IGF signaling has been implicated in the pathogenesis and progression of ovarian carcinoma (OC). Single agent activity and safety of ganitumab (AMG 479), a fully human monoclonal antibody against ...IGF1R that blocks binding of IGF1 and IGF2, were evaluated in patients with platinum-sensitive recurrent OC.
Patients with CA125 progression (GCIG criteria) or measurable disease per RECIST following primary platinum-based therapy received 18 mg/kg of ganitumab q3w. The primary endpoint was objective response rate (ORR) assessed per RECIST 1.1 by an independent radiology review committee (IRC) and/or GCIG CA125 criteria. Secondary endpoints included clinical benefit rate (CBR), progression free survival (PFS) and overall survival (OS).
61 pts. were accrued. Objective responses were seen in 5/61 patients (ORR 8.2%, 95% CI, 3.1–18.8) with 1 partial response (PR) by RECIST and 2 complete responses (CR) as well as 2 PR by CA125 criteria. CBR was 80.3% (95% CI, 67.8–89.0%). The median PFS according to RECIST by IRC was 2.1 months (95% CI, 2.0–3.1). The median PFS per RECIST IRC and/or CA125 was 2.0 months (95% CI, 1.8–2.2). The median OS was 21 months (95% CI, 19.5-NA). The most common overall adverse events were fatigue (36.1%) and hypertension (34.4%). Grade 1/2 hyperglycemia occurred in 30.4% of patients. Hypertension (11.5%) and hypersensitivity (8.2%) were the most frequent grade 3 adverse events.
IGF1R inhibition with ganitumab was well-tolerated, however, our results do not support further study of ganitumab as a single agent in unselected OC patients.
•Ganitumab is a fully human monoclonal antibody against IGF1R that blocks binding of IGF1 and IGF2•Ganitumab as a single agent in unselected ovarian cancer patients does not show promising activity•Ganitumab was well-tolerated in ovarian cancer patients•The IGF pathway has significant signaling redundancy which causes resistance to single receptor inhibition
Amyotrophic lateral sclerosis (ALS) is a rare fatal motor neuron disease. Although many potential mechanisms have been proposed, the pathophysiology of the disease remains unknown. Currently ...available treatments can only delay the progression of the disease and prolong life expectancy by a few months. There is still no definitive cure for ALS, and the development of new treatments is limited by a lack of understanding of the underlying biological processes that trigger and promote neurodegeneration. Several scientific results suggest a neurovascular impairment in ALS providing perspectives for the development of new biomarkers and treatments. In this article, we performed a systematic review using PRISMA guidelines including PubMed, EmBase, GoogleScholar, and Web of Science Core Collection to analyze the scientific literature published between 2000 and 2021 discussing the neurocardiovascular involvement and ophthalmologic abnormalities in ALS. In total, 122 articles were included to establish this systematic review. Indeed, microvascular pathology seems to be involved in ALS, affecting all the neurovascular unit components. Retinal changes have also been recently highlighted without significant alteration of the visual pathways. Despite the peripheral location of the retina, it is considered as an extension of the central nervous system (CNS) as it displays similarities to the brain, the inner blood–retinal barrier, and the blood–brain barrier. This suggests that the eye could be considered as a ‘window’ into the brain in many CNS disorders. Thus, studying ocular manifestations of brain pathologies seems very promising in understanding neurodegenerative disorders, mainly ALS. Optical coherence tomography angiography (OCT-A) could therefore be a powerful approach for exploration of retinal microvascularization allowing to obtain new diagnostic and prognostic biomarkers of ALS.
Gaia Data Release 2 Andrae, René; Fouesneau, Morgan; Creevey, Orlagh ...
Astronomy and astrophysics (Berlin),
8/2018, Letnik:
616
Journal Article
Recenzirano
Odprti dostop
The second
Gaia
data release (
Gaia
DR2) contains, beyond the astrometry, three-band photometry for 1.38 billion sources. One band is the
G
band, the other two were obtained by integrating the
Gaia
...prism spectra (BP and RP). We have used these three broad photometric bands to infer stellar effective temperatures,
T
eff
, for all sources brighter than
G
= 17 mag with
T
eff
in the range 3000–10 000 K (some 161 million sources). Using in addition the parallaxes, we infer the line-of-sight extinction,
A
G
, and the reddening,
E
(BP − RP), for 88 million sources. Together with a bolometric correction we derive luminosity and radius for 77 million sources. These quantities as well as their estimated uncertainties are part of
Gaia
DR2. Here we describe the procedures by which these quantities were obtained, including the underlying assumptions, comparison with literature estimates, and the limitations of our results. Typical accuracies are of order 324 K (
T
eff
), 0.46 mag (
A
G
), 0.23 mag (
E
(BP − RP)), 15% (luminosity), and 10% (radius). Being based on only a small number of observable quantities and limited training data, our results are necessarily subject to some extreme assumptions that can lead to strong systematics in some cases (not included in the aforementioned accuracy estimates). One aspect is the non-negativity contraint of our estimates, in particular extinction, which we discuss. Yet in several regions of parameter space our results show very good performance, for example for red clump stars and solar analogues. Large uncertainties render the extinctions less useful at the individual star level, but they show good performance for ensemble estimates. We identify regimes in which our parameters should and should not be used and we define a “clean” sample. Despite the limitations, this is the largest catalogue of uniformly-inferred stellar parameters to date. More precise and detailed astrophysical parameters based on the full BP/RP spectrophotometry are planned as part of the third
Gaia
data release.
Context. Direct imaging of circumstellar disks at high angular resolution is mandatory to provide morphological information that constrains their properties, in particular the spatial distribution of ...dust. For a long time, this challenging objective was, in most cases, only within the realm of space telescopes from the visible to the infrared. New techniques combining observing strategy and data processing now allow very high-contrast imaging with 8-m class ground-based telescopes (10-4 to 10-5 at ~1′′) and complement space telescopes while improving angular resolution at near infrared wavelengths. Aims. We present the results of a program carried out at the VLT with NACO to image known debris disks with higher angular resolution in the near-infrared than ever before in order to study morphological properties and ultimately detect the signpost of planets. Methods. The observing method makes use of advanced techniques of adaptive optics, coronagraphy, and differential imaging, a combination designed to directly image exoplanets with the upcoming generation of “planet finders” such as GPI (Gemini Planet Imager) and SPHERE (Spectro-Polarimetric High contrast Exoplanet REsearch). Applied to extended objects such as circumstellar disks, the method is still successful but produces significant biases in terms of photometry and morphology. We developed a new model-matching procedure to correct for these biases and hence provide constraints on the morphology of debris disks. Results. From our program, we present new images of the disk around the star HD 32297 obtained in the H (1.6 μm) and Ks (2.2 μm) bands with an unprecedented angular resolution (~65 mas). The images show an inclined thin disk detected at separations larger than 0.5−0.6″. The modeling stage confirms a very high inclination (i = 88°) and the presence of an inner cavity inside r0 ≈ 110 AU. We also find that the spine (line of maximum intensity along the midplane) of the disk is curved, which we attribute to a large anisotropic scattering-factor (g ≈ 0.5, which is valid for an non-edge-on disk). Conclusions. Our modeling procedure is relevant to interpreting images of circumstellar disks observed with angular differential imaging. It allows us to both reduce the biases and estimate the disk parameters.
First stellar parameters from Apsis Andrae, Rene; Fouesneau, Morgan; Creevey, Orlagh ...
Astronomy and astrophysics (Berlin),
08/2018, Letnik:
616
Journal Article
Recenzirano
Odprti dostop
The second Gaia data release (Gaia DR2) contains, beyond the astrometry, three-band photometry for 1.38 billion sources. One band is the G band, the other two were obtained by integrating the Gaia ...prism spectra (BP and RP). We have used these three broad photometric bands to infer stellar effective temperatures, T-eff, for all sources brighter than G = 17 mag with T-eff in the range 3000-10 000K (some 161 million sources). Using in addition the parallaxes, we infer the line-of-sight extinction, A(G), and the reddening, E(BP-RP), for 88 million sources. Together with a bolometric correction we derive luminosity and radius for 77 million sources. These quantities as well as their estimated uncertainties are part of Gaia DR2. Here we describe the procedures by which these quantities were obtained, including the underlying assumptions, comparison with literature estimates, and the limitations of our results. Typical accuracies are of order 324K (T-eff), 0.46 mag (A(G)), 0.23 mag (E(BP-RP)), 15% (luminosity), and 10% (radius). Being based on only a small number of observable quantities and limited training data, our results are necessarily subject to some extreme assumptions that can lead to strong systematics in some cases (not included in the aforementioned accuracy estimates). One aspect is the non-negativity contraint of our estimates, in particular extinction, which we discuss. Yet in several regions of parameter space our results show very good performance, for example for red clump stars and solar analogues. Large uncertainties render the extinctions less useful at the individual star level, but they show good performance for ensemble estimates. We identify regimes in which our parameters should and should not be used and we define a "clean" sample. Despite the limitations, this is the largest catalogue of uniformly-inferred stellar parameters to date. More precise and detailed astrophysical parameters based on the full BP/RP spectrophotometry are planned as part of the third Gaia data release.
Gaia Early Data Release 3 Brown, A. G. A.; Prusti, T.; Eyer, L. ...
Astronomy and astrophysics (Berlin),
05/2021, Letnik:
649
Journal Article, Web Resource
Recenzirano
Odprti dostop
Context.
We present the early installment of the third
Gaia
data release,
Gaia
EDR3, consisting of astrometry and photometry for 1.8 billion sources brighter than magnitude 21, complemented with the ...list of radial velocities from
Gaia
DR2.
Aims.
A summary of the contents of
Gaia
EDR3 is presented, accompanied by a discussion on the differences with respect to
Gaia
DR2 and an overview of the main limitations which are present in the survey. Recommendations are made on the responsible use of
Gaia
EDR3 results.
Methods.
The raw data collected with the
Gaia
instruments during the first 34 months of the mission have been processed by the
Gaia
Data Processing and Analysis Consortium and turned into this early third data release, which represents a major advance with respect to
Gaia
DR2 in terms of astrometric and photometric precision, accuracy, and homogeneity.
Results. Gaia
EDR3 contains celestial positions and the apparent brightness in
G
for approximately 1.8 billion sources. For 1.5 billion of those sources, parallaxes, proper motions, and the (
G
BP
−
G
RP
) colour are also available. The passbands for
G
,
G
BP
, and
G
RP
are provided as part of the release. For ease of use, the 7 million radial velocities from
Gaia
DR2 are included in this release, after the removal of a small number of spurious values. New radial velocities will appear as part of
Gaia
DR3. Finally,
Gaia
EDR3 represents an updated materialisation of the celestial reference frame (CRF) in the optical, the
Gaia
-CRF3, which is based solely on extragalactic sources. The creation of the source list for
Gaia
EDR3 includes enhancements that make it more robust with respect to high proper motion stars, and the disturbing effects of spurious and partially resolved sources. The source list is largely the same as that for
Gaia
DR2, but it does feature new sources and there are some notable changes. The source list will not change for
Gaia
DR3.
Conclusions. Gaia
EDR3 represents a significant advance over
Gaia
DR2, with parallax precisions increased by 30 per cent, proper motion precisions increased by a factor of 2, and the systematic errors in the astrometry suppressed by 30–40% for the parallaxes and by a factor ~2.5 for the proper motions. The photometry also features increased precision, but above all much better homogeneity across colour, magnitude, and celestial position. A single passband for
G
,
G
BP
, and
G
RP
is valid over the entire magnitude and colour range, with no systematics above the 1% level
Gaia Data Release 2 Andrae, René; Fouesneau, Morgan; Creevey, Orlagh ...
Astronomy and astrophysics (Berlin),
08/2018, Letnik:
616
Journal Article
Recenzirano
Odprti dostop
The second Gaia data release (Gaia DR2) contains, beyond the astrometry, three-band photometry for 1.38 billion sources. One band is the G band, the other two were obtained by integrating the Gaia ...prism spectra (BP and RP). We have used these three broad photometric bands to infer stellar effective temperatures, Teff, for all sources brighter than G = 17 mag with Teff in the range 3000–10 000 K (some 161 million sources). Using in addition the parallaxes, we infer the line-of-sight extinction, AG, and the reddening, E(BP − RP), for 88 million sources. Together with a bolometric correction we derive luminosity and radius for 77 million sources. These quantities as well as their estimated uncertainties are part of Gaia DR2. Here we describe the procedures by which these quantities were obtained, including the underlying assumptions, comparison with literature estimates, and the limitations of our results. Typical accuracies are of order 324 K (Teff), 0.46 mag (AG), 0.23 mag (E(BP − RP)), 15% (luminosity), and 10% (radius). Being based on only a small number of observable quantities and limited training data, our results are necessarily subject to some extreme assumptions that can lead to strong systematics in some cases (not included in the aforementioned accuracy estimates). One aspect is the non-negativity contraint of our estimates, in particular extinction, which we discuss. Yet in several regions of parameter space our results show very good performance, for example for red clump stars and solar analogues. Large uncertainties render the extinctions less useful at the individual star level, but they show good performance for ensemble estimates. We identify regimes in which our parameters should and should not be used and we define a “clean” sample. Despite the limitations, this is the largest catalogue of uniformly-inferred stellar parameters to date. More precise and detailed astrophysical parameters based on the full BP/RP spectrophotometry are planned as part of the third Gaia data release.
Mate finding and recognition in animals evolves during niche adaptation and involves social signals and habitat cues. Drosophila melanogaster and related species are known to be attracted to ...fermenting fruit for feeding and egg-laying, which poses the question of whether species-specific fly odours contribute to long-range premating communication.
We have discovered an olfactory channel in D. melanogaster with a dual affinity to sex and food odorants. Female flies release a pheromone, (Z)-4-undecenal (Z4-11Al), that elicits flight attraction in both sexes. Its biosynthetic precursor is the cuticular hydrocarbon (Z,Z)-7,11-heptacosadiene (7,11-HD), which is known to afford reproductive isolation between the sibling species D. melanogaster and D. simulans during courtship. Twin olfactory receptors, Or69aB and Or69aA, are tuned to Z4-11Al and food odorants, respectively. They are co-expressed in the same olfactory sensory neurons, and feed into a neural circuit mediating species-specific, long-range communication; however, the close relative D. simulans, which shares food resources with D. melanogaster, does not respond to Z4-11Al.
The Or69aA and Or69aB isoforms have adopted dual olfactory traits. The underlying gene yields a collaboration between natural and sexual selection, which has the potential to drive speciation.
Gaia Data Release 3 Recio-Blanco, A.; de Laverny, P.; Palicio, P. A. ...
Astronomy and astrophysics (Berlin),
06/2023, Letnik:
674
Journal Article
Recenzirano
Odprti dostop
Context.
The chemo-physical parametrisation of stellar spectra is essential for understanding the nature and evolution of stars and of Galactic stellar populations. A worldwide observational effort ...from the ground has provided, in one century, an extremely heterogeneous collection of chemical abundances for about two million stars in total, with fragmentary sky coverage.
Aims.
This situation is revolutionised by the
Gaia
third data release (DR3), which contains the parametrisation of Radial Velocity Spectrometer (RVS) data performed by the General Stellar Parametriser-spectroscopy, GSP-Spec, module. Here we describe the parametrisation of the first 34 months of
Gaia
RVS observations.
Methods.
GSP-Spec estimates the chemo-physical parameters from combined RVS spectra of single stars, without additional inputs from astrometric, photometric, or spectro-photometric BP/RP data. The main analysis workflow described here, MatisseGauguin, is based on projection and optimisation methods and provides the stellar atmospheric parameters; the individual chemical abundances of N, Mg, Si, S, Ca, Ti, Cr, Fe
I
, Fe
II
, Ni, Zr, Ce and Nd; the differential equivalent width of a cyanogen line; and the parameters of a diffuse interstellar band (DIB) feature. Another workflow, based on an artificial neural network (ANN) and referred to with the same acronym, provides a second set of atmospheric parameters that are useful for classification control. For both workflows, we implement a detailed quality flag chain considering different error sources.
Results.
With about 5.6 million stars, the
Gaia
DR3 GSP-Spec all-sky catalogue is the largest compilation of stellar chemo-physical parameters ever published and the first one from space data. Internal and external biases have been studied taking into account the implemented flags. In some cases, simple calibrations with low degree polynomials are suggested. The homogeneity and quality of the estimated parameters enables chemo-dynamical studies of Galactic stellar populations, interstellar extinction studies from individual spectra, and clear constraints on stellar evolution models. We highly recommend that users adopt the provided quality flags for scientific exploitation.
Conclusions.
The
Gaia
DR3 GSP-Spec catalogue is a major step in the scientific exploration of Milky Way stellar populations. It will be followed by increasingly large and higher quality catalogues in future data releases, confirming the
Gaia
promise of a new Galactic vision.
The Gaia satellite will survey the entire celestial sphere down to 20th magnitude, obtaining astrometry, photometry, and low resolution specfrophotometry on one billion astronomical sources, plus ...radial velocities for over one hundred million stars. Its main objective is to take a census of the stellar content of our Galaxy, with the goal of revealing its formation and evolution. Gaia's unique feature is the measurement of parallaxes and proper motions with hitherto unparalleled accuracy for many objects. Here we describe the data analysis system put together by the Gaia consortium to classify these objects and to infer their astrophysical properties using the satellite's data. After its launch in December 2013, Gaia will nominally observe for five years, during which the system we describe will continue to evolve in light of experience with the real data.
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