Patient outcomes influenced by reduced lymphocyte counts after dimethyl fumarate initiation

Objective: To examine the temporal profile of absolute and lymphocyte subset data from dimethyl fumarate (DMF) start and relationships to disease behavior. Methods: A retrospective study performed on patients with an existing diagnosis of MS and a history of DMF exposure from a single MS center. Demographic, laboratory, and corresponding clinical relapse and MRI data were recorded from baseline and in 3-4-month intervals after treatment initiation extending to 3 years. The Spearman rank coefficient and mixed-effects models were used to assess longitudinal correlations between cell counts and measures of disease activity. Results: A total of 292 patients with MS (228 women; median age at DMF initiation: 40.6 years, range: 16.1-66.7 years) were identified. An increased risk of disease activity was associated with higher absolute lymphocyte count (ALC) values at 3 months (p = 0.001, OR: 1.82) and at 6 months (p = 0.032, hazard ratio: 1.73). A reduced risk of disease evolution in patients with lower ALC values < 1,200 cells/L compared with midtier (1,210-1,800 cells/L) and the highest tertile (>1,810 cells/L) was observed (p = 0.01). Conclusions: Reductions in ALC values at months 3 and 6 after treatment initiation appear to be associated with improved clinical and radiologic outcomes. These data alone may help to provide a better understanding of both the safety and efficacy of DMF

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

Acquisition and preliminary analysis of multi-channel seismic reflection data, acquired during the oceanographic cruises of the TOMO-ETNA experiment

The TOMO-ETNA experiment was performed in the framework of the FP7 “MED-SUV” (MEDiterranean SUpersite Volcanoes) in order to gain a detailed geological and structural model of the continental and oceanic crust concerning Etna and Aeolian Islands volcanoes (Sicily, Italy), by means of active and passive seismic exploration methodologies. Among all data collected, some 1410 km of marine multi-channel seismic (MCS) reflection profiles were acquired in the Ionian and Tyrrhenian Seas during two of the three oceanographic cruises of the TOMO-ETNA experiment, in July and November 2014, with the aim of shading light to deep, intermediate and shallow stratigraphy and crustal structure of the two above mentioned areas. The MCS sections, targeted to deep exploration, were acquired during the oceanographic cruise on board of the R/V “Sarmiento de Gamboa”, using an active seismic source of 16 air-guns, for a total volume of 4340 cu. in., and a 3000 m long, 240-channels digital streamer as receiving system. High-resolution seismic profiles were instead collected through the R/V “Aegaeo”, using two smaller air-guns (overall 270 cu. in. volume) and a 96 channels, 300 m long digital streamer. This paper provides a detailed description of the acquisition parameters and main processing steps adopted for the MCS data. Some processed lines are shown and preliminarily interpreted, to highlight the overall good quality and the high potential of the MCS sections collected during the TOMO-ETNA experiment. © 2016 by the Istituto Nazionale di Geofisica e Vulcanologia. All rights reserved

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

Simulations of the Milky Way's central molecular zone -- I. Gas dynamics

We use hydrodynamical simulations to study the Milky Way's central molecular zone (CMZ). The simulations include a non-equilibrium chemical network, the gas self-gravity, star formation and supernova feedback. We resolve the structure of the interstellar medium at sub-parsec resolution while also capturing the interaction between the CMZ and the bar-driven large-scale flow out to R\sim 5\kpc. Our main findings are as follows: (1) The distinction between inner ($R\lesssim120$~pc) and outer ($120\lesssim R\lesssim450$~pc) CMZ that is sometimes proposed in the literature is unnecessary. Instead, the CMZ is best described as single structure, namely a star-forming ring with outer radius $R\simeq 200$~pc which includes the 1.3$^\circ$ complex and which is directly interacting with the dust lanes that mediate the bar-driven inflow. (2) This accretion can induce a significant tilt of the CMZ out of the plane. A tilted CMZ might provide an alternative explanation to the $\infty$-shaped structure identified in Herschel data by Molinari et al. 2011. (3) The bar in our simulation efficiently drives an inflow from the Galactic disc ($R\simeq 3$~kpc) down to the CMZ ($R\simeq200$~pc) of the order of $1\rm\,M_\odot\,yr^{-1}$, consistent with observational determinations. (4) Supernova feedback can drive an inflow from the CMZ inwards towards the circumnuclear disc of the order of $\sim0.03\,\rm M_\odot\,yr^{-1}$. (5) We give a new interpretation for the 3D placement of the 20 and 50 km s$^{-1}$ clouds, according to which they are close ($R\lesssim30$~pc) to the Galactic centre, but are also connected to the larger-scale streams at $R\gtrsim100$~pc.Comment: Accepted for publication in MNRAS. Movies of the simulations can be found at: https://www.youtube.com/channel/UCwnzfO-xLxzRDz9XsexfPo

Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses

Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms. However, anti-inflammatory therapies may modify these damaged pathways, but with a therapeutic lag that may take years to manifest. Based on these observations we propose that clinically apparent neurodegenerative components of progressive MS may occur in a length-dependent manner and asynchronously. If this hypothesis is confirmed it may have major implications for the future design of progressive MS trials

A CO Funnel in the Galactic Centre: Molecular Counterpart of the Northern Galactic Chimney?

We report the discovery of a velocity coherent, funnel shaped ^13CO emission feature in the Galactic centre (GC) using data from the SEDIGISM survey. The molecular cloud appears as a low velocity structure (V_LSR=[-3.5, +3.5] km/s) with an angular extent of 0.95{\deg} x 1{\deg}, extending toward positive Galactic latitudes. The structure is offset from Sgr A* toward negative Galactic longitudes and spatially and morphologically correlates well with the northern lobe of the 430 pc radio bubble, believed to be the radio counterpart of the multiwavelength GC chimney. Spectral line observations in the frequency range of 85-116 GHz have been carried out using the IRAM 30 metre telescope toward 12 positions along the funnel-shaped emission. We examine the ^12C/^13C isotopic ratios using various molecules and their isotopologues. The mean ^12C/^13C isotope ratio (30.6+-2.9) is consistent with the structure located within inner 3 kpc of the Galaxy and possibly in the GC. The velocity of the molecular funnel is consistent with previous radio recombination line measurements of the northern lobe of radio bubble. Our multiwavelength analysis suggests that the funnel shaped structure extending over 100 pc above the Galactic plane is the molecular counterpart of the northern GC chimney.Comment: Accepted for publication in A&A Letter

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

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

Persistent left ventricular dysfunction after acute lymphocytic myocarditis: Frequency and predictors.

BACKGROUND: Persistent left ventricular (LV) systolic dysfunction in patients with acute lymphocytic myocarditis (LM) is widely unexplored. OBJECTIVES: To assess the frequency and predictors of persistent LV dysfunction in patients with LM and reduced LVEF at admission. METHODS AND RESULTS: We retrospectively evaluated 89 consecutive patients with histologically-proven acute myocarditis enrolled at three Italian referral hospitals. A subgroup of 48 patients with LM, baseline systolic impairment and an available echocardiographic assessment at 12 months (6-18) from discharge constituted the study population. The primary study end-point was persistent LV dysfunction, defined as LVEF <50% at 1-year, and was observed in 27/48 patients (56.3%). Higher LV end-diastolic diameter at admission (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.04-1.43, p = 0.002), non-fulminant presentation (OR 8.46, 95% CI 1.28-55.75, p = 0.013) and presence of a poor lymphocytic infiltrate (OR 12.40, 95% CI 1.23-124.97, p = 0.010) emerged as independent predictors of persistent LV dysfunction at multivariate analysis (area under the curve 0.91, 95% CI 0.82-0.99). Pre-discharge LVEF was lower in patients with persistent LV dysfunction compared to the others (32%±8 vs. 53%±8, p <0.001), and this single variable showed the best accuracy in predicting the study end-point (area under the curve 0.95, 95% CI 0.89-1.00). CONCLUSIONS: More than half of patients presenting with acute LM and LVEF <50% who survive the acute phase show persistent LV dysfunction after 1-year from hospital discharge. Features of subacute inflammatory process and of established myocardial damage at initial hospitalization emerged as predictors of this end-point