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BepiColombo is a joint mission between the European Space Agency, ESA, and the Japanese Aerospace Exploration Agency, JAXA, to perform a comprehensive exploration of Mercury. Launched on 20 th October 2018 from the European spaceport in Kourou, French Guiana, the spacecraft is now en route to Mercury. Two orbiters have been sent to Mercury and will be put into dedicated, polar orbits around the planet to study the planet and its environment. One orbiter, Mio, is provided by JAXA, and one orbiter, MPO, is provided by ESA. The scientific payload of both spacecraft will provide detailed information necessary to understand the origin and evolution of the planet itself and its surrounding environment. Mercury is the planet closest to the Sun, the only terrestrial planet besides Earth with a self-sustained magnetic field, and the smallest planet in our Solar System. It is a key planet for understanding the evolutionary history of our Solar System and therefore also for the question of how the Earth and our Planetary System were formed. The scientific objectives focus on a global characterization of Mercury through the investigation of its interior, surface, exosphere, and magnetosphere. In addition, instrumentation onboard BepiColombo will be used to test Einstein’s theory of general relativity. Major effort was put into optimizing the scientific return of the mission by defining a payload such that individual measurements can be interrelated and complement each other.

Background There have been ongoing efforts to understand when and how data from observational studies can be applied to clinical and regulatory decision making. The objective of this review was to assess the comparability of relative treatment effects of pharmaceuticals from observational studies and randomized controlled trials (RCTs). Methods We searched PubMed and Embase for systematic literature reviews published between January 1, 1990, and January 31, 2020, that reported relative treatment effects of pharmaceuticals from both observational studies and RCTs. We extracted pooled relative effect estimates from observational studies and RCTs for each outcome, intervention-comparator, or indication assessed in the reviews. We calculated the ratio of the relative effect estimate from observational studies over that from RCTs, along with the corresponding 95% confidence interval (CI) for each pair of pooled RCT and observational study estimates, and we evaluated the consistency in relative treatment effects. Results Thirty systematic reviews across 7 therapeutic areas were identified from the literature. We analyzed 74 pairs of pooled relative effect estimates from RCTs and observational studies from 29 reviews. There was no statistically significant difference (based on the 95% CI) in relative effect estimates between RCTs and observational studies in 79.7% of pairs. There was an extreme difference (ratio < 0.7 or > 1.43) in 43.2% of pairs, and, in 17.6% of pairs, there was a significant difference and the estimates pointed in opposite directions. Conclusions Overall, our review shows that while there is no significant difference in the relative risk ratios between the majority of RCTs and observational studies compared, there is significant variation in about 20% of comparisons. The source of this variation should be the subject of further inquiry to elucidate how much of the variation is due to differences in patient populations versus biased estimates arising from issues with study design or analytical/statistical methods.

The high prevalence of chronic hepatitis C (CHC) and its consequent cirrhosis has been associated with bone fragility. Whether CHC may cause bone and mineral abnormalities in the absence of hepatocellular dysfunction is still unknown. In this study we aimed to determine the prevalence of osteoporotic vertebral fractures and low BMD measurements in men with non-cirrhotic CHC. Risk factors for low BMD and fractures were also investigated. Morphometric vertebral fractures and BMD measurements were performed in 60 non-cirrhotic untreated men with CHC and 59 healthy controls, matched for age and gender, weight and current smoking. Serum CTx, calcium, phosphate, intact PTH, alkaline phosphatase and vitamin D (25OHD) concentrations were measured in all participants. Clinical risk factors for low BMD and fractures were evaluated by a structured questionnaire as well as details regarding HCV infection. Trochanter and total femur BMD were significantly lower in CHC patients as compared to healthy men (p = 0.04). In men 50 years and older, the prevalence of osteoporosis was significantly higher among CHC patients (p = 0.01). Lower levels of physical activities and more often report of prolonged immobilization were observed among CHC patients (p<0.05). Liver inflammation and fibrosis, viral load and genotype did not correlate with BMD measurements. Bone markers and 25OHD concentrations were similar in both groups. Only a few vertebral fractures were observed. Our results demonstrate that non-cirrhotic untreated CHC patients have lower BMD at the femur as compared to healthy men in spite of the absence of significant bone and mineral abnormalities.

Astronauts have been previously shown to exhibit decreased salivary lysozyme and increased dental calculus and gingival inflammation in response to space flight, host factors that could contribute to oral diseases such as caries and periodontitis. However, the specific physiological response of caries-causing bacteria such as Streptococcus mutans to space flight and/or ground-based simulated microgravity has not been extensively investigated. In this study, high aspect ratio vessel S. mutans simulated microgravity and normal gravity cultures were assessed for changes in metabolite and transcriptome profiles, H 2 O 2 resistance, and competence in sucrose-containing biofilm media. Stationary phase S. mutans simulated microgravity cultures displayed increased killing by H 2 O 2 compared to normal gravity control cultures, but competence was not affected. RNA-seq analysis revealed that expression of 153 genes was up-regulated ≥2-fold and 94 genes down-regulated ≥2-fold during simulated microgravity high aspect ratio vessel growth. These included a number of genes located on extrachromosomal elements, as well as genes involved in carbohydrate metabolism, translation, and stress responses. Collectively, these results suggest that growth under microgravity analog conditions promotes changes in S. mutans gene expression and physiology that may translate to an altered cariogenic potential of this organism during space flight missions. Microbiology: Cavities-causing bacteria altered by space-like conditions The gene expression patterns, metabolism and physiology of tooth cavities-causing microbes change in a space-like gravity environment. These findings could help explain why astronauts are at a greater risk for dental diseases when in space. Kelly Rice and colleagues from the University of Florida, Gainesville, USA, cultured Streptococcus mutans bacteria under simulated microgravity and normal gravity conditions. The bacteria grown in microgravity were more susceptible to killing with hydrogen peroxide, tended to aggregate in more compact cellular structures, showed changes in their metabolite profile and expressed around 250 genes at levels that were either much higher or lower than normal gravity control cultures. These genes included many involved in carbohydrate metabolism, protein production and stress responses. The observed changes collectively suggest that space flight and microgravity could alter the cavities-causing potential of S. mutans .

Auroras are caused by accelerated charged particles precipitating along magnetic field lines into a planetary atmosphere, the auroral brightness being roughly proportional to the precipitating particle energy flux. The Analyzer of Space Plasma and Energetic Atoms experiment on the Mars Express spacecraft has made a detailed study of acceleration processes on the nightside of Mars. We observed accelerated electrons and ions in the deep nightside high-altitude region of Mars that map geographically to interface/cleft regions associated with martian crustal magnetization regions. By integrating electron and ion acceleration energy down to the upper atmosphere, we saw energy fluxes in the range of 1 to 50 milliwatts per square meter per second. These conditions are similar to those producing bright discrete auroras above Earth. Discrete auroras at Mars are therefore expected to be associated with plasma acceleration in diverging magnetic flux tubes above crustal magnetization regions, the auroras being distributed geographically in a complex pattern by the many multipole magnetic field lines extending into space.

Bacterial nitric oxide (NO) synthases (bNOS) play diverse and important roles in microbial physiology, stress resistance, and virulence. Although bacterial and mammalian NOS enzymes have been well‐characterized, comparatively little is known about the prevalence and function of NOS enzymes in Archaea. Analysis of archaeal genomes revealed that highly conserved bNOS homologs were restricted to members of the Halobacteria. Of these, Natronomonas pharaonis NOS (npNOS) was chosen for further characterization. NO production was confirmed in heterologously expressed His‐tagged npNOS by coupling nitrite production from N‐hydroxy‐L‐arginine in an H2O2‐supported reaction. Additionally, the nos gene was successfully targeted and disrupted to create a Nmn. pharaonis nos mutant by adapting an established Natrialba magadii transformation protocol. Genome re‐sequencing of this mutant revealed an additional frameshift in a putative cation–acetate symporter gene, which could contribute to altered acetate metabolism in the nos mutant. Inactivation of Nmn. pharaonis nos was also associated with several phenotypes congruent with bacterial nos mutants (altered growth, increased oxygen consumption, increased pigment, increased UV susceptibility), suggesting that NOS function may be conserved between bacteria and archaea. These studies are the first to describe genetic inactivation and characterization of a Nmn. pharaonis gene and provides enhanced tools for probing its physiology. This study details the first characterization of an Archaeal NOS enzyme, whereby bioinformatic and biochemical approaches confirm that Natronomonas pharaonis ORF NP_1908A encodes a bacterial NOS‐like protein which can catalyze NO production in vitro. This study is also the first to describe genetic manipulation of Nmn. pharaonis, whereby a nos mutant was generated and characterized. These investigations suggest that Nmn. pharaonis NOS appears to have similar effects on physiology and stress resistance as its bacterial counterparts.

The general scientific objective of the ASPERA-3 experiment is to study the solar wind – atmosphere interaction and to characterize the plasma and neutral gas environment with within the space near Mars through the use of energetic neutral atom (ENA) imaging and measuring local ion and electron plasma. The ASPERA-3 instrument comprises four sensors: two ENA sensors, one electron spectrometer, and one ion spectrometer. The Neutral Particle Imager (NPI) provides measurements of the integral ENA flux (0.1–60 keV) with no mass and energy resolution, but high angular resolution. The measurement principle is based on registering products (secondary ions, sputtered neutrals, reflected neutrals) of the ENA interaction with a graphite-coated surface. The Neutral Particle Detector (NPD) provides measurements of the ENA flux, resolving velocity (the hydrogen energy range is 0.1–10 keV) and mass (H and O) with a coarse angular resolution. The measurement principle is based on the surface reflection technique. The Electron Spectrometer (ELS) is a standard top-hat electrostatic analyzer in a very compact design which covers the energy range 0.01–20 keV. These three sensors are located on a scanning platform which provides scanning through 180∘ of rotation. The instrument also contains an ion mass analyzer (IMA). Mechanically IMA is a separate unit connected by a cable to the ASPERA-3 main unit. IMA provides ion measurements in the energy range 0.01–36 keV/charge for the main ion components H+, He++, He+, O+, and the group of molecular ions 20–80 amu/q. ASPERA-3 also includes its own DC/DC converters and digital processing unit (DPU).

The emergence of Artificial Intelligence's Deep Neural Networks (DNNs) as a method for analysis of spatial and temporal data gives us a new avenue for research of the processes inherent to planetary exospheres and their interaction with the planetary environment. Hereby, it will be presented a particular study on how in-situ observations of the elemental composition of Mercury's exosphere may serve as an indication of the surface regolith mineral composition below, through predictions given by pre-trained DNNs. In this case the main driver, considered to generate the exosphere, is the micrometeoroid impact vaporization (MIV), which is seen as the dominant process in the night-side hemisphere of the planet. The training datasets will be constructed from randomly generated virtual surfaces, which will aim to generalize the training of the AI models to various types and compositions of the regolith. Different Neural Network models, which include fully-connected networks and Convolutional Neural Networks, will be compared both in giving supervised classification through multivariate regression predictions, and in reconstructing the regolith mineralogy maps. Furthermore, ways to expand the Deep Neural Networks to pattern recognition and knowledge discovery will be explored beyond the surface-exosphere interaction, as well as the possibilities for transfer learning and online learning with the acquisition of real planetary data. The development of such data analysis algorithms will be shown especially in view of the upcoming arrival of the ESA/JAXA's BepiColombo mission to Mercury, the innermost planet, in 2025, with its variety of instruments able to capture the dynamics of the tenuous Hermean environment. Ultimately, would be targeted the implementation of such AI algorithms within the Ground Segment pipeline software architecture of the experiment BepiColombo/MPO/SERENA, composed by four ion and neutral particle detectors.

The molecular structure of three low-molecular-weight resins used as paint varnishes has been characterized by use of an approach based on three different mass spectrometric techniques. We investigated the ketone resin MS2A, the aldehyde resin Laropal A81, and the hydrocarbon resin Regalrez 1094, now commonly used in restoration. To date, the molecular structures of these resins have not been completely elucidated. To improve current knowledge of the chemical composition of these materials, information obtained by gas chromatography–mass spectrometry (GC/MS), pyrolysis–gas chromatography–mass spectrometry (Py/GC/MS), and electrospray ionization mass spectrometry (ESI–Q–ToF) was combined. Analysis, in solution, of the whole polymeric fraction of the resins by flow-injection ESI–Q–ToF, and of the non-polymeric fraction by GC–MS, enabled us to identify previously unreported features of the polymer structures. In addition, the Py–GC/MS profiles that we obtained will help to enhance the databases currently available in the literature. The proposed approach can be extended to other low-molecular-weight resins used as varnishes in conservation.

The elbow, intermediate joint of the upper limb, frequently undergoes to pathological events and is especially prone to stiffness. Rehabilitation plays an important role in recovering functional activities. For the rehabilitation team, this goal always represents a challenge, as the treatment has to be continuously modeled and calibrated on the needs of the individual patient, even many times during the same rehabilitation cycle. Containing the effects of immobilization, avoiding to excessively stress the healing tissues, satisfying specific clinical criteria before moving to the next rehabilitation stage, basing the rehabilitation plan on up-to-date clinical and scientific data that can be adapted to each patient and to his/her needs are the basic principles of the rehabilitation plan, which can be chronologically grouped into four rehabilitation stages. After summarizing the general principles of elbow treatment, the specific principles of rehabilitation after elbow fractures and elbow instability are presented, and then the rehabilitative approach to the most frequent and feared pathological conditions of the elbow, namely stiffness, is described.