The scientific thought of Salvador Reguant

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

Pharmacokinetic (Pk) Activity of Cabazitaxel (Cbz) in Patients (Pts) with Renal Impairment (Ri)

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Probing the Early Evolution of Young High-Mass Stars

Near-infrared imaging surveys of high-mass star-forming regions reveal an amazingly complex interplay between star formation and the environment (Churchwell et al. 2006; Alvarez et al. 2004). By means of near-IR spectroscopy the embedded massive young stars can be characterized and placed in the context of their birth site. However, so far spectroscopic surveys have been hopelessly incomplete, hampering any systematic study of these very young massive stars. New integral field instrumentation available at ESO has opened the possibility to take a huge step forward by obtaining a full spectral inventory of the youngest massive stellar populations in star-forming regions currently accessible. Simultaneously, the analysis of the extended emission allows the characterization of the environmental conditions. The Formation and Early Evolution of Massive Stars (FEMS) collaboration aims at setting up a large observing campaign to obtain a full census of the stellar content, ionized material, outflows and PDR's over a sample of regions that covers a large parameter space. Complementary radio, mm and infrared observations will be used for the characterization of the deeply embedded population. For the first eight regions we have obtained 40 hours of SINFONI observations. In this contribution, we present the first results on three regions that illustrate the potential of this strategy.Comment: To appear in ASP Conf. Proceedings of "Massive Star Formation: Observations confront Theory", H. Beuther et al. (eds.), held in Heidelberg, September 200

Herschel Observations of the W43 "mini-starburst"

Aims: To explore the infrared and radio properties of one of the closest Galactic starburst regions. Methods: Images obtained with the Herschel Space Observatory at wavelengths of 70, 160, 250, 350, and 500 microns using the PACS and SPIRE arrays are analyzed and compared with radio continuum VLA data and 8 micron images from the Spitzer Space Telescope. The morphology of the far-infrared emission is combined with radial velocity measurements of millimeter and centimeter wavelength transitions to identify features likely to be associated with the W43 complex. Results: The W43 star-forming complex is resolved into a dense cluster of protostars, infrared dark clouds, and ridges of warm dust heated by massive stars. The 4 brightest compact sources with L > 1.5 x 10^4 Lsun embedded within the Z-shaped ridge of bright dust emission in W43 remain single at 4" (0.1 pc) resolution. These objects, likely to be massive protostars or compact clusters in early stages of evolution are embedded in clumps with masses of 10^3 to 10^4 Msun, but contribute only 2% to the 3.6 x 10^6 Lsun far-IR luminosity of W43 measured in a 16 by 16 pc box. The total mass of gas derived from the far-IR dust emission inside this region is ~10^6 Msun. Cometary dust clouds, compact 6 cm radio sources, and warm dust mark the locations of older populations of massive stars. Energy release has created a cavity blowing-out below the Galactic plane. Compression of molecular gas in the plane by the older HII region near G30.684-0.260 and the bipolar structure of the resulting younger W43 HII region may have triggered the current mini-star burst.Comment: 5 pages, 3 figures, accepted for A&A Special Issu

Protective efficacy of an RBD-based Middle East respiratory syndrome coronavirus (MERS-CoV) particle vaccine in llamas

Ongoing outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) continue posing a global health threat. Vaccination of livestock reservoir species is a recommended strategy to prevent spread of MERS-CoV among animals and potential spillover to humans. Using a direct-contact llama challenge model that mimics naturally occurring viral transmission, we tested the efficacy of a multimeric receptor binding domain (RBD) particle-display based vaccine candidate. While MERS-CoV was transmitted to naïve animals exposed to virus-inoculated llamas, immunization induced robust virus-neutralizing antibody responses and prevented transmission in 1/3 vaccinated, in-contact animals. Our exploratory study supports further improvement of the RBD-based vaccine to prevent zoonotic spillover of MERS-CoV

Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma

Altres ajuts: This trial was funded by Eli Lilly and Company.The online version of this article contains supplementary material, which is available to authorized users

ALMA Observations of Asteroid 3 Juno at 60 Kilometer Resolution

We present Atacama Large Millimeter/submillimeter Array (ALMA) 1.3 mm continuum images of the asteroid 3 Juno obtained with an angular resolution of 0.042 arcseconds (60 km at 1.97 AU). The data were obtained over a single 4.4 hr interval, which covers 60% of the 7.2 hr rotation period, approximately centered on local transit. A sequence of ten consecutive images reveals continuous changes in the asteroid's profile and apparent shape, in good agreement with the sky projection of the three-dimensional model of the Database of Asteroid Models from Inversion Techniques. We measure a geometric mean diameter of 259pm4 km, in good agreement with past estimates from a variety of techniques and wavelengths. Due to the viewing angle and inclination of the rotational pole, the southern hemisphere dominates all of the images. The median peak brightness temperature is 215pm13 K, while the median over the whole surface is 197pm15 K. With the unprecedented resolution of ALMA, we find that the brightness temperature varies across the surface with higher values correlated to the subsolar point and afternoon areas, and lower values beyond the evening terminator. The dominance of the subsolar point is accentuated in the final four images, suggesting a reduction in the thermal inertia of the regolith at the corresponding longitudes, which are possibly correlated to the location of the putative large impact crater. These results demonstrate ALMA's potential to resolve thermal emission from the surface of main belt asteroids, and to measure accurately their position, geometric shape, rotational period, and soil characteristics.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

First Results from High Angular Resolution ALMA Observations Toward the HL Tau Region

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations from the 2014 Long Baseline Campaign in dust continuum and spectral line emission from the HL Tau region. The continuum images at wavelengths of 2.9, 1.3, and 0.87 mm have unprecedented angular resolutions of 0.075 arcseconds (10 AU) to 0.025 arcseconds (3.5 AU), revealing an astonishing level of detail in the circumstellar disk surrounding the young solar analogue HL Tau, with a pattern of bright and dark rings observed at all wavelengths. By fitting ellipses to the most distinct rings, we measure precise values for the disk inclination (46.72pm0.05 degrees) and position angle (+138.02pm0.07 degrees). We obtain a high-fidelity image of the 1.0 mm spectral index ($\alpha$), which ranges from $\alpha\sim2.0$ in the optically-thick central peak and two brightest rings, increasing to 2.3-3.0 in the dark rings. The dark rings are not devoid of emission, we estimate a grain emissivity index of 0.8 for the innermost dark ring and lower for subsequent dark rings, consistent with some degree of grain growth and evolution. Additional clues that the rings arise from planet formation include an increase in their central offsets with radius and the presence of numerous orbital resonances. At a resolution of 35 AU, we resolve the molecular component of the disk in HCO+ (1-0) which exhibits a pattern over LSR velocities from 2-12 km/s consistent with Keplerian motion around a ~1.3 solar mass star, although complicated by absorption at low blue-shifted velocities. We also serendipitously detect and resolve the nearby protostars XZ Tau (A/B) and LkHa358 at 2.9 mm.Comment: 11 pages, 5 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67/13)

BACKGROUND: PQR309 is an orally bioavailable, balanced pan-phosphatidylinositol-3-kinase (PI3K), mammalian target of rapamycin (mTOR) C1 and mTORC2 inhibitor. PATIENTS AND METHODS: This is an accelerated titration, 3 + 3 dose-escalation, open-label phase I trial of continuous once-daily (OD) PQR309 administration to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics in patients with advanced solid tumours. Primary objectives were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). RESULTS: Twenty-eight patients were included in six dosing cohorts and treated at a daily PQR309 dose ranging from 10 to 150 mg. Common adverse events (AEs; ≥30% patients) included fatigue, hyperglycaemia, nausea, diarrhoea, constipation, rash, anorexia and vomiting. Grade (G) 3 or 4 drug-related AEs were seen in 13 (46%) and three (11%) patients, respectively. Dose-limiting toxicity (DLT) was observed in two patients at 100 mg OD (>14-d interruption in PQR309 due to G3 rash, G2 hyperbilirubinaemia, G4 suicide attempt; dose reduction due to G3 fatigue, G2 diarrhoea, G4 transaminitis) and one patient at 80 mg (G3 hyperglycaemia >7 d). PK shows fast absorption (Tmax 1-2 h) and dose proportionality for Cmax and area under the curve. A partial response in a patient with metastatic thymus cancer, 24% disease volume reduction in a patient with sinonasal cancer and stable disease for more than 16 weeks in a patient with clear cell Bartholin's gland cancer were observed. CONCLUSION: The MTD and RP2D of PQR309 is 80 mg of orally OD. PK is dose-proportional. PD shows PI3K pathway phosphoprotein downregulation in paired tumour biopsies. Clinical activity was observed in patients with and without PI3K pathway dysregulation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov # NCT01940133