Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium

Background: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. Methods: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). Results: Kaplan\u2013Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02\u20131.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03\u20131.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02\u20131.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01\u20131.25, p = 0.04) and HR 1.10; 95% CI 1.01\u20131.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. Conclusions: HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population

Search for anomalies in the {\nu}e appearance from a {\nu}{\mu} beam

We report an updated result from the ICARUS experiment on the search for {\nu}{\mu} ->{\nu}e anomalies with the CNGS beam, produced at CERN with an average energy of 20 GeV and travelling 730 km to the Gran Sasso Laboratory. The present analysis is based on a total sample of 1995 events of CNGS neutrino interactions, which corresponds to an almost doubled sample with respect to the previously published result. Four clear {\nu}e events have been visually identified over the full sample, compared with an expectation of 6.4 +- 0.9 events from conventional sources. The result is compatible with the absence of additional anomalous contributions. At 90% and 99% confidence levels the limits to possible oscillated events are 3.7 and 8.3 respectively. The corresponding limit to oscillation probability becomes consequently 3.4 x 10-3 and 7.6 x 10-3 respectively. The present result confirms, with an improved sensitivity, the early result already published by the ICARUS collaboration

Precise 3D track reconstruction algorithm for the ICARUS T600 liquid argon time projection chamber detector

Liquid Argon Time Projection Chamber (LAr TPC) detectors offer charged particle imaging capability with remarkable spatial resolution. Precise event reconstruction procedures are critical in order to fully exploit the potential of this technology. In this paper we present a new, general approach of three-dimensional reconstruction for the LAr TPC with a practical application to track reconstruction. The efficiency of the method is evaluated on a sample of simulated tracks. We present also the application of the method to the analysis of real data tracks collected during the ICARUS T600 detector operation with the CNGS neutrino beam.Comment: Submitted to Advances in High Energy Physic

Responsive glyco-poly(2-oxazoline)s: synthesis, cloud point tuning, and lectin binding

A new sugar-substituted 2-oxazoline monomer was prepared using the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Its copolymerization with 2-ethyl-2-oxazoline as well as 2-(dec-9-enyl)-2-oxazoline, yielding well-defined copolymers with the possibility to tune the properties by thiol-ene "click" reactions, is described. Extensive solubility studies on the corresponding glycocopolymers demonstrated that the lower critical solution temperature behavior and pH-responsiveness of these copolymers can be adjusted in water and phosphate-buffered saline (PBS) depending on the choice of the thiol. By conjugation of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose and subsequent deprotection of the sugar moieties, the hydrophilicity of the copolymer could be increased significantly, allowing a cloud-point tuning in the physiological range. Furthermore, the binding capability of the glycosylated copoly(2-oxazoline) to concanavalin A was investigated

Precision measurement of the neutrino velocity with the ICARUS detector in the CNGS beam

During May 2012, the CERN-CNGS neutrino beam has been operated for two weeks for a total of 1.8 10^17 pot in bunched mode, with a 3 ns narrow width proton beam bunches, separated by 100 ns. This tightly bunched beam structure allows a very accurate time of flight measurement of neutrinos from CERN to LNGS on an event-by-event basis. Both the ICARUS-T600 PMT-DAQ and the CERN-LNGS timing synchronization have been substantially improved for this campaign, taking ad-vantage of additional independent GPS receivers, both at CERN and LNGS as well as of the deployment of the "White Rabbit" protocol both at CERN and LNGS. The ICARUS-T600 detector has collected 25 beam-associated events; the corresponding time of flight has been accurately evaluated, using all different time synchronization paths. The measured neutrino time of flight is compatible with the arrival of all events with speed equivalent to the one of light: the difference between the expected value based on the speed of light and the measured value is tof_c - tof_nu = (0.10 \pm 0.67stat. \pm 2.39syst.) ns. This result is in agreement with the value previously reported by the ICARUS collaboration, tof_c - tof_nu = (0.3 \pm 4.9stat. \pm 9.0syst.) ns, but with improved statistical and systematic errors.Comment: 21 pages, 13 figures, 1 tabl

Experimental search for the LSND anomaly with the ICARUS detector in the CNGS neutrino beam

We report an early result from the ICARUS experiment on the search for nu_mu to nu_e signal due to the LSND anomaly. The search was performed with the ICARUS T600 detector located at the Gran Sasso Laboratory, receiving CNGS neutrinos from CERN at an average energy of about 20 GeV, after a flight path of about 730 km. The LSND anomaly would manifest as an excess of nu_e events, characterized by a fast energy oscillation averaging approximately to sin^2(1.27 Dm^2_new L/ E_nu) = 1/2. The present analysis is based on 1091 neutrino events, which are about 50% of the ICARUS data collected in 2010-2011. Two clear nu_e events have been found, compared with the expectation of 3.7 +/- 0.6 events from conventional sources. Within the range of our observations, this result is compatible with the absence of a LSND anomaly. At 90% and 99% confidence levels the limits of 3.4 and 7.3 events corresponding to oscillation probabilities of 5.4 10^-3 and 1.1 10^-2 are set respectively. The result strongly limits the window of open options for the LSND anomaly to a narrow region around (Dm^2, sin^2(2 theta))_new = (0.5 eV^2, 0.005), where there is an overall agreement (90% CL) between the present ICARUS limit, the published limits of KARMEN and the published positive signals of LSND and MiniBooNE Collaborations.Comment: 10 pages, 7 figure

Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia.

none25We report a study of an alternative treatment schedule of imatinib (IM) in chronic myeloid leukemia (CML). Seventy-six Philadelphia-positive (Ph+), BCR-ABL-positive patients aged 65 years or older who had been treated with IM for more than 2 years and who were in stable complete cytogenetic response (CCgR) and major molecular response (MMR) were enrolled in a single-arm study to test the effects of a policy of intermittent IM (INTERIM) therapy for 1 month on and 1 month off. With a minimum follow-up of 4 years, 13 patients (17%) lost CCgR and MMR and 14 (18%) lost MMR only. All these patients resumed continuous IM and all but one (lost to follow-up) regained CCgR and MMR. No patients progressed to accelerated or blastic phase or developed clonal chromosomal abnormalities in Ph+ cells or BCR-ABL mutations. In elderly Ph+ CML patients carefully selected for a stable CCgR (lasting >2 years), the policy of INTERIM treatment affected the markers of residual disease, but not the clinical outcomes (overall and progression-free survival). This trial was registered at www.clinicaltrials.gov as NCT 00858806.noneRusso D; Martinelli G; Malagola M; Skert C; Soverini S; Iacobucci I; De Vivo A; Testoni N; Castagnetti F; Gugliotta G; Turri D; Bergamaschi M; Pregno P; Pungolino E; Stagno F; Breccia M; Martino B; Intermesoli T; Fava C; Abruzzese E; Tiribelli M; Bigazzi C; Cesana BM; Rosti G; Baccarani M.Russo D; Martinelli G; Malagola M; Skert C; Soverini S; Iacobucci I; De Vivo A; Testoni N; Castagnetti F; Gugliotta G; Turri D; Bergamaschi M; Pregno P; Pungolino E; Stagno F; Breccia M; Martino B; Intermesoli T; Fava C; Abruzzese E; Tiribelli M; Bigazzi C; Cesana BM; Rosti G; Baccarani M

Underground operation of the ICARUS T600 LAr-TPC: first results

Open questions are still present in fundamental Physics and Cosmology, like the nature of Dark Matter, the matter-antimatter asymmetry and the validity of the particle interaction Standard Model. Addressing these questions requires a new generation of massive particle detectors exploring the subatomic and astrophysical worlds. ICARUS T600 is the first large mass (760 ton) example of a novel detector generation able to combine the imaging capabilities of the old famous "bubble chamber" with an excellent energy measurement in huge electronic detectors. ICARUS T600 now operates at the Gran Sasso underground laboratory, studying cosmic rays, neutrino oscillation and proton decay. Physical potentialities of this novel telescope are presented through few examples of neutrino interactions reconstructed with unprecedented details. Detector design and early operation are also reported.Comment: 14 pages, 8 figures, 2 tables. Submitted to Jins

Measurement of Through-Going Particle Momentum By Means Of Multiple Scattering With The ICARUS T600 TPC

The ICARUS collaboration has demonstrated, following the operation of a 600 ton (T600) detector at shallow depth, that the technique based on liquid Argon TPCs is now mature. The study of rare events, not contemplated in the Standard Model, can greatly benefit from the use of this kind of detectors. In particular, a deeper understanding of atmospheric neutrino properties will be obtained thanks to the unprecedented quality of the data ICARUS provides. However if we concentrate on the T600 performance, most of the $\nu_\mu$ charged current sample will be partially contained, due to the reduced dimensions of the detector. In this article, we address the problem of how well we can determine the kinematics of events having partially contained tracks. The analysis of a large sample of atmospheric muons collected during the T600 test run demonstrate that, in case the recorded track is at least one meter long, the muon momentum can be reconstructed by an algorithm that measures the Multiple Coulomb Scattering along the particle's path. Moreover, we show that momentum resolution can be improved by a factor two using an algorithm based on the Kalman Filtering technique