What information could the main actors of liquid biopsy provide? A representative case of non-small cell lung cancer (NSCLC)

In non-small cell lung cancer (NSCLC), there is a consensus regarding the use of liquid biopsy, generally, to detect "druggable" mutations and, in particular, to monitor tyrosine kinase inhibitor (TKI) treatments. However, whether circulating tumor cells (CTCs) are better tools than cell-free DNA (cfDNA), is still a matter of debate, mainly concerning which antigen(s) we should use to investigating simultaneously both epithelial and epithelial-to-mesenchymal transient (EMT) phenotype in the same sample of CTCs. To address this item, we exploited here a single-tube liquid biopsy, to detect both epithelial cell adhesion molecule (EpCAM)-positive CTCs and EpCAM-low/negative CTCs, because down-modulation of EpCAM is considered the first step in EMT. Furthermore, we analyzed the DNA from CTCs of four different phenotypes (ctcDNA), according to their EpCAM expression and cytokeratin pattern, and circulating tumor DNA (ctDNA) by droplet digital PCR (ddPCR), in order to disclose activating and resistancedriving mutations. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution

On the shape of the mass-function of dense clumps in the Hi-GAL fields. II. Using Bayesian inference to study the clump mass function

Context. Stars form in dense, dusty clumps of molecular clouds, but little is known about their origin, their evolution and their detailed physical properties. In particular, the relationship between the mass distribution of these clumps (also known as the "clump mass function", or CMF) and the stellar initial mass function (IMF), is still poorly understood. Aims. In order to better understand how the CMF evolve toward the IMF, and to discern the "true" shape of the CMF, large samples of bona-fide pre- and proto-stellar clumps are required. Two such datasets obtained from the Herschel infrared GALactic Plane Survey (Hi-GAL) have been described in paper I. Robust statistical methods are needed in order to infer the parameters describing the models used to fit the CMF, and to compare the competing models themselves. Methods. In this paper we apply Bayesian inference to the analysis of the CMF of the two regions discussed in Paper I. First, we determine the Bayesian posterior probability distribution for each of the fitted parameters. Then, we carry out a quantitative comparison of the models used to fit the CMF. Results. We have compared the results from several methods implementing Bayesian inference, and we have also analyzed the impact of the choice of priors and the influence of various constraints on the statistical conclusions for the preferred values of the parameters. We find that both parameter estimation and model comparison depend on the choice of parameter priors. Conclusions. Our results confirm our earlier conclusion that the CMFs of the two Hi-GAL regions studied here have very similar shapes but different mass scales. Furthermore, the lognormal model appears to better describe the CMF measured in the two Hi-GAL regions studied here. However, this preliminary conclusion is dependent on the choice of parameters priors.Comment: Submitted for publication to A&A on November 12, 2013. This paper contains 11 pages and 7 figure

EChO Payload electronics architecture and SW design

EChO is a three-modules (VNIR, SWIR, MWIR), highly integrated spectrometer, covering the wavelength range from 0.55 $\mu$m, to 11.0 $\mu$m. The baseline design includes the goal wavelength extension to 0.4 $\mu$m while an optional LWIR module extends the range to the goal wavelength of 16.0 $\mu$m. An Instrument Control Unit (ICU) is foreseen as the main electronic subsystem interfacing the spacecraft and collecting data from all the payload spectrometers modules. ICU is in charge of two main tasks: the overall payload control (Instrument Control Function) and the housekeepings and scientific data digital processing (Data Processing Function), including the lossless compression prior to store the science data to the Solid State Mass Memory of the Spacecraft. These two main tasks are accomplished thanks to the Payload On Board Software (P-OBSW) running on the ICU CPUs.Comment: Experimental Astronomy - EChO Special Issue 201

Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension

BACKGROUND: Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to evaluate the incremental prognostic value of echocardiography of the RV and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients. METHODS: One hundred-thirty treatment-naïve IPAH patients were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6-minute walk distance plus an increase in functional class, or non elective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done. RESULTS: During a mean period of 528 ± 304 days, 54 patients experienced CW (53%). Among demographic, clinical and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (Model-1). With addition of echocardiographic and CPET variables (Model-2), peak O2 pulse (peak VO2/heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (AUC: 0.81 vs 0.66, respectively; p=0.005). Patients with low RVFAC and low O2 pulse (low RVFAC + low O2 pulse) and high RVFAC+low O2 pulse showed 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk -RR- of 41.1 and 25.3, respectively), compared with high RVFAC+high O2 pulse (p=0.0001). CONCLUSIONS: Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O2 pulse identifies patients at a particularly high risk of clinical deterioration

Herschel Hi-GAL imaging of massive young stellar objects

We used Herschel Hi-GAL (Herschel infrared Galactic Plane survey) data to determine whether massive young stellar objects (MYSOs) are resolved at 70 μm and to study their envelope density distribution. Our analysis of three relatively isolated sources in the l = 30° and 59° Galactic fields show that the objects are partially resolved at 70 μm. The Herschel Hi-GAL survey data have a high scan velocity which makes unresolved and partially resolved sources appear elongated in the 70 μm images. We analysed the two scan directions separately and examine the intensity profile perpendicular to the scan direction. Spherically symmetric radiative transfer models with a power-law density distribution were used to study the circumstellar matter distribution. Single dish submm data were also included to study how different spatial information affects the fitted density distribution. The density distribution which best fits both the 70 μm intensity profile and spectral energy distribution has an average index of ∼0.5. This index is shallower than expected and is probably due to the dust emission from bipolar outflow cavity walls not accounted for in the spherical models. We conclude that 2D axisymmetric models and Herschel images at low scan speeds are needed to better constrain the matter distribution around MYSOs

ISO-LWS study of pre-main sequence sources

We present the results obtained with the ISO Long Wavelength Spectrometer on a sample of Pre-MS sources, where several molecular lines of CO, H2O and OH have been detected. The analysis of the CO lines indicates that gas temperatures as low as 200 K are consistent with the data. This would be in agreement with the relatively low abundance of water in the gas phase measured in most of the objects

The YSO Population in the Vela-D Molecular Cloud

We investigate the young stellar population in the Vela Molecular Ridge, Cloud-D (VMR-D), a star forming (SF) region observed by both Spitzer/NASA and Herschel/ESA space telescope. The point source, band-merged, Spitzer-IRAC catalog complemented with MIPS photometry previously obtained is used to search for candidate young stellar objects (YSO), also including sources detected in less than four IRAC bands. Bona fide YSO are selected by using appropriate color-color and color-magnitude criteria aimed to exclude both Galatic and extragalactic contaminants. The derived star formation rate and efficiency are compared with the same quantities characterizing other SF clouds. Additional photometric data, spanning from the near-IR to the submillimeter, are used to evaluate both bolometric luminosity and temperature for 33 YSOs located in a region of the cloud observed by both Spitzer and Herschel. The luminosity-temperature diagram suggests that some of these sources are representative of Class 0 objects with bolometric temperatures below 70 K and luminosities of the order of the solar luminosity. Far IR observations from the Herschel/Hi-GAL key project for a survey of the Galactic plane are also used to obtain a band-merged photometric catalog of Herschel sources aimed to independently search for protostars. We find 122 Herschel cores located on the molecular cloud, 30 of which are protostellar and 92 starless. The global protostellar luminosity function is obtained by merging the Spitzer and Herschel protostars. Considering that 10 protostars are found in both Spitzer and Herschel list it follows that in the investigated region we find 53 protostars and that the Spitzer selected protostars account for approximately two-thirds of the total.Comment: 40 pages, 12 figures, accepted for publication in Ap

Characterizing the structure of diffuse emission in Hi-GAL maps

We present a study of the structure of the Galactic interstellar medium through the Delta-variance technique, related to the power spectrum and the fractal properties of infrared/sub-mm maps. Through this method, it is possible to provide quantitative parameters which are useful to characterize different morphological and physical conditions, and to better constrain the theoretical models. In this respect, the Herschel Infrared Galactic Plane Survey carried out at five photometric bands from 70 to 500 \mu m constitutes an unique database for applying statistical tools to a variety of regions across the Milky Way. In this paper, we derive a robust estimate of the power-law portion of the power spectrum of four contiguous 2{\deg}x2{\deg} Hi-GAL tiles located in the third Galactic quadrant (217{\deg} < l < 225{\deg}, -2{\deg} < b < 0{\deg}). The low level of confusion along the line of sight testified by CO observations makes this region an ideal case. We find very different values of the power spectrum slope from tile to tile but also from wavelength to wavelength (2 < \beta < 3), with similarities between fields attributable to components located at the same distance. Thanks to the comparison with models of turbulence, an explanation of the determined slopes in terms of the fractal geometry is also provided, and possible relations with the underlying physics are investigated. In particular, an anti-correlation between ISM fractal dimension and star formation efficiency is found for the two main distance components observed in these fields. A possible link between the fractal properties of the diffuse emission and the resulting clump mass function is discussed.Comment: Accepted by Ap