The ANTARES Optical Beacon System

ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented.Comment: 21 pages, 18 figures, submitted to Nucl. Instr. and Meth. Phys. Res.

Inhibition of the β-lactamase BlaMab by avibactam improves the in vitro and in vivo efficacy of imipenem against mycobacterium abscessus

Mycobacterium abscessus pulmonary infections are treated with a macrolide (clarithromycin or azithromycin), an aminoglycoside (amikacin), and a β-lactam (cefoxitin or imipenem). The triple combination is used without any β-lactamase inhibitor, even though M. abscessus produces the broad-spectrum β-lactamase BlaMab. We determine whether inhibition of BlaMab by avibactam improves the activity of imipenem against M. abscessus. The bactericidal activity of drug combinations was assayed in broth and in human macrophages. The in vivo efficacy of the drugs was tested by monitoring the survival of infected zebrafish embryos. The level of BlaMab production in broth and in macrophages was compared by quantitative reverse transcription-PCR and Western blotting. The triple combination of imipenem (8 or 32 μg/ml), amikacin (32 μg/ml), and avibactam (4 μg/ml) was bactericidal in broth (<0.1% survival), with 3.2- and 4.3-log10 reductions in the number of CFU being achieved at 72 h when imipenem was used at 8 and 32 μg/ml, respectively. The triple combination achieved significant intracellular killing, with the bacterial survival rates being 54% and 7% with the low (8 μg/ml) and high (32 μg/ml) dosages of imipenem, respectively. In vivo inhibition of BlaMab by avibactam improved the survival of zebrafish embryos treated with imipenem. Expression of the gene encoding BlaMab was induced (20-fold) in the infected macrophages. Inhibition of BlaMab by avibactam improved the efficacy of imipenem against M. abscessus in vitro, in macrophages, and in zebrafish embryos, indicating that this β-lactamase inhibitor should be clinically evaluated. The in vitro evaluation of imipenem may underestimate the impact of BlaMab, since the production of the β-lactamase is inducible in macrophages

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

First results of the Instrumentation Line for the deep-sea ANTARES neutrino telescope

In 2005, the ANTARES Collaboration deployed and operated at a depth of 2500 m a so-called Mini Instrumentation Line equipped with Optical Modules (MILOM) at the ANTARES site. The various data acquired during the continuous operation from April to December 2005 of the MILOM confirm the satisfactory performance of the Optical Modules, their front-end electronics and readout system. as well as the calibration devices of the detector. The in situ measurement of the Optical Module time response yields a resolution better than 0.5 ns. The performance of the acoustic positioning system, which enables the spatial reconstruction of the ANTARES detector with a precision of about 10 cm, is verified. These results demonstrate that with the full ANTARES neutrino telescope the design angular resolution of better than 0.3 degrees can be realistically achieved

The data acquisition system for the ANTARES neutrino telescope

The ANTARES neutrino telescope is being constructed in the Mediterranean Sea. It consists of a large three-dimensional array of photo-multiplier tubes. The data acquisition system of the detector takes care of the digitisation of the photo-multiplier tube signals, data transport, data filtering, and data storage. The detector is operated using a control program interfaced with all elements. The design and the implementation of the data acquisition system are described.Comment: 20 pages, 6 figures, accepted for publication in Nucl. Instrum. Meth.

Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

ANTARES: the first undersea neutrino telescope

The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given

Detection potential of the KM3NeT detector for high-energy neutrinos from the Fermi bubbles

A recent analysis of the Fermi Large Area Telescope data provided evidence for a high-intensity emission of high-energy gamma rays with a E 2 spectrum from two large areas, spanning 50 above and below the Galactic centre (the ‘‘Fermi bubbles’’). A hadronic mechanism was proposed for this gamma-ray emission making the Fermi bubbles promising source candidates of high-energy neutrino emission. In this work Monte Carlo simulations regarding the detectability of high-energy neutrinos from the Fermi bubbles with the future multi-km3 neutrino telescope KM3NeT in the Mediterranean Sea are presented. Under the hypothesis that the gamma-ray emission is completely due to hadronic processes, the results indicate that neutrinos from the bubbles could be discovered in about one year of operation, for a neutrino spectrum with a cutoff at 100 TeV and a detector with about 6 km3 of instrumented volume. The effect of a possible lower cutoff is also considered.Published7–141.8. Osservazioni di geofisica ambientaleJCR Journalrestricte

Expansion cone for the 3-inch PMTs of the KM3NeT optical modules

[EN] Detection of high-energy neutrinos from distant astrophysical sources will open a new window on the Universe. The detection principle exploits the measurement of Cherenkov light emitted by charged particles resulting from neutrino interactions in the matter containing the telescope. A novel multi-PMT digital optical module (DOM) was developed to contain 31 3-inch photomultiplier tubes (PMTs). In order to maximize the detector sensitivity, each PMT will be surrounded by an expansion cone which collects photons that would otherwise miss the photocathode. Results for various angles of incidence with respect to the PMT surface indicate an increase in collection efficiency by 30% on average for angles up to 45 degrees with respect to the perpendicular. Ray-tracing calculations could reproduce the measurements, allowing to estimate an increase in the overall photocathode sensitivity, integrated over all angles of incidence, by 27% (for a single PMT). Prototype DOMs, being built by the KM3NeT consortium, will be equipped with these expansion cones.This work is supported through the EU, FP6 Contract no. 011937, FP7 grant agreement no. 212252, and the Dutch Ministry of Education, Culture and Science.Adrián Martínez, S.; Ageron, M.; Aguilar, JA.; Aharonian, F.; Aiello, S.; Albert, A.; Alexandri, M.... (2013). Expansion cone for the 3-inch PMTs of the KM3NeT optical modules. Journal of Instrumentation. 8(3):1-19. https://doi.org/10.1088/1748-0221/8/03/T03006S1198