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The role of simulation keeps increasing for the reliability analysis of complex systems. Most of the time, these analyses can be reduced to estimating the probability of occurrence of an undesirable event, also called failure probability, using a stochastic model of the system. If the considered event is rare, sophisticated sample-based procedures are generally introduced to get a relevant estimate of the failure probability. Based on the samples constructed for the evaluation of this estimate, this work considers two types of reliability-oriented sensitivity indices (ROSI). The first ones are introduced to identify the model inputs whose variability has to be reduced in priority to decrease this probability. The second ones are used to find the model inputs whose distribution has to be particularly well-characterized for the available estimate to be realistic. It is also shown how these ROSI can be derived when the true model is approximated by a surrogate model. In particular, an innovative procedure is proposed to take into account the surrogate model uncertainty in the estimation of these ROSI. The proposed approach is then applied to the reliability analysis of a series of numerical and industrial examples.

Red supergiants are the most common final evolutionary stage of stars that have initial masses between 8 and 35 times that of the Sun. During this stage, which lasts roughly 100,000 years, red supergiants experience substantial mass loss. However, the mechanism for this mass loss is unknown. Mass loss may affect the evolutionary path, collapse and future supernova light curve of a red supergiant, and its ultimate fate as either a neutron star or a black hole. From November 2019 to March 2020, Betelgeuse—the second-closest red supergiant to Earth (roughly 220 parsecs, or 724 light years, away)—experienced a historic dimming of its visible brightness. Usually having an apparent magnitude between 0.1 and 1.0, its visual brightness decreased to 1.614 ± 0.008 magnitudes around 7–13 February 2020—an event referred to as Betelgeuse’s Great Dimming. Here we report high-angular-resolution observations showing that the southern hemisphere of Betelgeuse was ten times darker than usual in the visible spectrum during its Great Dimming. Observations and modelling support a scenario in which a dust clump formed recently in the vicinity of the star, owing to a local temperature decrease in a cool patch that appeared on the photosphere. The directly imaged brightness variations of Betelgeuse evolved on a timescale of weeks. Our findings suggest that a component of mass loss from red supergiants is inhomogeneous, linked to a very contrasted and rapidly changing photosphere.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH) 1 – 3 . These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase 4 – 6 . A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8–12 billion years ago (redshifts 1–3) 7 . Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-μas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 10 8  solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 10 11  solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems. Using the GRAVITY+ instrument, dynamical measurement of the black hole mass in a quasar at a redshift of 2.3 (11 billion years ago) shows how the relationship between galaxies and black holes evolves with time.

The broadening of atomic emission lines by high-velocity motion of gas near accreting supermassive black holes is an observational hallmark of quasars 1 . Observations of broad emission lines could potentially constrain the mechanism for transporting gas inwards through accretion disks or outwards through winds 2 . The size of regions for which broad emission lines are observed (broad-line regions) has been estimated by measuring the delay in light travel time between the variable brightness of the accretion disk  continuum and the emission lines 3 —a method known as reverberation mapping. In some models the emission lines arise from a continuous outflow 4 , whereas in others they arise from orbiting gas clouds 5 . Directly imaging such regions has not hitherto been possible because of their small angular size (less than 10 −4 arcseconds 3 , 6 ). Here we report a spatial offset (with a spatial resolution of 10 −5 arcseconds, or about 0.03 parsecs for a distance of 550 million parsecs) between the red and blue photo-centres of the broad Paschen-α line of the quasar 3C 273 perpendicular to the direction of its radio jet. This spatial offset corresponds to a gradient in the velocity of the gas and thus implies that the gas is orbiting the central supermassive black hole. The data are well fitted by a broad-line-region model of a thick disk of gravitationally bound material orbiting a black hole of 3 × 10 8 solar masses. We infer a disk radius of 150 light days; a radius of 100–400 light days was found previously using reverberation mapping 7 – 9 . The rotation axis of the disk aligns in inclination and position angle with the radio jet. Our results support the methods that are often used to estimate the masses of accreting supermassive black holes and to study their evolution over cosmic time. High-angular-resolution observations of the quasar 3C 273 reveal that it has a relatively small but thick disk, viewed nearly face-on, in which material is orbiting the central supermassive black hole.

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case–control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value ( p  < 0.001; p  < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

PurposeAlthough more practical for use, the impact of ferric carboxymaltose (FCM) on the hospital budget is considerable, and intravenous iron sucrose complex (ISC) represents a cost-saving alternative for the management of iron deficiency anemia in patients during hospitalization. The Drug Committee decided to reserve FCM for day hospitalizations and contraindications to ISC, especially allergy. ISC was available for prescription for all other situations.MethodsThe impact of a multifaceted intervention promoting a switch from FCM to ISC was evaluated using an interrupted time series model with segmented regression analysis. The standardized rate of the dispensing of FCM, ISC, and oral iron by the hospital pharmacy, as well as the rate of the dispensing of packed red blood cells and the number of biological iron status measurements, was analyzed before and after the intervention.ResultsThere was an immediate decrease in FCM consumption following the intervention, with a reduction of 88% (RR: 0.12 [CI95% 0.10 to 0.15]). Conversely, there was a large increase in ISC use (RR: 5.1 [CI95% 4.4 to 5.9]). We did not observe a prescription shift to packed red blood cells or oral iron after the intervention. The time series analysis showed the frequency of iron status testing to remain stable before and after. The direct savings for intravenous iron for 8 months were 187,417.54 €.ConclusionOur intervention to lower the impact of intravenous iron therapy on the hospital budget was effective.

This paper deals with the identification in high dimensions of a polynomial chaos expansion of random vectors from a set of realizations. Due to numerical and memory constraints, the usual polynomial chaos identification methods are based on a series of truncations that induce a numerical bias. This bias becomes very detrimental to the convergence analysis of polynomial chaos identification in high dimensions. This paper therefore proposes a new formulation of the usual polynomial chaos identification algorithms to avoid this numerical bias. After a review of the polynomial chaos identification method, the influence of the numerical bias on the identification accuracy is quantified. The new formulation is then described in detail and illustrated using two examples. [PUBLICATION ABSTRACT]

Our Solar System was formed from a cloud of gas and dust. Most of the dust mass is contained in amorphous silicates 1 , yet crystalline silicates are abundant throughout the Solar System, reflecting the thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as comets contain crystalline silicates 2 .) Little is known about the evolution of the dust that forms Earth-like planets. Here we report spatially resolved detections and compositional analyses of these building blocks in the innermost two astronomical units of three proto-planetary disks. We find the dust in these regions to be highly crystallized, more so than any other dust observed in young stars until now. In addition, the outer region of one star has equal amounts of pyroxene and olivine, whereas the inner regions are dominated by olivine. The spectral shape of the inner-disk spectra shows surprising similarity with Solar System comets. Radial-mixing models naturally explain this resemblance as well as the gradient in chemical composition. Our observations imply that silicates crystallize before any terrestrial planets are formed, consistent with the composition of meteorites in the Solar System.

Gamma spectrometry is a passive non-destructive assay used to quantify radionuclides present in more or less complex objects. Basic methods using empirical calibration with a standard in order to quantify the activity of nuclear materials by determining the calibration coefficient are useless on non-reproducible, complex and single nuclear objects such as waste packages. Package specifications as composition or geometry change from one package to another and involve a high variability of objects. Current quantification process uses numerical modelling of the measured scene with few available data such as geometry or composition. These data are density, material, screen, geometric shape, matrix composition, matrix and source distribution. Some of them are strongly dependent on package data knowledge and operator backgrounds. The French Commissariat à l’Energie Atomique (CEA) is developing a new methodology to quantify nuclear materials in waste packages and waste drums without operator adjustment and internal package configuration knowledge. This method suggests combining a global stochastic approach which uses, among others, surrogate models available to simulate the gamma attenuation behaviour, a Bayesian approach which considers conditional probability densities of problem inputs, and Markov Chains Monte Carlo algorithms (MCMC) which solve inverse problems, with gamma ray emission radionuclide spectrum, and outside dimensions of interest objects. The methodology is testing to quantify actinide activity in different kind of matrix, composition, and configuration of sources standard in terms of actinide masses, locations and distributions. Activity uncertainties are taken into account by this adjustment methodology.

Active galactic nuclei (AGNs) display many energetic phenomena—broad emission lines, X-rays, relativistic jets, radio lobes—originating from matter falling onto a supermassive black hole. It is widely accepted that orientation effects play a major role in explaining the observational appearance of AGNs. Seen from certain directions, circum-nuclear dust clouds would block our view of the central powerhouse 1 , 2 . Indirect evidence suggests that the dust clouds form a parsec-sized torus-shaped distribution. This explanation, however, remains unproved, as even the largest telescopes have not been able to resolve the dust structures. Here we report interferometric mid-infrared observations that spatially resolve these structures in the galaxy NGC 1068. The observations reveal warm (320 K) dust in a structure 2.1 parsec thick and 3.4 parsec in diameter, surrounding a smaller hot structure. As such a configuration of dust clouds would collapse in a time much shorter than the active phase of the AGN 3 , this observation requires a continual input of kinetic energy to the cloud system from a source coexistent with the AGN.