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- Ageron, M., et al.
(författare)
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ANTARES : The first undersea neutrino telescope
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 656:1, s. 11-38
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Tidskriftsartikel (refereegranskat)abstract
- 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. (C) 2011 Elsevier B.V. All rights reserved.
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| 5. |
- Ageron, M., et al.
(författare)
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The ANTARES optical beacon system
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 578:3, s. 498-509
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Tidskriftsartikel (refereegranskat)abstract
- 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. (C) 2007 Elsevier B.V. All rights reserved.
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| 6. |
- Ageron, M., et al.
(författare)
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Studies of a full-scale mechanical prototype line for the ANTARES neutrino telescope and tests of a prototype instrument for deep-sea acoustic measurements
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 581:3, s. 695-708
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Tidskriftsartikel (refereegranskat)abstract
- full-scale mechanical prototype line was deployed to a depth of 2500 m to test the leak tightness of the electronics containers and the pressure-resistant properties of an electromechanical cable under evaluation for use in the ANTARES deep-sea neutrino telescope. During a month-long immersion study, line parameter data were taken using miniature autonomous data loggers and shore-based optical time domain reflectometry. Details of the mechanical prototype line, the electromechanical cable and data acquisition are presented. Data taken during the immersion study revealed deficiencies in the pressure resistance of the electromechanical cable terminations at the entry points to the electronics containers. The improvements to the termination, which have been integrated into subsequent detection lines, are discussed. The line also allowed deep-sea acoustic measurements with a prototype hydrophone system. The technical setup of this system is described, and the first results of the data analysis are presented. (c) 2007 Elsevier B.V. All rights reserved.
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- Eron, Joseph J., et al.
(författare)
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Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1
- 2019
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 170
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 The Authors Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
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| 9. |
- Ageron, M., et al.
(författare)
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Performance of the first ANTARES detector line
- 2009
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 31:4, s. 277-283
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we report on the data recorded with the first Antares detector line. The line was deployed on the 14th of February 2006 and was connected to the readout 2 weeks later. Environmental data for one and a half years of running are shown. Measurements of atmospheric muons from data taken from selected runs during the first 6 months of operation are presented. Performance figures in terms of time residuals and angular resolution are given. Finally the angular distribution of atmospheric muons is presented and from this the depth profile of the muon intensity is derived. (C) 2009 Elsevier B.V. All rights reserved.
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| 10. |
- Pantazis, N, et al.
(författare)
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Determining the likely place of HIV acquisition for migrants in Europe combining subject-specific information and biomarkers data
- 2019
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 28:7, s. 1979-1997
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Tidskriftsartikel (refereegranskat)abstract
- In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.
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| 16. |
- Benjamin, Daniel J., et al.
(författare)
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Redefine statistical significance
- 2018
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Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 2:1, s. 6-10
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 17. |
- Grankvist, Anna, et al.
(författare)
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Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis" Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases
- 2014
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 58:12, s. 1716-1722
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Tidskriftsartikel (refereegranskat)abstract
- Background. Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. Methods.aEuro integral We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. Results.aEuro integral The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. Conclusions.aEuro integral Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.
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| 18. |
- Cippà, Pietro E, et al.
(författare)
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Risk Stratification for Rejection and Infection after Kidney Transplantation.
- 2015
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Ingår i: Clinical Journal of the American Society of Nephrology. - 1555-905X. ; 10:12, s. 2213-2220
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Tidskriftsartikel (refereegranskat)abstract
- Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under- and overimmunosuppression after kidney transplantation.
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| 19. |
- Clausen, S., et al.
(författare)
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Outcome of Ordinary Polymorphous Adenocarcinomas of the Salivary Glands in Comparison With Papillary and Cribriform Subtypes
- 2022
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 42:3, s. 1455-1463
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Polymorphous adenocarcinoma (PAC) is a low-grade salivary gland malignancy in contrast to variants with papillary (PAP) or cribriform (CASG) architecture and confers the second most common malignancy of minor salivary glands. Our study aimed to identify prognostic factors and to evaluate histomorphological and molecular diagnostic criteria of PACs. Patients and Methods: A series of 155 PACs, including 10 PAPs and 12 CASGs from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW) and the Hamburg Salivary Gland Reference Centre (HRC) were analyzed. Results: One fifth of the tumors were located in the major salivary glands and PACS/CASGS invariably lacked p40 expression. Fifty-two percent of PACs showed a PRKD1 E710D mutation. Ordinary PACs had a disease-specific 10-year survival probability of 97% compared to 90% when combining PAPs and CASGs. T-stage at diagnosis was a prognostic factor with 98% for stages T1/T2 versus 75% for T3/T4. Conclusion: Diagnostic algorithms for the PAC/CASG spectrum of tumors need to be improved and should include molecular markers.
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- Fehr, Andre, et al.
(författare)
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Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping.
- 2021
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 479, s. 975-985
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Tidskriftsartikel (refereegranskat)abstract
- Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n=167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n=384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system). The reliability of both the AFIP and Brandwein grading systems was excellent (n=155). The weighted kappa for inter-rater agreement was 0.81 (95% CI 0.65-0.97) and 0.83 (95% CI 0.71-0.96) for the AFIP and Brandwein systems, respectively. The 5-year relative survival was 79.7% (95% CI 73.2-86.2%). Although the Brandwein system resulted in a higher rate of G3-MECs, survival in G3-tumors (AFIP or Brandwein grading) was markedly worse than in G1/G2-tumors. Survival in>T2 tumors was markedly worse than in those with lower T-stage. Also, fusion-negative MECs had a worse 5-year progression-free survival. The frequency of fusion-positive MECs in the HRC cohort was 78.4%, of which the majority (86.7%) was G1/G2-tumors. In conclusion, the AFIP and Brandwein systems are useful in estimating prognosis and to guide therapy for G3-MECs. However, their significance regarding young age (≤30years) and location-dependent heterogeneity of in particular G2-tumors is more questionable. We conclude that CRTC1/3-MAML2 testing is a useful adjunct to histologic scoring of MECs and for pinpointing tumors with poor prognosis with higher precision, thus avoiding overtreatment.
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| 22. |
- Jaeger, S.U., et al.
(författare)
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Cell-mediated reduction of human β-defensin 1 : a major role for mucosal thioredoxin
- 2013
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Ingår i: Mucosal Immunology. - : Nature Publishing Group. - 1933-0219 .- 1935-3456. ; 6:6, s. 1179-1190
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Tidskriftsartikel (refereegranskat)abstract
- Human β-defensin 1 (hBD-1) is an antimicrobial peptide expressed by epithelia and hematopoietic cells. We demonstrated recently that hBD-1 shows activity against enteric commensals and Candida species only after its disulfide bonds have been reduced by thioredoxin (TRX) or a reducing environment. Here we show that besides TRX, glutaredoxin (GRX) is also able to reduce hBD-1, although with far less efficacy. Moreover, living intestinal and lymphoid cells can effectively catalyze reduction of extracellular hBD-1. By chemical inhibition of the TRX system or specific knockdown of TRX, we demonstrate that cell-mediated reduction is largely dependent on TRX. Quantitative PCR in intestinal tissues of healthy controls and inflammatory bowel disease patients revealed altered expression of some, although not all, redox enzymes, especially in ulcerative colitis. Reduced hBD-1 and TRX localize to extracellular colonic mucus, suggesting that secreted or membrane-bound TRX converts hBD-1 to a potent antimicrobial peptide in vivo.
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| 23. |
- Janssens-Maenhout, G., et al.
(författare)
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Toward an operational anthropogenic CO2 emissions monitoring and verification support capacity
- 2020
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 101:8, s. 1439-1451
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Tidskriftsartikel (refereegranskat)abstract
- Under the Paris Agreement (PA), progress of emission reduction efforts is tracked on the basis of regular updates to national greenhouse gas (GHG) inventories, referred to as bottom-up estimates. However, only top-down atmospheric measurements can provide observation-based evidence of emission trends. Today, there is no internationally agreed, operational capacity to monitor anthropogenic GHG emission trends using atmospheric measurements to complement national bottom-up inventories. The European Commission (EC), the European Space Agency, the European Centre for Medium-Range Weather Forecasts, the European Organisation for the Exploitation of Meteorological Satellites, and international experts are joining forces to develop such an operational capacity for monitoring anthropogenic CO2 emissions as a new CO2 service under the EC's Copernicus program. Design studies have been used to translate identified needs into defined requirements and functionalities of this anthropogenic CO2 emissions Monitoring and Verification Support (CO2MVS) capacity. It adopts a holistic view and includes components such as atmospheric spaceborne and in situ measurements, bottom-up CO2 emission maps, improved modeling of the carbon cycle, an operational data-assimilation system integrating top-down and bottom-up information, and a policy-relevant decision support tool. The CO2MVS capacity with operational capabilities by 2026 is expected to visualize regular updates of global CO2 emissions, likely at 0.05° x 0.05°. This will complement the PA's enhanced transparency framework, providing actionable information on anthropogenic CO2 emissions that are the main driver of climate change. This information will be available to all stakeholders, including governments and citizens, allowing them to reflect on trends and effectiveness of reduction measures. The new EC gave the green light to pass the CO2MVS from exploratory to implementing phase.
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| 24. |
- North, J. P., et al.
(författare)
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Detection of MYB Alterations and Other Immunohistochemical Markers in Primary Cutaneous Adenoid Cystic Carcinoma
- 2015
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Ingår i: American Journal of Surgical Pathology. - : Ovid Technologies (Wolters Kluwer Health). - 0147-5185. ; 39:10, s. 1347-1356
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Tidskriftsartikel (refereegranskat)abstract
- Adenoid cystic carcinoma (ACC) can arise in several organs, and prognosis is highly dependent on the primary tumor site. Primary cutaneous ACC has an excellent prognosis compared with salivary or lacrimal ACC. Activation of MYB by gene fusion or other mechanisms has been found in salivary, breast, and lacrimal ACCs but has not been described in cutaneous ACC. We analyzed the histopathologic and immunohistochemical features of 19 primary cutaneous ACCs, 2 periorbital ACCs, and 12 salivary gland ACCs and assessed for MYB activation in primary cutaneous ACC by immunohistochemistry and molecular methods. The presence of perineural invasion differed significantly among ACCs of various sites (83% salivary, 50% eyelid, 11% skin, P=0.0002). Over 90% of all ACCs were grade 1 or 2 and exhibited diffuse (>50%) positivity with CD117, SOX-10, and smooth muscle actin immunostains. CK15 and vimentin showed diffuse positivity in 36% and 57% of cutaneous ACCs, respectively, and were negative or only focally positive in all salivary ACCs (P=0.04 and 0.002). Six of the 11 cutaneous and periorbital ACCs tested with reverse transcriptase polymerase chain reaction and/or fluorescence in situ hybridization had MYB rearrangements including 2 cases that expressed MYB-NFIB fusion transcripts. Diffuse expression of MYB protein assessed by immunostaining was present in 8 of 9 cutaneous ACCs, including cases both with and without MYB rearrangements. These results indicate that cutaneous ACCs possess the same types of MYB alterations as ACCs of other anatomic sites. Vimentin and CK15 appear to have some discriminatory value in differentiating between primary cutaneous and salivary gland ACCs.
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