The Use of Very High-Doses of Baclofen for the Treatment of Alcohol-Dependence: A Case Series

Baclofen, particularly high-dose baclofen, has recently emerged as a treatment of major interest for alcohol-dependence. However, baclofen has many potentially dangerous side effects, and the maximal dose of baclofen that may be used is a matter of discussion. Here, the author analyses the medical charts of the last 100 patients seen in his clinic, 17 of whom have been taking a very high dose of baclofen, that is to say, more than 300mg per day. The analysis of the charts shows that the very high doses baclofen were justified in almost all the cases. Side effects are analyzed

Concept of a laser-plasma based electron source for sub-10 fs electron diffraction

We propose a new concept of an electron source for ultrafast electron diffraction with sub-10~fs temporal resolution. Electrons are generated in a laser-plasma accelerator, able to deliver femtosecond electron bunches at 5 MeV energy with kHz repetition rate. The possibility of producing this electron source is demonstrated using Particle-In-Cell simulations. We then use particle tracking simulations to show that this electron beam can be transported and manipulated in a realistic beamline, in order to reach parameters suitable for electron diffraction. The beamline consists of realistic static magnetic optics and introduces no temporal jitter. We demonstrate numerically that electron bunches with 5~fs duration and containing 1.5~fC per bunch can be produced, with a transverse coherence length exceeding 2~nm, as required for electron diffraction

Signal epidetection in third-harmonic generation microscopy of turbid media

International audienceThird-harmonic generation (THG) imaging of thick samples or large organisms requires TH light to be epicollected through the focusing objective. In this study we first estimate the amount of backward-to-forward TH radiation created by an isolated object as a function of size and spatial frequencies in the object. Theory and model experiments indicate that no significant signal can be epidetected from a (biological) dielectric structure embedded in a transparent medium. In contrast, backward emission is observed from metal nanoparticles where THG is partly a surface effect. We then address the case of an object embedded in a turbid medium. Experiments and Monte Carlo simulations show that epidetection is possible when the absorption mean free path of harmonic light in the medium exceeds its reduced scattering length, and that epicollection efficiency critically depends on the microscope field-of-view even at shallow depths, because backscattered light is essentially diffusive. These observations provide guidelines for optimizing epidetection in third-harmonic, second-harmonic, or CARS imaging of thick tissues

Accuracy of correction in modal sensorless adaptive optics.

International audienceWe investigate theoretically and experimentally the parameters governing the accuracy of correction in modal sensorless adaptive optics for microscopy. On the example of two-photon fluorescence imaging, we show that using a suitable number of measurements, precise correction can be obtained for up to 2 radians rms aberrations without optimising the aberration modes used for correction. We also investigate the number of photons required for accurate correction when signal acquisition is shot-noise limited. We show that only 10(4) to 10(5) photons are required for complete correction so that the correction process can be implemented with limited extra-illumination and associated photoperturbation. Finally, we provide guidelines for implementing an optimal correction algorithm depending on the experimental conditions

Dynamic aberration correction for multiharmonic microscopy.

International audienceWe demonstrate image-based aberration correction in a third-harmonic generation (THG) microscope. We describe a robust, mostly sample-independent correction scheme relying on prior measurement of the influence of aberration modes produced by a deformable mirror on the quality of THG images. We find that using image sharpness as an image quality metric, correction of N aberration modes is achieved using 2(2N+1) measurements in a variety of samples. We also report aberration correction in combined multiharmonic and two-photon excited fluorescence experiments. Finally, we demonstrate time-dependent adaptive THG imaging in developing embryonic tissue

A Bayesian model updating procedure for dynamic health monitoring

Structures under dynamic excitation can undergo phenomena of crack growth and fracture. For safety reasons, it is of key importance to be able to detect and classify these cracks before the unwarned structural failure. Additionally, the cracks will also change the dynamic behaviour of the structures, impacting their performance. Here, a Bayesian model updating procedure has been implemented for the crack detection location and length estimation on a numerical model of a spring suspension arm. A highfidelity finite element model has been used to simulate experimental data, by inserting cracks of different extent at different locations and obtaining reference frequency response functions. In the following, a low fidelity parametric model has been used in the Bayesian framework to infer the crack location and length by comparing the dynamic responses. It is shown that the proposed methodology can be successfully adopted as a structural health monitoring tool

Structure sensitivity in third-harmonic generation microscopy

International audienceWe characterize experimentally the influence of sample structure and beam focusing on signal level in third-harmonic generation (THG) microscopy. In the case of a homogeneous spherical sample, the dependence of the signal on the size of the sphere can be controlled by modifying the Rayleigh length of the excitation beam. More generally, the influence of excitation focusing on the signal depends on sample geometry, allowing one to highlight certain structures within a complex system. We illustrate this point by focusing-based contrast modulation in THG images of Drosophila embryos

Fourier-transform coherent anti-Stokes Raman scattering microscopy.

International audienceWe report a novel Fourier-transform-based implementation of coherent anti-Stokes Raman scattering (CARS) microscopy. The method employs a single femtosecond laser source and a Michelson interferometer to create two pulse replicas that are fed into a scanning multiphoton microscope. By varying the time delay between the pulses, we time-resolve the CARS signal, permitting easy removal of the nonresonant background while providing high resolution, spectrally resolved images of CARS modes over the laser bandwidth (approximately 1500 cm(-1)). We demonstrate the method by imaging polystyrene beads in solvent