The detection of solid phosphorus and fluorine in the dust from the coma of comet 67P/Churyumov-Gerasimenko

Here, we report the detection of phosphorus and fluorine in solid particles collected from the inner coma of comet 67P/Churyumov-Gerasimenko measured with the COmetary Secondary Ion Mass Analyser (COSIMA) instrument on-board the Rosetta spacecraft, only a few kilometers away from the comet nucleus. We have detected phosphorus-containing minerals from the presented COSIMA mass spectra, and can rule out e.g. apatite minerals as the source of phosphorus. This result completes the detection of life-necessary CHNOPS-elements in solid cometary matter, indicating cometary delivery as a potential source of these elements to the young Earth. Fluorine was also detected with CF+ secondary ions originating from the cometary dust. </p

Carbon-rich dust in comet 67P/Churyumov-Gerasimenko measured by COSIMA/Rosetta

Cometary ices are rich in CO2, CO and organic volatile compounds, but the carbon content of cometary dust was only measured for the Oort Cloud comet 1P/Halley, during its flyby in 1986. The COmetary Secondary Ion Mass Analyzer (COSIMA)/Rosetta mass spectrometer analysed dust particles with sizes ranging from 50 to 1000 μm, collected over 2 yr, from 67P/Churyumov-Gerasimenko (67P), a Jupiter family comet. Here, we report 67P dust composition focusing on the elements C and O. It has a high carbon content (atomic |${\rm{C}}/{\rm{Si}} = 5.5{\rm{\ }}_{ - 1.2}^{ + 1.4}\ \ {\rm{on\ average}}$ |⁠) close to the solar value and comparable to the 1P/Halley data. From COSIMA measurements, we conclude that 67P particles are made of nearly 50 per cent organic matter in mass, mixed with mineral phases that are mostly anhydrous. The whole composition, rich in carbon and non-hydrated minerals, points to a primitive matter that likely preserved its initial characteristics since the comet accretion in the outer regions of the protoplanetary disc.</p

Nitrogen-to-carbon atomic ratio measured by COSIMA in the particles of comet 67P/Churyumov–Gerasimenko

The COmetary Secondary Ion Mass Analyzer (COSIMA) on board the Rosetta mission has analysed numerous cometary dust particles collected at very low velocities (a few m s−1) in the environment of comet 67P/Churyumov–Gerasimenko (hereafter 67P). In these particles, carbon and nitrogen are expected mainly to be part of the organic matter. We have measured the nitrogen-to-carbon (N/C) atomic ratio of 27 cometary particles. It ranges from 0.018 to 0.06 with an averaged value of 0.035 ± 0.011. This is compatible with the measurements of the particles of comet 1P/Halley and is in the lower range of the values measured in comet 81P/Wild 2 particles brought back to Earth by the Stardust mission. Moreover, the averaged value found in 67P particles is also similar to the one found in the insoluble organic matter extracted from CM, CI and CR carbonaceous chondrites and to the bulk values measured in most interplanetary dust particles and micrometeorites. The close agreement of the N/C atomic ratio in all these objects indicates that their organic matters share some similarities and could have a similar chemical origin. Furthermore, compared to the abundances of all the detected elements in the particles of 67P and to the elemental solar abundances, the nitrogen is depleted in the particles and the nucleus of 67P as was previously inferred also for comet 1P/Halley. This nitrogen depletion could constrain the formation scenarios of cometary nuclei.</p

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Characterization of the organic matter in the comet 67P/Churyumov-Gerasimenko

Les comètes comptent parmi les corps du Système Solaire les plus riches en matière organique. Les observations par télédétection ont déjà permis d’identifier plus d’une vingtaine de molécules organiques simples en phase gazeuse. D’autre part, les missions d’exploration in situ (Giotto, Véga-1 et Véga-2) et la mission avec retour d’échantillon Stardust, ont établi qu’en plus de ces molécules volatiles relativement simples, une fraction notable de la matière carbonée cométaire est présente sous forme d’un matériau réfractaire restant en phase solide dans les grains cométaires. COSIMA (Cometary Secondary Ion Mass Analyzer) est un spectromètre de masse d’ions secondaires à temps de vol se trouvant à bord de l’orbiteur de la mission Rosetta. Le LISA et le LPC2E participent à la définition des opérations et à l’interprétation des résultats de cet instrument. Les récentes observations réalisées par cet instrument permettent de confirmer la présence de matière organique dans les grains cométaires. Bien que les interprétations de ces observations soient encore préliminaires, il semble que la structure chimique de la matière organique observée ne soit pas celle à laquelle nous nous attendions. Aussi nous manquons de spectres de référence représentatifs des observations. Néanmoins, nous suspectons actuellement qu’il s’agisse d’une matière organique qui a été fortement chauffée et/ou irradiée. L’objectif de la thèse sera de caractériser le plus précisément possible la matière organique observée grâce à l’instrument COSIMA. Pour cela, de nouvelles synthèses de matière organique complexe seront effectuées en laboratoire (LISA) grâce au dispositif expérimental du projet « OREGOC » (Origine et Evolution des Glaces et des composés Organiques Cométaires) qui permet de photolyser dans l’ultraviolet et de chauffer des mélanges de glaces. Nous insisterons en particulier sur un dépôt d’énergie plus conséquent que ce que nous avons pu réaliser dans le passé. Une fois produits, ces échantillons seront analysés grâce aux deux instruments « sol » de COSIMA : le premier étant localisé au LPC2E à Orléans et le second au Max Planck Institute de Göttingen en Allemagne. L’objectif est naturellement de reproduire les observations réalisées sur des grains de la comète 67P/Churyumov Gerasimenko à partir d’échantillons synthétiques afin de préciser au mieux l’origine de la matière organique cométaire ainsi que son évolution chimique jusqu’à son éjection du noyauComets are among the richest body in organic matter of Solar System. The remote sensing observations have already identified more than two dozen of simple organic molecules in the gas phase. Moreover, in situ exploration missions (Giotto, Vega-1 and Vega-2), as well as the sample return of the Stardust mission, have established that in addition to these relatively simple volatile molecules, a significant fraction of cometary carbonaceous material remain solid in the cometary grains. COSIMA (Cometary Secondary Ion Mass Analyzer) is a time of flight - secondary ion mass spectrometer on board the orbiter of the Rosetta mission. LISA and LPC2E participate to the definition of the operations and to the interpretation of the observations of this instrument. Recent observations performed with this instrument can confirm the presence of solid organic matter in the cometary grains. While the interpretations of these findings are still preliminary, it appears that the chemical structure of this organic matter is not the one that we were expecting. Thus, we lack of representative reference spectra. However, we suspect that the cometary organic material has been strongly heated and / or irradiated before the accretion of the cometary nucleus. The aim of the thesis is to describe as accurately as possible the organic matter observed thank to the COSIMA instrument. New synthesis of complex organic material synthesis will be performed in our laboratory (LISA) thank to the experimental setup named 'OREGOC' (French acronym for ORigin and Evolution of Ices and Cometary Organic matter) that allows ultraviolet photolysis and heating ice mixtures. We will particularly insist on a higher energy deposition during the photolysis that what we have achieved in the past. Once produced, these samples will be analyzed using the two “ground” instruments of COSIMA: the first being located at LPC2E Orleans and the second at the Max Planck Institute in Göttingen, Germany. The aim is naturally to reproduce the observations made on the grains of the comet 67P / Churyumov-Gerasimenko thank to synthetic samples to clarify the nature of the cometary organic matter and its chemical evolution since its synthesis to its ejection from the cometary nucleus