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Background and aim Hydrocotyle bonariensis Comm ex Lamm (Araliaceae) is one of these plants sufficiently exploited in traditional African medicine for its hypotensive effect. However, the pharmacological effects of those plants on cardiac functions are not well known. The potassium currents IKs and IKr, responsible for the repolarization of cardiac cell action potential, strongly influence the human cardiac rhythm. Therefore, modulators of these currents have a beneficial or undesirable medical importance in relation to cardiac arrhythmias. In order to optimize the therapeutic use of this medicinal plant, we studied the effects of hydro-ethanolic leaf extract of Hydrocotyle bonariensis on both potassium currents. Experimental procedure The patch clamp experiments for IK currents recording were performed on the HEK 293 (Human Embryonic Kidney 293) cell line, stably transfected with either KCNQ1 and KCNE1 genes encoding the channel responsible for the "IKs" current (HEK293 IKs), or with hERG (human ether-a-go-go related gene) gene encoding "IKr" current (HEK293 IKr). Results and conclusion This study revealed that the hydro-ethanolic leaf extract of H. bonariensis significantly inhibits the slow potassium component (IKs) without altering the fast potassium component (IKr). The extract at 0.5 mg/ml decreases IKs conductance by 24 ± 4.1% (n = 6) without modifying its activation threshold suggesting a direct blockade of the slow potassium channel. This selective action of the extract on the IKs current reflects a class III anti-arrhythmic effect.

Engineering low-frequency phonon transport in nanostructures with the phonon resonant mechanism has become an important research direction. On the basis of non-equilibrium molecular dynamics simulations, the thermal transport in pristine and resonant Si-membranes bounded with {100}, {110} and {111} facets is investigated. It is found that the creation of surfaces can introduce anisotropic thermal transport due to the lattice symmetry breaking. Besides, ballistic phonon transport is found in pristine membranes with lengths up to 500 nm at low-frequencies with a critical frequency mainly dependent on the crystallographic orientation. Moreover, although surface resonances can dramatically reduce the thermal conductivity of all membranes, the resonant effect strongly relies on membrane orientation. Among the three studied membrane orientations, the resonant effect is maximized in the {111}-membrane, where the thermal conductivity is tuned from the largest one to the smallest one among the three membrane types by resonant pillars. The large thermal conductivity reduction in the {111}-membranes by resonances originated from the reduced spectral heat flux between 3 and 12 THz. Furthermore, the resonant coupling strength can be tuned by the interface vacancy between resonant pillars and the base material, which can enhance phonon transport at an intermediate frequency range. Our work provides further insights on thermal transport engineering by phonon resonances and could be useful for thermal conductivity engineering with surface orientations and resonances.

Resume Objectif Cette etude a pour objectif de mesurer la prevalence de l’etat de stress post-traumatique et de la detresse emotionnelle chez les victimes de la tempete Xynthia, sept ans apres son passage. Methode Les donnees ont ete obtenues aupres de 36 victimes d’exposition directe qui ont rempli trois echelles cliniques : le questionnaire de sante general (GHQ-12), l’echelle d’impact de l’evenement (IES) et le questionnaire d’evaluation du stress post-traumatique (QSPT). Resultats Cette etude montre un niveau eleve de detresse psychologique avec des scores pathologiques au GHQ-12 pour 29 victimes (81 %). Neuf victimes (25 %) presentent des symptomes de stress post-traumatique a l’IES avec trois cas (8 %) d’etats de stress post-traumatiques actifs au QSPT. Dans notre echantillon, le deuil apparait comme un facteur de risque significatif de developper un etat de stress post-traumatique avec un odd ratio de 15,43 (IC95 % : 1,56–152,37, p = 0,017). Conclusion Les consequences psychologiques de la tempete Xynthia sont toujours presentes sept ans apres son passage et dominees par la detresse emotionnelle. Les intervenants de la sante doivent etre sensibilises aux consequences psychologiques des catastrophes naturelles, meme sur le long terme.

Magnetite (Fe3O4) deposits in the secondary circuit of nuclear pressurized water reactors (PWRs), lead to the fouling of the steam generators (SG) which decreases their thermal performances and increases the risk of corrosion of the SG tubes. As a counteraction, preventive and curative chemical cleanings (CCC) are industrially implemented to remove oxides sludges and deposits in SGs. The use of chelating agents in chemical cleaning processes could affect the passive layer of SG tubes, and modify their surface reactivity. In order to better understand these phenomena, two experimental loops have been designed and operated: the FORTRAND loop to perform and investigate SG tube oxidation, fouling and refouling and the ECCLIPS loop used to investigate the effects of the chemical cleanings. A three steps strategy has been implemented as follows: (i) reproducing magnetite deposits on oxidized SG tubes, (ii) applying three different industrial chemical cleaning procedures (a curative and two preventive ones) and (iii) studying the redeposition (refouling) of magnetite. The fluid physico-chemical conditions upon these steps have been thoroughly followed and controlled. Magnetite deposits formed on the SG tubes upon the first fouling have been characterized by scanning and transmission electron microscopies (SEM and TEM) and X-ray diffraction (XRD). They are shown to be composed of a dense layer of small magnetite crystals. Secondly, three different SG industrial cleaning processes were reproduced. Their timing and thermo-chemical conditions were strictly respected and they were found to dissolve most of the fouling deposit. Disperse magnetite crystallites were present on the tube surface. Moreover, TEM cross-section images showed that no general attack of the tube passive layer occurred. Finally, the cleaned tubes were fouled again in the FORTRAND loop using the same experimental conditions as for the first fouling step. It could be concluded that chemical cleanings have no effect on the fouling kinetics of the SG tubes for a short one month period and that the amount of deposit formed before and after the cleanings was identical. The small crystallite dense layer observed before cleaning was not present on refouled tubes and the size of the crystallites was bigger after the cleanings. For a short time period, this morphology could result in the formation of a fouling deposit with more porosity. As the increase of deposit porosity can impact the thermal transfer at the SG tube surface, morphological changes, hardly predictable, could be important for the SG thermal performance after chemical cleaning. For a longer period, frequent SG cleaning applications should prevent the densification of the deposit and thus delay performance loss over time. To the best of our knowledge, this experimental program is the first study of chemical cleaning impacts on SG tubes reactivity.

The fibroblast growth factor receptor (FGFR) pathway has been implicated both as an escape mechanism from anti-angiogenic therapy and as a driver oncogene in different tumor types. Lucitanib is a small molecule inhibitor of vascular endothelial growth factor (VEGF) receptors 1 to 3 (VEGFR1 to 3), platelet derived growth factor α/β (PDGFRα/β) and FGFR1–3 tyrosine kinases and has demonstrated activity in a phase I/II clinical study, with objective RECIST responses in breast cancer patients with FGFR1 or FGF3/4/19 gene amplification, as well as in patients anticipated to benefit from anti-angiogenic agents. We report here the in vitro and in vivo antitumor activity of lucitanib in experimental models with or without FGFR1/2 amplification or mutations. In cell assays, lucitanib potently inhibited the growth of tumor cell lines with amplified FGFR1 or mutated/amplified FGFR2 . In all xenograft models studied, lucitanib demonstrated marked tumor growth inhibition due to potent inhibition of angiogenesis. Notably, in two lung cancer models with FGFR1 amplification, the antitumor efficacy was higher, suggesting that the simultaneous inhibition of VEGF and FGF receptors in FGFR1 dependent tumors can be therapeutically advantageous. Similar antitumor activity was observed in FGFR2 wild-type and amplified or mutated xenograft models. Pharmacokinetic studies showed lucitanib plasma concentrations in the micro/sub-micromolar range demonstrated drug accumulation following repeated lucitanib administration.

WOS:000373250400012; International audience; The effects of weakly absorbing material coating on soot have attracted considerable research attention in recent years due to the significant influence of such coating on soot radiative properties and the large differences predicted by different numerical models. Soot aggregates were first numerically generated using the diffusion limited cluster aggregation algorithm to produce fractal aggregates formed by log-normally distributed polydisperse spherical primary particles in point-touch. These aggregates were then processed by adding a certain amount of primary particle overlapping and necking to simulate the soot morphology observed from transmission electron microscopy images. After this process, a layer of WAM coating of different thicknesses was added to these more realistic soot aggregates. The radiative properties of these coated soot aggregates over the spectral range of 266-1064 nm were calculated by the discrete dipole approximation (DDA) using the spectrally dependent refractive index of soot for four aggregates containing N-p =1, 20, 51 and 96 primary particles. The considered coating thicknesses range from 0% (no coating) up to 100% coating in terms of the primary particle diameter. Coating enhances both the particle absorption and scattering cross sections, with much stronger enhancement to the scattering one, as well as the asymmetry factor and the single scattering albedo. The absorption enhancement is stronger in the UV than in the visible and the near infrared. The simple corrections to the Rayleigh-Debye-Gans fractal aggregates theory for uncoated soot aggregates are found not working for coated soot aggregates. The core-shell model significantly overestimates the absorption enhancement by coating in the visible and the near infrared compared to the DDA results of the coated soot particle. Treating an externally coated soot aggregate as an aggregate formed by individually coated primary particles significantly underestimates the absorption enhancement by coating in the visible and the near infrared. Crown Copyright (C) 2015 Published by Elsevier Ltd. All rights reserved.

Introduction Le burnout peut etre defini comme un syndrome psychologique associant un epuisement emotionnel, une depersonnalisation et une baisse de l’accomplissement personnel [1] . Le burnout affecte en particulier les professionnels d’aide a la personne, comme les sapeurs-pompiers. Les consequences du burnout sont nombreuses, allant de la baisse de la qualite de vie aux troubles relationnels, en passant par l’emergence de troubles physiques ou psychiques [2] , [3] . Notre hypothese est que certains sapeurs-pompiers vendeens presentent un burnout en association a une souffrance psychique et physique plus importante. Materiel Nous avons mene une etude observationnelle de prevalence du burnout chez des sapeurs-pompiers vendeens. Par auto-questionnaires, les participants ont rempli la Maslach Burnout Inventory - 22 item (MBI) et le General Health Questionnaire - 28 item (GHQ-28), qui evalue la presence de symptomes physiques ou psychiques associes au stress professionnel (cutoff > 4). Les variables qualitatives ont ete analysees par le test exact de Fisher, et les variables quantitatives par le test t de Student (p Resultats Nous avions 105 questionnaires valides : 13 femmes (12,4 %) et 92 hommes (87,6 %) ; 18 sapeurs-pompiers professionnels (17 %) et 87 sapeurs-pompiers volontaires (83 %). Les resultats de la MBI ont mis en evidence que seul un sapeur-pompier (0,95 %) presentait un burnout avec un score moyen au GHQ-28 de 3,00. Cependant, la majorite des pompiers (56,2 %) presentaient au moins une dimension severe a la MBI, dominee par une baisse de l’accomplissement personnel. Les sapeurs-pompiers ne rapportaient pas de souffrance psychique ou physique en lien avec le stress professionnel : la moyenne generale au GHQ-28 etait de 1,97 (SD = 3,64). Cependant, nous avions 17 sapeurs-pompiers (16,2 %) qui avaient un score pathologique au GHQ-28. On ne retrouve pas de majoration significative de l’effectif ou de la moyenne generale, entre ceux qui avaient ou n’avaient pas de dimension severe a la MBI. Conclusion Nos resultats sont encourageants avec un faible taux de burnout, et un faible taux de souffrance psychique ou physique, sans majoration chez ceux qui ont une dimension severe du burnout. Ces resultats tendent a confirmer que le burnout est une antichambre aux troubles psychologiques [1] . Neanmoins, la place de la baisse de l’accomplissement personnel dans la cinetique du burnout chez les sapeurs-pompiers reste encore a definir.

WOS:000358626000003; International audience; Effective density measurements are used extensively to convert submicron particle sizes based on a particle's mobility diameter into mass. Measurements of the effective density also provide information concerning the particle morphology. For example, the effective density curves of fractal aggregates reveal a scaling factor that seems to correlate with the fractal dimension of the particles. The present paper proposes a simple semi-empirical model that permits the quantitative interpretation of these measurements to determine parameters such as the fractal dimension, the primary particle size, and the bulk density of an aggregate particle. The proposed model is based on the assumption that the hydrodynamic drag force of an aggregate is proportional to the drag force applied to isolated primary spheres and to the number of primary spheres in the aggregate at power a. The model was applied to soot particles produced by either a spark discharge (PALAS GFG1000) or by combustion (miniCAST 5206)-both mechanisms enable the generation of aggregates or agglomerates with very different primary sphere diameters. The proposed model showed a good fit for all of the effective density measurements obtained in this study; the a parameter was driven by the aggregate fractal dimension and by the Knudsen number that was determined based on the primary particle diameter. Finally, for a known primary particle diameter, the fractal dimension and the bulk density were determined successfully with the proposed model. (C) 2015 Elsevier Ltd. All rights reserved.

WOS:000357543800021; International audience; There is a strong interest in accurately modelling the radiative properties of soot aggregates (also known as black carbon particles) emitted from combustion systems and fires to gain improved understanding of the role of black carbon to global warming. This study conducted a systematic investigation of the effects of overlapping and necking between neighbouring primary particles on the radiative properties of soot aggregates using the discrete dipole approximation. The degrees of overlapping and necking are quantified by the overlapping and necking parameters. Realistic soot aggregates were generated numerically by constructing overlapping and necking to fractal aggregates formed by point-touch primary particles simulated using a diffusion-limited cluster aggregation algorithm. Radiative properties (differential scattering, absorption, total scattering, specific extinction, asymmetry factor and single scattering albedo) were calculated using the experimentally measured soot refractive index over the spectral range of 266-1064 nm for 9 combinations of the overlapping and necking parameters. Overlapping and necking affect significantly the absorption and scattering properties of soot aggregates, especially in the near UV spectrum due to the enhanced multiple scattering effects within an aggregate. By using correctly modified aggregate properties (fractal dimension, prefactor, primary particle radius, and the number of primary particle) and by accounting for the effects of multiple scattering, the simple Rayleigh-Debye-Gans theory for fractal aggregates can reproduce reasonably accurate radiative properties of realistic soot aggregates. (C) 2015 Elsevier Ltd. All rights reserved.

Introduction Si l’usage therapeutique des dermocorticoides est relativement sur, il peut survenir des effets secondaires dans le cadre de traitements chroniques (atrophie cutanee, purpura, xerodermie, insuffisance surrenalienne). Dans les etablissements de soins, il arrive que ce soient les infirmiers et aides-soignants qui appliquent ces topiques. Notre etude a donc pour objectif d’evaluer le risque professionnel pour les soignants appliquant des dermocorticoides. Materiel et methodes Nous avons realise une etude monocentrique dans un CHU en deux etapes. Dans un premier temps, nous avons recense aupres de la pharmacie hospitaliere les references et les services les plus utilisateurs de dermocorticoides. Nous en avons recupere la composition dans une base de donnees validee par la HAS (Theriaque) et nous avons recupere les donnees concernant la toxicite des excipients (Toxnet). Dans un second temps, nous avons mene une etude observationnelle des pratiques soignantes, completee par des entretiens semi-diriges dans le service le plus utilisateur de dermocorticoides. Resultats Cinq references de dermocorticoides ont ete recensees (par ordre decroissant de delivrance : clobetasol 0,05 % en creme, hydrocortisone-17-butyrate a 0,1 % en creme et en gel, desonide a 0,1 % en creme, betamethasone propionate 0,05 % et acide salicylique en gel et en lotion). Le service de dermatologie etait le plus utilisateur de dermocorticoides avec 1852 unites communes de dispensation sur l’annee etudiee. Parmi les excipients figuraient quelques substances sensibilisantes (alcool cetostearylique) et des parabenes (parahydroxybenzoate propyle et butyle). L’etude observationnelle montrait un usage des gants et un lavage des mains systematique. En moyenne, 30 % du topique utilise restait sur le gant en fin de soin. Discussion Les faibles quantites utilisees, la securite clinique des dermocorticoides, la duree limitee d’application, le lavage des mains, nous permettent de penser que le risque lie a leur application par les soignants est tres faible. Les applications sur les surfaces cutanees accessibles sont realisees par les patients eux-memes quand cela leur est possible. L’arbitrage pour choisir d’utiliser un gant vinyle ou latex depend de nombreux parametres (etat de la peau du patient, impression que la creme penetre plus ou moins la peau, adherence du gant a la main, disponibilite immediate des gants). Conclusion Cette etude est donc rassurante mais il est important de realiser de telles etudes d’exposition pour preciser le risque professionnel reel.

We present a case of a non-provoked fatal shark attack on a 15-year old male kitesurfer in New Caledonia. The victim lost his board and was pulled by the sail along the water surface in a reef passage when a shark attacked. The shark inflicted at least two bites on the left leg, including a severe one around the knee, resulting in a quick hypovolemic shock that was fatal. The analysis of one of these bites indicated that a 2.8 m TL (est. length) tiger shark was responsible for this attack. The features of the attack are consistent with those of a predator response to a surface feeding stimulus.

International audience; Agelanthus dodoneifolius is one of the medicinal plants used in African pharmacopeia and traditional medicine for the treatment of cardiovascular diseases. A chemical analysis has identified one of the active principles: Dodoneine (Ddn). It is a new dihydropyranone which exerts hypotensive and vasorelaxant effects on rat. Since the mechanism of the hypotensive effect is unknown, we performed a variety of preclinical and mechanistic studies to characterize the specific cardiac effect of Ddn at tissue (ex-vivo) and cellular levels (in-vitro) in order to determine a molecular target. Ddn effects were evaluated in an isolated rat heart preparation using Langendorff retrograde perfusion and then, the effects of Ddn were characterized in freshly dissociated cardiac ventricular myocytes using the whole-cell patch-clamp configuration. Ex-vivo, Ddn produced a dose-dependent negative inotropic effect with an IC50 value of 10 µM without changed heart rate. 100 µM Ddn decreased left ventricular developed pressure of about 40%. In isolated cardiac myocytes, Ddn reduced I(Ca),L density of about 30% with an IC50 value estimated at 3 µM. Ddn did not change current-voltage relation but it shifted the inactivation curve toward negative potentials and modified the half inactivation potentials. Furthermore, Ddn induced a phasic-dependent blocking on ICa,L. This study demonstrates that the hypotensive property of dodoneine is likely associated with a negative inotropic effect and the blockade of the L-type calcium channels.

Abexinostat, an oral pan-histone deacetylase inhibitor (HDACi), was evaluated in patients with advanced solid tumours in two single agent phase I studies (PCYC-402 and CL1-78454-002). In PCYC-402 study testing four different administration schedules, the maximum tolerated dose (MTD) was established at 75 mg/m(2) BID (twice daily) and the recommended dose at 60 mg/m(2) BID regardless of the schedule tested. The dose limiting toxicity (DLT), consistently observed across all these schedules, was reversible thrombocytopenia. The CL1-78454-002 study was initially investigating an additional schedule of 14 days on/7 days off. While testing two first cohorts, thrombocytopenia was observed without reaching DLT. To address this issue, a pharmacokinetic/pharmacodynamic (PK/PD) model was used to predict the optimal schedule allowing higher doses with minimal thrombocytopenia. Several administration schedules were simulated using this model. A 4 days on/3 days off schedule was associated with the smallest platelet decrease. Accordingly, the CL1-78454-002 study was amended. After reaching MTD1 (75 mg/m(2) BID) with the initial schedule, subsequent cohorts received abexinostat on a revised schedule of 4 days on/3 days off, starting at one dose level below MTD1 (60 mg/m(2) BID). As expected, the dose-escalation continued for two more dose levels beyond MTD1. The MTD2 reached for this optimised schedule was 105 mg/m(2) BID and the recommended dose 90 mg/m(2) BID. In conclusion, early understanding of toxicities and PK determination allowed us to build a PK/PD model of thrombocytopenia, which predicted the optimal administration schedule. This optimised schedule is currently used in the trials in solid tumours with abexinostat.

A new three-component system for photoassisted oxypolymerization of alkyd resins containing a drier, a photosensitizer and a radical generator was investigated. Polymerization profiles were recorded by real-time infrared spectroscopy for a thin film exposed for 1 h to simulated sunlight radiation. The kinetic results showed that the system follows complex kinetics. Multiple regression analysis was used to model the influence of the drier, the photosensitizer and the radical generator on the final conversion and total polymerization rate during photooxidation. The mechanisms involved were studied through laser spectroscopies. Laser flash photolysis was used to measure the rate constants of reaction between the radicals formed from the photodissociation of the radical generator and the model compounds of alkyd resins, leading to the rapid formation of hydroperoxides. The photosensitizer was expected to produce singlet state molecular oxygen that reacts on the alkyd resin, and time-resolved chemiluminescence technique was used to determine the quenching rate constant of singlet oxygen by model compounds. On the basis of these results, a mechanism for the photoassisted oxypolymerization of alkyd resins is proposed that account for the all the different reaction pathways.

IF (2,26); International audience; Aim of the study: Effects of the different fractions obtained by partition of ethanolic extract (EE) of Agelanthus dodoneifolius through column chromatography were investigated on rat blood pressure and aortic relaxation and compared to those observed in the presence of crude EE. Materials and methods: The acute hypotensive activity of EE, fractions and dodoneine, administrated intravenously, was evaluated in anaesthetized rats using the invasive method of blood pressure recording. Bioassay-guided fractionation using rat aorta pre-contracted by norepinephrine to monitor the relaxant activity led to the isolation of dodoneine. Results: In normotensive rats, injection of EE (0.01–10 mg/kg) produced a dose-dependent decrease in both systolic and diastolic blood pressure without any significant change in heart rate. In a similar way, the EE (0.001–3 mg/mL) caused relaxation of rat pre-contracted aorta in a concentration-dependent manner. Fractionation of the EE afforded 14 fractions, F1–F14, that were tested on rat precontracted aortic rings. At the concentration level of 1 mg/mL, a maximum relaxation effect was observed for fractions F2–F5. F4 was the most effective to elicit a concentration-dependent relaxation effect with an ED50 = 160±1.1 g/mL (n = 5) and to decreased systolic and diastolic control pressure by 56.9% and 81.6% respectively. F4 contains most of the dihydropyranone dodoneine, with 93% of the sample mass. Dodoneine separated from this fraction was also able to decrease both systolic and diastolic arterial pressure by 32.5% and 38.7% at 100g/kg, respectively. Conclusion: For the first time, this study demonstrates the hypotensive property of the dodoneine present in Agelanthus dodoneifolius.

Resume Introduction La difficulte d’utilisation d’un collyre est un facteur de mauvaise observance des patients limitant l’efficacite therapeutique. L’objectif de cette etude etait d’evaluer la maniabilite et l’acceptabilite globale d’un collyre a base de timolol en flacon Abak® nouvelle generation (collyre multidose non conserve) par rapport a celles des autres modes d’administration (collyres multidoses conserves ou unidoses) chez des patients traites pour un glaucome ou une hypertonie oculaire. Methodes Etude transversale, retrospective et multicentrique impliquant 41 ophtalmologistes repartis sur toute la France. Les patients devaient avoir ete traites par le collyre en flacon Abak® nouvelle generation depuis au moins deux mois, suite au remplacement d’un autre collyre β-bloquant. La maniabilite et l’acceptabilite du flacon Abak® nouvelle generation par rapport au conditionnement utilise precedemment ont ete evaluees par un questionnaire rempli par l’ophtalmologiste. Resultats Les patients ont ete quasi unanimes concernant la maniabilite du flacon Abak® nouvelle generation : ouverture facile rapportee par 96,5 % des patients, prise en main aisee pour 96,0 % et sortie des gouttes facile pour 91,1 %. Sur tous ces criteres et de maniere globale, les patients ont prefere le flacon Abak® nouvelle generation par rapport au conditionnement precedent. Ces resultats ont ete confirmes chez les patients les plus âges. Conclusion Le flacon Abak® nouvelle generation a presente une acceptabilite superieure a celle des flacons multidoses conserves ou en unidoses. Sa maniabilite et l’absence de conservateur, qui laisse presager une meilleure tolerance locale, sont favorables a une meilleure observance therapeutique chez les patients traites au long cours.

Objectives With more children receiving cochlear implants during infancy, there is a need for validated assessments of pre-verbal and early verbal auditory skills. The LittlEARS® Auditory Questionnaire is presented here as the first module of the LittlEARS® test battery. The LittlEARS® Auditory Questionnaire was developed and piloted to assess the auditory behaviour of normal hearing children and hearing impaired children who receive a cochlear implant or hearing aid prior to 24 months of age. This paper presents results from two studies: one validating the LittlEARS® Auditory Questionnaire on children with normal hearing who are German speaking and a second validating the norm curves found after adaptation and administration of the questionnaire to children with normal hearing in 15 different languages. Methods Scores from a group of 218 German and Austrian children with normal hearing between 5 days and 24 months of age were used to create a norm curve. The questionnaire was adapted from the German original into English and then 15 other languages to date. Regression curves were found based on parental responses from 3309 normal hearing infants and toddlers. Curves for each language were compared to the original German validation curve. Results The results of the first study were a norm curve which reflects the age-dependence of auditory behaviour, reliability and homogeneity as a measure of auditory behaviour, and calculations of expected and critical values as a function of age. Results of the second study show that the regression curves found for all the adapted languages are essentially equal to the German norm curve, as no statistically significant differences were found. Conclusions The LittlEARS® Auditory Questionnaire is a valid, language-independent tool for assessing the early auditory behaviour of infants and toddlers with normal hearing. The results of this study suggest that the LittlEARS® Auditory Questionnaire could also be very useful for documenting children's progress with their current amplification, providing evidence of the need for implantation, or highlighting the need for follow-up in other developmental areas.

(IF : 5,246); International audience; The present work is aimed at identifying and characterizing, at a molecular and functional level, new ionic conductances potentially involved in the excitation–secretion coupling and proliferation of cardiac ventricular fibroblasts. Among potassium channel transcripts which were screened by high-throughput real-time PCR, SUR2 and Kir6.1 mRNAs were found to be the most abundant in ventricular fibroblasts. The corresponding proteins were not detected by western blot following 5 days of cell culture, but had appeared at 7 days, increasing with extended cell culture duration as the fibroblasts differentiated into myofibroblasts. Using the inside-out configuration of the patch-clamp technique, single potassium channels could be recorded. These had properties similar to those reported for SUR2/Kir6.1 channels, i.e. activation by pinacidil, inhibition by glibenclamide and activation by intracellular UDP. As already reported for this molecular signature, they were insensitive to intracellular ATP. In the whole-cell configuration, these channels have been shown to be responsible for a glibenclamide-sensitive macroscopic potassium current which can be activated not only by pinacidil, but also by nanomolar concentrations of the sphingolipid sphingosine- 1-phosphate (S1P). The activation of this current resulted in an increase in cell proliferation and a decrease in IL-6 secretion, suggesting it has a functional role in situations where S1P increases. Overall, this work demonstrates for the first time that SUR2/Kir6.1 channels represent a significant potassium conductance in ventricular fibroblasts which may be activated in physio-pathological conditions and which may impact on fibroblast proliferation and function.

As reported for cyclic nucleotide-gated channels in sensory neurons, we investigated the action of Ca 2+ –calmodulin and calmodulin antagonist (W7) on the apparent affinity of pacemaker ( I f ) channels for cAMP. In this study, we used the patch-clamp technique in inside–out macro-patch configuration in rabbit sino-atrial cells. Intracellular calmodulin perfusion had no effect on f-channel activity and did not change the cAMP-induced I f activation shift. Nevertheless, W7 decreased maximal conductance and induced a voltage shift of the current activation curve towards negative potentials. W7 did not modify the positive shift caused by cAMP, and cAMP did not prevent the effects of W7. Contrary to the cyclic nucleotide-gated channel, the f-channel is not directly modulated by Ca 2+ –calmodulin. The data suggest that W7 alters the voltage-dependent properties of I f independent of cAMP binding. This agent opens the pathway for a new family of bradycardic drugs.

4th European Workshop on Ultimate Integration of Silicon (ULIS 2003), Udine, ITALY, MAR, 2003; International audience; In this work, we present an atomic-scale modeling of a single conduction channel double-gate MOSFET based on the self-consistent solving of the two-dimensional Poisson equation with the Schrodinger equation. This later, expressed in tight-binding, is solved using the Green's function formalism in the axial part of the device (i.e. the source-channel-drain region) modeled as a single atomic linear chain and sandwiched between two gate dielectrics treated as perfect insulating media. For device with channel length typically below 10 nm, our results show that source-to-drain tunneling effect and electron reflection in the channel severely impact the device characteristics. Nevertheless, essential field-effect transistor behaviors are preserved, which demonstrates that the operation of double-gate devices can be still considered even at this ultimate limit of a single conduction channel depicted at the atomic-scale. (C) 2003 Elsevier Ltd. All rights reserved.

Metal oxide semiconductor field-effect transistors with channel lengths in the nanometer range have recently been the subject of many new modeling and simulation approaches. Unfortunately, semi-classical methods currently used in microelectronics are not suitable to describe accurately all physical effects when device integration approaches atomic scale. The aim of this study is to compare theoretical results obtained from different atomistic approaches with those classically deduced with the effective mass approximation. We calculated the transmission coefficient in the simple case of linear atomic chains or of several coupled chains by successively considering: (i) the effective mass approximation, (ii) a direct calculation of semi-infinite chains transmission using a simple one band tight binding approximation, (iii) the diffusion theory in the Green’s functions formalism expressed in the frame of tight binding. This last method offers several advantages since it is able to capture the essential physics of nanoscale devices (electron–electron and electron–phonon interactions). Finally, we summarize the discussion of the extension of this last approach to realistic devices.