An optoelectronic implantable neurostimulation platform allowing full MRI safety and optical sensing and communication.

A novel programmable implantable neurostimulation platform based on photonic power transfer has been developed for various clinical applications with the main focus of being safe to use with MRI scanners. The wires usually conveying electrical current from the neurostimulator to the electrodes are replaced by optical fibers. Photovoltaic cells at the tip of the fibers convert laser light to biphasic electrical impulses together with feedback signals with 54% efficiency. Furthermore, a biocompatible, implantable and ultra-flexible optical lead was developed including custom optical fibers. The neurostimulator platform incorporates advanced signal processing and optical physiological sensing capabilities thanks to a hermetically sealed transparent nonmetallic casing. Skin transparency also allowed the development of a high-speed optical transcutaneous communication channel. This implantable neurostimulation platform was first adapted to a vagus nerve stimulator for the treatment of epilepsy. This neurostimulator has been designed to fulfill the requirements of a class III long-term implantable medical device. It has been proven compliant with standard ISO/TS10974 for 1.5 T and 3 T MRI scanners. The device poses no related threat and patients can safely undergo MRI without specific or additional precautions. Especially, the RF induced heating near the implant remains below 2 °C whatever the MRI settings used. The main features of this unique advanced neurostimulator and its architecture are presented. Its functional performance is evaluated, and results are described with a focus on optoelectronics aspects and MRI safety.

Effects of Polyethylenimine and Its Molecular Weight on the Chemical Bath Deposition of ZnO Nanowires.

The addition of polyethylenimine (PEI) in the standard chemical bath deposition (CBD) of ZnO nanowires has received an increasing interest for monitoring their aspect ratio, but the physicochemical processes at work are still under debate. To address this issue, the effects of PEI are disentangled from the effects of ammonia and investigated over a broad range of molecular weight (i.e., chain length) and concentration, varying from 1300 to 750 000 and from 1.5 to 10 mM, respectively. It is shown that the addition of PEI strongly favors the elongation of ZnO nanowires by suppressing the homogeneous growth at the benefit of the heterogeneous growth as well as by changing the supersaturation level through a pH modification. PEI is further found to inhibit the development of the sidewalls of ZnO nanowires by adsorbing on their nonpolar m-planes, as supported by Raman scattering analysis. The inhibition proceeds even in the low pH range, which somehow rules out the present involvement of electrostatic interactions as the dominant mechanism for the adsorption. Furthermore, it is revealed that PEI drastically affects the nucleation process of ZnO nanowires on the polycrystalline ZnO seed layer by presumably adsorbing on the nanoparticles oriented with the m-planes parallel to the surface, reducing in turn their nucleation rate as well as inducing a significant vertical misalignment. These findings, specifically showing the effects of the PEI molecular weight and concentration, cast light onto its multiple roles in the CBD of ZnO nanowires.

Progression-free survival, overall survival and quality of life: What is their medicoeconomic importance in oncology?

Medico-economic evaluations estimate, for a given health technology, the added cost and the clinical benefit compared to a reference strategy. The objective here is to analyze the criteria used to measure clinical benefit as the basis for market access and reimbursement decisions for drugs in oncology both in France and in Europe. Prolonged overall survival is the criterion of choice to demonstrate the benefit of an anticancer drug; a survival gain of 2 to 3 months or more would be considered as relevant for a new product versus the comparator. In the absence of survival benefit or mature data on survival, progression-free survival or symptom-free survival and the availability of alternative curative treatments, decrease in drug toxicity and quality of life improvement may be considered. Differences in clinical benefit assessment between regulatory agencies and payers are not specific to France. Case studies show that it is difficult to find a consistency in reimbursement and pricing decisions and to identify factors that may fully explain reimbursement decisions when survival benefit is not demonstrated.

Sub-10 nm Silicon Nanopillar Fabrication Using Fast and Brushless Thermal Assembly of PS-b-PDMS Diblock Copolymer.

A new approach to obtaining spherical nanodomains using polystyrene-block-polydimethylsiloxane (PS-b-PDMS) is proposed. To reduce drastically the process time, we blended a copolymer with cylindrical morphology with a PS homopolymer. Adding PS homopolymer into a low-molar-mass cylindrical morphology PS-b-PDMS system drives it toward a spherical morphology. Besides, by controlling the as-spun state, spherical PDMS nanodomains could be kept and thermally arranged. This PS-homopolymer addition allows not only an efficient, purely thermal arrangement process of spheres but also the ability to work directly on nontreated silicon substrates. Indeed, as shown by STEM measurements, no PS brush surface treatment was necessary in our study to avoid a PDMS wetting layer at the interface with the Si substrate. Our approach was compared to a sphere-forming diblock copolymer, which needs a longer thermal annealing. Furthermore, GISAXS measurements provided complete information on PDMS sphere features. Excellent long-range order spherical microdomains were therefore produced on flat surfaces and inside graphoepitaxy trenches with a period of 21 nm, as were in-plane spheres with a diameter of 8 nm with a 15 min thermal annealing. Finally, direct plasma-etching transfer into the silicon substrate was demonstrated, and 20 nm high silicon nanopillars were obtained, which are very promising results for various nanopatterning applications.

Physical properties of annealed ZnO nanowire/CuSCN heterojunctions for self-powered UV photodetectors.

The low-cost fabrication of ZnO nanowire/CuSCN heterojunctions is demonstrated by combining chemical bath deposition with impregnation techniques. The ZnO nanowire arrays are completely filled by the CuSCN layer from their bottoms to their tops. The CuSCN layer is formed of columnar grains that are strongly oriented along the [003] direction owing to the polymeric form of the ß-rhombohedral crystalline phase. Importantly, an annealing step is found essential in a fairly narrow range of low temperatures, not only for outgassing the solvent from the CuSCN layer, but also for reducing the density of interfacial defects. The resulting electrical properties of annealed ZnO nanowire/CuSCN heterojunctions are strongly improved: a maximum rectification ratio of 2644 at ±2 V is achieved following annealing at 150 °C under air atmosphere, which is related to a strong decrease in the reverse current density. Interestingly, the corresponding self-powered UV photodetectors exhibit a responsivity of 0.02 A/W at zero bias and at 370 nm with a UV-to-visible (370-500 nm) rejection ratio of 100 under an irradiance of 100 mW/cm(2). The UV selectivity at 370 nm can also be readily modulated by tuning the length of ZnO nanowires. Eventually, a significant photovoltaic effect is revealed for this type of heterojunctions, leading to an open circuit voltage of 37 mV and a short circuit current density of 51 µA/cm(2), which may be useful for the self-powering of the complete device. These findings show the underlying physical mechanisms at work in ZnO nanowire/CuSCN heterojunctions and reveal their high potential as self-powered UV photodetectors.

Improvement of the physical properties of ZnO/CdTe core-shell nanowire arrays by CdCl2 heat treatment for solar cells.

CdTe is an important compound semiconductor for solar cells, and its use in nanowire-based heterostructures may become a critical requirement, owing to the potential scarcity of tellurium. The effects of the CdCl2 heat treatment are investigated on the physical properties of vertically aligned ZnO/CdTe core-shell nanowire arrays grown by combining chemical bath deposition with close space sublimation. It is found that recrystallization phenomena are induced by the CdCl2 heat treatment in the CdTe shell composed of nanograins: its crystallinity is improved while grain growth and texture randomization occur. The presence of a tellurium crystalline phase that may decorate grain boundaries is also revealed. The CdCl2 heat treatment further favors the chlorine doping of the CdTe shell with the formation of chlorine A-centers and can result in the passivation of grain boundaries. The absorption properties of ZnO/CdTe core-shell nanowire arrays are highly efficient, and more than 80% of the incident light can be absorbed in the spectral range of the solar irradiance. The resulting photovoltaic properties of solar cells made from ZnO/CdTe core-shell nanowire arrays covered with CuSCN/Au back-side contact are also improved after the CdCl2 heat treatment. However, recombination and trap phenomena are expected to operate, and the collection of the holes that are mainly photo-generated in the CdTe shell from the CuSCN/Au back-side contact is presumably identified as the main critical point in these solar cells.

Sulfonated macro-RAFT agents for the surfactant-free synthesis of cerium oxide-based hybrid latexes.

Three types of amphiphatic macro-RAFT agents were employed as compatibilizers to promote the polymerization reaction at the surface of nanoceria for the synthesis of CeO2-based hybrid latexes. Macro-RAFT copolymers and terpolymers were first synthesized employing various combinations of butyl acrylate as a hydrophobic monomer and acrylic acid (AA) and/or 2-acrylamido-2-methylpropane sulfonic acid (AMPS) as hydrophilic monomers. After characterizing the adsorption of these macro-RAFT agents at the cerium oxide surface by UV-visible spectrometry, emulsion copolymerization reactions of styrene and methyl acrylate were then carried out in the presence of the surface-modified nanoceria. Dynamic Light Scattering and cryo-Transmission Electron Microscopy were employed to confirm the hybrid structure of the final CeO2/polymer latexes, and proved that the presence of acrylic acid units in amphiphatic macro-RAFT agents enabled an efficient formation of hybrid structures, while the presence of AMPS units, when combined with AA units, resulted in a better distribution of cerium oxide nanoclusters between latex particles.

An emulsifier-free RAFT-mediated process for the efficient synthesis of cerium oxide/polymer hybrid latexes.

Hybrid latexes based on cerium oxide nanoparticles are synthesized via an emulsifier-free process of emulsion polymerization employing amphiphatic macro-RAFT agents. Poly(butyl acrylate-co-acrylic acid) random oligomers of various compositions and chain lengths are first obtained by RAFT copolymerization in the presence of a trithiocarbonate as controlling agent. In a second step, the seeded emulsion copolymerization of styrene and methyl acrylate is carried out in the presence of nanoceria with macro-RAFT agents adsorbed at their surface, resulting in a high incorporation efficiency of cerium oxide nanoparticles in the final hybrid latexes, as evidenced by cryo-transmission electron microscopy.

Results of a phase I trial of intravenous vinorelbine plus oral capecitabine as first-line chemotherapy of metastatic breast cancer.

The management of metastatic breast cancer becomes increasingly intricate, requiring new drugs and combinations. We present here the results of a phase I study evaluating the maximal tolerated dose of vinorelbine combined with capecitabine as first-line chemotherapy. Vinorelbine was administered intravenously on days 1 and 15, and capecitabine was given orally twice daily from day 1 to 14 (three cycles every 21 days). Three out of six patients receiving vinorelbine at 25mg/m2/day and capecitabine at 2000 mg/m2/day presented with a dose-limiting toxicity, consisting of protracted grade 3 neutropenia, hand-foot syndrome and/or liver test disturbances. Despite of a dose reduction in vinorelbine (20mg/m2/day), one patient among four developed a dose-limiting febrile neutropenia. This regimen cannot be recommended as first-line treatment of metastatic breast cancer. These findings are not in agreement with previous publications of this schedule, or with promising results using both drugs orally.