High-Throughput Qualitative and Quantitative Drug Checking by MALDI HRMS.

Illicit drugs are a global health problem, since both their acute and chronic consumption have negative impacts on the drug user's health. Drug checking facilities are receiving growing interest as they allow drug users to chemically analyze their product prior to consumption to assess the presence of adulterants or other non-expected substances. Such harm reduction programs allow the reduction of the risks associated with drug consumption without encouraging it. In particular, the emergence of new psychoactive substances (NPS) emphasizes the risk for the population increasing the diversity and the lability of illicit drugs on the market. Analytical developments are required to catch up with this rapid evolution and reduce the potential harm caused by such consumption. In this study, we developed a matrix-assisted laser desorption/ionization (MALDI) high-resolution mass spectrometry (HRMS) strategy for the high-throughput qualitative and quantitative analysis of drug checking samples. The use of online-based m/z cloud library for untargeted compound search improved the ability to identify unknown compounds. Sixty-seven drug checking samples were analyzed using this analytical strategy, allowing the detection of 10 designer drugs and several classical drugs of abuse (mainly cocaine and MDMA) as well as adulterants and contaminants. The results were then compared with routine analyses of the same samples using conventional approaches showing similar performance while removing the use of chromatographic separation thus resulting in a significant reduction of the time required for sample preparation and analysis. This study enlightens the potential of MALDI-HRMS as a high-throughput approach allowing to speed-up up to six times the identification and quantification of substances enabling to catch the fast changes on the drug of abuse market. This strategy could be an interesting alternative analytical approach, allowing better prevention and harm reduction for drug users

Horizontal partial laryngectomy for supraglottic squamous cell carcinoma

Between 1981-1999, 75 patients treated for supraglottic SCC with horizontal supraglottic laryngectomy (HSL) at the Otolaryngology Head and Neck Surgery Department of Lausanne University Hospital were retrospectively studied. There were 16 patients with T1, 46 with T2 and 13 with T3 tumors. Among these, 16 patients (21%) had clinical neck disease corresponding to stage I, II, III and IV in 12, 39, 18 and 6 patients, respectively. All patients had HSL. Most patients had either elective or therapeutic bilateral level II-IV selective neck dissection. Six patients (8%) with advanced neck disease had ipsilateral radical and controlateral elective II-IV selective neck dissections. Adjuvant radiotherapy was given to 25 patients (30%) for either positive surgical margins (n=8), pathological nodal status (n=14) or both (n=3). Median follow-up was 48months (range, 24-199). Five-year disease-specific survival and locoregional and local control were 92, 90 and 92.5%, respectively. Among five patients who were diagnosed with local recurrence, one had a total laryngectomy (1.4%); the others were treated by endoscopic laser surgery. Two patients had both a local and regional recurrence. They were salvaged with combined surgery and radiotherapy, but eventually died of their disease. Cartilage infiltration seems to influence both local control (P=0.03) and disease-specific survival (P=0.06). There was a trend for worse survival with pathological node involvement (P=0.15) and extralaryngeal extension of the cancer (P=0.1). All patients except one recovered a close to normal function after the treatment. Aspiration was present in 16 patients (26%) in the early postoperative period. A median of 16days (7-9) was necessary to recover a close to normal diet. Decannulation took a median of 17days (8-93). Seven patients kept a tracheotomy tube for up to 3months because of persistent aspiration. There was no permanent tracheostomy or total laryngectomy for functional purposes. Horizontal supraglottic laryngectomy remains an adequate therapeutic alternative for supraglottic squamous cell carcinoma, offering an excellent oncological outcome. The postoperative functional morbidity is substantial, indicating the need for careful patient selection, but good laryngeal function recovery is the rule. The surgical alternative is endoscopic laser surgery, which may offer comparable oncological results with less functional morbidity. Nevertheless, these two different techniques need to be compared prospectivel

The CORALIE survey for southern extrasolar planets. XVI. Discovery of a planetary system around HD 147018 and of two long period and massive planets orbiting HD 171238 and HD 204313

We report the detection of a double planetary system around HD 140718 as well as the discovery of two long period and massive planets orbiting HD 171238 and HD 204313. Those discoveries were made with the CORALIE Echelle spectrograph mounted on the 1.2-m Euler Swiss telescope located at La Silla Observatory, Chile. The planetary system orbiting the nearby G9 dwarf HD 147018 is composed of an eccentric inner planet (e=0.47) with twice the mass of Jupiter (2.1 MJup ) and with an orbital period of 44.24 days. The outer planet is even more massive (6.6 MJup) with a slightly eccentric orbit (e=0.13) and a period of 1008 days. The planet orbiting HD 171238 has a minimum mass of 2.6 MJup, a period of 1523 days and an eccentricity of 0.40. It orbits a G8 dwarfs at 2.5 AU. The last planet, HD 204313 b, is a 4.0 MJup -planet with a period of 5.3 years and has a low eccentricity (e = 0.13). It orbits a G5 dwarfs at 3.1 AU. The three parent stars are metal rich, which further strengthened the case that massive planets tend to form around metal rich stars.Comment: 6 pages, 6 figures, accepted for publication in A&

Data Analysis for Precision Spectroscopy: the ESPRESSO Case

Astronomical Spectroscopy is rapidly evolving into a precision science, with several science cases increasingly relying on long-term instrumental stability and centimeter-per-second accuracy in wavelength calibration. These requirements strongly call for integrated software tools to manage not only the reduction of data, but also the scientific analysis. The ultra-stable, high-resolution echelle spectrograph ESPRESSO, currently under integration for the ESO Very Large Telescope (first light: 2017) is the first instrument of its kind to include a dedicated Data Analysis Software among its deliverables, to process both stellar and quasar spectra. This software will extract physical information from the reduced data on the fly (e.g., stellar radial velocities, or characterisation of the absorption systems along the sightline to quasars) and will allow interaction through a configurable graphical user interface. In this article we present the features of the ESPRESSO Data Analysis Software and its development status at the first complete internal release. A particular attention is devoted to the algorithms developed for quasar spectral analysis (continuum determination and interpretation of the absorption systems)

ESPRESSO: The next European exoplanet hunter

The acronym ESPRESSO stems for Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations; this instrument will be the next VLT high resolution spectrograph. The spectrograph will be installed at the Combined-Coud\'e Laboratory of the VLT and linked to the four 8.2 m Unit Telescopes (UT) through four optical Coud\'e trains. ESPRESSO will combine efficiency and extreme spectroscopic precision. ESPRESSO is foreseen to achieve a gain of two magnitudes with respect to its predecessor HARPS, and to improve the instrumental radial-velocity precision to reach the 10 cm/s level. It can be operated either with a single UT or with up to four UTs, enabling an additional gain in the latter mode. The incoherent combination of four telescopes and the extreme precision requirements called for many innovative design solutions while ensuring the technical heritage of the successful HARPS experience. ESPRESSO will allow to explore new frontiers in most domains of astrophysics that require precision and sensitivity. The main scientific drivers are the search and characterization of rocky exoplanets in the habitable zone of quiet, nearby G to M-dwarfs and the analysis of the variability of fundamental physical constants. The project passed the final design review in May 2013 and entered the manufacturing phase. ESPRESSO will be installed at the Paranal Observatory in 2016 and its operation is planned to start by the end of the same year.Comment: 12 pages, figures included, accepted for publication in Astron. Nach

Stability of Modified Electroweak Strings

We discuss the stability of an electroweak string with axions in its core, which give to the configuration a quasi-topological property, and compare it with other modifications using instantons in the thin wall approximation.Comment: Minor changes and inclusion of one figure. To be published on Z. f. Physik C. 11 pages, 1 postcript figur

Data treatment towards the ELT age. The ESPRESSO case

Several ambitious scientific projects are currently pushing the limits of astrophysical spectroscopy, in terms of wavelength accuracy and long-term stability. These objectives put strong constraints also on the treatment of observational data, requiring dedicated software to be developed as an integral part of the instrument. In this context, a key role will be played by ESPRESSO, an ultra-stable, high-resolution spectrograph for the VLT. ESPRESSO will be the first ESO instrument to be delivered with a dedicated tool for data analysis, in addition to data reduction. New solutions to treat ESPRESSO data have been developed in view of their application to the the next-generation spectrographs. <P /

The Rossiter–McLaughlin effect revolutions: an ultra-short period planet and a warm mini-Neptune on perpendicular orbits

Comparisons of the alignment of exoplanets with a common host star can be used to distinguish among concurrent evolution scenarios. However, multi-planet systems usually host mini-Neptunes and super-Earths, whose size make orbital architecture measurements challenging. We introduce the Rossiter-McLaughlin effect Revolutions technique, which can access spin-orbit angles of small planets by exploiting the full information contained in spectral transit time series. We validated the technique on published HARPS-N data of the mini-Neptune HD3167c, refining its high sky-projected spin-orbit angle (-108.9+5.4-5.5 deg), and we applied it to new ESPRESSO observations of the super-Earth HD3167b, revealing an aligned orbit (-6.6+6.6-7.9 deg). Surprisingly different variations in the contrast of the stellar lines occulted by the planets can be reconciled with a latitudinal dependence of the stellar line shape. In this scenario, a joint fit to both datasets constrains the inclination of the star (111.6+3.1-3.3 deg) and the 3D spin-orbit angles of HD3167b (29.5+7.2-9.4 deg) and HD3167c (107.7+5.1-4.9 deg). The projected spin-orbit angles do not depend on the model for the line contrast variations, and so, with a mutual inclination of 102.3+7.4-8.0 deg, we conclude that the two planets are on perpendicular orbits. This could be explained by HD3167b being strongly coupled to the star and retaining its primordial alignment, whereas HD3167c would have been brought to a nearly polar orbit via secular gravitational interactions with an outer companion. Follow-up observations and dynamical evolution simulations are required to search for this companion and explore this scenario. HD3167b is the smallest exoplanet with a confirmed spectroscopic Rossiter-McLaughlin signal. Our new technique opens the way to determining the orbital architectures of the super-Earth and Earth-sized planet populations

From CODEX to ESPRESSO to HIRES@E-ELT: a view on cosmology and fundamental physics from the IGM perspective

The Italian community, thanks to the strong technological and scientific tradition in the field of high-resolution spectroscopy and the study of the Intergalactic Medium, has played a key role in the conception of a high-resolution spectrograph for the new generation of giant telescopes (initially focused on the COsmic Dynamics EXperiment at OWL). This expertise is being exploited in the construction of a precursor: the ESPRESSO instrument that will start operations at the ESO VLT in 2017 and will pave the way to the HIRES instrument at the E-ELT. Here we discuss the role that the (evolving) scientific themes of cosmology and fundamental physics - from the Intergalactic Medium perspective - have played and are playing to shape the E-ELT high resolution instrument