Neutropenia as an adverse event following vaccination : results from randomized clinical trials in healthy adults and systematic review

Background : In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology : We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings : Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions : It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events

The ARC-EN-CIEL radiation sources

MOPC005International audienceThe ARC-EN-CIEL (Accelerator-Radiation for Enhanced Coherent Intense Extended Light) project proposes a panoply of light sources for the scientific community on a 1 GeV superconducting LINAC (phase 2) on which two ERL loops (1 and 2 GeV) are added in phase 3. LEL1 (200-1.5 nm), LEL2 (10-0.5 nm) and LEL4 (2-0.2 nm) are three kHz High Gain Harmonic Generation Free Electron Laser sources seeded with the High order Harmonics generated in Gas, with 100-30 FWHM pulses. A collaboration, which has been set-up with the SCSS Prototype Accelerator in Japan to test this key concept of ARC-EN-CIEL, has led to the experimental demonstration of the seeding with HHG and the observation up the 7th non linear harmonic with a seed at 160 nm. LEL3 (40-8 nm) installed on the 1 GeV loop is a MHz FEL oscillator providing higher average power and brilliance. In addition, in vacuum undulator spontaneous emission source extend the spectral range above 10 keV and intense THz radiation is generated by edge radiation of bending magnets. Optimisations and light sources characteristics are described

CHIANTI - an Atomic Database for Emission Lines. Paper VI: Proton Rates and Other Improvements

The CHIANTI atomic database contains atomic energy levels, wavelengths, radiative transition probabilities and electron excitation data for a large number of ions of astrophysical interest. Version 4 has been released, and proton excitation data is now included, principally for ground configuration levels that are close in energy. The fitting procedure for excitation data, both electrons and protons, has been extended to allow 9 point spline fits in addition to the previous 5 point spline fits. This allows higher quality fits to data from close-coupling calculations where resonances can lead to significant structure in the Maxwellian-averaged collision strengths. The effects of photoexcitation and stimulated emission by a blackbody radiation field in a spherical geometry on the level balance equations of the CHIANTI ions can now be studied following modifications to the CHIANTI software. With the addition of H I, He I and N I, the first neutral species have been added to CHIANTI. Many updates to existing ion data-sets are described, while several new ions have been added to the database, including Ar IV, Fe VI and Ni XXI. The two-photon continuum is now included in the spectral synthesis routines, and a new code for calculating the relativistic free-free continuum has been added. The treatment of the free-bound continuum has also been updated.Comment: CHIANTI is available at http://wwwsolar.nrl.navy.mil/chianti.htm

Retrieving the paleoclimatic signal from the deeper part of the EPICA Dome C ice core

International audienceAn important share of paleoclimatic information is buried within the lowermost layers of deep ice cores. Because improving our records further back in time is one of the main challenges in the near future, it is essential to judge how deep these records remain unaltered, since the proximity of the bedrock is likely to interfere both with the recorded temporal sequence and the ice properties. In this paper, we present a multiparametric study (δD-δ18Oice , δ18Oatm , total air content, CO2 , CH4 , N2O, dust, high-resolution chemistry , ice texture) of the bottom 60 m of the EPICA (European Project for Ice Coring in Antarctica) Dome C ice core from central Antarctica. These bottom layers were subdivided into two distinct facies: the lower 12 m showing visible solid inclusions (basal dispersed ice facies) and the upper 48 m, which we will refer to as the " basal clean ice facies ". Some of the data are consistent with a pristine paleocli-matic signal, others show clear anomalies. It is demonstrated that neither large-scale bottom refreezing of subglacial water , nor mixing (be it internal or with a local basal end term from a previous/initial ice sheet configuration) can explain the observed bottom-ice properties. We focus on the high-resolution chemical profiles and on the available remote sensing data on the subglacial topography of the site to propose a mechanism by which relative stretching of the bottom-ice sheet layers is made possible, due to the progressively confining effect of subglacial valley sides

Progress of the LUNEX5 Project

http://accelconf.web.cern.ch/AccelConf/FEL2013/papers/wepso05.pdfInternational audienceLUNEX5 (free electron Laser Using a New accelerator for the Exploitation of X-ray radiation of 5th generation) aims at investigating the production of short, intense, and coherent pulses in the soft X-ray region. A 400 MeV superconducting linear accelerator and a laser wakefield accelerator (LWFA), will feed a single Free Electron Laser line with High order Harmonic in Gas and Echo Enable Harmonic Generation seeding. After the Conceptual Design Report (CDR), R&D has been launched on specific magnetic elements (cryo-ready 3 m long in-vacuum undulator, a variable strong permanent magnet quadrupoles), on diagnostics (Smith-Purcell, electro-optics). In recent transport studies of a LWFA based on more realistic beam parameters (1 % energy spread, 1 μm beam size and 1 mrad divergence) than the ones assumed in the CDR, a longitudinal and transverse manipulation enables to provide theoretical amplification. A test experiment is under preparation. It is noted in this context that among the French scientific community's interest in experiments at operating FELs is increasing

LUNEX5: A French FEL Test Facility Light Source Proposal

http://accelconf.web.cern.ch/AccelConf/IPAC2012/papers/tuppp005.pdfInternational audienceLUNEX5 is a new Free Electron Laser (FEL) source project aimed at delivering short and coherent X-ray pulses to probe ultrafast phenomena at the femto-second scale, to investigate extremely low density samples as well as to image individual nm scale objects

The LUNEX5 project

http://accelconf.web.cern.ch/AccelConf/FEL2012/papers/froa03.pdfInternational audienceLUNEX5 (free electron Laser Using a New accelerator for the Exploitation of X-ray radiation of 5th generation) aims at investigating the production of short, intense, and coherent pulses in the soft X-ray region. The project consists of a Free Electron Laser (FEL) line enabling the most advanced seeding configurations: High order Harmonic in Gas (HHG) seeding and Echo Enable Harmonic Generation (EEHG) with in-vacuum (potentially cryogenic) undulators of 15 and 30 mm period. Two accelerator types feed this FEL line : a 400 MeV Conventional Linear Accelerator (CLA) using superconducting cavities compatible with a future upgrade towards high repetition rate, for the investigations of the advanced FEL schemes; and a 0.4 - 1 GeV Laser Wake Field Accelerator (LWFA), to be qualified in view of FEL application, in the single spike or seeded regime. Two pilot user experiments for timeresolved studies of isolated species and solid state matter dynamics will take benefit of LUNEX5 FEL radiation and provide feedback of the performance of the different schemes under real user conditions

Retrieving the paleoclimatic signal from the deeper part of the EPICA Dome C ice core

An important share of paleoclimatic information is buried within the lowermost layers of deep ice cores. Because improving our records further back in time is one of the main challenges in the near future, it is essential to judge how deep these records remain unaltered, since the proximity of the bedrock is likely to interfere both with the recorded temporal sequence and the ice properties. In this paper, we present a multiparametric study (δD-δ18Oice, δ18Oatm, total air content, CO2, CH4, N2O, dust, high-resolution chemistry, ice texture) of the bottom 60 m of the EPICA (European Project for Ice Coring in Antarctica) Dome C ice core from central Antarctica. These bottom layers were subdivided into two distinct facies: the lower 12 m showing visible solid inclusions (basal dispersed ice facies) and the upper 48 m, which we will refer to as the "basal clean ice facies". Some of the data are consistent with a pristine paleoclimatic signal, others show clear anomalies. It is demonstrated that neither large-scale bottom refreezing of subglacial water, nor mixing (be it internal or with a local basal end term from a previous/initial ice sheet configuration) can explain the observed bottom-ice properties. We focus on the high-resolution chemical profiles and on the available remote sensing data on the subglacial topography of the site to propose a mechanism by which relative stretching of the bottom-ice sheet layers is made possible, due to the progressively confining effect of subglacial valley sides. This stress field change, combined with bottom-ice temperature close to the pressure melting point, induces accelerated migration recrystallization, which results in spatial chemical sorting of the impurities, depending on their state (dissolved vs. solid) and if they are involved or not in salt formation. This chemical sorting effect is responsible for the progressive build-up of the visible solid aggregates that therefore mainly originate "from within", and not from incorporation processes of debris from the ice sheet's substrate. We further discuss how the proposed mechanism is compatible with the other ice properties described. We conclude that the paleoclimatic signal is only marginally affected in terms of global ice properties at the bottom of EPICA Dome C, but that the timescale was considerably distorted by mechanical stretching of MIS20 due to the increasing influence of the subglacial topography, a process that might have started well above the bottom ice. A clear paleoclimatic signal can therefore not be inferred from the deeper part of the EPICA Dome C ice core. Our work suggests that the existence of a flat monotonic ice-bedrock interface, extending for several times the ice thickness, would be a crucial factor in choosing a future "oldest ice" drilling location in Antarctica