Thermalizing a telescope in Antarctica: Analysis of ASTEP observations

The installation and operation of a telescope in Antarctica represent particular challenges, in particular the requirement to operate at extremely cold temperatures, to cope with rapid temperature fluctuations and to prevent frosting. Heating of electronic subsystems is a necessity, but solutions must be found to avoid the turbulence induced by temperature fluctua- tions on the optical paths. ASTEP 400 is a 40 cm Newton telescope installed at the Concordia station, Dome C since 2010 for photometric observations of fields of stars and their exoplanets. While the telescope is designed to spread star light on several pixels to maximize photometric stability, we show that it is nonetheless sensitive to the extreme variations of the seeing at the ground level (between about 0.1 and 5 arcsec) and to temperature fluctuations between --30 degrees C and --80 degrees C. We analyze both day-time and night-time observations and obtain the magnitude of the seeing caused by the mirrors, dome and camera. The most important effect arises from the heating of the primary mirror which gives rise to a mirror seeing of 0.23 arcsec K--1 . We propose solutions to mitigate these effects.Comment: Appears in Astronomical Notes / Astronomische Nachrichten, Wiley-VCH Verlag, 2015, pp.1-2

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Arbitrary order monotonic finite-volume schemes for 2D elliptic problems

Monotonicity is very important in most applications solving elliptic problems. Many schemes preserving positivity has been proposed but are at most second-order convergent. Besides, in general, high-order schemes do not preserve positivity. In the present paper, we propose an arbitrary-order monotonic method for elliptic problems in 2D. We show how to adapt our method to the case of a discontinuous and/or tensorvalued diffusion coefficient, while keeping the order of convergence. We assess the new scheme on several test problems

Arbitrary-order monotone finite-volume schemes for 1D elliptic problems

International audienceWhen solving numerically an elliptic problem, it is important in most applications that the scheme used preserves the positivity of the solution. When using finite volume schemes on deformed mesh, the question has been solved rather recently. Such schemes are usually (at most) second order convergent, and nonlinear. On the other hand, many high-order schemes have been proposed, that do not ensure positivity of the solution. In this paper we propose a very high-order monotone (that is, positivity preserving) numerical method for elliptic problems in 1D. We prove that this method converges to an arbitrary order and is indeed monotone. We also show how to handle discontinuous sources or diffusion coefficients, while keeping the order of convergence. We assess the new scheme, on several test problems, with arbitrary (regular, distorted, random) meshes

Monotonic diamond and DDFV type finite-volume schemes for 2D elliptic problems

The DDFV (Discrete Duality Finite Volume) method is a finite volume scheme mainly dedicated to diffusion problems, with some outstanding properties. This scheme has been found to be one of the most accurate finite volume methods for diffusion problems. In the present paper, we propose a new monotonic extension of DDFV, which can handle discontinuous tensorial diffusion coefficient. Moreover, we compare its performance to a diamond type method with an original interpolation method relying on polynomial reconstructions. Monotonicity is achieved by adapting the method from [44, 19, 49, 18] to our schemes. Such a technique does not require the positiveness of the secondary unknowns. We show that the two new methods are second-order accurate and are indeed monotonic on some challenging benchmarks as a Fokker-Planck problem

Adverse events during treatment of nontuberculous mycobacterial lung disease: do they really matter?

28th International Congress of the European-Respiratory-Society (ERS), Paris, FRANCE, SEP 15-19, 2018International audienceTreatment of nontuberculous mycobacterial lung disease (NTM LD) is long and hampered with frequent adverse events. Side effects may explain the poor prognosis associated with this disease. Our hypothesis was that adverse events might be responsible of premature discontinuation of treatment, thus leading to an increased mortality. We conducted a retrospective study including adult patients treated for NTM LD at 5 French hospitals between January 1st 2010 and December 31st 2015. Patients with cystic fibrosis were excluded. 71 patients were included, of which 45 had a pulmonary disease due to Mycobacterium avium complex and 15 due to M. xenopi. All patients fulfilled the ATS clinical and microbiological criteria for NTM LD. While treated, 72% of patients presented at least one reported side effect, of which 65% were gastro-intestinal and 21% were ophthalmologic. 14 patients stopped prematurely their treatment while initial therapy was modified in 22 cases due to poor tolerance. Adverse events were more common in patients who had been previously treated for NTM LD (p=0.02). Early treatment cessation was associated with the absence of sputum conversion (p=0.014) but not with mortality (p=0.237). Occurrence of adverse events was not associated with mortality. 15 patients died, among them 6 were under treatment. Mortality was associated with use of systemic steroids and existence of comorbidities, especially pulmonary or cardiovascular ones, as well as extra pulmonary cancers. Side effects of drugs used to treat NTM LD are common and responsible for early cessation of treatment that may result in a lack of sputum conversion. However, they did not affect mortality in our cohort

Statistical mechanics of the human placenta : a stationary state of a near-equilibrium system in a linear regime

All near-equilibrium systems under linear regime evolve to stationary states in which there is constant entropy production rate. In an open chemical system that exchanges matter and energy with the exterior, we can identify both the energy and entropy flows associated with the exchange of matter and energy. This can be achieved by applying statistical mechanics (SM), which links the microscopic properties of a system to its bulk properties. In the case of contractile tissues such as human placenta, Huxley's equations offer a phenomenological formalism for applying SM. SM was investigated in human placental stem villi (PSV) (n = 40). PSV were stimulated by means of KCl exposure (n = 20) and tetanic electrical stimulation (n = 20). This made it possible to determine statistical entropy (S), internal energy (E), affinity (A), thermodynamic force (A / T) (T: temperature), thermodynamic flow (v) and entropy production rate (A / T x v). We found that PSV operated near equilibrium, i.e., A ≺≺ 2500 J/mol and in a stationary linear regime, i.e., (A / T) varied linearly with v. As v was dramatically low, entropy production rate which quantified irreversibility of chemical processes appeared to be the lowest ever observed in any contractile system

Comparative statistical mechanics of muscle and non-muscle contractile systems : stationary states of near-equilibrium systems in a linear regime

A. Huxley’s equations were used to determine the mechanical properties of muscle myosin II (MII) at the molecular level, as well as the probability of the occurrence of the different stages in the actin–myosin cycle. It was then possible to use the formalism of statistical mechanics with the grand canonical ensemble to calculate numerous thermodynamic parameters such as entropy, internal energy, affinity, thermodynamic flow, thermodynamic force, and entropy production rate. This allows us to compare the thermodynamic parameters of a non-muscle contractile system, such as the normal human placenta, with those of different striated skeletal muscles (soleus and extensor digitalis longus) as well as the heart muscle and smooth muscles (trachea and uterus) in the rat. In the human placental tissues, it was observed that the kinetics of the actin–myosin crossbridges were considerably slow compared with those of smooth and striated muscular systems. The entropy production rate was also particularly low in the human placental tissues, as compared with that observed in smooth and striated muscular systems. This is partly due to the low thermodynamic flow found in the human placental tissues. However, the unitary force of non-muscle myosin (NMII) generated by each crossbridge cycle in the myofibroblasts of the human placental tissues was similar in magnitude to that of MII in the myocytes of both smooth and striated muscle cells. Statistical mechanics represents a powerful tool for studying the thermodynamics of all contractile muscle and non-muscle systems