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Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510. Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60–1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69–1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77–1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. Ipsen.

In spray cleaning, a multitude of small drops, violently accelerated by a high-speed gas stream, strike a dirty surface. This process is extremely effective: very little dirt can resist it. This is true even for dirt particles whose characteristic size is less than 100 nm. Spray cleaning is classically modelled by balancing particle adhesion with either inertial stress or viscous shear near the surface, the latter being calculated using droplet size and velocity as the characteristic length and velocity. This results in dimensionless numbers that are often well below one, suggesting that the mechanical stress exerted on the surface by the drop impact that detaches the particle is not well captured. Using quantitative nanoscale measurements, we show that the remarkable efficiency of spray cleaning results from the forced spreading of each droplet on the surface, which generates an unsteady and inhomogeneous shear confined to a boundary layer entrained in the wake of the liquid–solid contact line. In the very first moments of impact, the boundary layer is extremely thin, yielding a gigantic stress: the contact line of the spreading droplets sweeps all the surface particles away. We propose a quantitative model of spray cleaning based on this unsteady surface stress, which agrees well with (i) experimental data obtained with spray droplets of $34\\ \\mathrm {\\mu }$m mean radius impacting the surface to be cleaned at a mean velocity ranging between 30 and 70 m s$^{-1}$ and contamination by nanoparticles of varying nature and shape and (ii) data in the literature on spray cleaning.

There is ample evidence for magnetic reconnection in the solar system, but it is a nontrivial task to visualize, to determine the proper approaches and frames to study, and in turn to elucidate the physical processes at work in reconnection regions from in-situ measurements of plasma particles and electromagnetic fields. Here an overview is given of a variety of single- and multi-spacecraft data analysis techniques that are key to revealing the context of in-situ observations of magnetic reconnection in space and for detecting and analyzing the diffusion regions where ions and/or electrons are demagnetized. We focus on recent advances in the era of the Magnetospheric Multiscale mission, which has made electron-scale, multi-point measurements of magnetic reconnection in and around Earth’s magnetosphere.

To assess the tolerance and potential nutritional consequences of long-term repeated doses of PEG 4000 (10 to 30 g/day) in elderly patients with chronic constipation as compared to lactulose (10-30 g/ day). Single blind, randomised, multicentre, parallel group comparative study. Community-dwelling patients and nursing homes residents aged 70 years and older with a history of chronic constipation. PEG 4000 (10-30 g/day) or lactulose (10-30 g/day) for six months. Clinical nutritional status (Mini Nutritional Assessment), blood and stool samples were taken at baseline and after three and six months for assay of nutritional and absorption parameters. A patient diary documented digestive symptoms and adverse events were recorded. Information on efficacy (stool frequency and consistency) was collected as a secondary outcome measure. Of the 316 patients screened, 245 eligible patients constituted the ITT population (PEG 4000: N = 118; lactulose group: N = 127). The proportion of patients receiving PEG 4000 with abnormal levels of electrolytes, nutritional markers or vitamins did not significantly change in the six months after initiating laxative treatment and do not differ between the two groups. After a D-xylose challenge test, the proportion of patients with abnormally low xylosaemia (suggesting malabsorption) varied from 24.6% at baseline to 35.8% after six months in the PEG 4000 group and from 29.1% to 42.4% in the lactulose group, with no significant between-group or within-group differences. The proportion of patients with poor nutritional status (MNA score <17) varied from 8.5% at baseline to 9.8% after 6 months in the PEG 4000 group and from 3.9% to 5.0% in the lactulose group. No changes in stool fat or total or soluble stool nitrogen were observed in the minority of patients for whom stool analysis was performed. A significantly higher stool frequency p <0.05) and improved stool consistency p <0.05) was observed in the PEG 4000 group compared to the lactulose group at each monthly evaluation period. After six months of treatment with PEG 4000, no clinically relevant changes in biochemical and nutritional parameters and no unanticipated treatment-related adverse events were detected, demonstrating the good clinical tolerance of PEG 4000 in this population of elderly constipated patients. This tolerance was associated with a better clinical efficacy of PEG 4000 compared to lactulose.

This paper deals with the simulation of microbial degradation of organic matter in soil within the pore space at a microscopic scale. Pore space was analysed with micro-computed tomography and described using a sphere network coming from a geometrical modelling algorithm. The biological model was improved regarding previous work in order to include the transformation of dissolved organic compounds and diffusion processes. We tested our model using experimental results of a simple substrate decomposition experiment (fructose) within a simple medium (sand) in the presence of different bacterial strains. Separate incubations were carried out in microcosms using five different bacterial communities at two different water potentials of −10 and −100 cm of water. We calibrated the biological parameters by means of experimental data obtained at high water content, and we tested the model without changing any parameters at low water content. Same as for the experimental data, our simulation results showed that the decrease in water content caused a decrease of mineralization rate. The model was able to simulate the decrease of connectivity between substrate and microorganism due the decrease of water content.

Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

The introduction of the athlete's biological passport (ABP) has been a milestone in the fight against doping. The ABP is a collection of measurements of different biological parameters influenced by the administration of doping agents through the time and for each athlete. Two different modules have been developed and validated so far: the haematological module, which aims to identify enhancement of oxygen transport, including use of erythropoiesis-stimulating agents and any form of blood transfusion or manipulation, which became effective in 2010; and the steroidal module, which intends to detect the use of endogenous anabolic androgenic steroids when administered exogenously and other anabolic agents, which was introduced in 2014. Prior to the implementation of the haematological module, it is important to define an athlete’s testing pool on whom to collect blood and/or urine in-competition and out-of-competition (for the steroidal module, this is irrelevant because all collected urine samples will be subjected to analysis for the steroidal variables) and to be compliant with the strict requirements of the World Anti-Doping Agency ABP Operating Guidelines. The established individual profile can be used either to target traditional antidoping tests (recombinant erythropoietins, or homologous blood transfusion tests for the haematological module; isotope ratio mass spectrometry (IRMS) for the steroidal module) or to support an antidoping rule violation due to the use of a forbidden substance or method. In this article, we present the experience of four major International Federations which have implemented an ABP programme, focusing on the haematological module. They constitute examples which could be followed by other antidoping organisations wishing to introduce this new, efficient and innovative antidoping tool.

After 3 years and 31 close flybys of Titan by the Cassini Orbiter, Titan was finally observed in the shocked solar wind, outside of Saturn's magnetosphere. These observations revealed that Titan's flow-induced magnetosphere was populated by \"fossil\" fields originating from Saturn, to which the satellite was exposed before its excursion through the magnetopause. In addition, strong magnetic shear observed at the edge of Titan's induced magnetosphere suggests that reconnection may have been involved in the replacement of the fossil fields by the interplanetary magnetic field.

Enceladus, an icy moon of Saturn, possesses an internal water ocean and jets expelling ocean material into space. Cassini investigations indicated that the subsurface ocean could be a habitable environment having a complex interaction with the rocky core. Further investigation of the composition of the plume formed by the jets is necessary to fully understand the ocean, its potential habitability, and what it tells us about Enceladus’s origin. Moonraker has been proposed as an ESA M-class mission designed to orbit Saturn and perform multiple flybys of Enceladus, focusing on traversals of the plume. The proposed Moonraker mission consists of an ESA-provided platform with strong heritage from JUICE and Mars Sample Return and carrying a suite of instruments dedicated to plume and surface analysis. The nominal Moonraker mission has a duration of ∼13.5 yr. It includes a 23-flyby segment with 189 days allocated for the science phase and can be expanded with additional segments if resources allow. The mission concept consists of investigating (i) the habitability conditions of present-day Enceladus and its internal ocean, (ii) the mechanisms at play for the communication between the internal ocean and the surface of the South Polar Terrain, and (iii) the formation conditions of the moon. Moonraker, thanks to state-of-the-art instruments representing a significant improvement over Cassini's payload, would quantify the abundance of key species in the plume, isotopic ratios, and the physical parameters of the plume and the surface. Such a mission would pave the way for a possible future landed mission.

This article presents 18 magnetic reconnection electron diffusion region (EDR) candidates found using a neural network algorithm with the Magnetospheric Multiscale Mission phase 1a data at the Earth's dayside magnetopause. These new candidates are compared to the 32 previously reported dayside EDRs listed in Webster et al. (2018), https://doi.org/10.1029/2018ja025245, which constitute the training database of our algorithm. One of the main parameters used is a scalar quantity called “MeanRL” which is based on the asymmetry of the electron velocity distribution function and better identifies electron agyrotropy in the plane perpendicular to the magnetic field. In the light of the new EDR candidates found, we discuss and analyze the sign of the energy dissipation during the reconnection process and the distinction between the inner and outer EDRs, with 40% of the candidates showing negative or oscillating dissipation. We also present in details one of the new identified EDR candidates. Key Points We report 18 new electron diffusion region (EDR) candidates close to the Earth magnetopause in the Magnetospheric Multiscale Mission (MMS) phase 1a data using a neural network The algorithm makes use of a scalar quantity called “MeanRL” to identify the electron perpendicular agyrotropy typical of EDRs from MMS distribution functions We analyze and discuss the geometry of EDR based on energy dissipation signatures