The LOFAR Transients Pipeline

Current and future astronomical survey facilities provide a remarkably rich opportunity for transient astronomy, combining unprecedented fields of view with high sensitivity and the ability to access previously unexplored wavelength regimes. This is particularly true of LOFAR, a recently-commissioned, low-frequency radio interferometer, based in the Netherlands and with stations across Europe. The identification of and response to transients is one of LOFAR's key science goals. However, the large data volumes which LOFAR produces, combined with the scientific requirement for rapid response, make automation essential. To support this, we have developed the LOFAR Transients Pipeline, or TraP. The TraP ingests multi-frequency image data from LOFAR or other instruments and searches it for transients and variables, providing automatic alerts of significant detections and populating a lightcurve database for further analysis by astronomers. Here, we discuss the scientific goals of the TraP and how it has been designed to meet them. We describe its implementation, including both the algorithms adopted to maximize performance as well as the development methodology used to ensure it is robust and reliable, particularly in the presence of artefacts typical of radio astronomy imaging. Finally, we report on a series of tests of the pipeline carried out using simulated LOFAR observations with a known population of transients.Comment: 30 pages, 11 figures; Accepted for publication in Astronomy & Computing; Code at https://github.com/transientskp/tk

Orbital and superorbital variability of LS I +61 303 at low radio frequencies with GMRT and LOFAR

LS I +61 303 is a gamma-ray binary that exhibits an outburst at GHz frequencies each orbital cycle of $\approx$ 26.5 d and a superorbital modulation with a period of $\approx$ 4.6 yr. We have performed a detailed study of the low-frequency radio emission of LS I +61 303 by analysing all the archival GMRT data at 150, 235 and 610 MHz, and conducting regular LOFAR observations within the Radio Sky Monitor (RSM) at 150 MHz. We have detected the source for the first time at 150 MHz, which is also the first detection of a gamma-ray binary at such a low frequency. We have obtained the light-curves of the source at 150, 235 and 610 MHz, all of them showing orbital modulation. The light-curves at 235 and 610 MHz also show the existence of superorbital variability. A comparison with contemporaneous 15-GHz data shows remarkable differences with these light-curves. At 15 GHz we see clear outbursts, whereas at low frequencies we see variability with wide maxima. The light-curve at 235 MHz seems to be anticorrelated with the one at 610 MHz, implying a shift of $\sim$ 0.5 orbital phases in the maxima. We model the shifts between the maxima at different frequencies as due to changes in the physical parameters of the emitting region assuming either free-free absorption or synchrotron self-absorption, obtaining expansion velocities for this region close to the stellar wind velocity with both mechanisms.Comment: 12 pages, 10 figures, accepted for publication in MNRA

BMC Med

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates

IRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network

Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity

Etude exploratoire du surcoût lié à l'exposition antérieure à une chirurgie abdomino-pelvienne

L'absence de littérature médicale sur les coûts liés à la prise en charge de patients présentant des ATCD chirurgicaux et la mise en œuvre de la future convergence tarifaire T2A dont l'objectif est le rapprochement des tarifs MCO du secteur public et privé, légitime la nécessité d'évaluer le potentiel surcoût de prise en charge de patients ayant des ATCD de chirurgie abdominopelvienne au sein d'un CHU. Pour répondre à cette hypothèse de recherche innovante, nous avons mené une étude exploratoire de type observationelle, contrôlée à inclusion prospective et médico-économique. Le recrutement des cas et témoins s'est déroulé sur la période de novembre 2010 à juin 2011 dans le service de chirurgie digestive du CHU de Clermont-Ferrand. L'objectif principal est d'évaluer la différence de coût partiel de prise en charge entre des patients naïfs de tout ATCD chirurgical abdominopelvien et ceux présentant des ATCD de chirurgie abdominopelvienne. Un des objectifs secondaires est d'évaluer l'écart de durée de séjour par rapport à la durée moyenne nationale selon la présence ou non de ces antécédents. Cette étude dont la comparabilité des groupes est vérifiée, montre une différence significative (p=0,022) sur l'écart de durée de séjour à la DMS nationale de 5 jours entre les 2 groupes quel que soit la chirurgie réalisée au cours du séjour. Toutefois, elle ne met pas en évidence de différence statistiquement significative sur le coût partiel entre ces 2 groupes de patients (p=0,93). Il existe une différence marquée d'écart de durée de séjour à la DMS nationale entre les patients avec ou sans ATCD chirurgicaux abdominopelviens mais une absence de surcoût partiel lié à la présence d'ATCD chirurgicaux abdominopelviens. Cette étude exploratoire est une ébauche pour la réalisation d'une étude de plus grande envergure.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

Fast nongenomic effects of steroids on synaptic transmission and role of endogenous neurosteroids in spinal pain pathways.

Steroids exert long-term modulatory effects on numerous physiological functions by acting at intracellular/nuclear receptors influencing gene transcription. Steroids and neurosteroids can also rapidly modulate membrane excitability and synaptic transmission by interacting with ion channels, that is, ionotropic neurotransmitter receptors or voltage-dependent Ca2+ or K+ channels. More recently, the cloning of a plasma membrane-located G protein-coupled receptor for progestins in various species has suggested that steroids/neurosteroids could also influence second-messenger pathways by directly interacting with specific membrane receptors. Here we review the experimental evidence implicating steroids/neurosteroids in the modulation of synaptic transmission and the evidence for a role of endogenously produced neurosteroids in such modulatory effects. We present some of our recent results concerning inhibitory synaptic transmission in lamina II of the spinal cord and show that endogenous 5alpha-reduced neurosteroids are produced locally in lamina II and modulate synaptic gamma-aminobutyric acid A(GABAA) receptor function during development, as well as during inflammatory pain. The production of 5alpha-reduced neurosteroids is controlled by the endogenous activation of the peripheral benzodiazepine receptor (PBR), which initiates the first step of neurosteroidogenesis by stimulating the translocation of cholesterol across the inner mitochondrial membrane. Tonic neurosteroidogenesis observed in immature animals was decreased during postnatal development, resulting in an acceleration of GABAA receptor-mediated miniature inhibitory postsynaptic current (mIPSC) kinetics observed in the adult. Stimulation of the PBR resulted in a prolongation of GABAergic mIPSCs at all ages and was observed during inflammatory pain. Neurosteroidogenesis might play an important role in the control of nociception at least at the spinal cord level

Reference ranges for serum S100B protein during the first three years of life

International audienceClinical and diagnostic management of traumatic brain injuries is problematic in young children. To facilitate this management, we describe blood reference ranges for the well established biomarker S100B in children younger than 3 years

Personalized Dosimetry with Intensification Using 90Y-Loaded Glass Microsphere Radioembolization Induces Prolonged Overall Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis.

International audienceThe objective of this study was to evaluate the response rate and survival of hepatocellular carcinoma portal vein thrombosis (PVT) patients treated with (90)Y-loaded glass microspheres using a personalized dosimetry and intensification concept. The microspheres were administered to 41 hepatocellular carcinoma PVT patients (main = 12; lobar/segmental = 29). (99m)Tc-macroaggregated albumin SPECT/CT quantitative analysis was used to calculate the tumor dose (TD), healthy injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 mo using the criteria of the European Association for the Study of the Liver, with CT follow-up lasting until disease progression or death. Survival was assessed using the Kaplan-Meier method. The mean injected activity was 3.1 ± 1.5 GBq, and mean ILD was 143 ± 49 Gy. When a TD threshold of 205 Gy was applied, (99m)Tc-macroaggregated albumin SPECT/CT achieved a 100% sensitivity and 90% overall accuracy (0 false-negatives; 4 false-positives) in response prediction. On the basis of TD and HILD values, 37% of patients received an intensification of the treatment (increased injected activity with the aim of achieving a TD ≥ 205 Gy and HILD 150 Gy). This intensification resulted in a high response rate (85%) without increased liver toxicity of grade 3 or higher (6% vs. 12% in the patients who did not receive treatment intensification; not statistically significant). For the total 41 patients, median overall survival (OS) was 18 mo (95% confidence interval, 11-25 mo). For patients with a TD of less than 205 Gy, median OS was 4.3 mo (3.7-5 mo), versus 18.2 mo (8.5-28.7 mo) for those with a TD of 205 Gy or more (P = 0.005). Median OS was 20.9 mo for patients with a TD of 205 Gy or more and good PVT targeting (n = 36). OS was 12 mo (3 mo to ∞) for patients with main PVT, versus 21.5 mo (12-28.7 mo) for those with segmental or lobar PVT (not statistically significant). For the 5 patients with complete portal vein revascularization who underwent lobar hepatectomy, median OS was not reached yet exceeded 24.5 mo and was significantly higher than that of other patients (P = 0.0493). Using a (99m)Tc-macroaggregated albumin SPECT/CT personalized dosimetry and intensification concept with (90)Y-loaded glass microspheres induced prolonged OS for PVT patients as compared with the standard of care (sorafenib), without increasing liver toxicity. Prospective randomized studies are therefore warranted