Université Rennes 2

On 17 August 2017, the LIGO and Virgo observatories made the first direct detection of gravitational waves from the coalescence of a neutron star binary system. The detection of this gravitational-wave signal, GW170817, offers a novel opportunity to directly probe the properties of matter at the extreme conditions found in the interior of these stars. The initial, minimal-assumption analysis of the LIGO and Virgo data placed constraints on the tidal effects of the coalescing bodies, which were then translated to constraints on neutron star radii. Here, we expand upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation of state and have spins within the range observed in Galactic binary neutron stars. Our analysis employs two methods: the use of equation-of-state-insensitive relations between various macroscopic properties of the neutron stars and the use of an efficient parametrization of the defining function p(ρ) of the equation of state itself. From the LIGO and Virgo data alone and the first method, we measure the two neutron star radii as R_{1}=10.8_{-1.7}^{+2.0} km for the heavier star and R_{2}=10.7_{-1.5}^{+2.1} km for the lighter star at the 90% credible level. If we additionally require that the equation of state supports neutron stars with masses larger than 1.97 M_{⊙} as required from electromagnetic observations and employ the equation-of-state parametrization, we further constrain R_{1}=11.9_{-1.4}^{+1.4} km and R_{2}=11.9_{-1.4}^{+1.4} km at the 90% credible level. Finally, we obtain constraints on p(ρ) at supranuclear densities, with pressure at twice nuclear saturation density measured at 3.5_{-1.7}^{+2.7}×10^{34} dyn cm^{-2} at the 90% level.

The EACVI/ASE/Industry Task Force to standardize deformation imaging prepared this consensus document to standardize definitions and techniques for using two-dimensional (2D) speckle tracking echocardiography (STE) to assess left atrial, right ventricular, and right atrial myocardial deformation. This document is intended for both the technical engineering community and the clinical community at large to provide guidance on selecting the functional parameters to measure and how to measure them using 2D STE.This document aims to represent a significant step forward in the collaboration between the scientific societies and the industry since technical specifications of the software packages designed to post-process echocardiographic datasets have been agreed and shared before their actual development. Hopefully, this will lead to more clinically oriented software packages which will be better tailored to clinical needs and will allow industry to save time and resources in their development.

On August 17, 2017, the Advanced LIGO and Advanced Virgo gravitational-wave detectors observed a low-mass compact binary inspiral. The initial sky localization of the source of the gravitational-wave signal, GW170817, allowed electromagnetic observatories to identify NGC 4993 as the host galaxy. In this work, we improve initial estimates of the binary’s properties, including component masses, spins, and tidal parameters, using the known source location, improved modeling, and recalibrated Virgo data. We extend the range of gravitational-wave frequencies considered down to 23 Hz, compared to 30 Hz in the initial analysis. We also compare results inferred using several signal models, which are more accurate and incorporate additional physical effects as compared to the initial analysis. We improve the localization of the gravitational-wave source to a 90% credible region of 16 deg 2 . We find tighter constraints on the masses, spins, and tidal parameters, and continue to find no evidence for nonzero component spins. The component masses are inferred to lie between 1.00 and 1.89 M ⊙ when allowing for large component spins, and to lie between 1.16 and 1.60 M ⊙ (with a total mass 2.73 − 0.01 + 0.04 M ⊙ ) when the spins are restricted to be within the range observed in Galactic binary neutron stars. Using a precessing model and allowing for large component spins, we constrain the dimensionless spins of the components to be less than 0.50 for the primary and 0.61 for the secondary. Under minimal assumptions about the nature of the compact objects, our constraints for the tidal deformability parameter Λ ˜ are (0,630) when we allow for large component spins, and 300 − 230 + 420 (using a 90% highest posterior density interval) when restricting the magnitude of the component spins, ruling out several equation-of-state models at the 90% credible level. Finally, with LIGO and GEO600 data, we use a Bayesian analysis to place upper limits on the amplitude and spectral energy density of a possible postmerger signal. Published by the American Physical Society 2019

BACKGROUND: There is no consensus regarding the definition of frailty for clinical uses. METHODS: A modified Delphi process was used to attempt to achieve consensus definition. Experts were selected from different fields and organized into five Focus Groups. A questionnaire was developed and sent to experts in the area of frailty. Responses and comments were analyzed using a pre-established strategy. Statements with an agreement more than or equal to 80% were accepted. RESULTS: Overall, 44% of the statements regarding the concept of frailty and 18% of the statements regarding diagnostic criteria were accepted. There was consensus on the value of screening for frailty and about the identification of six domains of frailty for inclusion in a clinical definition, but no agreement was reached concerning a specific set of clinical/laboratory biomarkers useful for diagnosis. CONCLUSIONS: There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions. However, additional research is needed before an operative definition of frailty can be established.

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star–black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc − 3 yr − 1 and the neutron star–black hole merger rate to be between 7.8 and 140 Gpc − 3 yr − 1 , assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc − 3 yr − 1 at a fiducial redshift ( z = 0.2 ). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to ( 1 + z ) κ with κ = 2. 9 − 1.8 + 1.7 for z ≲ 1 . Using both binary neutron star and neutron star–black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2 − 0.2 + 0.1 to 2.0 − 0.3 + 0.3 M ⊙ . We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3 − 0.5 + 0.3 and 27.9 − 1.8 + 1.9 M ⊙ . While we continue to find that the mass distribution of a binary’s more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60 M ⊙ , which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χ i ≈ 0.25 . While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidenc

Abstract A subset of cancer-associated fibroblasts (FAP+/CAF-S1) mediates immunosuppression in breast cancers, but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 19,000 single CAF-S1 fibroblasts from breast cancer. We validate the five most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extracellular matrix proteins and TGFβ signaling, respectively, are indicative of primary resistance to immunotherapies. Cluster 0/ecm-myCAF upregulates PD-1 and CTLA4 protein levels in regulatory T lymphocytes (Tregs), which, in turn, increases CAF-S1 cluster 3/TGFβ-myCAF cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance. Significance: Our work provides a significant advance in characterizing and understanding FAP+ CAF in cancer. We reached a high resolution at single-cell level, which enabled us to identify specific clusters associated with immunosuppression and immunotherapy resistance. Identification of cluster-specific signatures paves the way for therapeutic options in combination with immunotherapies. This article is highlighted in the In This Issue feature, p. 1241

Abstract Urban shrinkage is not a new phenomenon. It has been documented in a large literature analyzing the social and economic issues that have led to population flight, resulting, in the worse cases, in the eventual abandonment of blocks of housing and neighbourhoods. Analysis of urban shrinkage should take into account the new realization that this phenomenon is now global and multidimensional — but also little understood in all its manifestations. Thus, as the world's population increasingly becomes urban, orthodox views of urban decline need redefinition. The symposium includes articles from 10 urban analysts working on 30 cities around the globe. These analysts belong to the Shrinking Cities International Research Network (SCIRN), whose collaborative work aims to understand different types of city shrinkage and the role that different approaches, policies and strategies have played in the regeneration of these cities. In this way the symposium will inform both a rich diversity of analytical perspectives and country‐based studies of the challenges faced by shrinking cities. It will also disseminate SCIRN's research results from the last 3 years. Résumé La décroissance urbaine n'est pas un phénomène nouveau. De nombreux travaux ont analysé les problèmes sociaux et économiques conduisant au départ de populations et résultant dans les pires des cas à l'abandon d'îlots d'habitat et de quartiers entiers. Cependant, l'étude de la décroissance urbaine doit aujourd'hui tenir compte du constat récent selon lequel ce phénomène est désormais global et multidimensionnel, tout en restant peu appréhendé dans toutes ses composantes. Ainsi, alors que la population mondiale est de plus en plus urbaine, les conceptions classiques du déclin urbain méritent d'être réexaminées. Ce symposium inclut des articles de dix chercheurs travaillant sur trente villes à travers le monde. Ils appartiennent au Shrinking Cities International Research Netwok (SCIRN), dont le travail collectif a pour objectif d'analyser différents types de décroissance urbaine et le rôle que les multiples approches, politiques et stratégies ont joué dans la régénération des villes touchées par ce processus. Ce numéro s'appuie sur une diversité d'approches et sur l'étude de contextes urbains variés, ayant pour point commun d'être concernés par les enjeux de la décroissance urbaine. Il permet de diffuser les résultats des recherches menées au sein du SCIRN au cours des trois dernières années.

AIMS: This European Association Cardiovascular Imaging (EACVI) Expert Consensus document aims at defining the main quantitative information on cardiac structure and function that needs to be included in standard echocardiographic report following recent ASE/EACVI chamber quantification, diastolic function, and heart valve disease recommendations. The document focuses on general reporting and specific pathological conditions such as heart failure, coronary artery and valvular heart disease, cardiomyopathies, and systemic diseases. METHODS AND RESULTS: Demographic data (age, body surface area, blood pressure, and heart rhythm and rate), type (vendor and model) of ultrasound system used and image quality need to be reported. In addition, measurements should be normalized for body size. Reference normal values, derived by ASE/EACVI recommendations, shall always be reported to differentiate normal from pathological conditions. This Expert Consensus document suggests avoiding the surveillance of specific variable using different ultrasound techniques (e.g. in echo labs with high expertise in left ventricular ejection fraction by 3D and not by 2D echocardiography). The report should be also tailored in relation with different cardiac pathologies, quality of images, and needs of the caregivers. CONCLUSION: The conclusion should be concise reflecting the status of left ventricular structure and function, the presence of left atrial and/or aortic dilation, right ventricular dysfunction, and pulmonary hypertension, leading to an objective communication with the patient health caregiver. Variation over time should be considered carefully, taking always into account the consistency of the parameters used for comparison.

The detection of gravitational waves by Advanced LIGO and Advanced Virgo provides an opportunity to test general relativity in a regime that is inaccessible to traditional astronomical observations and laboratory tests. We present four tests of the consistency of the data with binary black hole gravitational waveforms predicted by general relativity. One test subtracts the best-fit waveform from the data and checks the consistency of the residual with detector noise. The second test checks the consistency of the low- and high-frequency parts of the observed signals. The third test checks that phenomenological deviations introduced in the waveform model (including in the post-Newtonian coefficients) are consistent with 0. The fourth test constrains modifications to the propagation of gravitational waves due to a modified dispersion relation, including that from a massive graviton. We present results both for individual events and also results obtained by combining together particularly strong events from the first and second observing runs of Advanced LIGO and Advanced Virgo, as collected in the catalog GWTC-1. We do not find any inconsistency of the data with the predictions of general relativity and improve our previously presented combined constraints by factors of 1.1 to 2.5. In particular, we bound the mass of the graviton to be ${m}_{g}\ensuremath{\le}4.7\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}23}\text{ }\text{ }\mathrm{eV}/{c}^{2}$ (90% credible level), an improvement of a factor of 1.6 over our previously presented results. Additionally, we check that the four gravitational-wave events published for the first time in GWTC-1 do not lead to stronger constraints on alternative polarizations than those published previously.

Cardiovascular remodelling in the conditioned athlete is frequently associated with physiological ECG changes. Abnormalities, however, may be detected which represent expression of an underlying heart disease that puts the athlete at risk of arrhythmic cardiac arrest during sports. It is mandatory that ECG changes resulting from intensive physical training are distinguished from abnormalities which reflect a potential cardiac pathology. The present article represents the consensus statement of an international panel of cardiologists and sports medical physicians with expertise in the fields of electrocardiography, imaging, inherited cardiovascular disease, cardiovascular pathology, and management of young competitive athletes. The document provides cardiologists and sports medical physicians with a modern approach to correct interpretation of 12-lead ECG in the athlete and emerging understanding of incomplete penetrance of inherited cardiovascular disease. When the ECG of an athlete is examined, the main objective is to distinguish between physiological patterns that should cause no alarm and those that require action and/or additional testing to exclude (or confirm) the suspicion of an underlying cardiovascular condition carrying the risk of sudden death during sports. The aim of the present position paper is to provide a framework for this distinction. For every ECG abnormality, the document focuses on the ensuing clinical work-up required for differential diagnosis and clinical assessment. When appropriate the referral options for risk stratification and cardiovascular management of the athlete are briefly addressed.

BACKGROUND: Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms (24-hour cycles) in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing based on an internal 24-hour clock. METHODS: First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release. Then, research related to the physiological effects of melatonin is reviewed. RESULTS: The physiological effects of melatonin are various and include detoxification of free radicals and antioxidant actions, bone formation and protection, reproduction, and cardiovascular, immune or body mass regulation. Also, protective and therapeutic effects of melatonin are reported, especially with regard to brain or gastrointestinal protection, psychiatric disorders, cardiovascular diseases and oncostatic effects. CONCLUSION: This review highlights the high number and diversity of major melatonin effects and opens important perspectives for measuring melatonin as a biomarker (biomarker of early identification of certain disorders and also biomarker of their follow-up) and using melatonin with clinical preventive and therapeutic applications in newborns, children and adults based on its physiological regulatory effects.

Gravitational waves enable tests of general relativity in the highly dynamical and strong-field regime. Using events detected by LIGO-Virgo up to 1 October 2019, we evaluate the consistency of the data with predictions from the theory. We first establish that residuals from the best-fit waveform are consistent with detector noise, and that the low- and high-frequency parts of the signals are in agreement. We then consider parametrized modifications to the waveform by varying post-Newtonian and phenomenological coefficients, improving past constraints by factors of $\ensuremath{\sim}2$; we also find consistency with Kerr black holes when we specifically target signatures of the spin-induced quadrupole moment. Looking for gravitational-wave dispersion, we tighten constraints on Lorentz-violating coefficients by a factor of $\ensuremath{\sim}2.6$ and bound the mass of the graviton to ${m}_{g}\ensuremath{\le}1.76\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}23}\text{ }\text{ }\mathrm{eV}/{c}^{2}$ with 90% credibility. We also analyze the properties of the merger remnants by measuring ringdown frequencies and damping times, constraining fractional deviations away from the Kerr frequency to $\ensuremath{\delta}{\stackrel{^}{f}}_{220}=0.0{3}_{\ensuremath{-}0.35}^{+0.38}$ for the fundamental quadrupolar mode, and $\ensuremath{\delta}{\stackrel{^}{f}}_{221}=0.0{4}_{\ensuremath{-}0.32}^{+0.27}$ for the first overtone; additionally, we find no evidence for postmerger echoes. Finally, we determine that our data are consistent with tensorial polarizations through a template-independent method. When possible, we assess the validity of general relativity based on collections of events analyzed jointly. We find no evidence for new physics beyond general relativity, for black hole mimickers, or for any unaccounted systematics.

The genus Roseburia consists of obligate Gram-positive anaerobic bacteria that are slightly curved, rod-shaped and motile by means of multiple subterminal flagella. It includes five species: Roseburia intestinalis, R. hominis, R. inulinivorans, R. faecis and R. cecicola. Gut Roseburia spp. metabolize dietary components that stimulate their proliferation and metabolic activities. They are part of commensal bacteria producing short-chain fatty acids, especially butyrate, affecting colonic motility, immunity maintenance and anti-inflammatory properties. Modification in Roseburia spp. representation may affect various metabolic pathways and is associated with several diseases (including irritable bowel syndrome, obesity, Type 2 diabetes, nervous system conditions and allergies). Roseburia spp. could also serve as biomarkers for symptomatic pathologies (e.g., gallstone formation) or as probiotics for restoration of beneficial flora.

Heart failure with preserved ejection fraction (HFPEF) is increasingly recognized as a major public health problem worldwide. Significant advances have been made in our understanding of the epidemiology of HFPEF over the past two decades, with the publication of numerous population-based epidemiological studies, large heart failure registries, and randomized clinical trials. These recent studies have provided detailed characterization of larger numbers of patients with HFPEF than ever before. This review summarizes the state of current knowledge with regards to the disease burden, patient characteristics, clinical course, and outcomes of HFPEF. Despite the wealth of available data, substantive gaps in knowledge were identified. These gaps represent opportunities for further research in HFPEF, a syndrome that is clearly a rising societal burden and that is associated with substantial morbidity and mortality.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

The recent discovery by Advanced LIGO and Advanced Virgo of a gravitational wave signal from a binary neutron star inspiral has enabled tests of general relativity (GR) with this new type of source. This source, for the first time, permits tests of strong-field dynamics of compact binaries in the presence of matter. In this Letter, we place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime. Bounds on modified dispersion of gravitational waves are obtained; in combination with information from the observed electromagnetic counterpart we can also constrain effects due to large extra dimensions. Finally, the polarization content of the gravitational wave signal is studied. The results of all tests performed here show good agreement with GR.

Summary Agricultural intensification poses a serious threat to biodiversity as a consequence of increased land‐use intensity, decreased landscape heterogeneity and reduced habitat diversity. Although there is interest in the preservation of total species richness of an agricultural landscape (γ diversity), the effects of intensification have been assessed primarily by species richness at a local scale (α diversity). This ignores species richness between local communities (β diversity), which is an important component of total species richness. In this study, measures of land‐use intensity, landscape structure and habitat diversity were related to γ, α and β diversity of wild bees (Apoidea), carabid beetles (Carabidae), hoverflies (Syrphidae), true bugs (Heteroptera) and spiders (Araneae) within 16 local communities in 24 temperate European agricultural landscapes. The total landscape species richness of all groups was most strongly affected by increased proximity of semi‐natural habitat patches. Bees also decreased in landscapes with a high intensity of farmland management, demonstrating additive effects of both factors. Separating total species diversity into components, the decrease in total species richness could be attributed primarily to a decrease in species diversity between local communities. Species richness of the local communities of all investigated groups decreased with increasing land‐use intensity and, in the case of spiders, decreasing proximity of the semi‐natural habitat patches. The effect of increased habitat diversity appeared to be of secondary importance to total species richness but caused a shift in the relative contribution of α and β diversity towards the latter. Synthesis and applications. This study demonstrates that the effects of agricultural change operate at a landscape level and that examining species diversity at a local level fails to explain the total species richness of an agricultural landscape. The coincidence of patterns of β diversity with those of γ diversity emphasizes that such information is of crucial importance for the implementation and evaluation of restoration programmes aiming to restore sustainable countryside diversity. As local extinction processes in highly fragmented landscapes shape biodiversity, priority should be given to the conservation of diverse agricultural landscape remnants in Europe.

Image inpainting refers to the process of restoring missing or damaged areas in an image. This field of research has been very active over recent years, boosted by numerous applications: restoring images from scratches or text overlays, loss concealment in a context of impaired image transmission, object removal in a context of editing, or disocclusion in image-based rendering (IBR) of viewpoints different from those captured by the cameras. Although earlier work dealing with disocclusion has been published in [1], the term inpainting first appeared in [2] by analogy with a process used in art restoration.

Autosomal dominant polycystic kidney disease (ADPKD) is heterogeneous with regard to genic and allelic heterogeneity, as well as phenotypic variability. The genotype-phenotype relationship in ADPKD is not completely understood. Here, we studied 741 patients with ADPKD from 519 pedigrees in the Genkyst cohort and confirmed that renal survival associated with PKD2 mutations was approximately 20 years longer than that associated with PKD1 mutations. The median age at onset of ESRD was 58 years for PKD1 carriers and 79 years for PKD2 carriers. Regarding the allelic effect on phenotype, in contrast to previous studies, we found that the type of PKD1 mutation, but not its position, correlated strongly with renal survival. The median age at onset of ESRD was 55 years for carriers of a truncating mutation and 67 years for carriers of a nontruncating mutation. This observation allows the integration of genic and allelic effects into a single scheme, which may have prognostic value.

GWTC-2.1 is a catalog of gravitational wave events from compact binary coalescences from the first half of the third observing run of Advanced LIGO and Advanced Virgo. It improves on GWTC-2, which covered the same period but with less refined analysis methods. GWTC-2.1 identifies 8 new events, all identified as sourced by binary black holes with one exception identified as a neutron star-black hole coalescence. These events expand significantly on the parameters characterizing the sources of observed gravitational-wave transients.