Achievements in workplace neutron dosimetry in the last decade: lessons learned from the EVIDOS project

The availability of active neutron personal dosemeters has made real time monitoring of neutron doses possible. This has obvious benefits, but is only of any real assistance if the dose assessments made are of sufficient accuracy and reliability. Preliminary assessments of the performance of active neutron dosemeters can be made in calibration facilities, but these can never replicate the conditions under which the dosemeter is used in the workplace. Consequently, it is necessary to assess their performance in the workplace, which requires the field in the workplace to be fully characterised in terms of the energy and direction dependence of the fluence. This paper presents an overview of developments in workplace neutron dosimetry but concentrates on the outcomes of the EVIDOS project, which has made significant advances in the characterisation of workplace fields and the analysis of dosemeter responses in those field

Methods to Determine Neutrino Flux at Low Energies:Investigation of the Low ν\nu Method

We investigate the "low-$\nu$" method (developed by the CCFR/NUTEV collaborations) to determine the neutrino flux in a wide band neutrino beam at very low energies, a region of interest to neutrino oscillations experiments. Events with low hadronic final state energy $\nu<\nu_{cut}$ (of 1, 2 and 5 GeV) were used by the MINOS collaboration to determine the neutrino flux in their measurements of neutrino ($\nu_\mu$) and antineutrino (\nub_\mu) total cross sections. The lowest $\nu_\mu$ energy for which the method was used in MINOS is 3.5 GeV, and the lowest \nub_\mu energy is 6 GeV. At these energies, the cross sections are dominated by inelastic processes. We investigate the application of the method to determine the neutrino flux for $\nu_\mu$, \nub_\mu energies as low as 0.7 GeV where the cross sections are dominated by quasielastic scattering and $\Delta$(1232) resonance production. We find that the method can be extended to low energies by using $\nu_{cut}$ values of 0.25 and 0.50 GeV, which is feasible in fully active neutrino detectors such as MINERvA.Comment: 25 pages, 32 figures, to be published in European Physics Journal

A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia

BACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks

Neutron area survey instrument measurements in the EVIDOS project

Neutron survey instruments have been exposed at all the measurement locations used in the EVIDOS project. These results have an important impact in the interpretation of the results from the project, since operationally the survey instrument will be used for an initial assessment of and routine monitoring of the ambient dose equivalent dose rate. Additionally, since the response of these instruments is in some cases very well characterised, their systematic deviations from the reference quantities provide an important verification of the determination of those quantitie

Evaluation of individual dosimetry in mixed neutron and photon radiation fields (EVIDOS). Part II: conclusions and recommendations

The paper presents the main conclusions and recommendations derived from the EVIDOS project, which is supported by the European Commission within the 5th Framework Programme. EVIDOS aims at evaluating state of the art neutron dosimetry techniques in representative workplaces of the nuclear industry with complex mixed neutron-photon radiation fields. This analysis complements a series of individual papers which present detailed results and it summarises the main findings from a practical point of view. Conclusions and recommendations are given concerning characterisation of radiation fields, methods to derive radiation protection quantities and dosemeter result

Evaluation of individual dosimetry in mixed neutron and photon radiation fields (EVIDOS). Part I: scope and methods of the project

Supported by the European Commission, the EVIDOS project started in November 2001 with the broad goal of evaluating state of the art dosimetry techniques in representative workplaces of the nuclear industry. Seven European institutes joined efforts with end users at nuclear power plants, at fuel processing and reprocessing plants, and at transport and storage facilities. A comprehensive programme was devised to evaluate capabilities and limitations of standard and innovative personal dosemeters in relation to the mixed neutron-photon fields of concern to the nuclear industry. This paper describes the criteria behind the selection of dosimetry techniques and workplaces that were analysed, as well as the organisation of the measurement campaigns. Particular emphasis was placed on the evaluation of a variety of electronic personal dosemeters, either commercially available or previously developed by the partners. The estimates provided by these personal dosemeters were compared to reference values of dose equivalent quantities derived from spectrometry and fluence-to-dose equivalent conversion coefficients. Spectrometry was performed both with conventional multisphere and with some original instrumentation providing energy and direction resolution, based on silicon detectors and superheated drop detectors mounted on or in spherical moderators. The results were collected in a large, searchable database and are intended to be used in the harmonisation of dosimetric procedures for mixed radiation fields and for the approval of dosimetry services in Europ

Impact of presentation and transfer delays on complete ST-segment resolution before primary percutaneous coronary intervention: Insights from the ATLANTIC trial

Aims: The aim of this study was to identify predictors of complete ST-segment resolution (STR) pre-primary percutaneous coronary intervention (PCI) in patients enrolled in the ATLANTIC trial. Methods and results: ECGs recorded at the time of inclusion (pre-hospital [pre-H]-ECG) and in the catheterisation laboratory before angiography (pre-PCI-ECG) were analysed by an independent core laboratory. Complete STR was defined as 6570%. Complete STR occurred pre-PCI in 12.8% (204/1, 598) of patients and predicted lower 30-day composite MACCE (OR=0.10, 95% CI: 0.002-0.57, p=0.001) and total mortality (OR=0.16, 95% CI: 0.004-0.95, p=0.035). Independent predictors of complete STR included the time from index event to pre-H-ECG (OR=0.94, 95% CI: 0.89-1.00, p=0.035), use of heparins before pre- PCI-ECG (OR=1.75, 95% CI: 1.25-2.45, p=0.001) and time from pre-H-ECG to pre-PCI-ECG (OR=1.09, 95% CI: 1.03-1.16, p=0.005). In the pre-H ticagrelor group, patients with complete STR had a significantly longer delay between pre-H-ECG and pre-PCI-ECG compared to patients without complete STR (median 53 [44-73] vs. 49 [38.5-61] mins, p=0.001); however, this was not observed in the control group (in-hospital ticagrelor) (50 [40-67] vs. 49 [39-61] mins, p=0.258). Conclusions: Short patient delay, early administration of anticoagulant and ticagrelor if a long transfer delay is expected may help to achieve reperfusion prior to PCI. Pre-H treatment may be beneficial in patients with longer transfer delays, allowing the drug to become biologically active. ClinicalTrials.gov Identifier: NCT01347580

Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial

Objective: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM. Background: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population. Methods: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested. Results: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution ( 6570%) after PCI (OR 0.59, 95% CI 0.43\u20130.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62\u20134.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08\u20135.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54\u201328.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding. Conclusions: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580

Effect of Pre-Hospital Ticagrelor During the First 24 Hours After Primary PCI in Patients With ST-Segment Elevation Myocardial Infarction: The ATLANTIC-H Analysis

OBJECTIVES: The aim of this landmark exploratory analysis, ATLANTIC-H24, was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery study). BACKGROUND: The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min). METHODS: The ATLANTIC-H24 analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction grade 3 flow, >/=70% ST-segment elevation resolution, and clinical endpoints over the first 24 h. RESULTS: Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%, p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%, p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%, p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. CONCLUSIONS: The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580])

Evaluation of individual monitoring in mixed neutron/photon fields: mid-term results from the EVIDOS project

EVIDOS is an EC sponsored project that aims at an evaluation and improvement of radiation protection dosimetry in mixed neutron/photon fields. This is performed through spectrometric and dosimetric investigations during different measurement campaigns in representative workplaces of the nuclear industry. The performance of routine and, in particular, novel personal dosemeters and survey instruments is tested in selected workplace fields. Reference values for the dose equivalent quantities, H*(10) and Hp(10) and the effective dose E, are determined using different spectrometers that provide the energy distribution of the neutron fluence and using newly developed devices that determine the energy and directional distribution of the neutron fluence. The EVIDOS project has passed the mid-term, and three measurement campaigns have been performed. This paper will give an overview and some new results from the third campaign that was held in Mol (Belgium), around the research reactor VENUS and in the MOX producing plant of Belgonucléair