Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis

Background: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. Objectives: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. Methods: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years’ follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. Results: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. Conclusions: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR

High sensitivity C reactive protein, fibrinogen levels and the onset of major depressive disorder in post-acute coronary syndrome

BACKGROUND: Major depression disorder (MDD) is a common condition in patients suffering from acute coronary syndrome (ACS), and depression is a risk factor for mortality following an ACS. Growing evidence suggests that there is an intricate interplay between atherosclerosis, inflammation and depression. The aim of this study was to investigate the role of atherosclerosis-induced inflammation in the mediation of MDD. METHODS: 87 patients without depression were recruited at the time of an ACS, evaluated at 3 and 7 days and followed at 1, 3 and 9 months for the occurrence of a MDD as assessed by structured interviews (MINI). At each time point, they were monitored for inflammatory markers (high sensitivity C Reactive Protein {hsCRP} and fibrinogen), cardiovascular risk factors and atherosclerosis burden. Association between possible predictive characteristics and depression was assessed using a multivariable logistic regression model. RESULTS: The overall incidence of MDD, in this population, was 28.7% [95% CI: 19.5 - 39.4] during the 9-month follow up period. Elevated hsCRP was not associated with depression onset after an ACS (adjusted OR: 1.07 [0.77 - 1.48]; p = 0.70), and similarly no association was found with fibrinogen. Furthermore, we found no association between hsCRP, fibrinogen or atherosclerosis burden at any time-point, and the occurrence of a MDD (or HDRS-17 and MADRS). The only factor associated with depression occurrence after an ACS was a previous personal history of depression (adjusted OR: 11.02 [2.74 to 44.34]; p = 0.0007). CONCLUSIONS: The present study shows that after an ACS, patients treated with optimal medications could have a MDD independent of elevated hsCRP or fibrinogen levels. Personal history of depression may be a good marker to select patients who should be screened for depression after an ACS

The SHiP experiment at the proposed CERN SPS Beam Dump Facility

The Search for Hidden Particles (SHiP) Collaboration has proposed a general-purpose experimental facility operating in beam-dump mode at the CERN SPS accelerator to search for light, feebly interacting particles. In the baseline configuration, the SHiP experiment incorporates two complementary detectors. The upstream detector is designed for recoil signatures of light dark matter (LDM) scattering and for neutrino physics, in particular with tau neutrinos. It consists of a spectrometer magnet housing a layered detector system with high-density LDM/neutrino target plates, emulsion-film technology and electronic high-precision tracking. The total detector target mass amounts to about eight tonnes. The downstream detector system aims at measuring visible decays of feebly interacting particles to both fully reconstructed final states and to partially reconstructed final states with neutrinos, in a nearly background-free environment. The detector consists of a 50 m long decay volume under vacuum followed by a spectrometer and particle identification system with a rectangular acceptance of 5 m in width and 10 m in height. Using the high-intensity beam of 400 GeV protons, the experiment aims at profiting from the 4 x 10(19) protons per year that are currently unexploited at the SPS, over a period of 5-10 years. This allows probing dark photons, dark scalars and pseudo-scalars, and heavy neutral leptons with GeV-scale masses in the direct searches at sensitivities that largely exceed those of existing and projected experiments. The sensitivity to light dark matter through scattering reaches well below the dark matter relic density limits in the range from a few MeV/c(2) up to 100 MeV-scale masses, and it will be possible to study tau neutrino interactions with unprecedented statistics. This paper describes the SHiP experiment baseline setup and the detector systems, together with performance results from prototypes in test beams, as it was prepared for the 2020 Update of the European Strategy for Particle Physics. The expected detector performance from simulation is summarised at the end

Fast simulation of muons produced at the SHiP experiment using generative adversarial networks

This paper presents a fast approach to simulating muons produced in interactions of the SPS proton beams with the target of the SHiP experiment. The SHiP experiment will be able to search for new long-lived particles produced in a 400 GeV/c SPS proton beam dump and which travel distances between fifty metres and tens of kilometers. The SHiP detector needs to operate under ultra-low background conditions and requires large simulated samples of muon induced background processes. Through the use of Generative Adversarial Networks it is possible to emulate the simulation of the interaction of 400 GeV/c proton beams with the SHiP target, an otherwise computationally intensive process. For the simulation requirements of the SHiP experiment, generative networks are capable of approximating the full simulation of the dense fixed target, offering a speed increase by a factor of Script O(106). To evaluate the performance of such an approach, comparisons of the distributions of reconstructed muon momenta in SHiP's spectrometer between samples using the full simulation and samples produced through generative models are presented. The methods discussed in this paper can be generalised and applied to modelling any non-discrete multi-dimensional distribution

The experimental facility for the Search for Hidden Particles at the CERN SPS

The International School for Advanced Studies (SISSA) logo The International School for Advanced Studies (SISSA) logo The following article is OPEN ACCESS The experimental facility for the Search for Hidden Particles at the CERN SPS C. Ahdida44, R. Albanese14,a, A. Alexandrov14, A. Anokhina39, S. Aoki18, G. Arduini44, E. Atkin38, N. Azorskiy29, J.J. Back54, A. Bagulya32Show full author list Published 25 March 2019 • © 2019 CERN Journal of Instrumentation, Volume 14, March 2019 Download Article PDF References Download PDF 543 Total downloads 7 7 total citations on Dimensions. Article has an altmetric score of 1 Turn on MathJax Share this article Share this content via email Share on Facebook Share on Twitter Share on Google+ Share on Mendeley Article information Abstract The Search for Hidden Particles (SHiP) Collaboration has shown that the CERN SPS accelerator with its 400 GeV/c proton beam offers a unique opportunity to explore the Hidden Sector [1–3]. The proposed experiment is an intensity frontier experiment which is capable of searching for hidden particles through both visible decays and through scattering signatures from recoil of electrons or nuclei. The high-intensity experimental facility developed by the SHiP Collaboration is based on a number of key features and developments which provide the possibility of probing a large part of the parameter space for a wide range of models with light long-lived super-weakly interacting particles with masses up to Script O(10) GeV/c2 in an environment of extremely clean background conditions. This paper describes the proposal for the experimental facility together with the most important feasibility studies. The paper focuses on the challenging new ideas behind the beam extraction and beam delivery, the proton beam dump, and the suppression of beam-induced background

Morpho-sedimentary evidence of Holocene coastal changes near the mouth of the Gironde and on the Medoc Peninsula, SW France

The Medoc Peninsula is a triangular area of land between the Atlantic Ocean on the west and the Gironde estuary on the east. The Gironde, orientated SE-NW, is the largest estuary in France. On the Medoc Peninsula Holocene sediments cover a substratum of Tertiary limestones and Plio-Pleistocene fluvial terraces. The Gironde originated as an incised valley during the Weichselian glacio-eustatic fall (100 000-18 000 B.P.) and has acted as a sink for fine sediment throughout the Holocene sea level rise (SLR) (18 000 B.P. onwards). Conversely, the Atlantic littoral zone, characterised by sandy beaches and dunes, has been subjected to erosion throughout the Holocene transgression. The incised valley of the present Gironde was inundated by the sea approximately 10 000 B.P. At this time, the rate of SLR exceeded that of sediment supply, producing a large accommodation space in which transgressive tidal-estuarine muds and sands were deposited. As the rate of SLR decreased around 6000-4000 B.P., sedimentation became more pronounced and the available accommodation space began to decrease significantly. Landward-derived fluvial sediments began to prograde over the tidal muds and sands, and a first generation of salt marshes formed in the lateral valleys. Around 2575-1420 B.P., a sandy chenier ridge formed at the edge of a first generation of salt marshes and wholly or partly separated them from the Gironde. On the eastern side of the ridge a second generation of marshes began to form after 1200 B.P. Reclamation of the first and second generations of marshes occurred during the seventeenth and eighteenth centuries, respectively. On the estuarine side of the eighteenth century dyke the modern intertidal flats and salt marshes began to form after the eighteenth century. Sedimentation within the estuary decreased the accommodation space and led to the increased transport of sediment to the shelf after 2 000 B.P. This process was also aided by climatic and anthropogenic factors. Future evolution of the Gironde estuary is likely to consist of further marsh growth and chenier development. However, future increases in the rate of SLR, and the degree of storminess, may cause a shift to an erosional regime in parts of the lower estuary. According to previous work [25, 66], three different dune fields migrated landwards across the Atlantic littoral zone over the Holocene period. A field of isolated barchan dunes moved landwards over the Plio-Pleistocene fluvial terraces before 5100 B.P. From some time after this, until around 3000 B.P., a field of parabolic dunes was active. Finally, a barchan dune field was active from around 3000-2000 B.P to the end of the eighteenth century/beginning of the nineteenth century, when the dunes were stabilised by pine plantations. It is tentatively suggested, using these dates and dune morphology, that dune formation was controlled by sand supply governed by the rate of SLR. However, the role of climatic changes such as aridity, storminess, windiness and the associated effects of vegetation cover, is also Likely to be important. In the future the Atlantic coast is likely to continue to erode, although the extensive plantation of the aeolian dunes with pine forests is likely to prevent large-scale transgressive activity.Le Médoc est une péninsule triangulaire séparant l'Océan Atlantique à l'Ouest de l'estuaire de la Gironde à l'Est. Ce dernier, orienté SE-NW, est le plus grand estuaire français. La couverture sédimentaire holocène du Médoc repose sur un substratum de calcaires tertiaires et de terrasses fluviatiles plio-pléistocènes. A l'origine, la Gironde était une vallée incisée formée lors du bas niveau marin correspondant an Weichselien (100 000 – 18 000 B.P.). Cette vallée a joué le rôle de piège à sédiments fins au cours de la remontée du niveau marin depuis le début de l'Holocène (après 18 000 B.P.). A l'inverse, la zone littorale atlantique, caractérisée par des plages sableuses et des dunes, a été soumise à l'érosion. La vallée incisée de la Gironde est pénétrée par les eaux marines vers 10 000 B.P. A cette époque, la remontée du niveau marin est plus importante que les apports sédimentaires; des vases et sables estuariens transgressifs s'accumulent dans l'espace d'accomodation ainsi créé. Entre 6000 et 4000 B.P., la remontée du niveau marin s'étant ralentie, la sédimentation devient plus importante, ce qui réduit sensiblement l'espace d'accomodation. Les sédiments terrigènes apportés par le fleuve commencent à prograder sur les vases et sables tidaux et une première génération de marais estuariens se forme dans les vallées latérales. Autour de 2575-1420 B.P., un cordon sableux se met en place sur la bordure externe de ces marais anciens, en les isolant partiellement ou totalement de l'estuaire. Une seconde génération de marais commence alors à se former à l'Est de ce cordon, après 1200 B.P. La poldérisation de ces deux générations de marais a lieu aux XVIIe et XVIIIe siècles, respectivement. La sédimentation à l'intérieur de l'estuaire réduit encore l'espace d'accomodation; les matériaux commencent à être exportés vers la plate-forme, après 2000 B.P. Ce processus est renforcé par des facteurs climatiques et anthropiques. L'évolution future de l'estuaire de la Gironde devrait probablement comprendre de nouvelles phases de croissance des marais et de mise en place d'une ride sableuse coquillière, de type « chenier å. Toutefois, de futurs accroissements du taux de remontée du niveau marin et de la frèquence des tempêtes pourraient provoquer l'apparition de conditions érosives dans certaines parties de l'estuaire aval. D'après les travaux [25, 66], la zone littorale atlantique est caractérisée par l'existence de trois champs dunaires distincts ayant migré vers l'intérieur des terres au cours de l'Holocène: (1) un champ de barkhanes isolées se déplaçant sur les terrasses fluviatiles plio-plèistocènes avant 5100 B.P.; (2) un champ de dunes paraboliques actives entre 5100 et 3000 B.P.; et enfin (3), un deuxième champ de barkhanes, mobiles entre 3000/2000 B.P. et la fin du XVIIIe siècle ou le début du XIXe, époque à laquelle les dunes sont stabilisées par des plantations de pins. Sur la base de ces dates et en considérant la morphologie des dunes, il est suggéré que la formation des dunes est contrôlée par la disponibilité du sable, elle-même gouvernée par le taux de remontée du niveau marin. Toutefois, le rôle de facteurs climatiques, tels l'aridité, la fréquence des tempêtes, le vent et leurs effets combinés sur la couverture végétale, est probablement important. Dans le futur, la côte atlantique devrait continuer à être soumise à l'érosion que la fixation extensive des dunes éoliennes par la pinède entrave cependant

Holocene coastal changes and infilling of the La Perroche marsh (French Atlantic coast)

The La Perroche marsh is a small Holocene marsh on the south-western coast of the Oleron island (Bay of Biscay, France) presently occupied by a freshwater swamp and separated from the ocean by a continuous sand dune ridge. The study of its infill shows first basal conglomeratic deposits with calcareous pebbles on a Cenomanian rough substrate. The Holocene infill since 6000 years BP begins with a very fast sedimentation of sands. Then, the sedimentation becomes finer, with lagoonal to freshwater influences recorded by ostracods. The distribution of these deposits inside the marsh is asymmetric, with a thick sandy-gravely layer in the eastern part and a succession of sands, clays and organic layers in the western part. Communication with the sea is episodic, and the sedimentation is controlled by an active channel, as shown by the presence of displaced coastal-marine faunas at some sites. Around 5000 years BP, a coastal marsh began to develop with high organic matter contents. These organic deposits presently outcrop on the beach, suggesting a more seaward location of the shoreline at that time. Generally, these sediments are azoic. When fauna is present, it indicates brackish to freshwater environments showing a progressive isolation of the system. A second phase of terrigenous sedimentation occurred after a transgressive event around 2800-2500 years BP, but the communication with the sea was then very reduced, as indicated by mainly freshwater faunas. This transgressive event appears to be synchronous with a positive sea-level tendency recorded, throughout north-western European coasts, between 3000 and 2000 years BP. The definitive closing of the marsh occurred around 2100 years BP, after a second phase of freshwater marsh. (Le marais holocène de La Perroche, localisé sur la côte sud-ouest de l’île d’Oléron (golfe de Gascogne, France), est actuellement un marais d’eau douce séparé du domaine océanique par un cordon dunaire continu. L’étude de son comblement au cours des 6 000 dernières années montre d’abord une invasion marine sur un substrat très accidenté d’âge cénomanien. Ensuite, se déposent probablement rapidement des sédiments sableux, témoins à la fois de l’établissement et du démantèlement de cordons dunaires et de l’érosion de l’arrière pays. Puis, la sédimentation devient plus fine et de type laguno-lacustre ainsi que le montrent les faunes d’ostracodes souvent associées aux sédiments. La distribution des dépôts dans le marais apparaît dés le début dissymétrique avec la présence d’épais niveaux sablo-graveleux à l’est et des successions de sables, d’argiles et de dépôts organiques à l’ouest. Les communications avec la mer sont épisodiques et le dépôt des sédiments est commandé par une chenalisation très active. Celle-ci est soulignée par la présence à proximité immédiate du chenal de faunes de type marin, le plus souvent déplacées et amenées en suspension. Vers 5000 ans BP s’installe un marais côtier, très riche en matière organique le plus souvent dépourvu de faune. Lorsque la faune est présente, elle indique des milieux laguno-saumâtres ou lacustres, confirmant ainsi l’isolation progressive du système. Des dépôts tourbeux trouvés sur la plage sont contemporains de ceux du marais actuel, ce qui implique une continuité sédimentaire entre ces deux sites et donc une situation des cordons dunaires plus au large qu’actuellement. Une seconde phase de sédimentation apparaît à la suite d’un événement transgressif vers 2800–2500 ans BP mais les communications avec le milieu marin sont très réduites comme le montrent les faunes majoritairement d’eaux douces. Cet épisode transgressif apparaît synchrone avec une tendance positive générale du niveau des eaux enregistrée entre 3000 et 2000 ans BP le long des côtes de l’Europe du nord-ouest. La fermeture définitive du marais intervient plus tard, après une seconde phase de développement de marécages vers 2100 ans BP

Extracellular myocardial volume in patients with aortic stenosis

Background:&nbsp;Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. Objectives:&nbsp;This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. Methods:&nbsp;Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery&ndash;based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. Results:&nbsp;Four-hundred forty patients (age 70 &plusmn; 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4&nbsp;to&nbsp;58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p &gt; 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p&nbsp;&lt;&nbsp;0.05 for all), the latter 2 associations being independent of all other clinical variables (p&nbsp;=&nbsp;0.035 and p&nbsp;&lt;&nbsp;0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p&nbsp;=&nbsp;0.009). Not only was ECV% associated with cardiovascular mortality (p&nbsp;=&nbsp;0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p&nbsp;=&nbsp;0.013). Conclusions:&nbsp;In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is&nbsp;a&nbsp;measure of left ventricular decompensation and a powerful independent predictor of mortality.</p