The future outlook on allergen immunotherapy in children: 2018 and beyond.

Allergen immunotherapy (AIT) is the only currently available immune-modifying and aetiological treatment for patients suffering from IgE-mediated diseases. In childhood, it represents a suitable therapeutic option to intervene during the early phases of respiratory allergic diseases such as rhino-conjunctivitis and asthma, which is when their progression may be more easily influenced. A growing body of evidence shows that oral immunotherapy represents a promising treatment option in children with persistent IgE- mediated food allergy. The efficacy of AIT is under investigation also in patients with extrinsic atopic dermatitis, currently with controversial results. Furthermore, AIT might be a strategy to prevent the development of a new sensitization or of a (new) allergic disease. However, there are still some methodological criticisms, such as: a) the regimen of administration and the amount of the maintenance dose are both largely variable; b) the protocols of administration are not standardized; c) the description and classification of side effects is variable among studies and needs to be standardized; d) quality of life and evaluation of health economics are overall missing. All these aspects make difficult to compare each study with another. In addition, the content of major allergen(s) remains largely variable among manufacturers and the availability of AIT products differences among countries. The interest and the attention to AIT treatment are currently fervent and increasing. Well-designed studies are awaited in the near future in order to overcome the current gaps in the evidence and furtherly promote implementation strategies

Garigliano nuclear power plant: seismic evaluation of the turbine building

The Italian Garigliano Nuclear Power Plant (NPP) started its energy production in 1963. At present it is in the decommissioning stage. In order to get a proper management of the radioactive waste that will be produced during the dismantling operations it has been considered convenient to convert the turbine building of the plant into a temporary waste repository. This decision posed a remarkable seismic safety assessment issue. As a matter of fact, the challenge was to extend, in satisfactory safety conditions, the use of an important facility that has reached the end of its designed lifetime and to have this extended use approved by nuclear safety agencies. In this context many tasks have been accomplished, of which the most important are: (a) a new appraisal of site seismic hazard; (b) the execution of many investigations and testing on the construction materials; (c) the set up of a detailed 3D finite element model including the explicit representation of foundation piles and soil; (d) consideration of soil structure kinematic and dynamic nteraction effects. This paper describes the adopted seismic safety assessment criteria which are based on a performance objectives design approach. While performance based design is the approach currently recommended by European Regulations to manage seismic risk and it is fully incorporated in the Italian code for conventional buildings, bridges and plants, NPP are not explicitly considered. Therefore it was necessary to delineate a consistent interpretation of prescribed rules in order to properly select the maximum and operating design earthquakes on one side and corresponding acceptable limit states on the other side. The paper further provides an outline of the numerical analyses carried out, of the main results obtained and of the principal retrofitting actions that will be realized

High density Schottky barrier IRCCD sensors for SWIR applications at intermediate temperature

Monolithic 32 x 64 and 64 x 1:128 palladium silicide (Pd2Si) interline transfer infrared charge coupled devices (IRCCDs) sensitive in the 1 to 3.5 micron spectral band were developed. This silicon imager exhibits a low response nonuniformity of typically 0.2 to 1.6% rms, and was operated in the temperature range between 40 to 140 K. Spectral response measurements of test Pd2Si p-type Si devices yield quantum efficiencies of 7.9% at 1.25 microns, 5.6% at 1.65 microns 2.2% at 2.22 microns. Improvement in quantum efficiency is expected by optimizing the different structural parameters of the Pd2Si detectors. The spectral response of the Pd2Si detectors fit a modified Fowler emission model. The measured photo-electric barrier height for the Pd2Si detectors is 0.34 eV and the measured quantum efficiency coefficient, C1, is 19%/eV. The dark current level of Pd2Si Schottky barrier focal plane arrays (FPAs) is sufficiently low to enable operation at intermediate temperatures at TV frame rates. Typical dark current level measured at 120 K on the FPA is 2 nA/sq cm. The operating temperature of the Pd2Si FPA is compatible with passive cooler performance. In addition, high density Pd2Si Schottky barrier FPAs are manufactured with high yield and therefore represent an economical approach to short wavelength IR imaging. A Pd2Si Schottky barrier image sensor for push-broom multispectral imaging in the 1.25, 1.65, and 2.22 micron bands is being studied. The sensor will have two line arrays (dual band capability) of 512 detectors each, with 30 micron center-to-center detector spacing. The device will be suitable for chip-to-chip abutment, thus providing the capability to produce large, multiple chip focal planes with contiguous, in-line sensors

Flux control of cytochrome c oxidase in human skeletal muscle

In the present work, by titrating cytochrome c oxidase (COX) with the specific inhibitor KCN, the flux control coefficient and the metabolic reserve capacity of COX have been determined in human saponin-permeabilized muscle fibers. In the presence of the substrates glutamate and malate, a 2.3 ± 0.2-fold excess capacity of COX was observed in ADP-stimulated human skeletal muscle fibers. This value was found to be dependent on the mitochondrial substrate supply. In the combined presence of glutamate, malate, and succinate, which supported an approximately 1.4-fold higher rate of respiration, only a 1.4 ± 0.2-fold excess capacity of COX was determined. In agreement with these findings, the flux control of COX increased, in the presence of the three substrates, from 0.27 ± 0.03 to 0.36 ± 0.08. These results indicate a tight in vivo control of respiration by COX in human skeletal muscle. This tight control may have significant implications for mitochondrial myopathies. In support of this conclusion, the analysis of skeletal muscle fibers from two patients with chronic progressive external ophthalmoplegia, which carried deletions in 11 and 49% of their mitochondrial DNA, revealed a substantially lowered reserve capacity and increased flux control coefficient of COX, indicating severe rate limitations of oxidative phosphorylation by this enzyme

On the uniqueness for the spatially homogeneous Boltzmann equation with a strong angular singularity

We prove an inequality on the Wasserstein distance with quadratic cost between two solutions of the spatially homogeneous Boltzmann equation without angular cutoff, from which we deduce some uniqueness results. In particular, we obtain a local (in time) well-posedness result in the case of (possibly very) soft potentials. A global well-posedeness result is shown for all regularized hard and soft potentials without angular cutoff. Our uniqueness result seems to be the first one applying to a strong angular singularity, except in the special case of Maxwell molecules. Our proof relies on the ideas of Tanaka: we give a probabilistic interpretation of the Boltzmann equation in terms of a stochastic process. Then we show how to couple two such processes started with two different initial conditions, in such a way that they almost surely remain close to each other

Behavior of CCN to CN fraction during aging and mixing processes of atmospheric particles

International audienceDuring Spring 2003, field experiments were conducted at the summit of Puy de Dôme (1465 m a.s.l.), in Central France, mainly in the free troposphere and during cloudy conditions. During this experiment, cloud condensation nuclei (CCN) concentrations were measured with a thermal gradient CCN counter at applied supersaturations that ranged between 0.2 and 2%. Aerosol size distributions were obtained with a TSI scanning mobility particle sizer (SMPS) consisting of a DMA and a CPC, and aerosol number (CN) concentrations were derived by integrating the SMPS size spectra between 0.015 and 0.3 µm. The isentropic back trajectories were computed for the altitude of the observation site using the Hybrid Single Particle Lagrangian Integrated Trajectory (HY-SPLIT) code from NOAA. For each air mass type, the aerosol bulk chemical composition used was that previously determined from cascade impactor samples by Sellegri et al. (2003). The methodological approach of this study was, firstly, to determine the relationships between CN and CCN concentrations for various air mass types arriving on the observation site. According to their origin, air masses arriving on the observation site are classified into 4 types: continental, clean marine, modified marine and polar. The CN concentrations appear to clearly depend on the type of air mass with the highest concentrations for the continental event and the lowest ones for the marine events. Moreover, a typical range can be attributed for the CCN/CN ratio to each air mass type. Then, the objective was to observe the hygroscopic behavior of aerosol particles upon heating of the sample in a thermo-desorber. Since the heated sample can be considered as representative of the original state of the aerosol, it appears that the evolution of CN to CCN is much more affected when the air mass is modified by aging and mixing processes with the contact of various atmospheric species all along the transport pathway. This result shows indirectly but clearly the presence of an active chemical layer containing more hygroscopic properties on the aerosol particle surface that can favour the particle growth. However, the role played by organic species is not clear and more work is needed to know if organic compounds may act to increase the CCN concentration

On the speed of approach to equilibrium for a collisionless gas

We investigate the speed of approach to Maxwellian equilibrium for a collisionless gas enclosed in a vessel whose wall are kept at a uniform, constant temperature, assuming diffuse reflection of gas molecules on the vessel wall. We establish lower bounds for potential decay rates assuming uniform $L^p$ bounds on the initial distribution function. We also obtain a decay estimate in the spherically symmetric case. We discuss with particular care the influence of low-speed particles on thermalization by the wall.Comment: 22 pages, 1 figure; submitted to Kinetic and Related Model