Nuclear rings are the inner edge of a gap around the Lindblad Resonance

Gaseous nuclear rings are large-scale coherent structures commonly found at the centres of barred galaxies. We propose that they are an accumulation of gas at the inner edge of an extensive gap that forms around the Inner Lindblad Resonance (ILR). The gap initially opens because the bar potential excites strong trailing waves near the ILR, which remove angular momentum from the gas disc and transport the gas inwards. The gap then widens because the bar potential continuously excites trailing waves at the inner edge of the gap, which remove further angular momentum, moving the edge further inwards until it stops at a distance of several wavelengths from the ILR. The gas accumulating at the inner edge of the gap forms the nuclear ring. The speed at which the gap edge moves and its final distance from the ILR strongly depend on the sound speed, explaining the puzzling dependence of the nuclear ring radius on the sound speed in simulations.Comment: Submitted to MNRAS. Comments welcom

Defining responders to therapies by a statistical modeling approach applied to randomized clinical trial data

Background: Personalized medicine is the tailoring of treatment to the individual characteristics of patients. Once a treatment has been tested in a clinical trial and its effect overall quantified, it would be of great value to be able to use the baseline patients' characteristics to identify patients with larger/lower benefits from treatment, for a more personalized approach to therapy. Methods: We show here a previously published statistical method, aimed at identifying patients' profiles associated to larger treatment benefits applied to three identical randomized clinical trials in multiple sclerosis, testing laquinimod vs placebo (ALLEGRO, BRAVO, and CONCERTO). We identified on the ALLEGRO patients' specific linear combinations of baseline variables, predicting heterogeneous response to treatment on disability progression. We choose the best score on the BRAVO, based on its ability to identify responders to treatment in this dataset. We finally got an external validation on the CONCERTO, testing on this new dataset the performance of the score in defining responders and non-responders. Results: The best response score defined on the ALLEGRO and the BRAVO was a linear combination of age, sex, previous relapses, brain volume, and MRI lesion activity. Splitting patients into responders and non-responders according to the score distribution, in the ALLEGRO, the hazard ratio (HR) for disability progression of laquinimod vs placebo was 0.38 for responders, HR = 1.31 for non-responders (interaction p = 0.0007). In the BRAVO, we had similar results: HR = 0.40 for responders and HR = 1.24 for non-responders (interaction p = 0.006). These findings were successfully replicated in the CONCERTO study, with HR = 0.44 for responders and HR=1.08 for non-responders (interaction p = 0.033). Conclusions: This study demonstrates the possibility to refine and personalize the treatment effect estimated in randomized studies by using the baseline demographic and clinical characteristics of the included patients. The method can be applied to any randomized trial in any medical condition to create a treatment-specific score associated to different levels of response to the treatment tested in the trial. This is an easy and affordable method toward therapy personalization, indicating patient profiles related to a larger benefit from a specific drug, which may have implications for taking clinical decisions in everyday clinical practice

The cytosolic glutamine synthetase GLN1;2 plays a role in the control of plant growth and ammonium homeostasis in Arabidopsis rosettes when nitrate supply is not limiting

Glutamine synthetase (EC 6.3.1.2) is a key enzyme of ammonium assimilation and recycling in plants where it catalyses the synthesis of glutamine from ammonium and glutamate. In Arabidopsis, five GLN1 genes encode GS1 isoforms. GLN1;2 is the most highly expressed in leaves and is over-expressed in roots by ammonium supply and in rosettes by ample nitrate supply compared with limiting nitrate supply. It is shown here that the GLN1;2 promoter is mainly active in the minor veins of leaves and flowers and, to a lower extent, in the parenchyma of mature leaves. Cytoimmunochemistry reveals that the GLN1;2 protein is present in the companion cells. The role of GLN1;2 was determined by examining the physiology of gln1;2 knockout mutants. Mutants displayed lower glutamine synthetase activity, higher ammonium concentration, and reduced rosette biomass compared with the wild type (WT) under ample nitrate supply only. No difference between mutant and WT can be detected under limiting nitrate conditions. Despite total amino acid concentration was increased in the old leaves of mutants at high nitrate, no significant difference in nitrogen remobilization can be detected using 15N tracing. Growing plants in vitro with ammonium or nitrate as the sole nitrogen source allowed us to confirm that GLN1;2 is induced by ammonium in roots and to observe that gln1;2 mutants displayed, under such conditions, longer root hair and smaller rosette phenotypes in ammonium. Altogether the results suggest that GLN1;2 is essential for nitrogen assimilation under ample nitrate supply and for ammonium detoxification

Learning ability correlates with brain atrophy and disability progression in RRMS

Objective To assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis. Methods We compared screening (day a '14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years. Results The mean PASAT score at screening was 45.38, increasing on average by 3.18 from day a '14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates. Conclusions Short-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment

First metallicity determination from Near-Infrared spectra for five obscured Cepheids discovered in the inner Disk

We report the discovery of five new classical Cepheids located in the inner Galactic Disk at longitude l ≃ −40° in our IRSF/SIRIUS Near-Infrared (NIR) variability survey. The new Cepheids are unique in probing the kinematics and metallicity of young stars at the transition between the inner Disk and the minor axis of the central Bar, where they are expected to be less affected by its dynamical influence. This is also the first time that metallicity of Cepheids is estimated on the basis of medium-resolution (R ∼ 3, 000) NIR spectra, and we validated our results with data in the literature, finding a minimal dependence on the adopted spectroscopic diagnostics. This result is very promising for using Cepheids as stellar proxy of the present-time chemical content of the obscured regions in the Disk. We found that the three Cepheids within 8–10 kpc from us have metallicities consistent with the mean radial metallicity gradient, and kinematics consistent with the Galactic rotation curve. Instead, the closest (∼4 kpc)/farthest (∼12 kpc) Cepheids have significant negative/positive residuals, both in velocity and in iron content. We discuss the possibility that such residuals are related to large-scale dynamical instabilities, induced by the bar/spiral-arm pattern, but the current sample is too limited to reach firm conclusion

Synthetic dust polarization emission maps at 353 GHz for an observer placed inside a Local Bubble-like cavity

We present a study of synthetic observations of polarized dust emission at 353 GHz as seen by an observer within a cavity in the interstellar medium (ISM). The cavity is selected from a magnetohydrodynamic simulation of the local ISM with time-dependent chemistry, star formation, and stellar feedback in form of supernova explosions with physical properties comparable to the Local Bubble ones. We find that the local density enhancement together with the coherent magnetic field in the cavity walls makes the selected candidate a translucent polarization filter to the emission coming from beyond its domains. This underlines the importance of studying the Local Bubble in further detail. The magnetic field lines inferred from synthetic dust polarization data are qualitatively in agreement with the all-sky maps of polarized emission at 353 GHz from the Planck satellite in the latitudes interval 15deg <= |b| <= 65deg. As our numerical simulation allows us to track the Galactic midplane only out to distances of 250 pc, we exclude the region |b|<15deg from our analysis. At large Galactic latitudes, our model exhibits a high degree of small-scale structures. On the contrary, the observed polarization pattern around the Galactic poles is relatively coherent and regular, and we argue that the global toroidal magnetic field of the Milky Way is important for explaining the data at |b| > 65deg. We show that from our synthetic polarization maps, it is difficult to distinguish between an open and a closed Galactic cap using the inferred magnetic field morphology alone

ALMA uncovers highly filamentary structure towards the Sgr E region

We report on the discovery of linear filaments observed in CO(1-0) emission for a $\sim2'$ field of view toward the Sgr E star forming region centered at (l,b)=(358.720$^\circ$, 0.011$^\circ$). The Sgr E region is thought to be at the turbulent intersection of the ''far dust lane'' associated with the Galactic bar and the Central Molecular Zone (CMZ). This region is subject to strong accelerations which are generally thought to inhibit star formation, yet Sgr E contains a large number of HII regions. We present $^{12}$CO(1-0), $^{13}$CO(1-0), and C$^{18}$O(1-0) spectral line observations from ALMA and provide measurements of the physical and kinematic properties for two of the brightest filaments. These filaments have widths (FWHM) of $\sim0.1$ pc and are oriented nearly parallel to the Galactic plane, with angles from the Galactic plane of $\sim2^\circ$. The filaments are elongated, with lower limit aspect ratios of $\sim$5:1. For both filaments we detect two distinct velocity components that are separated by about 15 km s$^{-1}$. In the C$^{18}$O spectral line data with $\sim$0.09 pc spatial resolution, we find that these velocity components have relatively narrow ($\sim$1-2 km s$^{-1}$) FWHM linewidths when compared to other sources towards the Galactic center. The properties of these filaments suggest that the gas in the Sgr E complex is being ''stretched'' as it is rapidly accelerated by the gravitational field of the Galactic bar while falling towards the CMZ, a result that could provide insight into the extreme environment surrounding this region and the large-scale processes which fuel this environment.Comment: 20 pages, 17 figures, accepted for publication in Ap

Near-equality of the Penrose Inequality for rotationally symmetric Riemannian manifolds

This article is the sequel to our previous paper [LS] dealing with the near-equality case of the Positive Mass Theorem. We study the near-equality case of the Penrose Inequality for the class of complete asymptotically flat rotationally symmetric Riemannian manifolds with nonnegative scalar curvature whose boundaries are outermost minimal hypersurfaces. Specifically, we prove that if the Penrose Inequality is sufficiently close to being an equality on one of these manifolds, then it must be close to a Schwarzschild space with an appended cylinder, in the sense of Lipschitz Distance. Since the Lipschitz Distance bounds the Intrinsic Flat Distance on compact sets, we also obtain a result for Intrinsic Flat Distance, which is a more appropriate distance for more general near-equality results, as discussed in [LS]Comment: 19 pages, 2 figure

The Morpho-kinematic Architecture of Super Star Clusters in the Center of NGC 253

The center of the nearby galaxy NGC 253 hosts a population of more than a dozen super star clusters (SSCs) that are still in the process of forming. The majority of the star formation of the burst is concentrated in these SSCs, and the starburst is powering a multiphase outflow from the galaxy. In this work, we measure the 350 GHz dust continuum emission toward the center of NGC 253 at 47 mas (0.8 pc) resolution using data from the Atacama Large Millimeter/submillimeter Array. We report the detection of 350 GHz (dust) continuum emission in the outflow for the first time, associated with the prominent South-West streamer. In this feature, the dust emission has a width of approximate to 8 pc, is located at the outer edge of the CO emission, and corresponds to a molecular gas mass of similar to(8-17)x10(6) M (circle dot). In the starburst nucleus, we measure the resolved radial profiles, sizes, and molecular gas masses of the SSCs. Compared to previous work at the somewhat lower spatial resolution, the SSCs here break apart into smaller substructures with radii 0.4-0.7 pc. In projection, the SSCs, dust, and dense molecular gas appear to be arranged as a thin, almost linear, structure roughly 155 pc in length. The morphology and kinematics of this structure can be well explained as gas following x (2) orbits at the center of a barred potential. We constrain the morpho-kinematic arrangement of the SSCs themselves, finding that an elliptical, angular-momentum-conserving ring is a good description of both the morphology and kinematics of the SSCs

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20–12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021