI]$\lambda$6300 emission lines to analyse the turbulent velocity field of the region covered with MUSE. We find that the spectral and spatial resolution of MUSE is not able to faithfully reproduce the structure functions of previous works.Comment: 34 pages, 31 figures, published in MNRAS, added missing citatio