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We build a model to predict from first principles the properties of major mergers. We predict these from the coalescence of peaks and saddle points in the vicinity of a given larger peak, as one increases the smoothing scale in the initial linear density field as a proxy for cosmic time. To refine our results, we also ensure, using a suite of ∼400 power-law Gaussian random fields smoothed at ∼30 different scales, that the relevant peaks and saddles are topologically connected: they should belong to a persistent pair before coalescence. Our model allows us to (a) compute the probability distribution function of the satellite-merger separation in Lagrangian space: they peak at three times the smoothing scale; (b) predict the distribution of the number of mergers as a function of peak rarity: haloes typically undergo two major mergers (>1:10) per decade of mass growth; (c) recover that the typical spin brought by mergers: it is of the order of a few tens of per cent. [ABSTRACT FROM AUTHOR]

We study the geometry and Hodge theory of the cubic hypersurfaces attached to two-loop Feynman integrals for generic physical parameters. We show that the Hodge structure attached to planar two-loop Feynman graphs decomposes into mixed Tate pieces and the Hodge structures of families of hyperelliptic, elliptic or rational curves depending on the space-time dimension. For two-loop graphs with a small number of edges, we give more precise results. In particular, we recover a result of Bloch (Double box motive. SIGMA 2021; 17 ,048) that in the well-known double-box example, there is an underlying family of elliptic curves, and we give a concrete description of these elliptic curves. We show that the motive for the non-planar two-loop tardigrade graph is that of a K3 surface. In an appendix by Eric Pichon-Pharabod, we argue via high-precision numerical computations that the Picard number of this K3 surface is generically 11 and we compute the expected lattice polarization. Lastly, we show that generic members of the ice cream cone family of graph hypersurfaces correspond to the pairs of sunset Calabi–Yau varieties. [ABSTRACT FROM AUTHOR]

Metallicity offers a unique window into the baryonic history of the cosmos, being instrumental in probing evolutionary processes in galaxies between different cosmic environments. We aim to quantify the contribution of these environments to the scatter in the mass–metallicity relation (MZR) of galaxies. By analysing the galaxy distribution within the cosmic skeleton of the Horizon Run 5 cosmological hydrodynamical simulation at redshift z  = 0.625, computed using a careful calibration of the T-ReX filament finder, we identify galaxies within three main environments: nodes, filaments, and voids. We also classify galaxies based on the dynamical state of the clusters and the length of the filaments in which they reside. We find that the cosmic environment significantly contributes to the scatter in the MZR; in particular, both the gas metallicity and its average relative standard deviation increase when considering denser large-scale environments. The difference in the average metallicity between galaxies within relaxed and unrelaxed clusters is ≈0.1dex, with both populations displaying positive residuals, δ Z g, from the averaged MZR. Moreover, the difference in metallicity between node and void galaxies accounts for |$\approx 0.14 \, \text{dex}$| in the scatter of the MZR at stellar mass |$M_{\star } \approx 10^{9.35}\, \text{M}_{\odot }$|⁠. Finally, both the average [O/Fe] in the gas and the galaxy gas fraction decrease when moving to higher large-scale densities in the simulation, suggesting that the cores of cosmic environments host – on average – older and more massive galaxies, whose enrichment is affected by a larger number of Type Ia Supernova events. [ABSTRACT FROM AUTHOR]

Background A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman–Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®). Methods This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was >−5% at D28. Safety was assessed up to 6 months after the last injection. Results Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines. Conclusions In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines. Clinical Trials Registration NCT03965962. [ABSTRACT FROM AUTHOR]

We present LinearResponse.jl , an efficient, versatile public library written in julia to compute the linear response of self-gravitating (three-dimensional spherically symmetric) stellar spheres and (two-dimensional axisymmetric razor-thin) discs. LinearResponse.jl can scan the whole complex frequency plane, probing unstable, neutral and (weakly) damped modes. Given a potential model and a distribution function, this numerical toolbox estimates the modal frequencies as well as the shapes of individual modes. The libraries are validated against a combination of previous results for the spherical isochrone model and Mestel discs, and new simulations for the spherical Plummer model. Beyond linear response theory, the realm of applications of LinearResponse.jl also extends to the kinetic theory of self-gravitating systems through a modular interface. [ABSTRACT FROM AUTHOR]

Exclusion zones in the cross-correlations between critical points (peak-void, peak-wall, filament-wall, and filament-void) of the density field define quasi-standard rulers that can be used to constrain dark matter and dark energy cosmological parameters. The average size of the exclusion zone is found to scale linearly with the typical distance between extrema. The latter changes as a function of the matter content of the universe in a predictable manner, but its comoving size remains essentially constant in the linear regime of structure growth on large scales, unless the incorrect cosmology is assumed in the redshift–distance relation. This can be used to constrain the dark energy parameters when considering a survey that scans a range of redshifts. The precision of the parameter estimation is assessed using a set of cosmological simulations, and is found to be a 4σ detection of a change in matter content of 5 per cent, or about 3.8σ detection of 50 per cent shift in the dark energy parameter using a full sky survey up to redshift 0.5. [ABSTRACT FROM AUTHOR]

The 'core-cusp' problem is considered a key challenge to the ΛCDM paradigm. Haloes in dark matter only simulations exhibit 'cuspy' profiles, where density continuously increases towards the centre. However, the dark matter profiles of many observed galaxies (particularly in the dwarf regime) deviate strongly from this prediction, with much flatter central regions ('cores'). We use NewHorizon (NH), a hydrodynamical cosmological simulation, to investigate core formation, using a statistically significant number of galaxies in a cosmological volume. Haloes containing galaxies in the upper (M⋆ ≥ 1010.2 M⊙) and lower (M⋆ ≤ 108 M⊙) ends of the stellar mass distribution contain cusps. However, Haloes containing galaxies with intermediate (108 M⊙ ≤ M⋆ ≤ 1010.2 M⊙) stellar masses are generally cored, with typical halo masses between 1010.2 M⊙ and 1011.5 M⊙. Cores form through supernova-driven gas removal from halo centres, which alters the central gravitational potential, inducing dark matter to migrate to larger radii. While all massive (M⋆ ≥ 109.5 M⊙) galaxies undergo a cored-phase, in some cases cores can be removed and cusps reformed. This happens if a galaxy undergoes sustained star formation at high redshift, which results in stars (which, unlike the gas, cannot be removed by baryonic feedback) dominating the central gravitational potential. After cosmic star formation peaks, the number of cores, and the mass of the Haloes they are formed in, remain constant, indicating that cores are being routinely formed over cosmic time after a threshold halo mass is reached. The existence of cores is, therefore, not in tension with the standard paradigm. [ABSTRACT FROM AUTHOR]

Here, we use the Horizon–active galactic nucleus (AGN) simulation to test whether the spins of supermassive black hole (SMBH) in merger-free galaxies are higher. We select samples using an observationally motivated bulge-to-total mass ratio of <0.1, along with two simulation-motivated thresholds selecting galaxies which have not undergone a galaxy merger since z  = 2, and those SMBHs with |$\lt 10~{{\ \rm per\ cent}}$| of their mass due to SMBH mergers. We find higher spins (>5σ) in all three sample compared to the rest of the population. In addition, we find that SMBHs with their growth dominated by BH mergers following galaxy mergers are less likely to be aligned with their galaxy spin than those that have grown through accretion in the absence of galaxy mergers (3.4σ). We discuss the implications this has for the impact of active galactic nucleus (AGN) feedback, finding that merger-free SMBHs spend on average 91 per cent of their lifetimes since z  = 2 in a radio mode of feedback (88 per cent for merger-dominated galaxies). Given that previous observational and theoretical works have concluded that merger-free processes dominate SMBH-galaxy co-evolution, our results suggest that this co-evolution could be regulated by radio mode AGN feedback. [ABSTRACT FROM AUTHOR]

Aims We aim to evaluate the clinical relevance and the prognostic value of arterial and venous renal Doppler in acute decompensated precapillary pulmonary hypertension (PH). Methods and results The renal resistance index (RRI) and the Doppler-derived renal venous stasis index (RVSI) were monitored at admission and on Day 3 in a prospective cohort of precapillary PH patients managed in intensive care unit for acute right heart failure (RHF). The primary composite endpoint included death, circulatory assistance, urgent transplantation, or rehospitalization for acute RHF within 90 days following inclusion. Ninety-one patients were enrolled (58% female, age 58 ± 16 years). The primary endpoint event occurred in 32 patients (33%). In univariate logistic regression analysis, variables associated with RRI higher than the median value were non-variable parameters (age and history of hypertension), congestion (right atrial pressure and renal pulse pressure), cardiac function [tricuspid annular plane systolic excursion (TAPSE) and left ventricular outflow tract- velocity time integral], systemic pressures and NT-proBNP. Variables associated with RVSI higher than the median value were congestion (high central venous pressure, right atrial pressure, and renal pulse pressure), right cardiac function (TAPSE), severe tricuspid regurgitation, and systemic pressures. Inotropic support was more frequently required in patients with high RRI (P = 0.01) or high RVSI (P = 0.003) at the time of admission. At Day 3, a RRI value <0.9 was associated with a better prognosis after adjusting to the estimated glomerular filtration rate. Conclusion Renal Doppler provides additional information to assess the severity of patients admitted to the intensive care unit for acute decompensated precapillary PH. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis or ALS is a devastating and fatal neurodegenerative disease of motor neurons with very few treatment options. We had previously found that motor neuron degeneration in a mouse model of ALS can be delayed by deleting the axon damage sensor MAP3K12 or Dual Leucine Zipper Kinase (DLK)1. However, DLK is also involved in axon regeneration2-5, prompting us to ask whether combining DLK deletion with a way to promote axon regeneration would result in greater motor neuron protection. To achieve this, we used a mouse line that constitutively expresses ATF3, a master regulator of regeneration in neurons6,7. Although there is precedence for each individual strategy in the SOD1G93A mouse model of ALS1,8, these have not previously been combined. By several lines of evidence including motor neuron electrophysiology, histology and behavior, we observed a powerful synergy when combining DLK deletion with ATF3 expression. The combinatorial strategy resulted in significant protection of motor neurons with fewer undergoing cell death, reduced axon degeneration, and preservation of motor function and connectivity to muscle. This study provides a demonstration of the power of combinatorial therapy to treat neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Efficient and precise gene editing is the gold standard of any reverse genetic study. The recently developed prime editing approach, a modified CRISPR/Cas9 [clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein] editing method, has reached the precision goal but its editing rate can be improved. We present an improved methodology that allows for routine prime editing in the model plant Physcomitrium patens , whilst exploring potential new prime editing improvements. Using a standardized protoplast transfection procedure, multiple prime editing guide RNA (pegRNA) structural and prime editor variants were evaluated targeting the APT reporter gene through direct plant selection. Together, enhancements of expression of the prime editor, modifications of the 3ʹ extension of the pegRNA, and the addition of synonymous mutation in the reverse transcriptase template sequence of the pegRNA dramatically improve the editing rate without affecting the quality of the edits. Furthermore, we show that prime editing is amenable to edit a gene of interest through indirect selection, as demonstrated by the generation of a Ppdek1 0 mutant. Additionally, we determine that a plant retrotransposon reverse transcriptase enables prime editing. Finally, we show for the first time the possibility of performing prime editing with two independently coded peptides. [ABSTRACT FROM AUTHOR]

In perilous and stressful situations, the ability to suppress pain can be critical for survival. The rostral ventromedial medulla contains neurons that robustly inhibit nocioception at the level of the spinal cord through a top-down modulatory pathway. Although much is known about the role of the rostral ventromedial medulla in the inhibition of pain, the precise ability to directly manipulate pain-inhibitory neurons in the rostral ventromedial medulla has never been achieved. We now expose a cellular circuit that inhibits nocioception and itch in mice. Through a combination of molecular, tracing and behavioural approaches, we found that rostral ventromedial medulla neurons containing the kappa-opioid receptor inhibit itch and nocioception. With chemogenetic inhibition, we uncovered that these neurons are required for stress-induced analgesia. Using intersectional chemogenetic and pharmacological approaches, we determined that rostral ventromedial medulla kappa-opioid receptor neurons inhibit nocioception and itch through a descending circuit. Lastly, we identified a dynorphinergic pathway arising from the periaqueductal grey that modulates nociception within the rostral ventromedial medulla. These discoveries highlight a distinct population of rostral ventromedial medulla neurons capable of broadly and robustly inhibiting itch and nocioception. [ABSTRACT FROM AUTHOR]

With the numerous advances and broad applications of mobile health (mHealth), establishing concrete data sharing, privacy, and governance strategies at national (or regional) levels is essential to protect individual privacy and data usage. This article applies the recent Health Data Governance Principles to provide a guiding framework for low- and middle-income countries (LMICs) to create a comprehensive mHealth data governance strategy. We provide three objectives: (1) establish data rights and ownership to promote equitable benefits from health data, (2) protect people through building trust and addressing patients' concerns, and (3) promote health value by enhancing health systems and services. We also recommend actions for realizing each objective to guide LMICs based on their unique mHealth data ecosystems. These objectives require adopting a regulatory framework for data rights and protection, building trust for data sharing, and enhancing interoperability to use new datasets in advancing healthcare services and innovation. [ABSTRACT FROM AUTHOR]

Residuals between measured galactic radii and those predicted by the Fundamental Plane (FP) are possible tracers of weak lensing magnification. However, observations have shown these to be systematically correlated with the large-scale structure. We use the Horizon-AGN hydrodynamical cosmological simulation to analyse these intrinsic size correlations (ISCs) for both elliptical (early-type) and spiral (late-type) galaxies at |$z$|  = 0.06. We fit separate FPs to each sample, finding similarly distributed radius residuals, λ, in each case. We find persistent λλ correlations over three-dimensional separations |$0.5\hbox{--}17\, h^{-1}\, {\rm {Mpc}}$| in the case of spiral galaxies, at >3σ significance. When relaxing a mass-selection, applied for better agreement with galaxy clustering constraints, the spiral λλ detection strengthens to 9σ; we detect a 5σ density-λ correlation; and we observe intrinsically-large spirals to cluster more strongly than small spirals over scales |${\lesssim}10\, h^{-1}\, {\rm {Mpc}}$| at >5σ significance. Conversely, and in agreement with the literature, we observe lower-mass, intrinsically-small ellipticals to cluster more strongly than their large counterparts over scales |$0.5\hbox{--}17\, h^{-1}\, {\rm {Mpc}}$| at >5σ significance. We model λλ correlations using a phenomenological non-linear size model, and predict the level of contamination for cosmic convergence analyses. We find the systematic contribution to be of similar order to, or dominant over the cosmological signal. We make a mock measurement of an intrinsic, systematic contribution to the projected surface mass density Σ(r), and find statistically significant low-amplitude, positive (negative) contributions from lower-mass spirals (ellipticals), which may be of concern for large-scale (⁠|${\gtrsim}7\, h^{-1}$|  Mpc) measurements. [ABSTRACT FROM AUTHOR]

Evolution stands as a foundational pillar within modern biology, shaping our understanding of life. Studies related to evolution, for example constructing phylogenetic trees, are often carried out using DNA or protein sequences. These data, readily accessible from public databases, represent a treasure trove of resources that can be harnessed to create engaging activities with the public. At the heart of our project lies a collection of "stories" about evolution, each rooted in genuine scientific publications that furnish both biological context and supporting evidence. These narratives serve as the focal point of our LightOfEvolution.org website. Each story is accompanied by a dedicated "Your Turn to Play" section. Within this section, we furnish user-friendly activities and step-by-step guidelines, equipping visitors with the means to replicate analyses showcased in the highlighted publications. For example, the website OhMyGenes.org, relying on authentic scientific data, provides the capability to compute the proportion of shared genes across different species. Here, visitors can address the captivating question: "How many genes do we share with a banana?" To extend the educational reach, we have developed a series of modular activities, also related to the stories. These activities have been thoughtfully designed to be adaptable for face-to-face workshops held in classrooms or presented during public events. We aim to create stories and activities that resonate with participants, offering a tangible and enjoyable experience. By providing opportunities that reflect real-world scientific practices, we seek to offer participants valuable insights into the current workings of scientists "in the light of evolution." [ABSTRACT FROM AUTHOR]

Modelling the spatial distribution of infrasound attenuation (or transmission loss, TL) is key to understanding and interpreting microbarometer data and observations. Such predictions enable the reliable assessment of infrasound source characteristics such as ground pressure levels associated with earthquakes, man-made or volcanic explosion properties, and ocean-generated microbarom wavefields. However, the computational cost inherent in full-waveform modelling tools, such as parabolic equation (PE) codes, often prevents the exploration of a large parameter space, that is variations in wind models, source frequency and source location, when deriving reliable estimates of source or atmospheric properties—in particular for real-time and near-real-time applications. Therefore, many studies rely on analytical regression-based heuristic TL equations that neglect complex vertical wind variations and the range-dependent variation in the atmospheric properties. This introduces significant uncertainties in the predicted TL. In the current contribution, we propose a deep learning approach trained on a large set of simulated wavefields generated using PE simulations and realistic atmospheric winds to predict infrasound ground-level amplitudes up to 1000 km from a ground-based source. Realistic range dependent atmospheric winds are constructed by combining ERA5, NRLMSISE-00 and HWM-14 atmospheric models, and small-scale gravity-wave perturbations computed using the Gardner model. Given a set of wind profiles as input, our new modelling framework provides a fast (0.05 s runtime) and reliable (∼5 dB error on average, compared to PE simulations) estimate of the infrasound TL. [ABSTRACT FROM AUTHOR]

Variants in RAC3, encoding a small GTPase RAC3 which is critical for the regulation of actin cytoskeleton and intracellular signal transduction, are associated with a rare neurodevelopmental disorder with structural brain anomalies and facial dysmorphism. We investigated a cohort of 10 unrelated participants presenting with global psychomotor delay, hypotonia, behavioural disturbances, stereotyped movements, dysmorphic features, seizures and musculoskeletal abnormalities. MRI of brain revealed a complex pattern of variable brain malformations, including callosal abnormalities, white matter thinning, grey matter heterotopia, polymicrogyria/dysgyria, brainstem anomalies and cerebellar dysplasia. These patients harboured eight distinct de novo RAC3 variants, including six novel variants (NM_005052.3): c.34G > C p.G12R, c.179G > A p.G60D, c.186_188delGGA p.E62del, c.187G > A p.D63N, c.191A > G p.Y64C and c.348G > C p.K116N. We then examined the pathophysiological significance of these novel and previously reported pathogenic variants p.P29L, p.P34R, p.A59G, p.Q61L and p.E62K. In vitro analyses revealed that all tested RAC3 variants were biochemically and biologically active to variable extent, and exhibited a spectrum of different affinities to downstream effectors including p21-activated kinase 1. We then focused on the four variants p.Q61L, p.E62del, p.D63N and p.Y64C in the Switch II region, which is essential for the biochemical activity of small GTPases and also a variation hot spot common to other Rho family genes, RAC1 and CDC42. Acute expression of the four variants in embryonic mouse brain using in utero electroporation caused defects in cortical neuron morphology and migration ending up with cluster formation during corticogenesis. Notably, defective migration by p.E62del, p.D63N and p.Y64C were rescued by a dominant negative version of p21-activated kinase 1. Our results indicate that RAC3 variants result in morphological and functional defects in cortical neurons during brain development through variant-specific mechanisms, eventually leading to heterogeneous neurodevelopmental phenotypes. [ABSTRACT FROM AUTHOR]

Galaxies form from the accretion of cosmological infall of gas. In the high redshift Universe, most of this gas infall is expected to be dominated by cold filamentary flows which connect deep down inside haloes, and, hence, to the vicinity of galaxies. Such cold flows are important since they dominate the mass and angular momentum acquisition that can make up rotationally-supported discs at high-redshifts. We study the angular momentum acquisition of gas into galaxies, and in particular, the torques acting on the accretion flows, using hydrodynamical cosmological simulations of high-resolution zoomed-in haloes of a few |$10^{11}\, \rm M_\odot$| at z  = 2. Torques can be separated into those of gravitational origin, and hydrodynamical ones driven by pressure gradients. We find that coherent gravitational torques dominate over pressure torques in the cold phase, and are hence responsible for the spin-down and realignment of this gas. Pressure torques display small-scale fluctuations of significant amplitude, but with very little coherence on the relevant galaxy or halo-scale that would otherwise allow them to effectively re-orientate the gas flows. Dark matter torques dominate gravitational torques outside the galaxy, while within the galaxy, the baryonic component dominates. The circum-galactic medium emerges as the transition region for angular momentum re-orientation of the cold component towards the central galaxy's mid-plane. [ABSTRACT FROM AUTHOR]

We present LyMAS2, an improved version of the 'Lyman- α Mass Association Scheme' aiming at predicting the large-scale 3D clustering statistics of the Lyman- α forest (Ly  α) from moderate-resolution simulations of the dark matter (DM) distribution, with prior calibrations from high-resolution hydrodynamical simulations of smaller volumes. In this study, calibrations are derived from the Horizon-AGN suite simulations, (100 Mpc  h)−3 comoving volume, using Wiener filtering, combining information from DM density and velocity fields (i.e. velocity dispersion, vorticity, line-of-sight 1D-divergence and 3D-divergence). All new predictions have been done at z  = 2.5 in redshift space, while considering the spectral resolution of the SDSS-III BOSS Survey and different DM smoothing (0.3, 0.5, and 1.0 Mpc  h −1 comoving). We have tried different combinations of DM fields and found that LyMAS2, applied to the Horizon-noAGN DM fields, significantly improves the predictions of the Ly  α  3D clustering statistics, especially when the DM overdensity is associated with the velocity dispersion or the vorticity fields. Compared to the hydrodynamical simulation trends, the two-point correlation functions of pseudo-spectra generated with LyMAS2 can be recovered with relative differences of ∼5 per cent even for high angles, the flux 1D power spectrum (along the light of sight) with ∼2 per cent and the flux 1D probability distribution function exactly. Finally, we have produced several large mock BOSS spectra (1.0 and 1.5 Gpc  h −1) expected to lead to much more reliable and accurate theoretical predictions. [ABSTRACT FROM AUTHOR]

Supermassive black holes dominate the gravitational potential in galactic nuclei. In these dense environments, stars follow nearly Keplerian orbits and see their orbital planes relax through the potential fluctuations generated by the stellar cluster itself. For typical astrophysical galactic nuclei, the most likely outcome of this vector resonant relaxation is that the orbital planes of the most massive stars spontaneously self-align within a narrow disc. We present a maximum entropy method to systematically determine this long-term distribution of orientations and use it for a wide range of stellar orbital parameters and initial conditions. The heaviest stellar objects are found to live within a thin equatorial disc. The thickness of this disk depends on the stars' initial mass function, and on the geometry of the initial cluster. This work highlights a possible (indirect) novel method to constrain the distribution of intermediate mass black holes in galactic nuclei. [ABSTRACT FROM AUTHOR]

Background Campylobacter spp. bacteremia is a severe infection. A nationwide 5-year retrospective study was conducted to characterize its clinical features and prognostic factors. Methods The study included patients with Campylobacter spp. bacteremia diagnosed in 37 French hospitals participating in the surveillance network of the National Reference Center for Campylobacters and Helicobacters, from 1 January 2015 to 31 December 2019. The goal was to analyze the effects of a delay of appropriate antibiotic therapy and other risk factors on 30-day mortality rates, antibiotic resistance, patient characteristics, and prognosis according to the Campylobacter species. Results Among the 592 patients, Campylobacter jejuni and Campylobacter fetus were the most commonly identified species (in 42.9% and 42.6%, respectively). The patients were elderly (median age 68 years), and most had underlying conditions, mainly immunodepression (43.4%), hematologic cancers (25.9%), solid neoplasms (23%), and diabetes (22.3%). C. jejuni and Campylobacter coli were associated with gastrointestinal signs, and C. fetus was associated with secondary localizations. Among the 80 patients (13.5%) with secondary localizations, 12 had endocarditis, 38 vascular, 24 osteoarticular, and 9 ascitic fluid infections. The 30-day mortality rate was 11.7%, and an appropriate antibiotic treatment was independently associated with 30-day survival (odds ratio, 0.47 [95% confidence interval,.24–.93]; P  = .03). The median efficient therapy initiation delay was quite short (2 days [interquartile range, 0–4 days]) but it had no significant impact on the 30-day mortality rate (P  = .78). Conclusions Campylobacter spp. bacteremia mainly occurred in elderly immunocompromised individuals with variable clinical presentations according to the species involved. Appropriate antimicrobial therapy was associated with improved 30-day survival. [ABSTRACT FROM AUTHOR]

The upcoming WEAVE-QSO survey will target a high density of quasars over a large area, enabling the reconstruction of the 3D density field through Lyman- α (Ly- α) tomography over unprecedented volumes smoothed on intermediate cosmological scales (≈ 16 Mpc  h −1). We produce mocks of the Ly- α forest using Ly- α Mass Association Scheme, and reconstruct the 3D density field between sightlines through Wiener filtering in a configuration compatible with the future WEAVE-QSO observations. The fidelity of the reconstruction is assessed by measuring one- and two-point statistics from the distribution of critical points in the cosmic web. In addition, initial Lagrangian statistics are predicted from the first principles, and measurements of the connectivity of the cosmic web are performed. The reconstruction captures well the expected features in the auto- and cross-correlations of the critical points. This remains true after a realistic noise is added to the synthetic spectra, even though sparsity of sightlines introduces systematics, especially in the cross-correlations of points with mixed signature. Specifically, the most striking clustering features involving filaments and walls could be measured with up to 4 σ of significance with a WEAVE-QSO-like survey. Moreover, the connectivity of each peak identified in the reconstructed field is globally consistent with its counterpart in the original field, indicating that the reconstruction preserves the geometry of the density field not only statistically, but also locally. Hence, the critical points' relative positions within the tomographic reconstruction could be used as standard rulers for dark energy by WEAVE-QSO and similar surveys. [ABSTRACT FROM AUTHOR]

Globular clusters are dense stellar systems whose core slowly contracts under the effect of self-gravity. The rate of this process was recently found to be directly linked to the initial amount of velocity anisotropy: tangentially anisotropic clusters contract faster than radially anisotropic ones. Furthermore, initially anisotropic clusters are found to generically tend towards more isotropic distributions during the onset of contraction. Chandrasekhar's 'non-resonant' (NR) theory of diffusion describes this relaxation as being driven by a sequence of local two-body deflections along each star's orbit. We explicitly tailor this NR prediction to anisotropic clusters, and compare it with N -body realizations of Plummer spheres with varying degrees of anisotropy. The NR theory is shown to recover remarkably well the detailed shape of the orbital diffusion and the associated initial isotropization, up to a global multiplicative prefactor which increases with anisotropy. Strikingly, a simple effective isotropic prescription provides almost as good a fit, as long as the cluster's anisotropy is not too strong. For these more extreme clusters, accounting for long-range resonant relaxation may be necessary to capture these clusters' long-term evolution. [ABSTRACT FROM AUTHOR]

We use the NewHorizon simulation to study the redshift evolution of bar properties and fractions within galaxies in the stellar masses range M ⋆ = 107.25–1011.4 |$\, \rm {M}_\odot$| over the redshift range of z  = 0.25–1.3. We select disc galaxies using stellar kinematics as a proxy for galaxy morphology. We employ two different automated bar detection methods, coupled with visual inspection, resulting in observable bar fractions of f bar = 0.070 |$_{{-0.012}}^{{+0.018}}$| at z ∼ 1.3, decreasing to f bar = 0.011 |$_{{-0.003}}^{{+0.014}}$| at z ∼ 0.25. Only one galaxy is visually confirmed as strongly barred in our sample. This bar is hosted by the most massive disc and only survives from z  = 1.3 down to z  = 0.7. Such a low bar fraction, in particular amongst Milky Way-like progenitors, highlights a missing bars problem, shared by literally all cosmological simulations with spatial resolution <100 pc to date. The analysis of linear growth rates, rotation curves, and derived summary statistics of the stellar, gas and dark matter components suggest that galaxies with stellar masses below 109.5−1010 |$\, \rm {M}_\odot$| in NewHorizon appear to be too dominated by dark matter relative to stellar content to form a bar, while more massive galaxies typically have formed large bulges that prevent bar persistence at low redshift. This investigation confirms that the evolution of the bar fraction puts stringent constraints on the assembly history of baryons and dark matter on to galaxies. [ABSTRACT FROM AUTHOR]

Background: BaMaRa allows the secure collection and deidentified centralization of medical data from all patients followed-up in a rare disease expert network in France, based on a minimum data set (SDM-MR). The present article describes BaMaRa information system implementation and development across the whole national territory as well as data access requests through BNDMR, the data warehouse which centralizes all BaMaRa data, during the 2015-2020 period.Materials and Methods: SDM-MR is made up of 60 interoperable items and is routinely collected through BaMaRa in rare disease centers as part of care and discharged into BNDMR after deidentification and data reconciliation. Data access is regulated by a scientific committee.Results: In total, 668 002 affected patients had an SDM-MR recorded in BNDMR by the end of 2020 with a mean value of 3.4 activities per patients. Data access was provided for 66 projects.Conclusion: The BaMaRa-BNDMR infrastructure provides an administrative and epidemiological resources for rare diseases in France. [ABSTRACT FROM AUTHOR]

We propose a modelling technique to confidently estimate and optimize the performance of any infrasound network to remotely monitor sources of interest such as volcanic eruptions, while considering realistic atmospheric specifications along the propagation path, source frequency and noise levels at the station. To provide a more realistic picture of the network performance, we define a confidence level accounting for propagation and atmospheric uncertainties. Therefore, we consider 'numerical' uncertainties linked to the approximations made in the used propagation model, errors of the developed mathematical model and atmospheric uncertainties derived from measurement campaigns. In parallel, we perform a sensitivity analysis to determine how each input parameter contributes to the developed mathematical model output as well as to the attenuation model output. Such study is helpful for model simplification and uncertainty reduction by identifying, and thus paying more attention to the most influential model inputs. Below 1 Hz, the effect of 'numerical' errors on network performance modelling dominates. The same situation is observed during strong and stable downwind stratospheric winds along propagation paths. Conversely, when propagation occurs upwind, atmospheric uncertainties become predominant as the frequency increases. This method is then applied to assess the performance of the International Monitoring System (IMS) infrasound network in the Euro-Mediterranean and the Southeast Asian regions. We highlight a frequency, seasonal and spatial dependence of uncertainties in the modelling. Below 1 Hz, large errors are predicted in the shadow zone but the overall error is less than 20 dB. Above 1 Hz, errors with same order of magnitude are also observed, when strong stratospheric jets prevail. But during weak stratospheric duct, uncertainties associated to the modelled attenuation may exceed 30 dB. Such studies lead to significant improvement in assessing detection capability of infrasound network, which is of great interest for monitoring artificial or natural explosive sources like volcanic eruption. In particular this work will contribute into designing and prioritizing maintenance of any given infrasound network, in order to provide even better and more accurate predictions. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine trends in the intended users and functionalities advertised by menstrual tracking apps to identify gaps in personas and intended needs fulfilled by these technologies.Materials and Methods: Two types of materials were collected: a corpus of scientific articles related to the identities and needs of menstruators and a corpus of images and descriptions of menstrual tracking apps collected from the Google and Apple app stores. We conducted a scoping review of the literature to develop themes and then applied these as a framework to analyze the app corpus, looking for alignments and misalignments between the 2 corpora.Results: A review of the literature showed a wide range of disciplines publishing work relevant to menstruators. We identified 2 broad themes: "who are menstruators?" and "what are the needs of menstruators?" Descriptions of menstrual trackers exhibited misalignments with these themes, with narrow characterizations of menstruators and design for limited needs.Discussion: We synthesize gaps in the design of menstrual tracking apps and discuss implications for designing around: (1) an irregular menstrual cycle as the norm; (2) the embodied, leaky experience of menstruation; and (3) the varied biologies, identities, and goals of menstruators. An overarching gap suggests a need for a human-centered artificial intelligence approach for model and data provenance, transparency and explanations of uncertainties, and the prioritization of privacy in menstrual trackers.Conclusion: Comparing and contrasting literature about menstruators and descriptions of menstrual tracking apps provide a valuable guide to assess menstrual technology and their responsiveness to users and their needs. [ABSTRACT FROM AUTHOR]

North Korea conducted its sixth underground nuclear explosion test (⁠|${m_\mathrm{ b}}$| 6.3) on 2017 September 3. The underground explosion produced substantial low-frequency atmospheric waves, which were detected by infrasound arrays located up to a distance of 566 km. These infrasound waves are formed by the conversion of seismic energy to acoustic energy across the lithosphere–atmosphere interface. While infrasound records at regional distances produce estimates of ground motion amplitude over spatially extended regions covering about 26 500 km2, 3-D full seismo-acoustic simulations within the lithosphere and atmosphere provide quantitative information about seismo-acoustic energy partitioning. Our results demonstrate the capability of remote infrasound observations combined with 3-D propagation modelling to further develop discrimination methods for underground sources. These results contribute to enhance the confidence of source identification and characterization in nuclear test monitoring research, which is essential for the enforcement of the Comprehensive Nuclear-Test-Ban Treaty. [ABSTRACT FROM AUTHOR]

Globular clusters contain a finite number of stars. As a result, they inevitably undergo secular evolution ('relaxation') causing their mean distribution function (DF) to evolve on long time-scales. On one hand, this long-term evolution may be interpreted as driven by the accumulation of local deflections along each star's mean field trajectory – so-called 'non-resonant relaxation' (NR). On the other hand, it can be thought of as driven by non-local, collectively dressed, and resonant couplings between stellar orbits, a process termed 'resonant relaxation' (RR). In this paper, we consider a model globular cluster represented by a spherical, isotropic isochrone DF, and compare in detail the predictions of both RR and NR theories against tailored direct N -body simulations. In the space of orbital actions (namely the radial action and total angular momentum), we find that both RR and NR theories predict the correct morphology for the secular evolution of the cluster's DF, although the NR theory overestimates the amplitude of the relaxation rate by a factor of ∼2. We conclude that the secular relaxation of hot isotropic spherical clusters is not dominated by collectively amplified large-scale potential fluctuations, despite the existence of a strong ℓ = 1 damped mode. Instead, collective amplification affects relaxation only marginally even on the largest scales. The predicted contributions to relaxation from smaller scale fluctuations are essentially the same from RR and NR theories. [ABSTRACT FROM AUTHOR]

Supermassive black holes in the centre of galaxies dominate the gravitational potential of their surrounding stellar clusters. In these dense environments, stars follow nearly Keplerian orbits, which get slowly distorted as a result of the potential fluctuations generated by the stellar cluster itself. In particular, stars undergo a rapid relaxation of their eccentricities through both resonant and non-resonant processes. An efficient implementation of the resonant diffusion coefficients allows for detailed and systematic explorations of the parameter space describing the properties of the stellar cluster. In conjunction with recent observations of the S-cluster orbiting SgrA*, this framework can be used to jointly constrain the distribution of the unresolved, old, background stellar cluster and the characteristics of a putative dark cluster. Specifically, we show how this can be used to estimate the typical mass and cuspide exponent of intermediate-mass black holes consistent with the relaxed state of the distribution of eccentricities in the observed S-cluster. This should prove useful in constraining supermassive black hole formation scenarios. [ABSTRACT FROM AUTHOR]

Any germ of a complex analytic space is equipped with two natural metrics: the outer metric induced by the hermitian metric of the ambient space and the inner metric, which is the associated riemannian metric on the germ. A complex analytic germ is said Lipschitz normally embedded (LNE) if its outer and inner metrics are bilipschitz equivalent. LNE seems to be fairly rare among surface singularities; the only known LNE surface germs outside the trivial case (straight cones) are the minimal singularities. In this paper, we show that a superisolated hypersurface singularity is LNE if and only if its projectivized tangent cone has only ordinary singularities. This provides an infinite family of LNE singularities, which is radically different from the class of minimal singularities. [ABSTRACT FROM AUTHOR]

Metropolitan France is a region of slow tectonic deformation with sparse seismicity. On 11 November 2019, the M L 5.4 Le Teil earthquake became the largest seismic event recorded in the last 16 yr. This event was recorded by the national seismic networks and also by a wide variety of other geophysical techniques including infrasound and InSAR measurements. These complementary technologies offer the opportunity to investigate in detail the earthquake source characteristics and the associated ground motion attenuation. Both seismic waveform inversions and InSAR interferogram reveal a shallow rupture on a reverse fault with an associated moment magnitude of 4.8–4.9. Infrasound signals also provide fast evidences pointing towards the area of ground surface displacements, which coincides with La Rouvière fault, in the Cévennes fault system, known as a formerly active normal fault during the Oligocene. The very significant amount of seismic records also helps towards validating the GMPE laws available for the region. This multitechnology characterization documents the kinematics of this rare example of shallow intraplate fault reactivation. [ABSTRACT FROM AUTHOR]

The past decade has seen significant progress in understanding galaxy formation and evolution using large-scale cosmological simulations. While these simulations produce galaxies in overall good agreement with observations, they employ different sub-grid models for galaxies and supermassive black holes (BHs). We investigate the impact of the sub-grid models on the BH mass properties of the Illustris, TNG100, TNG300, Horizon-AGN, EAGLE, and SIMBA simulations, focusing on the M BH − M ⋆ relation and the BH mass function. All simulations predict tight M BH − M ⋆ relations, and struggle to produce BHs of |$M_{\rm BH}\leqslant 10^{7.5}\, \rm M_{\odot }$| in galaxies of |$M_{\star }\sim 10^{10.5}\!-\!10^{11.5}\, \rm M_{\odot }$|⁠. While the time evolution of the mean M BH − M ⋆ relation is mild (⁠|$\rm \Delta M_{\rm BH}\leqslant 1\, dex$| for 0 |$\leqslant z \leqslant$| 5) for all the simulations, its linearity (shape) and normalization varies from simulation to simulation. The strength of SN feedback has a large impact on the linearity and time evolution for |$M_{\star }\leqslant 10^{10.5}\, \rm M_{\odot }$|⁠. We find that the low-mass end is a good discriminant of the simulation models, and highlights the need for new observational constraints. At the high-mass end, strong AGN feedback can suppress the time evolution of the relation normalization. Compared with observations of the local Universe, we find an excess of BHs with |$M_{\rm BH}\geqslant 10^{9}\, \rm M_{\odot }$| in most of the simulations. The BH mass function is dominated by efficiently accreting BHs (⁠|$\log _{10}\, f_{\rm Edd}\geqslant -2$|⁠) at high redshifts, and transitions progressively from the high-mass to the low-mass end to be governed by inactive BHs. The transition time and the contribution of active BHs are different among the simulations, and can be used to evaluate models against observations. [ABSTRACT FROM AUTHOR]

Focusing on both small separations and baryonic acoustic oscillation scales, the cosmic evolution of the clustering properties of peak, void, wall, and filament-type critical points is measured using two-point correlation functions in ΛCDM dark matter simulations as a function of their relative rarity. A qualitative comparison to the corresponding theory for Gaussian random fields allows us to understand the following observed features: (i) the appearance of an exclusion zone at small separation, whose size depends both on rarity and signature (i.e. the number of negative eigenvalues) of the critical points involved; (ii) the amplification of the baryonic acoustic oscillation bump with rarity and its reversal for cross-correlations involving negatively biased critical points; (iii) the orientation-dependent small-separation divergence of the cross-correlations of peaks and filaments (respectively voids and walls) that reflects the relative loci of such points in the filament's (respectively wall's) eigenframe. The (cross-) correlations involving the most non-linear critical points (peaks, voids) display significant variation with redshift, while those involving less non-linear critical points seem mostly insensitive to redshift evolution, which should prove advantageous to model. The ratios of distances to the maxima of the peak-to-wall and peak-to-void over that of the peak-to-filament cross-correlation are |${\sim} \sqrt{2}$| and |${\sim} \sqrt{3}$|⁠ , respectively, which could be interpreted as the cosmic crystal being on average close to a cubic lattice. The insensitivity to redshift evolution suggests that the absolute and relative clustering of critical points could become a topologically robust alternative to standard clustering techniques when analysing upcoming surveys such as Euclid or Large Synoptic Survey Telescope (LSST). [ABSTRACT FROM AUTHOR]

Low-surface-brightness galaxies (LSBGs) – defined as systems that are fainter than the surface-brightness limits of past wide-area surveys – form the overwhelming majority of galaxies in the dwarf regime (M ⋆ < 109 M⊙). Using NewHorizon , a high-resolution cosmological simulation, we study the origin of LSBGs and explain why LSBGs at similar stellar mass show the large observed spread in surface brightness. NewHorizon galaxies populate a well-defined locus in the surface brightness–stellar mass plane, with a spread of ∼3 mag arcsec−2, in agreement with deep Sloan Digital Sky Survey (SDSS) Stripe 82 data. Galaxies with fainter surface brightnesses today are born in regions of higher dark matter density. This results in faster gas accretion and more intense star formation at early epochs. The stronger resultant supernova feedback flattens gas profiles at a faster rate, which, in turn, creates shallower stellar profiles (i.e. more diffuse systems) more rapidly. As star formation declines towards late epochs (z < 1), the larger tidal perturbations and ram pressure experienced by these systems (due to their denser local environments) accelerate the divergence in surface brightness, by increasing their effective radii and reducing star formation, respectively. A small minority of dwarfs depart from the main locus towards high surface brightnesses, making them detectable in past wide surveys (e.g. standard-depth SDSS images). These systems have anomalously high star formation rates, triggered by recent fly-by or merger-driven starbursts. We note that objects considered extreme or anomalous at the depth of current data sets, e.g. 'ultra-diffuse galaxies', actually dominate the predicted dwarf population and will be routinely visible in future surveys like the Legacy Survey of Space and Time (LSST). [ABSTRACT FROM AUTHOR]

In the standard ΛCDM (Lambda cold dark matter) paradigm, dwarf galaxies are expected to be dark matter-rich, as baryonic feedback is thought to quickly drive gas out of their shallow potential wells and quench star formation at early epochs. Recent observations of local dwarfs with extremely low dark matter content appear to contradict this picture, potentially bringing the validity of the standard model into question. We use NewHorizon , a high-resolution cosmological simulation, to demonstrate that sustained stripping of dark matter, in tidal interactions between a massive galaxy and a dwarf satellite, naturally produces dwarfs that are dark matter-deficient, even though their initial dark matter fractions are normal. The process of dark matter stripping is responsible for the large scatter in the halo-to-stellar mass relation in the dwarf regime. The degree of stripping is driven by the closeness of the orbit of the dwarf around its massive companion and, in extreme cases, produces dwarfs with halo-to-stellar mass ratios as low as unity, consistent with the findings of recent observational studies. ∼30 per cent of dwarfs show some deviation from normal dark matter fractions due to dark matter stripping, with 10 per cent showing high levels of dark matter deficiency (M halo/ M ⋆ < 10). Given their close orbits, a significant fraction of dark matter-deficient dwarfs merge with their massive companions (e.g. ∼70 per cent merge over time-scales of ∼3.5 Gyr), with the dark matter-deficient population being constantly replenished by new interactions between dwarfs and massive companions. The creation of these galaxies is therefore a natural by-product of galaxy evolution and their existence is not in tension with the standard paradigm. [ABSTRACT FROM AUTHOR]

Objectives The primary objective of this study was to assess the stressful life events preceding the onset of symptoms in RA. The secondary objectives were to assess how early RA patients perceive stress and cope with stressors. Methods A case–control study was performed, comparing patients recently diagnosed with RA to age- and gender-matched control subjects recently hospitalized for an unplanned surgical procedure not known to be influenced by stress. The Social Readjustment Rating Scale assessed the cumulative stress induced by stressful life events in the year preceding the onset of symptoms. Coping strategies, stress and anxiety symptoms were evaluated using validated psychological scales. Results Seventy-six subjects were included in each group. The mean Social Readjustment Rating Scale score was twice as high in cases compared with controls [respectively, 167.0 (172.5) vs 83.3 (124.4), P  < 0.001]. The association between cumulative stress and RA was statistically significant only in women, with a dose-dependent association between stress and RA. While female patients with RA attributed more often the onset of symptoms to a life event than female controls (70.2 vs 24.5%, P  < 0.001), no significant difference was found when comparing male RA patients with male controls (26.9 vs 18.5%, respectively, P  = 0.46). Increased perceived stress score (P  = 0.04) and coping based on emotions (P  = 0.001) were found in cases compared with controls. Conclusion Patients with early RA reported more life events in the year preceding the onset of symptoms than controls. Gender specificities were found with a significant association between cumulative stress and RA only in women. [ABSTRACT FROM AUTHOR]

We investigate the rate of orbital orientation dilution of young stellar clusters in the vicinity of supermassive black holes. Within the framework of vector resonant relaxation, we predict the time evolution of the two-point correlation function of the stellar orbital plane orientations as a function of their initial angular separation and diversity in orbital parameters (semimajor axis, eccentricity). As expected, the larger the spread in initial orientations and orbital parameters, the more efficient the dilution of a given set of co-eval stars, with a characteristic time-scale set up by the coherence time of the background potential fluctuations. A Markovian prescription that matches numerical simulations allows us to efficiently probe the underlying kinematic properties of the unresolved nucleus when requesting consistency with a given dilution efficiency, imposed by the observed stellar disc within the 1 arcsec of Sgr A*. As a proof of concept, we compute maps of constant dilution times as a function of the semimajor axis cusp index and fraction of intermediate-mass black holes in the old background stellar cluster. This computation suggests that vector resonant relaxation should prove useful in this context since it impacts orientations on time-scales comparable to the stars' age. [ABSTRACT FROM AUTHOR]

Introduction: The burden of disease attributable to tobacco use in Latin America is very high. Our objective was to evaluate the 10-year potential impact of current legislation related to cigarette packaging and warnings and expected effects of moving to a higher level of strategies implementing cigarette plain packaging on health and cost outcomes in Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, and Peru, using a microsimulation model.Aims and Methods: We used a probabilistic state-transition microsimulation model, considering natural history, costs, and quality of life losses associated with main tobacco-related diseases. We followed up individuals in hypothetical cohorts and calculated health outcomes annually to obtain aggregated long-term population health outcomes and costs. We performed a literature review to estimate effects and analyzed studies and information from ministries, relevant organizations, and national surveys. We calibrated the model comparing the predicted disease-specific mortality rates with local statistics.Results: Current graphic warnings already in place in each country could avert, during 10 years, 69 369 deaths and 638 295 disease events, adding 1.2 million years of healthy life and saving USD 5.3 billion in the seven countries. If these countries implemented plain packaging strategies, additional 155 857 premature deaths and 4 133 858 events could be averted, adding 4.1 million healthy years of life and saving USD 13.6 billion in direct health care expenses of diseases attributable to smoking.Conclusions: Latin American countries should not delay the implementation of this strategy that will alleviate part of the enormous health and financial burden that tobacco poses on their economies and health care systems.Implications: Tobacco smoking is the single most preventable and premature mortality cause in the world. The Framework Convention on Tobacco Control, supported by the World Health Organization, introduced a package of evidence-based measures for tobacco control. This study adds evidence on the potential health effects and savings of implementing cigarette plain packaging in countries representing almost 80% of the Latin American population; findings are valuable resources for policy makers in the region. [ABSTRACT FROM AUTHOR]

Massive black hole (MBH) coalescences are powerful sources of low-frequency gravitational waves. To study these events in the cosmological context, we need to trace the large-scale structure and cosmic evolution of a statistical population of galaxies, from dim dwarfs to bright galaxies. To cover such a large range of galaxy masses, we analyse two complementary simulations: horizon-AGN with a large volume and low resolution that tracks the high-mass (⁠|$\gt 10^7\, {\rm M_\odot }$|⁠) MBH population, and NewHorizon with a smaller volume but higher resolution that traces the low-mass (|$\lt 10^7\, {\rm M_\odot }$|⁠) MBH population. While Horizon-AGN can be used to estimate the rate of inspirals for pulsar timing arrays, NewHorizon  can investigate MBH mergers in a statistical sample of dwarf galaxies for LISA, which is sensitive to low-mass MBHs. We use the same method to analyse the two simulations, post-processing MBH dynamics to account for time delays mostly determined by dynamical friction and stellar hardening. In both simulations, MBHs typically merge long after galaxies do, so that the galaxy morphology at the time of the MBH merger is no longer determined by the structural disturbances engendered by the galaxy merger from which the MBH coalescence has originated. These time delays cause a loss of high- z MBH coalescences, shifting the peak of the MBH merger rate to z ∼ 1–2. This study shows how tracking MBH mergers in low-mass galaxies is crucial to probing the MBH merger rate for LISA and investigate the properties of the host galaxies. [ABSTRACT FROM AUTHOR]

Background: Polymyxins have re-entered use against problem Gram-negative bacteria. Resistance rates are uncertain, with estimates confounded by selective testing.Methods: The BSAC Resistance Surveillance Programme has routinely tested colistin since 2010; we reviewed data up to 2017 for relevant Enterobacterales (n = 10 914). Unexpectedly frequent resistance was seen among the Enterobacter cloacae complex isolates (n = 1749); for these, we investigated relationships to species, genome, carbon source utilization and LPS structure.Results: Annual colistin resistance rates among E. cloacae complex isolates were 4.4%-20%, with a rising trend among bloodstream organisms; in contrast, annual rates for Escherichia coli and Klebsiella spp. (including K. aerogenes) generally remained <2%. WGS split the E. cloacae complex isolates into seven genogroup clusters, designated A-G. Among isolates assigned to genogroups A-D, 47/50 sequenced were colistin resistant, and many of those belonging to genogroups A-C identified as E. asburiae. Isolates belonging to genogroups E-G consistently identified as E. cloacae and were rarely (only 3/45 representatives sequenced) colistin resistant. Genogroups F and G, the predominant colistin-susceptible clusters, were metabolically distinct from other clusters, notably regarding utilization or not of l-fucose, formic acid, d-serine, adonitol, myo-inositol, l-lyxose and polysorbates. LPS from resistant organisms grown without colistin pressure lacked substitutions with 4-amino-arabinose or ethanolamine but was more structurally complex, with more molecular species present.Conclusions: Colistin resistance is frequent in the E. cloacae complex and increasing among bloodstream isolates. It is associated with: (i) particular genomic and metabolic clusters; (ii) identification as E. asburiae; and (iii) with more complex LPS architectures. [ABSTRACT FROM AUTHOR]

We study shapes and alignments of 45 dark matter (DM) haloes and their brightest cluster galaxies (BCGs) using a sample of 39 massive clusters from Hubble Frontier Field (HFF), Cluster Lensing And Supernova survey with Hubble (CLASH), and Reionization Lensing Cluster Survey (RELICS). We measure shapes of the DM haloes by strong gravitational lensing, whereas BCG shapes are derived from their light profiles in Hubble Space Telescope images. Our measurements from a large sample of massive clusters presented here provide new constraints on DM and cluster astrophysics. We find that DM haloes are on average highly elongated with the mean ellipticity of 0.482 ± 0.028, and position angles of major axes of DM haloes and their BCGs tend to be aligned well with the mean value of alignment angles of 22.2 ± 3.9 deg. We find that DM haloes in our sample are on average more elongated than their BCGs with the mean difference of their ellipticities of 0.11 ± 0.03. In contrast, the Horizon-AGN cosmological hydrodynamical simulation predicts on average similar ellipticities between DM haloes and their central galaxies. While such a difference between the observations and the simulation may well be explained by the difference of their halo mass scales, other possibilities include the bias inherent to strong lensing measurements, limited knowledge of baryon physics, or a limitation of cold DM. [ABSTRACT FROM AUTHOR]

The diagnosis of the life-threatening invasive Candida infections is mainly established using culture of specimens that might be collected on different devices including ethylene diamine tetraacetic acid (EDTA)-coated tubes. Despite the knowledge that EDTA inhibits bacterial cultures, and its use to treat oral fungal infections, its impact on Candida cultures has not been completely assessed. This study aimed at assessing it on azole-resistant and azole-susceptible strains. Clinical and American Type Culture Collection (ATCC) strains for Candida albicans (CA), C. glabrata (CGS), C. krusei (CK), azole-susceptible and azole-resistant strains of C. glabrata (CGS and CGR), C. lipolytica (CL), and C. inconspicua (CI) were characterized using MALDI-TOF MS and susceptibility testing and then incubated (1) with serial dilutions of tripotassic EDTA (0%–500% of the concentration in a sample tube) for 2 hours before plating onto ChromID Can2 agar; (2) for 0, 2, 4, 6, 7, or 8 hours at EDTA concentrations at 20% and 33% before seeding; and (3) with sodium citrate or lithium heparinate instead of EDTA for 2 hours before plating. After 48 hours at 35°C, colony-forming units were automatically quantified. An inhibitory effect of EDTA was observed, at different concentrations, for CA (20%), CGS (100%), and CGR (500%) (P <.05), but none was observed for CL, CI, and CK. The effect increased with incubation duration, at a faster rate for azole-susceptible strains. K3-EDTA inhibits Candida growth and EDTA-coated tubes should not be used for mycological culture-based analyses. The correlation between EDTA inhibition and Candida azole-resistance offers perspectives for the development of selective agar and new antifungal strategies. [ABSTRACT FROM AUTHOR]

We study the spin alignment of galaxies and haloes with respect to filaments and walls of the cosmic web, identified with DisPerSE  , using the Simba  simulation from z  = 0 − 2. Massive haloes' spins are oriented perpendicularly to their closest filament's axis and walls, while low-mass haloes tend to have their spins parallel to filaments and in the plane of walls. A similar mass-dependent spin flip is found for galaxies, albeit with a weaker signal particularly at low mass and low- z , suggesting that galaxies' spins retain memory of their larger scale environment. Low- z star-forming and rotation-dominated galaxies tend to have spins parallel to nearby filaments, while quiescent and dispersion-dominated galaxies show preferentially perpendicular orientation; the star formation trend can be fully explained by the stellar mass correlation, but the morphology trend cannot. There is a dependence on HI mass, such that high-HI galaxies tend to have parallel spins while low-HI galaxies are perpendicular, suggesting that HI content may trace anisotropic infall more faithfully than the stellar component. Finally, at fixed stellar mass, the strength of spin alignments correlates with the filament's density, with parallel alignment for galaxies in high density environments. These findings are consistent with conditional tidal torque theory, and highlight a significant correlation between galactic spin and the larger scale tides that are important e.g., for interpreting weak lensing studies. Simba  allows us to rule out numerical grid locking as the cause of previously-seen low mass alignment. [ABSTRACT FROM AUTHOR]

The intrinsic correlations of galaxy shapes and orientations across the large-scale structure of the Universe are a known contaminant to weak gravitational lensing. They are known to be dependent on galaxy properties, such as their mass and morphologies. The complex interplay between alignments and the physical processes that drive galaxy evolution remains vastly unexplored. We assess the sensitivity of intrinsic alignments (shapes and angular momenta) to active galactic nuclei (AGN) feedback by comparing galaxy alignment in twin runs of the cosmological hydrodynamical Horizon simulation, which do and do not include AGN feedback, respectively. We measure intrinsic alignments in three dimensions and in projection at |$z$|  = 0 and |$z$|  = 1. We find that the projected alignment signal of all galaxies with resolved shapes with respect to the density field in the simulation is robust to AGN feedback, thus giving similar predictions for contamination to weak lensing. The relative alignment of galaxy shapes around galaxy positions is however significantly impacted, especially when considering high-mass ellipsoids. Using a sample of galaxy 'twins' across simulations, we determine that AGN changes both the galaxy selection and their actual alignments. Finally, we measure the alignments of angular momenta of galaxies with their nearest filament. Overall, these are more significant in the presence of AGN as a result of the higher abundance of massive pressure-supported galaxies. [ABSTRACT FROM AUTHOR]