85 research outputs found

    Immunoglobulin lambda light chain gene rearrangements in human B-cell malignancies

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    Lymphocytes form the specific immune system, capable of recognizing and responding to any foreign antigen, while remaining indifferent to self components. Throughout human life, lymphocytes are continuously generated from pluripotent hematopoietic stem cells. These hematopoietic stem cells are already detectable in the yolk sac and in the fetal liver from the second month of gestation onwards. After birth, the hematopoietic stem cells are mainly found in the bone marrow (BM). Two types of lymphocytes exist: B-lymphocytes and T-lymphocytes. Progenitor Bcells differentiate into mature B-lymphocytes in the BM, while progenitor T-cells differentiate into mature T-lymphocytes in the thymus. Mature B- and T-lymphocytes recognize foreign antigens via smface receptor molecules, the so-called antigen specific receptors. The antigen specific receptors of B-and T-lymphocytes are called B-cell receptor (BCR) or immunoglobulin (Ig) molecules and T-cell receptor (TCR) molecules, respectively. Differentiation of progenitor B-cells into mature B-lymphocytes is regulated via interaction with stromal cells in the BM. In the earliest stages, progenitor B-cells must be in direct contact with the stromal cells, and fmiher differentiation is dependent on growth factors, such as cytokines and hematopoietic growth factors, which are secreted by the stroma. These growth factors and cytokines induce proliferation, differentiation, and maturation in an organized way

    Opioid use is associated with increased out-of-hospital cardiac arrest risk among 40,000-cases across two countries

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    AIMS: Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and out‐of‐hospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCA‐risk of opioids in the community. METHODS: We conducted 2 population‐based case–control studies separately in the Netherlands (2009–2018) and Denmark (2001–2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to 5 non‐OHCA‐controls according to age, sex and OHCA‐date. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 5473 OHCA‐cases matched with 21 866 non‐OHCA‐controls in the Netherlands, and 35 017 OHCA‐cases matched with 175 085 non‐OHCA‐controls in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCA‐risk in both regions (the Netherlands: OR 2.1 [95% CI 1.8–2.5]; Denmark: OR 1.8 [95% CI 1.5–2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95% CI 1.5–2.1]; Denmark: OR 1.6 [95% CI 1.5–1.7]) or without (the Netherlands: OR 3.4 [95% CI: 2.4–4.8], P (interaction) < .0001; Denmark: OR 2.3 [95% CI: 2.0–2.5], P (interaction) < .0001). CONCLUSION: Use of opioids is associated with increased OHCA‐risk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids

    A rapid and sensitive system for recovery of nucleic acids from Mycobacteria sp. on archived glass slides

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    The field of diagnostics continues to advance rapidly with a variety of novel approaches, mainly dependent upon high technology platforms. Nonetheless much diagnosis, particularly in developing countries, still relies upon traditional methods such as microscopy. Biological material, particularly nucleic acids, on archived glass slides is a potential source of useful information both for diagnostic and epidemiological purposes. There are significant challenges faced when examining archived samples in order that an adequate amount of amplifiable DNA can be obtained. Herein, we describe a model system to detect low numbers of bacterial cells isolated from glass slides using (laser capture microscopy) LCM coupled with PCR amplification of a suitable target. Mycobacterium smegmatis was used as a model organism to provide a proof of principle for a method to recover bacteria from a stained sample on a glass slide using a laser capture system. Ziehl-Neelsen (ZN) stained cells were excised and catapulted into tubes. Recovered cells were subjected to DNA extraction and pre-amplified with multiple displacement amplification (MDA). This system allowed a minimum of 30 catapulted cells to be detected following a nested real-time PCR assay, using rpoB specific primers. The combination of MDA and nested real-time PCR resulted in a 30-fold increase in sensitivity for the detection of low numbers of cells isolated using LCM. This study highlights the potential of LCM coupled with MDA as a tool to improve the recovery of amplifiable nucleic acids from archived glass slides. The inclusion of the MDA step was essential to enable downstream amplification. This platform should be broadly applicable to a variety of diagnostic applications and we have used it as a proof of principle with a Mycobacterium sp. model system

    Association of beta-blockers and first-registered heart rhythm in out-of-hospital cardiac arrest: real-world data from population-based cohorts across two European countries

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    AIMS: Conflicting results have been reported regarding the effect of beta-blockers on first-registered heart rhythm in out-of-hospital cardiac arrest (OHCA). We aimed to establish whether the use of beta-blockers influences first-registered rhythm in OHCA. METHODS AND RESULTS: We included patients with OHCA of presumed cardiac cause from two large independent OHCA-registries from Denmark and the Netherlands. Beta-blocker use was defined as exposure to either non-selective beta-blockers, ÎČ1-selective beta-blockers, or α-ÎČ-dual-receptor blockers within 90 days prior to OHCA. We calculated odds ratios (ORs) for the association of beta-blockers with first-registered heart rhythm using multivariable logistic regression. We identified 23 834 OHCA-patients in Denmark and 1584 in the Netherlands: 7022 (29.5%) and 519 (32.8%) were treated with beta-blockers, respectively. Use of non-selective beta-blockers, but not ÎČ1-selective blockers, was more often associated with non-shockable rhythm than no use of beta-blockers [Denmark: OR 1.93, 95% confidence interval (CI) 1.48-2.52; the Netherlands: OR 2.52, 95% CI 1.15-5.49]. Non-selective beta-blocker use was associated with higher proportion of pulseless electrical activity (PEA) than of shockable rhythm (OR 2.38, 95% CI 1.01-5.65); the association with asystole was of similar magnitude, although not statistically significant compared with shockable rhythm (OR 2.34, 95% CI 0.89-6.18; data on PEA and asystole were only available in the Netherlands). Use of α-ÎČ-dual-receptor blockers was significantly associated with non-shockable rhythm in Denmark (OR 1.21; 95% CI 1.03-1.42) and not significantly in the Netherlands (OR 1.37; 95% CI 0.61-3.07). CONCLUSION: Non-selective beta-blockers, but not ÎČ1-selective beta-blockers, are associated with non-shockable rhythm in OHCA

    Measurement of the 77Se(n,Îł)^{77}Se ( n , Îł ) cross section up to 200 keV at the n_TOF facility at CERN

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    The 77Se(n,γ)^{77}Se ( n , γ ) reaction is of importance for 77Se^{77}Se abundance during the slow neutron capture process in massive stars. We have performed a new measurement of the 77Se^{77}Se radiative neutron capture cross section at the Neutron Time-of-Flight facility at CERN. Resonance capture kernels were derived up to 51 keV and cross sections up to 200 keV. Maxwellian-averaged cross sections were calculated for stellar temperatures between kT=5 keVkT=5 \space keV and kT=100 keVkT=100\space keV, with uncertainties between 4.2% and 5.7%. Our results lead to substantial decreases of 14% and 19% in 77Se^{77}Se abundances produced through the slow neutron capture process in selected stellar models of 15M⊙15M⊙ and 2M⊙2M⊙, respectively, compared to using previous recommendation of the cross section

    Measurement of the 14^{14}N(n,p)14^{14}C cross section at the CERN n_TOF facility from sub-thermal energy to 800 keV

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    Background: The 14^{14}N(n,p)14^{14}C reaction is of interest in neutron capture therapy, where nitrogen-related dose is the main component due to low-energy neutrons, and in astrophysics, where 14N acts as a neutron poison in the s-process. Several discrepancies remain between the existing data obtained in partial energy ranges: thermal energy, keV region and resonance region. Purpose: Measuring the 14N(n,p)14C cross section from thermal to the resonance region in a single measurement for the first time, including characterization of the first resonances, and providing calculations of Maxwellian averaged cross sections (MACS). Method: Time-of-flight technique. Experimental Area 2 (EAR-2) of the neutron time-of-flight (n_TOF) facility at CERN. 10^{10}B(n,α{\alpha})7^7Li and 235^{235}U(n,f) reactions as references. Two detection systems running simultaneously, one on-beam and another off-beam. Description of the resonances with the R-matrix code sammy. Results: The cross section has been measured from sub-thermal energy to 800 keV resolving the two first resonances (at 492.7 and 644 keV). A thermal cross-section (1.809±\pm0.045 b) lower than the two most recent measurements by slightly more than one standard deviation, but in line with the ENDF/B-VIII.0 and JEFF-3.3 evaluations has been obtained. A 1/v energy dependence of the cross section has been confirmed up to tens of keV neutron energy. The low energy tail of the first resonance at 492.7 keV is lower than suggested by evaluated values, while the overall resonance strength agrees with evaluations. Conclusions: Our measurement has allowed to determine the 14^{14}N(n,p) cross-section over a wide energy range for the first time. We have obtained cross-sections with high accuracy (2.5 %) from sub-thermal energy to 800 keV and used these data to calculate the MACS for kT = 5 to kT = 100 keV.Comment: 18 pages, 15 figures, 4 table

    Production of Mass-Separated Erbium-169 Towards the First Preclinical in vitro Investigations

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    The ÎČ−-particle-emitting erbium-169 is a potential radionuclide toward therapy of metastasized cancer diseases. It can be produced in nuclear research reactors, irradiating isotopically-enriched 168Er2O3. This path, however, is not suitable for receptor-targeted radionuclide therapy, where high specific molar activities are required. In this study, an electromagnetic isotope separation technique was applied after neutron irradiation to boost the specific activity by separating 169Er from 168Er targets. The separation efficiency increased up to 0.5% using resonant laser ionization. A subsequent chemical purification process was developed as well as activity standardization of the radionuclidically pure 169Er. The quality of the 169Er product permitted radiolabeling and pre-clinical studies. A preliminary in vitro experiment was accomplished, using a 169Er-PSMA-617, to show the potential of 169Er to reduce tumor cell viability. © Copyright © 2021 Talip, Borgna, MĂŒller, Ulrich, Duchemin, Ramos, Stora, Köster, Nedjadi, Gadelshin, Fedosseev, Juget, Bailat, Fankhauser, Wilkins, Lambert, Marsh, Fedorov, Chevallay, Fernier, Schibli and van der Meulen.The authors thank CERN ISOLDE and RILIS teams for the laser operation (Maxim D. Seliverstov, Katerina Chrysalidis), radiation protection and logistic teams of PSI (Tobias Schneider) and CERN (Alexandre Dorsival, Matthieu Deschamps and Elodie Aubert, Philippe Bertreix, Nicolas Riggaz, Nabil Menaa, Aurore Boscher, Jeremie Comte, Benjamin Juif); the LARISSA workgroup of Mainz University for the laser preparation and erbium laser ionization scheme development (Prof. Dr. Klaus Wendt and Dr. Dominik Studer). The authors are grateful to Fan Sozzi-Guo, Muhamet Djelili, Alexander V?gele and Walter Hirzel (PSI) and Bernard Cr?pieux, Giacomo Lunghi, Francesco Riccardi, Miranda Van Stenis, Thomas Schneider (CERN) for technical support. Funding. ZT and NM received funding from the Swiss National Science Foundation (SNF Grant Number: 200021_188495). CM obtained funding for this project from the Swiss Cancer Research (KFS-4678-02-2019-R). FB received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie Grant Agreement No 701647

    Neutron capture cross section measurements of Am-241 at the n_TOF facility

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    Neutron capture on Am-241 plays an important role in the nuclear energy production and also provides valuable information for the improvement of nuclear models and the statistical interpretation of the nuclear properties. A new experiment to measure the Am-241(n,gamma) cross section in the thermal region and the first few resonances below 10 eV has been carried out at EAR2 of the n_TOF facility at CERN. Three neutron-insensitive C6D6 detectors have been used to measure the neutron-capture gamma cascade as a function of the neutron time of flight, and then deduce the neutron capture yield. Preliminary results will be presented and compared with previously obtained results at the same facility in EAR1. In EAR1 the gamma-ray background at thermal energies was about 90% of the signal while in EAR2 is up to a 25 factor much more favorable signal to noise ratio. We also extended the low energy limit down to subthermal energies. This measurement will allow a comparison with neutron capture measurements conducted at reactors and using a different experimental technique

    Measurement of the radiative capture cross section of the s-process branching points 204Tl and 171Tm at the n-TOF facility (CERN)

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    The neutron capture cross section of some unstable nuclei is especially relevant for s-process nucleosynthesis studies. This magnitude is crucial to determine the local abundance pattern, which can yield valuable information of the s-process stellar environment. In this work we describe the neutron capture (n,Îł) measurement on two of these nuclei of interest, 204Tl and 171Tm, from target production to the final measurement, performed successfully at the n-TOF facility at CERN in 2014 and 2015. Preliminary results on the ongoing experimental data analysis will also be shown. These results include the first ever experimental observation of capture resonances for these two nuclei