Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment and evolution within swine worldwide [3]. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations [4]. We performed an infection and transmission study in pigs with A/California/07/09. In combination, clinical, pathological, modified influenza A matrix gene real time RT-PCR and viral genomic analyses have shown that infection results in the induction of clinical signs, viral pathogenesis restricted to the respiratory tract, infection dynamics consistent with endemic strains of influenza A in pigs, virus transmissibility between pigs and virus-host adaptation events. Our results demonstrate that extant H1N1/09 is fully capable of becoming established in global pig populations. We also show the roles of viral receptor specificity in both transmission and tissue tropism. Remarkably, following direct inoculation of pigs with virus quasispecies differing by amino acid substitutions in the haemagglutinin receptor-binding site, only virus with aspartic acid at position 225 (225D) was detected in nasal secretions of contact infected pigs. In contrast, in lower respiratory tract samples from directly inoculated pigs, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic [5]

Lateral diffusivity coefficients from the dynamics of a SF6 patch in a coastal environment

The dispersion of a patch of the tracer sulfur hexafluoride (SF6) is used to assess the lateral diffusivity in the coastal waters of the western part of the Gulf of Lion (GoL), northwestern Mediterranean Sea, during the Latex10 experiment (September 2010). Immediately after the release, the spreading of the patch is associated with a strong decrease of the SF6 concentrations due to the gas exchange from the ocean to the atmosphere. This has been accurately quantified, evidencing the impact of the strong wind conditions during the first days of this campaign. Few days after the release, as the atmospheric loss of SF6 decreased, lateral diffusivity coefficient at spatial scales of 10 km has been computed using two approaches. First, the evolution of the patch with time was combined with a diffusion-strain model to obtain estimates of the strain rate (γ = 2.5 10- 6 s- 1) and of the lateral diffusivity coefficient (Kh = 23.2 m2s− 1). Second, a steady state model was applied, showing Kh values similar to the previous method after a period of adjustment between 2 and 4.5 days. This implies that after such period, our computation of Kh becomes insensitive to the inclusion of further straining of the patch. Analysis of sea surface temperature satellite imagery shows the presence of a strong front in the study area. The front clearly affected the dynamics within the region and thus the temporal evolution of the patch. Our results are consistent with previous studies in open ocean and demonstrate the success and feasibility of those methods also under small-scale, rapidly-evolving dynamics typical of coastal environments

Complete event-by-event α/γ(β) separation in a full-size TeO2 CUORE bolometer by simultaneous heat and light detection

The CUORE project began recently a search for neutrinoless double-beta decay ($0\nu\beta\beta$) of $^{130}$Te with a $\mathcal{O}$(1 ton) TeO$_2$ bolometer array. In this experiment, the background suppression relies essentially on passive shielding, material radiopurity and anti-coincidences. The lack of particle identification in CUORE makes $\alpha$ decays at the detector surface the dominant background, at the level of $\sim$0.01 counts/(keV kg y) in the region of interest ($Q$-value of $0\nu\beta\beta$ of the order of 2.5 MeV). In the present work we demonstrate, for the first time with a CUORE-size (5$\times$5$\times$5 cm) TeO$_2$ bolometer and using the same technology as CUORE for the readout of the bolometric signals, an efficient $\alpha$ particle discrimination (99.9\%) with a high acceptance of the $0\nu\beta\beta$ signal (about 96\%). This unprecedented result was possible thanks to the superior performance (10 eV RMS baseline noise) of a Neganov-Luke-assisted germanium bolometer used to detect a tiny (70 eV) light signal dominated by $\gamma$($\beta$)-induced Cherenkov radiation in the TeO$_2$ detector. The obtained results represent a major breakthrough towards the TeO$_2$-based version of CUPID, a ton-scale cryogenic $0\nu\beta\beta$ experiment proposed as a follow-up to CUORE with particle identification

Optimizing EDELWEISS detectors for low-mass WIMP searches

The physics potential of EDELWEISS detectors for the search of low-mass weakly interacting massive particles (WIMPs) is studied. Using a data-driven background model, projected exclusion limits are computed using frequentist and multivariate analysis approaches, namely, profile likelihood and boosted decision tree. Both current and achievable experimental performances are considered. The optimal strategy for detector optimization depends critically on whether the emphasis is put on WIMP masses below or above ∼5  GeV/c2. The projected sensitivity for the next phase of the EDELWEISS-III experiment at the Modane Underground Laboratory (LSM) for low-mass WIMP search is presented. By 2018 an upper limit on the spin-independent WIMP-nucleon cross section of σSI=7×10−42  cm2 is expected for a WIMP mass in the range 2–5  GeV/c2. The requirements for a future hundred-kilogram-scale experiment designed to reach the bounds imposed by the coherent scattering of solar neutrinos are also described. By improving the ionization resolution down to 50  eVee, we show that such an experiment installed in an even lower background environment (e.g., at SNOLAB) together with an exposure of 1000   kg⋅yr, should allow us to observe about 80 8B neutrino events after discrimination

Signals induced by charge-trapping in EDELWEISS FID detectors: Analytical modeling and applications

The EDELWEISS-III direct dark matter search experiment uses cryogenic HP-Ge detectors Fully covered with Inter-Digitized electrodes (FID). They are operated at low fields (< 1 V/cm), and as a consequence charge-carrier trapping significantly affects both the ionization and heat energy measurements. This paper describes an analytical model of the signals induced by trapped charges in FID detectors based on the Shockley-Ramo theorem. It is used to demonstrate that veto electrodes, initially designed for the sole purpose of surface event rejection, can be used to provide a sensitivity to the depth of the energy deposits, characterize the trapping in the crystals, perform heat and ionization energy corrections and improve the ionization baseline resolutions. These procedures are applied successfully to actual data

Measurement of the cosmogenic activation of germanium detectors in EDELWEISS-III

International audienceWe present a measurement of the cosmogenic activation in the germanium cryogenic detectors of the EDELWEISS III direct dark matter search experiment. The decay rates measured in detectors with different exposures to cosmic rays above ground are converted into production rates of different isotopes. The measured production rates in units of nuclei/kg/day are 82 $\pm$ 21 for $^3$H, 2.8 $\pm$ 0.6 for $^{49}$V, 4.6 $\pm$ 0.7 for $^{55}$Fe, and 106 $\pm$ 13 for $^{65}$Zn. These results are the most accurate for these isotopes. A lower limit on the production rate of $^{68}$Ge of 74 nuclei/kg/day is also presented. They are compared to model predictions present in literature and to estimates calculated with the ACTIVIA code

Improved EDELWEISS-III sensitivity for low-mass WIMPs using a profile likelihood approach

We report on a dark matter search for a Weakly Interacting Massive Particle (WIMP) in the mass range mχ∈[4,30]GeV/c2 with the EDELWEISS-III experiment. A 2D profile likelihood analysis is performed on data from eight selected detectors with the lowest energy thresholds leading to a combined fiducial exposure of 496 kg-days. External backgrounds from γ- and β-radiation, recoils from 206Pb and neutrons as well as detector intrinsic backgrounds were modelled from data outside the region of interest and constrained in the analysis. The basic data selection and most of the background models are the same as those used in a previously published analysis based on boosted decision trees (BDT) [1]. For the likelihood approach applied in the analysis presented here, a larger signal efficiency and a subtraction of the expected background lead to a higher sensitivity, especially for the lowest WIMP masses probed. No statistically significant signal was found and upper limits on the spin-independent WIMP-nucleon scattering cross section can be set with a hypothesis test based on the profile likelihood test statistics. The 90 % C.L. exclusion limit set for WIMPs with mχ=4GeV/c2 is 1.6×10-39cm2, which is an improvement of a factor of seven with respect to the BDT-based analysis. For WIMP masses above 15GeV/c2 the exclusion limits found with both analyses are in good agreement

Correction: Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

BACKGROUND: Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations. METHODS: Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up. RESULTS: At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%). CONCLUSIONS: Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov)