A randomized phase III trial in patients with recurrent platinum sensitive ovarian cancer comparing efficacy and safety of paclitaxel micellar and Cremophor EL-paclitaxel.

OBJECTIVE: Paclitaxel micellar was developed to avoid Cremophor-EL (Cr-EL) associated dose limiting toxicity and to allow a shorter infusion time. The efficacy and safety of paclitaxel micellar (+carboplatin) was compared to Cr-EL paclitaxel (+carboplatin) in recurrent platinum-sensitive ovarian, fallopian tube or peritoneal carcinoma. METHODS: This was a multicentre, open-label, randomized phase III trial. Adult patients with recurrent disease was assigned to six 3-week cycles of paclitaxel micellar (250 mg/m2) administered as 1-h infusion or Cr-EL paclitaxel (175 mg/m2) as 3-h infusion. Both arms received carboplatin (AUC 5-6). Primary objective was non-inferiority for progression free survival (PFS) using computed tomography scans. Overall survival (OS) was included as secondary endpoint. RESULTS: Between 2009 and 2013, 789 patients were randomized to receive experimental (N = 397) or control (N = 392) treatment. PFS for paclitaxel micellar was non-inferior to Cr-EL paclitaxel with a hazard ratio of 0.86 (95% CI: 0.72;1.03) in the per protocol population (PP), favouring paclitaxel micellar (non-inferiority margin was 1.2). Non-inferiority of OS was shown in the PP population with a hazard ratio of 0.95 (95% CI: 0.78; 1.16), favouring paclitaxel micellar (non-inferiority margin was 1.185). The most common adverse event was neutropenia (grade ≥ 3); 245 patients (79%) for paclitaxel micellar vs 213 patients (66%) for Cr-EL paclitaxel. The frequency of peripheral sensory neuropathy (any grade) was similar between the arms; 16% for paclitaxel micellar and 20% for Cr-EL paclitaxel. CONCLUSION: Paclitaxel micellar (+ carboplatin) is non-inferior to Cr-EL paclitaxel (+ carboplatin) in terms of PFS and OS in the studied population. It provides a treatment option of a higher paclitaxel dose with a shorter infusion time without mandatory premedication. TRIAL REGISTRATION NUMBER: 2008-002668-32 (EudraCT), NCT00989131 (ClinicalTrials.gov).

Direct imaging and manipulation of ionic diffusion in mixed electronic-ionic conductors.

Next generation Li-ion batteries require improved energy densities, power output and safety to satisfy the demands of emerging technologies. All solid state 3D thin-film batteries (ASB) based on nanoionics are considered as frontrunners to enable all this. In order to facilitate the introduction of this new architecture, a homogeneous electrochemical activity and a high ionic diffusivity of the electrodes is key. However, nanometer-resolved techniques to probe structural, electrical and electrochemical properties of the battery components are still limited. Here we propose a study that combines conductive atomic force microscopy (C-AFM) and secondary ion mass spectrometry (SIMS) for structural and electrical characterization. In addition, a novel concept called ion-modulated C-AFM (imC-AFM) is introduced to also sense the electrochemical activity of ions in confined volumes. Using the aforementioned methodologies, LixMn2O4 thin film cathodes are studied observing: (1) a direct correlation between electrical conductivity and local chemistry. (2) A non-uniform Li-ion electrochemical activity (i.e. ionic conductivity) on the cathode's surface with a clear enhancement in grain boundaries (GBs). Finally, (3) imC-AFM observes a high volume expansion associated with high Li incorporation. This work introduces a novel pathway for the rapid analysis of materials to be used in ASB.

Wet-chemical etching of atom probe tips for artefact free analyses of nanoscaled semiconductor structures.

We introduce an innovative specimen preparation method employing the selectivity of a wet-chemical etching step to improve data quality and success rates in the atom probe analysis of contemporary semiconductor devices. Firstly, on the example of an SiGe fin embedded in SiO2 we demonstrate how the selective removal of SiO2 from the final APT specimen significantly improves accuracy and reliability of the reconstructed data. With the oxide removal, we eliminate the origin of shape artefacts, i.e. the formation of a non-hemispherical tip shape, that are typically observed in the reconstructed volume of complex systems. Secondly, using the same approach, we increase success rates to ∼90% for the damage-free, 3D site-specific localization of short (250 nm), vertical Si nanowires at the specimen apex. The impact of the abrupt emitter radius change that is introduced by this specimen preparation method is evaluated as being minor using field evaporation simulation and comparison of different reconstruction schemes. The Ge content within the SiGe fin as well as the 3D boron distribution in the Si NW as resolved by atom probe analysis are in good agreement with TEM/EDS and ToF-SIMS analysis, respectively.

Nucleation and growth mechanisms of Al2O3 atomic layerdeposition on synthetic polycrystalline MoS2.

Two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs) are of great interest for applications in nano-electronic devices. Their incorporation requires the deposition of nm-thin and continuous high-k dielectric layers on the 2D TMDs. Atomic layer deposition (ALD) of high-k dielectric layers is well established on Si surfaces: the importance of a high nucleation density for rapid layer closure is well known and the nucleation mechanisms have been thoroughly investigated. In contrast, the nucleation of ALD on 2D TMD surfaces is less well understood and a quantitative analysis of the deposition process is lacking. Therefore, in this work, we investigate the growth of Al2O3 (using Al(CH3)3/H2O ALD) on MoS2 whereby we attempt to provide a complete insight into the use of several complementary characterization techniques, including X-ray photo-electron spectroscopy, elastic recoil detection analysis, scanning electron microscopy, and time-of-flight secondary ion mass spectrometry. To reveal the inherent reactivity of MoS2, we exclude the impact of surface contamination from a transfer process by direct Al2O3 deposition on synthetic MoS2 layers obtained by a high temperature sulfurization process. It is shown that Al2O3 ALD on the MoS2 surface is strongly inhibited at temperatures between 125°C and 300°C, with no growth occurring on MoS2 crystal basal planes and selective nucleation only at line defects or grain boundaries at MoS2 top surface. During further deposition, the as-formed Al2O3 nano-ribbons grow in both vertical and lateral directions. Eventually, a continuous Al2O3 film is obtained by lateral growth over the MoS2 crystal basal plane, with the point of layer closure determined by the grain size at the MoS2 top surface and the lateral growth rate. The created Al2O3/MoS2 interface consists mainly of van der Waals interactions. The nucleation is improved by contributions of reversible adsorption on the MoS2 basal planes by using low deposition temperature in combination with short purge times. While this results in a more two-dimensional growth, additional H and C impurities are incorporated in the Al2O3 layers. To conclude, our growth study reveals that the inherent reactivity of the MoS2 basal plane for ALD is extremely low, and this confirms the need for functionalization methods of the TMD surface to enable ALD nucleation.

Identification of the in vivo elastic properties of common carotid arteries from MRI: a study on subjects with and without atherosclerosis.

The stiffness of the arterial wall, which is modified by many cardiovascular diseases such as atherosclerosis, is known to be an indicator of vulnerability. This work focuses on the in vivo quantification of the stiffness of the common carotid artery (CCA) by applying the Magnitude Based Finite Element Model Updating (MB-FEMU) method to 13 healthy and diseased volunteers aged from 24 to 76 years old. The MB-FEMU method is based on the minimisation of the deviation between the image of a deformed artery and a registered image of this artery deformed by means of a finite elements analysis. Cross sections of the neck of each subject at different times of the cardiac cycle are recorded using a Phase Contrast cine-MRI. Applanation tonometry is then performed to obtain the blood pressure variations in the CCA throughout a heart beat. First, a time averaged elastic modulus of each CCA between diastole and systole is identified and a stiffening of the artery with age and disease is observed. Second, four elastic moduli are identified during a single heart beat for each artery, highlighting the nonlinear mechanical behaviour of the artery. A stiffening of the artery is observed and quantified at systole in comparison to diastole.

First record of the rare species Aeromonas culicicola from a drinking water supply.

We describe the recovery of the rare species Aeromonas culicicola, so far known only in mosquitoes in India, from a drinking water supply in Spain. Typing, using enterobacterial repetitive intergenic consensus-PCR, revealed that the 27 new isolates belonged to 3 very closely related strains. These strains were genetically identified by 16S rRNA gene sequencing. Spanish strains differed from the mosquito strains in three nucleotide positions. The AHCYTOEN gene was present in these water strains, which may have a public health significance.

[Sandhoff disease]. / Enfermedad de Sandhoff.

A new case of Sandhoff disease is presented (gangliosidosis GM2 type II or variant O) with enzymatic study in serum and leukocytes from the patient, as well as in serum from the newborn's, father and mother. The clinical expression, enzymatic study and evolution are discussed comparing them with Tay-Sachs disease (gangliosidosis GM2 type I o variant B).