Le syndrome de Miller-Fisher (à propos d'une observation pédiatrique)

CAEN-BU Médecine pharmacie (141182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Determination of snow avalanche return periods using a tree-ring based reconstruction in the French Alps: cross validation with the predictions of a statistical-dynamical model

International audienceDocumenting past avalanche activity represents an indispensable step in avalanche hazard assessment. Nevertheless, (i) archival records of past avalanche events do not normally yield data with satisfying spatial and temporal resolution and (ii) precision concerning runout distance is generally poorly defined. In addition, historic documentation is most often (iii) biased toward events that caused damage to structure or loss of life on the one hand and (iv) undersampled in unpopulated areas on the other hand. On forested paths dendrogeomorphology has been demonstrated to represent a powerful tool to reconstruct past activity of avalanches with annual resolution and for periods covering the past decades to centuries. This method is based on the fact that living trees may be affected by snow avalanches during their flow and deposition phases. Affected trees will react upon these disturbances with a certain growth response. An analysis of the responses recorded in tree rings coupled with an evaluation of the position of reacting trees within the path allows the dendrogeomorphic expert to identify past snow avalanche events and deduced their minimum runout distance. The objective of the work presented here is firstly to dendrochronogically -reconstruct snow avalanche activity in the Château Jouan path located near Montgenèvre in the French Alps. Minimal runout distances are then determined for each reconstructed event by considering the point of further reach along the topographic profile. Related empirical return intervals are evaluated, combining the extent of each event with the average local frequency of the dendrological record. In a second step, the runout distance distribution derived from dendrochronological reconstruction is compared to the one derived from historical archives and to high return period avalanches predicted by an up-to-date locally calibrated statistical-numerical model. It appears that dendrochronological reconstructions correspond mostly to rare events, i.e. to the tail of the local runout distance distribution. Furthermore, a good agreement exists with the statistical-numerical model’s prediction, i.e. a 10-40 m difference for return periods ranging between 10 and 300 years, which is rather small with regards to the uncertainty levels to be considered in avalanche probabilistic modeling and dendrochronological reconstructions. It is important to note that such a cross validation on independent extreme predictions has never been undertaken before. It suggest that i) dendrochronological reconstruction can provide valuable information for anticipating future extreme avalanche events in the context of risk management, and, in turn, that ii) the statisticalnumerical model, while properly calibrated, can be used with reasonable confidence to refine these predictions, with for instance evaluation of pressure and flow depth distributions at each position of the runout zone. A strong sensitivity to the determination of local avalanche and dendrological record frequencies is however highlighted, indicating that this step is an essential step for an accurate probabilistic characterization of large-extent event

Influence of phosphorus on the growth and the photoluminescence properties of Si-NCs formed in P-doped SiO/SiO 2 multilayers

International audienceThis work reports on the influence of phosphorous atoms on the phase separation process and optical properties of silicon nanocrystals (Si-NCs) embedded in phosphorus doped SiO/SiO 2 multilayers. Doped SiO/SiO 2 multilayers with different P contents have been prepared by coevaporation and subsequently annealed at different temperatures up to 1100 °C. The sample structure and the localization of P atoms were both studied at the nanoscale by scanning transmission electron microscopy and atom probe tomography. It is found that P incorporation modifies the mechanism of Si-NC growth by promoting the phase separation during the postgrowth-annealing step, leading to nanocrystals formation at lower annealing temperatures as Page 38 of 72 Nanoscale compared to undoped Si-NCs. Hence, the maximum of Si-NC related photoluminescence (PL) intensity is achieved for annealing temperatures lower than 900 °C. It is also demonstrated that the Si-NCs mean size increases in the presence of P, which is accompanied by a redshift of the Si-NC related emission. The influence of the phosphorus content on the PL properties is studied using both room temperature and low temperature measurements. It is shown that for a P content lower than about 0.1 at. %, P atoms contribute to significantly improve the PL intensity. This effect is attributed to the P-induced-reduction of the number of non-radiative defects at the interface between Si-NCs and SiO 2 matrix, which is discussed in comparison with hydrogen passivation of Si-NCs. In contrast, for increasing P contents, the PL intensity strongly decreases, which is explained by the growth of Si-NCs reaching sizes that are too large to ensure quantum confinement and to the localization of P atoms inside Si-NCs

Influence of phosphorus on the growth and the photoluminescence properties of Si-NCs formed in P-doped SiO/SiO 2 multilayers

International audienceThis work reports on the influence of phosphorous atoms on the phase separation process and optical properties of silicon nanocrystals (Si-NCs) embedded in phosphorus doped SiO/SiO 2 multilayers. Doped SiO/SiO 2 multilayers with different P contents have been prepared by coevaporation and subsequently annealed at different temperatures up to 1100 °C. The sample structure and the localization of P atoms were both studied at the nanoscale by scanning transmission electron microscopy and atom probe tomography. It is found that P incorporation modifies the mechanism of Si-NC growth by promoting the phase separation during the postgrowth-annealing step, leading to nanocrystals formation at lower annealing temperatures as Page 38 of 72 Nanoscale compared to undoped Si-NCs. Hence, the maximum of Si-NC related photoluminescence (PL) intensity is achieved for annealing temperatures lower than 900 °C. It is also demonstrated that the Si-NCs mean size increases in the presence of P, which is accompanied by a redshift of the Si-NC related emission. The influence of the phosphorus content on the PL properties is studied using both room temperature and low temperature measurements. It is shown that for a P content lower than about 0.1 at. %, P atoms contribute to significantly improve the PL intensity. This effect is attributed to the P-induced-reduction of the number of non-radiative defects at the interface between Si-NCs and SiO 2 matrix, which is discussed in comparison with hydrogen passivation of Si-NCs. In contrast, for increasing P contents, the PL intensity strongly decreases, which is explained by the growth of Si-NCs reaching sizes that are too large to ensure quantum confinement and to the localization of P atoms inside Si-NCs

In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels

Most known pathogenic point mutations in humans are C center dot G to T center dot A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up to 34% editing (on average, 26%) in macaques. Plasma PCSK9 and LDL levels were stably reduced by 95% and 58% in mice and by 32% and 14% in macaques, respectively. ABE mRNA was cleared rapidly, and no off-target mutations in genomic DNA were found. Re-dosing in macaques did not increase editing, possibly owing to the detected humoral immune response to ABE upon treatment. These findings support further investigation of ABEs to treat patients with monogenic liver diseases.Base editors are effective and safe for cholesterol reduction in non-human primates.ISSN:1546-1696ISSN:1087-015

In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels

Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up to 34% editing (on average, 26%) in macaques. Plasma PCSK9 and LDL levels were stably reduced by 95% and 58% in mice and by 32% and 14% in macaques, respectively. ABE mRNA was cleared rapidly, and no off-target mutations in genomic DNA were found. Re-dosing in macaques did not increase editing, possibly owing to the detected humoral immune response to ABE upon treatment. These findings support further investigation of ABEs to treat patients with monogenic liver diseases