Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging

[EN] A new method to tag the barium daughter in the double-beta decay of Xe-136 is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba++) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (similar to 2 nm), and detected with a statistical significance of 12.9 sigma over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under Advanced Grant No. 339787-NEXT, the Ministerio de Economia y Competitividad of Spain under Grants No. FIS2014-53371-C04 and the Severo Ochoa Program SEV-2014-0398, the Generalitat Valenciana (GVA) of Spain under Grant No. PROMETEO/2016/120, the Portuguese FCT and FEDER through the program COMPETE, project PTDC/FIS/103860/2008, the U.S. Department of Energy under Contracts No. DE-AC02-07CH11359 (Fermi National Accelerator Laboratory) and No. DE-FG02-13ER42020 (Texas A&M) and No. DE-SC0017721 (University of Texas at Arlington), and the University of Texas at Arlington.Mcdonald, A.; Jones, B.; Nygren, D.; Adams, C.; Álvarez-Puerta, V.; Azevedo, C.; Benlloch-Rodríguez, J.... (2018). Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging. Physical Review Letters. 120(13):1-6. https://doi.org/10.1103/PhysRevLett.120.132504S1612013Chang, D., & Mohapatra, R. N. (1985). On a mechanism for small neutrino masses. Physical Review D, 32(5), 1248-1249. doi:10.1103/physrevd.32.1248Minkowski, P. (1977). μ→eγ at a rate of one out of 109 muon decays? Physics Letters B, 67(4), 421-428. doi:10.1016/0370-2693(77)90435-xMohapatra, R. N., & Senjanović, G. (1981). Neutrino masses and mixings in gauge models with spontaneous parity violation. Physical Review D, 23(1), 165-180. doi:10.1103/physrevd.23.165Fukugita, M., & Yanagida, T. (1986). Barygenesis without grand unification. Physics Letters B, 174(1), 45-47. doi:10.1016/0370-2693(86)91126-3Ostrovskiy, I., & O’Sullivan, K. (2016). Search for neutrinoless double beta decay. Modern Physics Letters A, 31(18), 1630017. doi:10.1142/s0217732316300172Ostrovskiy, I., & O’Sullivan, K. (2016). Errata: «Search for neutrinoless double beta decay». Modern Physics Letters A, 31(23), 1692004. doi:10.1142/s0217732316920048Dell’Oro, S., Marcocci, S., Viel, M., & Vissani, F. (2016). Neutrinoless Double Beta Decay: 2015 Review. Advances in High Energy Physics, 2016, 1-37. doi:10.1155/2016/2162659Gómez-Cadenas, J. ., Martín-Albo, J., Sorel, M., Ferrario, P., Monrabal, F., Muñoz, J., … Poves, A. (2011). Sense and sensitivity of double beta decay experiments. Journal of Cosmology and Astroparticle Physics, 2011(06), 007-007. doi:10.1088/1475-7516/2011/06/007Aseev, V. N., Belesev, A. I., Berlev, A. I., Geraskin, E. V., Golubev, A. A., Likhovid, N. A., … Zadorozhny, S. V. (2011). Upper limit on the electron antineutrino mass from the Troitsk experiment. Physical Review D, 84(11). doi:10.1103/physrevd.84.112003Gonzalez-Garcia, M. C., Maltoni, M., & Schwetz, T. (2016). Global analyses of neutrino oscillation experiments. Nuclear Physics B, 908, 199-217. doi:10.1016/j.nuclphysb.2016.02.033Álvarez, V., Borges, F. I. G. M., Cárcel, S., Carmona, J. M., Castel, J., Catalá, J. M., … Conde, C. A. N. (2012). NEXT-100 Technical Design Report (TDR). Executive summary. Journal of Instrumentation, 7(06), T06001-T06001. doi:10.1088/1748-0221/7/06/t06001Auger, M., Auty, D. J., Barbeau, P. S., Beauchamp, E., Belov, V., Benitez-Medina, C., … Cleveland, B. (2012). Search for Neutrinoless Double-Beta Decay inXe136with EXO-200. Physical Review Letters, 109(3). doi:10.1103/physrevlett.109.032505Moe, M. K. (1991). Detection of neutrinoless double-beta decay. Physical Review C, 44(3), R931-R934. doi:10.1103/physrevc.44.r931Danilov, M., DeVoe, R., Dolgolenko, A., Giannini, G., Gratta, G., Picchi, P., … Zeldovich, O. (2000). Detection of very small neutrino masses in double-beta decay using laser tagging. Physics Letters B, 480(1-2), 12-18. doi:10.1016/s0370-2693(00)00404-4Mong, B., Cook, S., Walton, T., Chambers, C., Craycraft, A., Benitez-Medina, C., … Auty, D. J. (2015). Spectroscopy of Ba andBa+deposits in solid xenon for barium tagging in nEXO. Physical Review A, 91(2). doi:10.1103/physreva.91.022505Brunner, T., Fudenberg, D., Varentsov, V., Sabourov, A., Gratta, G., Dilling, J., … Albert, J. B. (2015). An RF-only ion-funnel for extraction from high-pressure gases. International Journal of Mass Spectrometry, 379, 110-120. doi:10.1016/j.ijms.2015.01.003Flatt, B., Green, M., Wodin, J., DeVoe, R., Fierlinger, P., Gratta, G., … Weber, P. (2007). A linear RFQ ion trap for the Enriched Xenon Observatory. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 578(2), 399-408. doi:10.1016/j.nima.2007.05.123Sinclair, D., Rollin, E., Smith, J., Mommers, A., Ackeran, N., Aharmin, B., … Breidenbach, M. (2011). Prospects for Barium Tagging in Gaseous Xenon. Journal of Physics: Conference Series, 309, 012005. doi:10.1088/1742-6596/309/1/012005Lu, Y., & Paige, M. F. (2007). An Ensemble and Single-molecule Fluorescence Spectroscopy Investigation of Calcium Green 1, a Calcium-ion Sensor. Journal of Fluorescence, 17(6), 739-748. doi:10.1007/s10895-007-0185-1Álvarez, V., Borges, F. I. G. M., Cárcel, S., Castel, J., Cebrián, S., Cervera, A., … Díaz, J. (2013). Near-intrinsic energy resolution for 30–662keV gamma rays in a high pressure xenon electroluminescent TPC. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 708, 101-114. doi:10.1016/j.nima.2012.12.123Green, A. E. S. (1957). Single Electron Shakeoff Probability Following the Beta Decay of Krypton. Physical Review, 107(6), 1646-1650. doi:10.1103/physrev.107.1646Albert, J. B., Auty, D. J., Barbeau, P. S., Beck, D., Belov, V., Breidenbach, M., … Chambers, C. (2015). Measurements of the ion fraction and mobility ofα−andβ-decay products in liquid xenon using the EXO-200 detector. Physical Review C, 92(4). doi:10.1103/physrevc.92.045504Bolotnikov, A., & Ramsey, B. (1997). The spectroscopic properties of high-pressure xenon. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 396(3), 360-370. doi:10.1016/s0168-9002(97)00784-5Jones, B. J. P., McDonald, A. D., & Nygren, D. R. (2016). Single molecule fluorescence imaging as a technique for barium tagging in neutrinoless double beta decay. Journal of Instrumentation, 11(12), P12011-P12011. doi:10.1088/1748-0221/11/12/p12011Arai, F., Ito, Y., Wada, M., Schury, P., Sonoda, T., & Mita, H. (2014). Investigation of the ion surfing transport method with a circular rf carpet. International Journal of Mass Spectrometry, 362, 56-58. doi:10.1016/j.ijms.2014.01.005Burghardt, T. P. (2012). Measuring incidence angle for through-the-objective total internal reflection fluorescence microscopy. Journal of Biomedical Optics, 17(12), 126007. doi:10.1117/1.jbo.17.12.126007Stemmer, A., Beck, M., & Fiolka, R. (2008). Widefield fluorescence microscopy with extended resolution. Histochemistry and Cell Biology, 130(5), 807-817. doi:10.1007/s00418-008-0506-8Fish, K. N. (2009). Total Internal Reflection Fluorescence (TIRF) Microscopy. Current Protocols in Cytometry, 50(1). doi:10.1002/0471142956.cy1218s50Habuchi, S., Ando, R., Dedecker, P., Verheijen, W., Mizuno, H., Miyawaki, A., & Hofkens, J. (2005). From The Cover: Reversible single-molecule photoswitching in the GFP-like fluorescent protein Dronpa. Proceedings of the National Academy of Sciences, 102(27), 9511-9516. doi:10.1073/pnas.0500489102Thomas, D., Tovey, S. C., Collins, T. J., Bootman, M. D., Berridge, M. J., & Lipp, P. (2000). A comparison of fluorescent Ca2+indicator properties and their use in measuring elementary and global Ca2+signals. Cell Calcium, 28(4), 213-223. doi:10.1054/ceca.2000.0152Thompson, R. E., Larson, D. R., & Webb, W. W. (2002). Precise Nanometer Localization Analysis for Individual Fluorescent Probes. Biophysical Journal, 82(5), 2775-2783. doi:10.1016/s0006-3495(02)75618-

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Ideal cardiovascular health and inflammation in European adolescents: The HELENA study

Background and aims Inflammation plays a key role in atherosclerosis and this process seems to appear in childhood. The ideal cardiovascular health index (ICHI) has been inversely related to atherosclerotic plaque in adults. However, evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to assess the association between ICHI and inflammation in European adolescents. Methods and results As many as 543 adolescents (251 boys and 292 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional multi-center study including 9 European countries, were measured. C-reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell counts were used to compute an inflammatory score. Multilevel linear models and multilevel logistic regression were used to assess the association between ICHI and inflammation controlling by covariates. Higher ICHI was associated with a lower inflammatory score, as well as with several individual components, both in boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal components of the ICHI had significantly lower inflammatory score and lower levels of the study biomarkers, except CRP. Finally, the multilevel logistic regression showed that for every unit increase in the ICHI, the probability of having an inflammatory profile decreased by 28.1% in girls. Conclusion Results from this study suggest that a better ICHI is associated with a lower inflammatory profile already in adolescence. Improving these health behaviors, and health factors included in the ICHI, could play an important role in CVD prevention

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Physical activity program for patients with dementia and their relative caregivers: randomized clinical trial in Primary Health Care (AFISDEMyF study)

BACKGROUND: The aging of the population has led to the increase of chronic diseases, especially dementia and cardiovascular diseases, and it has become necessary for their relatives to dedicate more time in caregiving. The objective in the first phase of this study is to evaluate the effectiveness of a Primary Health Care procedure to increase the physical activity of people with dementia and their relative caregivers. Also the effect on the cognitive state and cardiovascular risk will be assessed. METHODS/DESIGN: Design: Clinical, multicentric and randomized trial. A simple random sampling to select 134 patients diagnosed with dementia will be carried out. After contacting their relatives, his/her participation in the trial will be requested. A basal assessment will be made and the participants will be asigned to control or intervention group (1:1). Variables: The main measure will be the assessment of physical activity (podometer and 7-PAR) in patients and caregivers. In patients with dementia: ADAS-cog, functional degree and cardiovascular risk. In caregivers: cardiovascular risk, general health and quality of life. Intervention: For 3 months, participants will receive instructions to do physical activity with an adapted program. This program will be designed and applied by Primary Health Care professionals in patients with dementia and their caregivers. The control group will receive regular care. Analysis: An intention-to-treat analysis will be carried out by comparing the observed differences between basal, 6 and 12 months measures. Change in the mean of daily steps assessed with the podometer and 7-PAR will be the main result. DISCUSSION: If the main hypothesis is confirmed, it could be useful to improve the cognitive state of patients with dementia, as well as the cardiovascular risk of all of them. The results can be good to improve technical features of the devices that register the physical activity in the patients with dementia, and it could facilitate its commercialization. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT02044887

Preface

This special issue is devoted to the memory of Professor Padma Kant Shukla, who passed away 26 January 2013 on his travel to New Delhi, India to receive the prestigious Hind Rattan (Jewel of India) award. Padma was born in Tulapur, Uttar Pradesh, India, 7 July 1950, where he grew up and got his education. He received a PhD degree in Physics at the Banaras Hindu University, Varanasi, Uttar Pradesh, India, in 1972, under the supervision of late Prof. R. N. Singh, and a second PhD degree in Theoretical Plasma Physics from Umeå University in Sweden in 1975, under the supervision of Prof. Lennart Stenflo. He worked at the Faculty of Physics & Astronomy, Ruhr-University Bochum, Germany since January 1973, where he was a permanent faculty member and Professor of International Affairs, a position that was created for him to honour his international accomplishments and reputation

Gaia Data Release 2 Kinematics of globular clusters and dwarf galaxies around the Milky Way

This article has an erratum: Doi 10.1051/0004-6361/201832698 This article has an erratum: Doi 10.1051/0004-6361/202039217Aims. The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds. Methods. Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community. Results. Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (i v) derive a lower limit for the mass of the Milky Way of 9.1(-2.6)(+6.2) x 10(11) M-circle dot based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (v i) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud. Conclusions. All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.Peer reviewe

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

International audienceBackground: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects.Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients