[Digital and territorial health inequalities: The online sale of drugs, a new tool in the face of a possible pharmacy shortage?] / Numérique et inégalités territoriales de santé : la vente en ligne de médicaments, nouvel outil face à une pénurie éventuelle de pharmacies ?

When it comes to thinking about the links that the digital question territorial inequalities and patient rights can have, a question arises quite naturally beyond just telemedicine: the online sale of drugs and its impact on a potentially insufficient pharmacy supply. This contribution therefore proposes to study the reality of this effect in favor of the right of access to healthcare. Two key ideas emerge: not only, despite appearances, this online sale can produce little effect to compensate for a lack of supply, but, what is more, this mode of sale causes indirect effects quite negative for patients and public health.

Test of the Einstein Equivalence Principle near the Galactic Center Supermassive Black Hole.

During its orbit around the four million solar mass black hole Sagittarius A* the star S2 experiences significant changes in gravitational potential. We use this change of potential to test one part of the Einstein equivalence principle: the local position invariance (LPI). We study the dependency of different atomic transitions on the gravitational potential to give an upper limit on violations of the LPI. This is done by separately measuring the redshift from hydrogen and helium absorption lines in the stellar spectrum during its closest approach to the black hole. For this measurement we use radial velocity data from 2015 to 2018 and combine it with the gravitational potential at the position of S2, which is calculated from the precisely known orbit of S2 around the black hole. This results in a limit on a violation of the LPI of |ß_{He}-ß_{H}|=(2.4±5.1)×10^{-2}. The variation in potential that we probe with this measurement is six magnitudes larger than possible for measurements on Earth, and a factor of 10 larger than in experiments using white dwarfs. We are therefore testing the LPI in a regime where it has not been tested before.

Analytical expression of long-exposure adaptive-optics-corrected coronagraphic image. First application to exoplanet detection.

In this paper we derive an analytical model of a long-exposure star image for an adaptive-optics(AO)-corrected coronagraphic imaging system. This expression accounts for static aberrations upstream and downstream of the coronagraphic mask as well as turbulence residuals. It is based on the perfect coronagraph model. The analytical model is validated by means of simulations using the design and parameters of the SPHERE instrument. The analytical model is also compared to a simulated four-quadrant phase-mask coronagraph. Then, its sensitivity to a miscalibration of structure function and upstream static aberrations is studied, and the impact on exoplanet detectability is quantified. Last, a first inversion method is presented for a simulation case using a single monochromatic image with no reference. The obtained result shows a planet detectability increase by two orders of magnitude with respect to the raw image. This analytical model presents numerous potential applications in coronographic imaging, such as exoplanet direct detection, and circumstellar disk observation.

High-order adaptive optics requirements for direct detection of extrasolar planets: Application to the SPHERE instrument.

The detection of extrasolar planets implies an extremely high-contrast, long-exposure imaging capability at near infrared and probably visible wavelengths. We present here the core of any Planet Finder instrument, that is, the extreme adaptive optics (XAO) subsystem. The level of AO correction directly impacts the exposure time required for planet detection. In addition, the capacity of the AO system to calibrate all the instrument static defects ultimately limits detectivity. Hence, the extreme AO system has to adjust for the perturbations induced by the atmospheric turbulence, as well as for the internal aberrations of the instrument itself. We propose a feasibility study for an extreme AO system in the frame of the SPHERE (Spectro-Polarimetry High-contrast Exoplanet Research) instrument, which is currently under design and should equip one of the four VLT 8-m telescopes in 2010.

Closed-loop experimental validation of the spatially filtered Shack-Hartmann concept.

An experimental validation of the spatially filtered Shack-Hartmann concept (F-SH) is presented that allows aliasing effects to be decreased. This effect is studied by use of an adaptive optical testbed with a focal plane pinhole in front of the wave-front sensor. First, the ability to close the loop on turbulence is demonstrated. Then the performance gain conferred by the device is quantified and compared with end-to-end simulation results. Another property of the F-SH concept, i.e., the reduction of the waffle modes, is highlighted.

Improvement of Shack-Hartmann wave-front sensor measurement for extreme adaptive optics.

The development of high-performance adaptive optics systems requires the optimization of wave-front sensors (WFSs) working in the high-order correction regime. We propose a new method to improve the wave-front slope estimation of a Shack-Hartmann WFS in such a regime. Based on a detailed analysis of the different errors in the slope estimation with a classical centroid and with the new method, the gain in terms of wave-front-sensing accuracy in both the detector and the photon noise regimes is stressed. This improvement is proposed without major system disruption.

A star in a 15.2-year orbit around the supermassive black hole at the centre of the Milky Way.

Many galaxies are thought to have supermassive black holes at their centres-more than a million times the mass of the Sun. Measurements of stellar velocities and the discovery of variable X-ray emission have provided strong evidence in favour of such a black hole at the centre of the Milky Way, but have hitherto been unable to rule out conclusively the presence of alternative concentrations of mass. Here we report ten years of high-resolution astrometric imaging that allows us to trace two-thirds of the orbit of the star currently closest to the compact radio source (and massive black-hole candidate) Sagittarius A*. The observations, which include both pericentre and apocentre passages, show that the star is on a bound, highly elliptical keplerian orbit around Sgr A*, with an orbital period of 15.2 years and a pericentre distance of only 17 light hours. The orbit with the best fit to the observations requires a central point mass of (3.7 +/- 1.5) x 10(6) solar masses (M(*)). The data no longer allow for a central mass composed of a dense cluster of dark stellar objects or a ball of massive, degenerate fermions.

Optimal wave-front reconstruction strategies for multiconjugate adaptive optics.

We propose an optimal approach for the phase reconstruction in a large field of view (FOV) for multiconjugate adaptive optics. This optimal approach is based on a minimum-mean-square-error estimator that minimizes the mean residual phase variance in the FOV of interest. It accounts for the C2n profile in order to optimally estimate the correction wave front to be applied to each deformable mirror (DM). This optimal approach also accounts for the fact that the number of DMs will always be smaller than the number of turbulent layers, since the C2n profile is a continuous function of the altitude h. Links between this optimal approach and a tomographic reconstruction of the turbulence volume are established. In particular, it is shown that the optimal approach consists of a full tomographic reconstruction of the turbulence volume followed by a projection onto the DMs accounting for the considered FOV of interest. The case where the turbulent layers are assumed to match the mirror positions [model-approximation (MA) approach], which might be a crude approximation, is also considered for comparison. This MA approach will rely on the notion of equivalent turbulent layers. A comparison between the optimal and MA approaches is proposed. It is shown that the optimal approach provides very good performance even with a small number of DMs (typically, one or two). For instance, good Strehl ratios (greater than 20%) are obtained for a 4-m telescope on a 150-arc sec x 150-arc sec FOV by using only three guide stars and two DMs.

Myopic deconvolution of adaptive optics images by use of object and point-spread function power spectra: reply to comment.

Partial correction in adaptive optics (AO) is well understood now. This partial correction is due to the limitations of the AO system performance, which leaves residual phase fluctuations in the instrument pupil. Knowledge of these residuals allows the optical transfer function (OTF) of the high-angular-resolution imaging system to be estimated accurately. Therefore, light scattering by aerosols cannot be invoked to justify the shape of an AO partial-correction OTF in astronomical conditions. The light scattering does not modify the high-angular-resolution OTF but merely contributes to a slight increase of the sky background.

Sky implementation of modal predictive control in adaptive optics.

We present what we believe are the first experimental results obtained with modal linear predictive control of an adaptive optics system operating on sky at a visible wavelength on a 1.52-m telescope (Observatoire de Haute-Provence, France). This system yields substantially better results than optimized integral control: a 30% relative gain in Strehl ratio is measured, even in conditions of low wind speed.

Efficient phase estimation for large-field-of-view adaptive optics.

We propose a maximum a posteriori-based estimation of the turbulent phase in a large field of view (FOV) to overcome the anisoplanatism limitation in adaptive optics. We show that, whatever the true atmospheric profile, a small number of equivalent layers (two or three) is required for accurate restoration of the phase in the whole FOV. The implications for multiconjugate adaptive optics are discussed in terms of the number and conjugated heights of the deformable mirrors. The number of guide stars required for wave-front measurements in the field is also discussed: three (or even two) guide stars are sufficient to produce good performance.

Noise propagation in wave-front sensing with phase diversity.

The phase diversity technique is studied as a wave-front sensor to be implemented with widely extended sources. The wave-front phase expanded on the Zernike polynomials is estimated from a pair of images (in focus and out of focus) by use of a maximum-likelihood approach. The propagation of the photon noise in the images on the estimated phase is derived from a theoretical analysis. The covariance matrix of the phase estimator is calculated, and the optimal distance between the observation planes that minimizes the noise propagation is determined. The phase error is inversely proportional to the number of photons in the images. The noise variance on the Zernike polynomials increases with the order of the polynomial. These results are confirmed with both numerical and experimental validations. The influence of the spectral bandwidth on the phase estimator is also studied with simulations.

Myopic deconvolution of adaptive optics images by use of object and point-spread function power spectra.

Adaptive optics systems provide a real-time compensation for atmospheric turbulence. However, the correction is often only partial, and a deconvolution is required for reaching the diffraction limit. The need for a regularized deconvolution is discussed, and such a deconvolution technique is presented. This technique incorporates a positivity constraint and some a priori knowledge of the object (an estimate of its local mean and a model for its power spectral density). This method is then extended to the case of an unknown point-spread function, still taking advantage of similar a priori information on the point-spread function. Deconvolution results are presented for both simulated and experimental data.

Optimization of a predictive controller for closed-loop adaptive optics.

For closed-loop adaptive optics systems limited by time delay and measurement noise, we demonstrate that the ideal rejection transfer function is proportional to the frequency signal-to-noise ratio of the wave-front input. We describe a new modal linear predictive controller that approaches this ideal transfer function. Its parameters are optimized by minimization of the residual wave-front error with a modified recursive least-squares algorithm. The optimization can be performed with closed-loop data in the case of evolving turbulent conditions. We present numerical simulations to show the significant improvements brought by the predictor.

Encapsulation of all-trans retinoic acid into wheat ceramides micro vesicles enhanced influence on collagenase and tissue inhibitor of metalloproteinase-1 production by human skin fibroblasts.

The influence of all-trans retinoic acid (RA), either in its free or encapsulated form into wheat ceramides (CER), on the production of collagenase (MMP-1), and tissue inhibitor of metalloproteinase (TIMP-1) by human skin fibroblasts (HSF) at early and late stages of their proliferative life span (PLS) was examined. The level of MMP-1 was elevated and that of TIMP-1 decreased in late as compared to early passage cells. All-trans retinoic acid significantly decreased and increased the secretions of MMP-1 and TIMP-1 respectively, in a dose-dependent manner, from 10-7 m to 10-5 m. Entrapment of RA into CER vesicles potentiated its effect on MMP-1 and TIMP-1 secretions by HSF, independently of cell passages. The extent of variations obtained on MMP-1 and TIMP-1 levels, when HSF culture medium was supplemented with 10-5 m RA, could be obtained using a 100-fold lower concentration of RA encapsulated into CER vesicles. CER had no effect on TIMP-1 and MMP production by HSF in culture, and simultaneous addition of CER and RA did not potentiate the effects of RA alone, indicating that formation of RA-CER liposomes was responsible for the enhancing effects. The rate of internalization of RA into HSF was increased when used in its CER encapsulated form. Therefore, the use of retinoid within CER potentiates its beneficial influence on the MMP-1:TIMP-1 imbalance with fibroblastageing.

Modal prediction for closed-loop adaptive optics.

The correction efficiency of adaptive optics is limited mainly by measurement noise and time delay. To overcome this problem, we describe a new modal linear predictive controller whose parameters are optimized by means of a recursive least-squares algorithm to minimize the residual optical phase variance. The method copes with the recursivity of the closed-loop operation. We demonstrate that the optimal rejection transfer function for adaptive optics is proportional to the frequency signal-to-noise ratio. Finally, we present what we believe to be the first experimental results obtained with a predictor used to control the tip-tilt mirror of an adaptive-optics system.

Increase of singlet oxygen protection of erythrocytes by vitamin E, vitamin C, and beta carotene intakes.

Substantial evidence supports the theory that free radicals, especially oxygen radicals, are involved in the process of aging. The human organisms have two ways to fight them: an enzymatic way with enzymatic intervention like superoxide dismutase, catalase... and a chemical way with the intervention of scavengers such as vitamins, cysteine, methionine, gluthatione... The aim of this work was to determine that an intakes of vitamins association: vitamin E, vitamin C and beta carotene induce an increase of singlet oxygen protection of erythrocytes' subjects. The method was based on the haemolytic effect of singlet oxygen which is generated by irradiation of hematoporphyrine at 365 nm, in 22 p. cent suspension of erythrocytes' subjects. Results show that a supply of beta carotene (15 or 30 mg/day), vitamin E (15 mg/day) and vitamin C (30 mg/day) involves an increase of singlet oxygen protection of erythrocytes of subjects. This protection appears very quickly after 15 days of treatment.

Inhibition of human neutrophil elastase by wheat ceramides.

Synopsis Ceramides, composed of sphingosine N-acyl linked to fatty acids have become widely used in cosmetology. They play several physiological roles in the regulation of skin barrier function. Human neutrophil elastase (HNE) can be inhibited by long-chain fatty acids and their derivatives; it was therefore postulated that plant ceramides could be inhibitors of HNE. Ceramides were extracted from wheat, isolated and characterized. The main fatty acids were 16:0, 18:1, 18:2 and the sphingoid moiety was phytosphingosine. Concentrations necessary to reach 50% inhibition of HNE were, respectively, 33 and 41 mug ml(-1) for non-glycosyl ceramides (CER) and glycosyl ceramides (gly-CER) when using a synthetic specific substrate. Similar extents of inhibition were obtained using a physiological substrate, insoluble elastin. Ex vivo studies showed that CER protected human skin elastic fibres against HNE degradation. Ceramides, being natural non-toxic substances, besides their role in cosmetics, could be of pharmacological interest in dermal inflammatory disorders.

Influence of beta carotene, vitamin E, and vitamin C on endogenous antioxidant defenses in erythrocytes.

OBJECTIVE: To evaluate the in vivo radical scavenger activity of vitamin E, vitamin C, and beta carotene on erythrocyte membranes. DESIGN: A prospective, open trial without placebo. SETTING: Department of Clinical Pharmacy. PATIENTS: Ten healthy volunteers being supplemented with beta carotene, vitamin E, and vitamin C. MEASUREMENTS: Erythrocytes were incubated in water bath with 2,2' azobis (2 amidinopropane) hydrochloride (AAPH). AAPH decomposes spontaneously at 37 degrees C to generate free radicals inducing membrane cellular damage and hemolysis. The absorbance was measured at 405 nm at 0, 30, and 60 min, and then every 20 minutes for four hours. The time for 50 percent of maximal hemolysis (T50%), which expresses the radical scavenger activity of erythrocytes, was determined. RESULTS: The physiologic T50% value determined in 52 healthy volunteers is 117 +/- 12 min. Patients receiving these supplements have a higher value of T50% (143.2 +/- 11.6 min at 30 d and 145.7 +/- 10.5 min at 60 d) than the physiologic value (p < 0.001). CONCLUSIONS: These data suggest that vitamin C, vitamin E, and beta carotene stimulate the radical scavenger activity of erythrocyte membranes after 30 days.

Plasma concentrations of beta-carotene, vitamin A and vitamin E after beta-carotene and vitamin E intake.

We have studied the metabolism (absorption) of beta-carotene and vitamin E by assigning eleven volunteers to receive daily two capsules of OENOBIOL, each containing 15 mg of beta-carotene and 15 mg of vitamin E, over 60 days. The beta-carotene, vitamin E and vitamin A plasma levels were then determined using new methods developed in our laboratory. After two months, the actively treated group's median beta-carotene and vitamin E levels were significantly higher than those of a control group. However, no significant change between treated and control groups in the mean of vitamin A (retinol) plasma levels were observed. Treatment with beta-carotene, a vitamin A precursor, does not significantly modify the vitamin A levels. This conclusion had already been observed and it is assumed that a plasma level of beta-carotene equal or higher than 0.3 mg/L reflects a nutritional intake of provitamins sufficient to support homeostasis of retinol (Brubacher et al., 1982).