First light of VLT/HiRISE: High-resolution spectroscopy of young giant exoplanets

A major endeavor of this decade is the direct characterization of young giant exoplanets at high spectral resolution to determine the composition of their atmosphere and infer their formation processes and evolution. Such a goal represents a major challenge owing to their small angular separation and luminosity contrast with respect to their parent stars. Instead of designing and implementing completely new facilities, it has been proposed to leverage the capabilities of existing instruments that offer either high-contrast imaging or high-dispersion spectroscopy by coupling them using optical fibers. In this work, we present the implementation and first on-sky results of the High-Resolution Imaging and Spectroscopy of Exoplanets (HiRISE) instrument at the Very Large Telescope (VLT), which combines the exoplanet imager SPHERE with the recently upgraded high-resolution spectrograph CRIRES using single-mode fibers. The goal of HiRISE is to enable the characterization of known companions in the H band at a spectral resolution on the order of R = λ/∆λ = 100 000 in a few hours of observing time. We present the main design choices and the technical implementation of the system, which is constituted of three major parts: the fiber injection module inside of SPHERE, the fiber bundle around the telescope, and the fiber extraction module at the entrance of CRIRES. We also detail the specific calibrations required for HiRISE and the operations of the instrument for science observations. Finally, we detail the performance of the system in terms of astrometry, temporal stability, optical aberrations, and transmission, for which we report a peak value of ~3.9% based on sky measurements in median observing conditions. Finally, we report on the first astrophysical detection of HiRISE to illustrate its potential

First light of VLT/HiRISE: High-resolution spectroscopy of young giant exoplanets

A major endeavor of this decade is the direct characterization of young giant exoplanets at high spectral resolution to determine the composition of their atmosphere and infer their formation processes and evolution. Such a goal represents a major challenge owing to their small angular separation and luminosity contrast with respect to their parent stars. Instead of designing and implementing completely new facilities, it has been proposed to leverage the capabilities of existing instruments that offer either high contrast imaging or high dispersion spectroscopy, by coupling them using optical fibers. In this work we present the implementation and first on-sky results of the HiRISE instrument at the very large telescope (VLT), which combines the exoplanet imager SPHERE with the recently upgraded high resolution spectrograph CRIRES using single-mode fibers. The goal of HiRISE is to enable the characterization of known companions in the $H$ band, at a spectral resolution of the order of $R = \lambda/\Delta\lambda = 100\,000$, in a few hours of observing time. We present the main design choices and the technical implementation of the system, which is constituted of three major parts: the fiber injection module inside of SPHERE, the fiber bundle around the telescope, and the fiber extraction module at the entrance of CRIRES. We also detail the specific calibrations required for HiRISE and the operations of the instrument for science observations. Finally, we detail the performance of the system in terms of astrometry, temporal stability, optical aberrations, and transmission, for which we report a peak value of $\sim$3.9% based on sky measurements in median observing conditions. Finally, we report on the first astrophysical detection of HiRISE to illustrate its potential.Comment: 17 pages, 15 figures, 3 tables. Submitted to A&A on 19 September 202

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Risk of biochemical recurrence based on extent and location of positive surgical margins after robot-assisted laparoscopic radical prostatectomy

Abstract Background There are no published studies on the simultaneous effect of extent and location of positive surgical margins (PSMs) on biochemical recurrence (BCR) after robot-assisted laparoscopic prostatectomy (RALP). The aim was to report the incidence, extent, and location of PSMs over the inclusion period as well as the rates of BCR and cancer-related mortality, and determine if BCR is associated with PSM extent and/or location. Methods Retrospective review of 530 consecutive patients who underwent RALP between 2003 and 2012. Kaplan-Meier (KM) survival analyses and Cox regressions were performed to determine variables associated with BCR. Results For the 530 operated patients, evaluated at a median of 92 months (IQR, 87–99), PSMs were observed in 156 (29%), of which 24% were focal. Out of 172 PSMs, 126 (73%) were focal and 46 (27%) were extensive. The KM survival using BCR as endpoint was 0.81 (CI, 0.78–0.85) at 5 years and was 0.67 (CI, 0.61–0.72) at 10 years; and using cancer-related mortality as endpoint was 0.99 (CI, 0.99–1.00) at 5 years and 0.95 (CI, 0.92–0.98) at 10 years. Multi-variable analysis revealed the strongest predictors of BCR to be Gleason score ≥ 8 (HR = 7.97; CI, 4.38–14.51) and 4 + 3 (HR = 3.88; CI, 2.12–7.07), lymph nodes invasion (HR = 3.42; CI, 1.70–6.91), pT stage 3b or 4 (HR = 3.07; CI, 1.93–4.90), and extensive apical PSMs (HR = 2.62; CI, 1.40–4.90) but not focal apical PSMs (HR = 0.86; CI, 0.49–1.50; p = 0.586). Conclusion Extensive apical PSMs significantly increased the risk of BCR, independently from pT stage, Gleason score and lymph nodes invasion, while focal apical PSMs had no significant effect on BCR

A Novel Method Combining Linkage Disequilibrium Information and Imputed Functional Knowledge for tagSNP Selection

Analyses of high-density SNPs in genetic studies have the potential problems of prohibitive genotyping costs and inflated false discovery rates. Current methods select subsets of representative SNPs (tagSNPs) using information either on potential biologic functionality of the SNPs or on the underlying linkage disequilibrium (LD) structure, but not both. Combining the two types of information may lead to more effective tagSNP selection. The proposed method combines both functional and LD information using a weighted factor analysis (WFA) model. The WFA was applied to the dense SNP collection from 129 genes sequenced by the SeattleSNPs Program for Genomic Application. TagSNPs selected by WFA were compared with those selected by an LD-based method. WFA allowed prioritization of SNPs that would otherwise share equivalent ranking due to underlying LD structure alone. Furthermore, WFA consistently included SNPs not selected by function or by LD alone. A literature review of a subset of genes revealed that SNPs selected by WFA were more likely represented in published reports

Volume and market share of anti-epileptic drugs in The Netherlands: impact of new drugs.

Item does not contain fulltextOBJECTIVE: In the past decade, several new anti-epileptic drugs (AEDs) were introduced in The Netherlands. These new drugs, one of which is lamotrigine, are 6 to 10 times more expensive than conventional anti-convulsants. In 1997, the high cost of lamotrigine, together with a lack of clinical data supporting its superiority over conventional drugs, prompted the Dutch Health Insurance Board to release a guideline in which the use of lamotrigine was restricted to difficult-to-treat patients. Other new drugs that were marketed after 1997 also became subject to this guideline. The utilisation of new AEDs and the cost consequences are the subject of this paper. METHODS: Data from extramurally prescribed AEDs was obtained from the Dutch Drug Information Project, which is a database containing prescriptions for about 5.5 million inhabitants of the Netherlands. This data was used to study the impact of new AEDs on volume and market share of AEDs in the period from 1995 to 2001 in The Netherlands. RESULTS: Between 1995 and 2001, the total volume of AEDs increased by 130%, 60% of which consisted of new AEDs. Gabapentin, lamotrigine and oxcarbazepine were the most frequently prescribed new compounds. The volume share of new AEDs increased from 5% in 1995 to 18% in 2001. The market share amounted to 21.5 million euros in 1995 and rose to 47 million euros in 2001; 80% of this increase was due to the introduction of new AEDs. DISCUSSION: Although in 2001 the volume share of new AEDs was still modest, their introduction has led to a strong increase in the cost. New data is emerging on the effectiveness and cost-benefit sum of the new AEDs; this may change the place in therapy of these drugs. Because of their strong potential to force up cost, the positioning of new AEDs requires further attention