Design and operation of a field telescope for cosmic ray geophysical tomography

International audienceThe cosmic ray muon tomography gives an access to the density structure of geological targets. In the present article we describe a muon telescope adapted to harsh environmental conditions. In particular the design optimizes the total weight and power consumption to ease the deployment and increase the autonomy of the detector. The muon telescopes consist of at least two scintillator detection matrices readout by photosensors via optical fibres. Two photosensor options have been studied. The baseline option foresees one multianode photomultiplier (MAPM) per matrix. A second option using one multipixel photon counter (MPPC) per bar is under development. The readout electronics and data acquisition system developed for both options are detailed. We present a first data set acquired in open-sky conditions compared with the muon flux detected across geological objects

Concomitant heterochromatinisation and down-regulation of gene expression unveils epigenetic silencing of RELB in an aggressive subset of chronic lymphocytic leukemia in males

<p>Abstract</p> <p>Background</p> <p>The sensitivity of chronic lymphocytic leukemia (CLL) cells to current treatments, both <it>in vitro </it>and <it>in vivo</it>, relies on their ability to activate apoptotic death. CLL cells resistant to DNA damage-induced apoptosis display deregulation of a specific set of genes.</p> <p>Methods</p> <p>Microarray hybridization (Human GeneChip, Affymetrix), immunofluorescent <it>in situ </it>labeling coupled with video-microscopy recording/analyses, chromatin-immunoprecipitation (ChIP), polymerase chain reactions (PCR), real-time quantitative PCR (RT-QPCR) and bisulfite genome sequencing were the main methods applied. Statistical analyses were performed by applying GCRMA and SAM analysis (microarray data) and Student's t-test or Mann & Whitney's U-test.</p> <p>Results</p> <p>Herein we show that, remarkably, in a resistant male CLL cells the vast majority of genes were down-regulated compared with sensitive cells, whereas this was not the case in cells derived from females. This gene down-regulation was found to be associated with an overall gain of heterochromatin as evidenced by immunofluorescent labeling of heterochromatin protein 1α (HP-1), trimethylated histone 3 lysine 9 (3metH3K9), and 5-methylcytidine (5metC). Notably, 17 genes were found to be commonly deregulated in resistant male and female cell samples. Among these, <it>RELB </it>was identified as a discriminatory candidate gene repressed in the male and upregulated in the female resistant cells.</p> <p>Conclusion</p> <p>The molecular defects in the silencing of <it>RELB </it>involve an increase in H3K9- but not CpG-island methylation in the promoter regions. Increase in acetyl-H3 in resistant female but not male CLL samples as well as a decrease of total cellular level of RelB after an inhibition of histone deacetylase (HDAC) by trichostatin A (TSA), further emphasize the role of epigenetic modifications which could discriminate two CLL subsets. Together, these results highlighted the epigenetic <it>RELB </it>silencing as a new marker of the progressive disease in males.</p

Density muon radiography of La Soufrière of Guadeloupe volcano: comparison with geological, electrical resistivity and gravity data

International audienceDensity muon radiography is a new method to determine the average density of geological bodies by measuring the attenuation produced by rocks on the flux of cosmic muons. We present such density radiographies obtained for the Soufri'ere of Guadeloupe lava dome, both in the north-south and east-west planes. These radiographies reveal the highly heterogeneous density structure of the volcano, with low-density regions corresponding to recognized hydrothermally altered areas. The main structures observed in the density radiographies correlate with anomalies in electrical resistivity cross-sections and a density model obtained from gravity data

Muon tomography and Volcanic Risks in the Lesser Antilles: the Example of the Soufrière of Guadeloupe

International audienceThe Lesser Antilles is a subduction volcanic arc counting a dozen of either potentially or presently eruptingvolcanoes located in populated areas. During the last century violent eruptions occurred, killing 29000 people in1902 with the explosion of La Montagne Pelée in Martinique, leading to the evacuation of 73000 persons during 6months during the 1976 crisis of La Soufrière of Guadeloupe, and devastating most of the Montserrat island sincethe beginning in 1995 of the yet ongoing eruption of the Soufrière Hills.The Soufrière of Guadeloupe volcano is subjected to an intense hydrothermal activity which alters the mechanicalintegrity of the lava dome with a high risk level of destabilisation. Indeed, 8 flank collapses occurred during thelast 8500 years, several of them were followed by the creation of new lava domes. The present dome is dated1530 B.P. And appears very heterogeneous as revealed by both seismic tomography and electrical resistivitytomography. Gravity data show that the bulk density of the dome is about 2.2 g/cm3. The hydrothermal activityat the summit of the Guadeloupe Soufrière is regularly increasing with emitted fluids becoming more and moreacid. Imaging the internal structure of such a volcano brings important informations for the hazard evaluation anddensity muon tomography is particularly adapted to brought constraints on collapse models.A muon telescope was placed at the base of the lava dome the Guadeloupe Soufrière in July 2010. This fieldinstruments is adapted to the extreme field conditions encountered during hurricane season and it is entirelyautonomous with a total power consumption of less than 40W. Ethernet link allows both daily downloading ofthe data and remote control of the electronic devices and on-board computers. The telescope is equipped with3 scintillator matrices completed with an iron shielding of 24 mm in thickness in order to efficiently filter outfortuitous events. The density radiographies obtained with this telescope are presented and compared with theother geophysical data available on this volcano

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review

Background: Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality. Methods: MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes. Results: Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3–65% and 3–42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266–1,381 versus 67.5–575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791–2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase). Conclusions: Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients.This study was sponsored by Ipsen

Cost-Effectiveness of Escitalopram in Major Depressive Disorder in the Dutch Health Care Setting

Objective: This study assessed the cost-effectiveness of escitalopram for the treatment of depression in the Netherlands from a societal perspective. Methods: A decision tree model was constructed using decision analytical techniques. Data sources included published literature, clinical trials, official price/tariff lists, national population statistics, and Delphi panel data. The comparators were venlafaxine XR and citalopram. The primary perspective of this health economic evaluation was that of the society in the Netherlands in 2010. The time horizon was 26 weeks. The effectiveness outcomes of the study were quality-adjusted life-years (QALYs). Results: Escitalopram was associated with a cost savings per patient of 263 versus venlafaxine XR and 1992 versus citalopram over a period of 26 weeks from a societal perspective. Escitalopram was also associated with a gains QALYs: 0.0062 versus venlafaxine XR and 0.0166 versus citalopram. Escitalopram was dominant over both venlafaxine XR and citalopram. Conclusion: Based on the findings from this cost-effectiveness analysis, the favorable clinical benefit of escitalopram resulted in a positive health economic benefit in the Netherlands. (Clin Ther. 2012; 34:1364-1378) (C) 2012 Published by Elsevier HS Journals, Inc

Readout architecture for sub-nanosecond resolution TDC

International audienceThe DIAPHANE project is pluri-disciplinary collaboration between particle physicists and geophysicists to perform the tomography of large geological structure mainly devoted to the study of active volcanoes. The detector used for this tomography, hereafter referred to as telescope, uses a standard, robust, cost-effective and well-known technology based on solid plastic scintillator readout by photomultiplier(s) (either multichannel pixelized PM or silicon PM). The electronics system is built on the concept of autonomous, triggerless, smart sensor directly connected on a standard fast Ethernet network. First radiographies have been performed on the Mont-Terri underground laboratory (St-Ursanne, Switzerland) and on the active volcano of La Soufrière (Guadeloupe, Lesser Antilles, France). We present an upgrade of the readout architecture allowing to embed a sub-nanosecond resolution TDC within the existing programmable logic to help in the background rejection (rear flux, random coincidences) and to improve the detection purity and the radiography quality. First results obtained are also presented and briefly discussed

Readout architecture based on the use of Silicon PhotoMultiplier (SiPM, or MMPC)

International audienceThe DIAPHANE project is pluri-disciplinary collaboration between particle physicists and geophysicists to perform the tomography of large geological structure mainly devoted to the study of active volcanoes. The detector used for this tomography, hereafter referred to as telescope, uses a standard, robust, cost-effective and well-known technology based on solid plastic scintillator readout by photomultiplier(s). The first generation of those telescopes, presently running in the Mont-Terri underground laboratory (St-Ursanne, Switzerland) and on the active volcano of La Soufrière (Guadeloupe, Lesser Antilles, France), uses Hamamatsu H8804-200mod photomultipliers.We present an upgrade of the readout architecture based on the use of Silicon PhotoMultiplier (SiPM, or MMPC) which allows to simplify the optical connections w.r.t. the present design and to benefit from the high photo-dectection efficiency of the SiPM. To ensure an effective increase in the muon detection efficiency one has to optimize the first trigger level and find the best compromise between photostatistics and the tails of the dark noise contributions. Several readout architectures, based or not on dedicated ASICs, are discussed and compared in this article