Efficacy and Safety of Insulin Glargine 300 U/mL in People with Type 2 Diabetes Uncontrolled on Basal Insulin: The 26-Week Interventional, Single-Arm ARTEMIS-DM Study

Introduction: The efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa. Methods: The ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5–10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed. Results: A total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (− 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event. Conclusion: In people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions. ClinicalTrials.gov identifier: NCT03760991.Fil: Sethi, Bipin. Care Hospital Hyderabad; IndiaFil: Al-Rubeaan, Khalid. Research and Scientific Center Sultan Bin Abdulaziz Humanitarian City; ArgentinaFil: Unubol, Mustafa. Adnan Menderes Universitesi; TurquíaFil: Mabunay, Maria A.. Sanofi; SingapurFil: Berthou, Baptiste. Sanofi; FranciaFil: Pilorget, Valerie. Sanofi; FranciaFil: Vethakkan, Shireene R.. University Malaya Medical Centre; MalasiaFil: Frechtel, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Formation of gullies on Mars by debris flows triggered by CO_2 sublimation

Martian gully landforms resemble terrestrial debris flows formed by the action of liquid water and have thus been interpreted as evidence for potential habitable environments on Mars within the past few millennia. However, ongoing gully formation has been detected under surface conditions much too cold for liquid water, but at times in the martian year when a thin layer of seasonal CO_2 frost is present and defrosting above the regolith. These observations suggest that the CO_2 condensation–sublimation cycle could play a role in gully formation. Here we use a thermo-physical numerical model of the martian regolith underlying a CO_2 ice layer and atmosphere to show that the pores beneath the ice layer can be filled with CO_2 ice and subjected to extreme pressure variations during the defrosting season. The subsequent gas fluxes can destabilize the regolith material and induce gas-lubricated debris flows with geomorphic characteristics similar to martian gullies. Moreover, we find that subsurface CO_2 ice condensation, sublimation and pressurization occurs at conditions found at latitudes and slope orientations where gullies are observed. We conclude that martian gullies can result from geologic dry ice processes that have no terrestrial analogues and do not require liquid water. Such dry ice processes may have helped shape the evolution of landforms elsewhere on the martian surface

Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration

Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) disease pathogenesis are unknown. Here we show that PilA binds collagen, which promotes GBS interaction with the α2β1 integrin resulting in activation of host chemokine expression and neutrophil recruitment during infection. Mice infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in neutrophil infiltration and bacterial CNS dissemination. We find that PilA-mediated virulence is dependent on neutrophil influx as neutrophil depletion results in a decrease in BBB permeability and GBS–BBB penetration. Our results suggest that the bacterial pilus, specifically the PilA adhesin, has a dual role in immune activation and bacterial entry into the CNS

The MicrOmega Investigation Onboard Hayabusa2

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Sample collection from asteroid (162173) Ryugu by Hayabusa2: Implications for surface evolution

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The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

Planetary Defense Ground Zero: MASCOT's View on the Rocks - an Update between First Images and Sample Return

At 01:57:20 UTC on October 3rd, 2018, after 3½ years of cruise aboard the JAXA spacecraft HAYABUSA2 and about 3 months in the vicinity of its target, the MASCOT lander was separated successfully by from an altitude of 41 m. After a free-fall of only ~5m51s MASCOT made first contact with C-type near-Earth and potentially hazardous asteroid (162173) Ryugu, by hitting a big boulder. MASCOT then bounced for ~11m3s, in the process already gathering valuable information on mechanical properties of the surface before it came to rest. It was able to perform science measurements at 3 different locations on the surface of Ryugu and took many images of its spectacular pitch-black landscape. MASCOT’s payload suite was designed to investigate the fine-scale structure, multispectral reflectance, thermal characteristics and magnetic properties of the surface. Somewhat unexpectedly, MASCOT encountered very rugged terrain littered with large surface boulders. Observing in-situ, it confirmed the absence of fine particles and dust as already implied by the remote sensing instruments aboard the HAYABUSA2 spacecraft. After some 17h of operations, MASCOT‘s mission ended with the last communication contact as it followed Ryugu’s rotation beyond the horizon as seen from HAYABUSA2. Soon after, its primary battery was depleted. We present a broad overview of the recent scientific results of the MASCOT mission from separation through descent, landing and in-situ investigations on Ryugu until the end of its operation and relate them to the needs of planetary defense interactions with asteroids. We also recall the agile, responsive and sometimes serendipitous creation of MASCOT, the two-year rush of building and delivering it to JAXA’s HAYABUSA2 spacecraft in time for launch, and the four years of in-flight operations and on-ground testing to make the most of the brief on-surface mission

Attributable risk in men in two French case-control studies on mesothelioma and asbestos

International audiencePleural mesothelioma is a primary tumor of the pleura that is mainly due to asbestos exposure. To study the relationship between mesothelioma and occupational asbestos exposure in France, two case-control studies (A and B) were conducted. A substantial difference in the attributable risk in the population (AR) was observed among men: 44.5% (95% CI: [32.6-56.4]) in study A and 83.2% (95% CI: [76.8-89.6]) in study B. As different exposure assessment expert methods were used, the main objective of this work was to re-estimate the AR men in two case-control studies according to a common standardized exposure assessment by using a Job Exposure Matrix (JEM) and to assess the role of subjects' selection. The initial observed AR difference was maintained: 36.3% (95% CI: [24.3-50.3]) in study A and 69.7% (95% CI: [51.7-83.2]) in study B. Further investigations highlighted the potential selection bias introduced in both studies, especially among controls. The AR could be underestimated in study A and overestimated in study B. After weighting subjects according to distribution of socio-economic status in the general population for controls and according to distribution of socio-economic status of cases registered by the French National Mesothelioma Surveillance Program, re-estimated AR values were 52.4% in study A and 70.2% in study B. These results provide additional information to describe the relationship between pleural mesothelioma and occupational asbestos exposure, but also confirm the importance of subjects' recruitment in case control studies, particularly control selection

Thermally altered subsurface material of asteroid (162173) Ryugu

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