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Key Clinical Message: Cardiophrenic metastasis is typically a late stage manifestation of ovarian high grade serous carcinoma. Here we present a case where this was the sole presentation of this disease. This case challenges our current understanding of the natural course of ovarian high grade serous carcinoma. Abstract: Ovarian cancer is typically described to spread from its primary site within the fallopian tubes or ovaries into the peritoneal cavity and beyond with cardiophrenic lymph node involvement being considered a late stage disease process. Here we present the case of a lady in her 60s where increased metabolic activity of the cardiophrenic lymph node was picked up in the investigation of an adenocarcinoma of the lung. Post-thoracoscopic resection histopathological analysis of this lymph node showing an epithelial structure with positive immunohistochemical markers PAX8, WT1, ER, and p16 with a p53 wild type-pattern were the sole presenting features of a high grade serous ovarian carcinoma, that was otherwise undetectable by radiological or hematological screening. Only histopathological analysis after modified radical hysterectomy in gynae-oncological fashion were able to identify a 4 mm lesion within the left fallopian tube. This case questions our current understanding of the natural history of ovarian carcinomas.
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The radius valley (or gap) in the observed distribution of exoplanet radii, which separates smaller super-Earths from larger sub-Neptunes, is a key feature that theoretical models must explain. Conventionally, it is interpreted as the result of the loss of primordial hydrogen and helium (H/He) envelopes atop rocky cores. However, planet formation models predict that water-rich planets migrate from cold regions outside the snowline towards the star. Assuming water to be in the form of solid ice in their interior, many of these planets would be located in the radius gap contradicting observations. Here we use an advanced coupled formation and evolution model that describes the planets' growth and evolution starting from solid, moon-sized bodies in the protoplanetary disk to mature Gyr-old planetary systems. Employing new equations of state and interior structure models to treat water as vapour mixed with H/He, we naturally reproduce the valley at the observed location. The model results demonstrate that the observed radius valley can be interpreted as the separation of less massive, rocky super-Earths formed in situ from more massive, ex situ, water-rich sub-Neptunes. Furthermore, the occurrence drop at larger radii, the so-called radius cliff, is matched by planets with water-dominated envelopes. Our statistical approach shows that the synthetic distribution of radii quantitatively agrees with observations for close-in planets, but only if low-mass planets initially containing H/He lose their atmosphere due to photoevaporation, which populates the super-Earth peak with evaporated rocky cores. Therefore, we provide a hybrid theoretical explanation of the radius gap and cliff caused by both planet formation (orbital migration) as well as evolution (atmospheric escape).
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The formation of protein precursors, due to the condensation of atomic carbon under the low-temperature conditions of the molecular phases of the interstellar medium, opens alternative pathways for the origin of life. We perform peptide synthesis under conditions prevailing in space and provide a comprehensive analytic characterization of its products. The application of 13C allowed us to confirm the suggested pathway of peptide formation that proceeds due to the polymerization of aminoketene molecules that are formed in the C + CO + NH3 reaction. Here, we address the question of how the efficiency of peptide production is modified by the presence of water molecules. We demonstrate that although water slightly reduces the efficiency of polymerization of aminoketene, it does not prevent the formation of peptides.
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Medio Ambiente Extraterrestre , Agua , Medio Ambiente Extraterrestre/química , Agua/química , PéptidosRESUMEN
Aqueous chemistry within carbonaceous planetesimals is promising for synthesizing prebiotic organic matter essential to all life. Meteorites derived from these planetesimals delivered these life building blocks to the early Earth, potentially facilitating the origins of life. Here, we studied the formation of vitamin B3 as it is an important precursor of the coenzyme NAD(P)(H), which is essential for the metabolism of all life as we know it. We propose a new reaction mechanism based on known experiments in the literature that explains the synthesis of vitamin B3. It combines the sugar precursors glyceraldehyde or dihydroxyacetone with the amino acids aspartic acid or asparagine in aqueous solution without oxygen or other oxidizing agents. We performed thermochemical equilibrium calculations to test the thermodynamic favorability. The predicted vitamin B3 abundances resulting from this new pathway were compared with measured values in asteroids and meteorites. We conclude that competition for reactants and decomposition by hydrolysis are necessary to explain the prebiotic content of meteorites. In sum, our model fits well into the complex network of chemical pathways active in this environment.
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WASP-107b is a warm (approximately 740 K) transiting planet with a Neptune-like mass of roughly 30.5 Mâ and Jupiter-like radius of about 0.94 RJ (refs. 1,2), whose extended atmosphere is eroding3. Previous observations showed evidence for water vapour and a thick, high-altitude condensate layer in the atmosphere of WASP-107b (refs. 4,5). Recently, photochemically produced sulfur dioxide (SO2) was detected in the atmosphere of a hot (about 1,200 K) Saturn-mass planet from transmission spectroscopy near 4.05 µm (refs. 6,7), but for temperatures below about 1,000 K, sulfur is predicted to preferably form sulfur allotropes instead of SO2 (refs. 8-10). Here we report the 9σ detection of two fundamental vibration bands of SO2, at 7.35 µm and 8.69 µm, in the transmission spectrum of WASP-107b using the Mid-Infrared Instrument (MIRI) of JWST. This discovery establishes WASP-107b as the second irradiated exoplanet with confirmed photochemistry, extending the temperature range of exoplanets exhibiting detected photochemistry from about 1,200 K down to about 740 K. Furthermore, our spectral analysis reveals the presence of silicate clouds, which are strongly favoured (around 7σ) over simpler cloud set-ups. Furthermore, water is detected (around 12σ) but methane is not. These findings provide evidence of disequilibrium chemistry and indicate a dynamically active atmosphere with a super-solar metallicity.
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BACKGROUND: This nationwide routine data analysis evaluates if oral anticoagulant (OAC) use in patients with heart failure (HF) and atrial fibrillation (AF) leads to a lower mortality and reduced readmission rate. Superiority of new oral anticoagulants (NOACs), compared to vitamin K antagonists (VKA), was analyzed for these endpoints. METHODS: Anonymous data of patients with a health insurance at the Allgemeine Ortskrankenkasse and a claims record for hospitalization with the main diagnosis of HF and secondary diagnosis of AF (2017-2019) were included. A hospital stay in the previous year was an exclusion criterion. Mortality and readmission for all-cause and stroke/intracranial bleeding (ICB) were analyzed 91-365 days after the index hospitalization. Kaplan-Meier survival curves and multivariable Cox regression models were used to evaluate the impact of medication on outcome. RESULTS: 180,316 cases were included [81 years (IQR 76-86), 55.6% female, CHA2DS2-VASc score ≥ 2 (96.81%)]. In 80.6%, OACs were prescribed (VKA: 21.7%; direct factor Xa inhibitors (FXaI): 60.0%; direct thrombin inhibitors (DTI): 3.4%; with multiple prescriptions per patient included). Mortality rate was 19.1%, readmission rate was 29.9% and stroke/ICB occurred in 1.9%. Risk of death was lower with any OAC (HR 0.77, 95% CI [0.75-0.79]) but without significant differences in OAC type (VKA: HR 0.73, [0.71-0.76]; FXaI: HR 0.77, [0.75-0.78]; DTI: HR 0.71, [0.66-0.77]). The total readmission rate (HR 0.97, [0.94 to 0.99]) and readmission for stroke/ICB (HR 0.71, [0.65-0.77]) was lower with OAC. CONCLUSIONS: Nationwide data confirm a reduction in mortality and readmission rate in HF-AF patients taking OACs, without NOAC superiority.
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Fibrilación Atrial , Insuficiencia Cardíaca , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Anticoagulantes/efectos adversos , Administración Oral , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Hemorragias Intracraneales , Factores de Riesgo , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Inhibidores del Factor Xa/uso terapéuticoRESUMEN
Brown dwarfs serve as ideal laboratories for studying the atmospheres of giant exoplanets on wide orbits, as the governing physical and chemical processes within them are nearly identical1,2. Understanding the formation of gas-giant planets is challenging, often involving the endeavour to link atmospheric abundance ratios, such as the carbon-to-oxygen (C/O) ratio, to formation scenarios3. However, the complexity of planet formation requires further tracers, as the unambiguous interpretation of the measured C/O ratio is fraught with complexity4. Isotope ratios, such as deuterium to hydrogen and 14N/15N, offer a promising avenue to gain further insight into this formation process, mirroring their use within the Solar System5-7. For exoplanets, only a handful of constraints on 12C/13C exist, pointing to the accretion of 13C-rich ice from beyond the CO iceline of the disks8,9. Here we report on the mid-infrared detection of the 14NH3 and 15NH3 isotopologues in the atmosphere of a cool brown dwarf with an effective temperature of 380 K in a spectrum taken with the Mid-Infrared Instrument (MIRI) of JWST. As expected, our results reveal a 14N/15N value consistent with star-like formation by gravitational collapse, demonstrating that this ratio can be accurately constrained. Because young stars and their planets should be more strongly enriched in the 15N isotope10, we expect that 15NH3 will be detectable in several cold, wide-separation exoplanets.
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The understanding of planet formation has changed recently, embracing the new idea of pebble accretion. This means that the influx of pebbles from the outer regions of planet-forming disks to their inner zones could determine the composition of planets and their atmospheres. The solid and molecular components delivered to the planet-forming region can be best characterized by mid-infrared spectroscopy. With Spitzer low-resolution (R = 100, 600) spectroscopy, this approach was limited to the detection of abundant molecules, such as H2O, C2H2, HCN and CO2. This contribution will present the first results of the MINDS (MIRI mid-INfrared Disk Survey, PI:Th Henning) project. Due do the sensitivity and spectral resolution provided by the James Webb Space Telescope (JWST), we now have a unique tool to obtain the full inventory of chemistry in the inner disks of solar-type stars and brown dwarfs, including also less-abundant hydrocarbons and isotopologues. The Integral Field Unit (IFU) capabilities will enable at the same time spatial studies of the continuum and line emission in extended sources such as debris disks, the flying saucer and also the search for mid-IR signatures of forming planets in systems such as PDS 70. These JWST observations are complementary to ALMA and NOEMA observations of outer-disk chemistry; together these datasets will provide an integral view of the processes occurring during the planet-formation phase.
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The origin of life might be sparked by the polymerization of the first RNA molecules in Darwinian ponds during wet-dry cycles. The key life-building block ribose was found in carbonaceous chondrites. Its exogenous delivery onto the Hadean Earth could be a crucial step toward the emergence of the RNA world. Here, we investigate the formation of ribose through a simplified version of the formose reaction inside carbonaceous chondrite parent bodies. Following up on our previous studies regarding nucleobases with the same coupled physico-chemical model, we calculate the abundance of ribose within planetesimals of different sizes and heating histories. We perform laboratory experiments using catalysts present in carbonaceous chondrites to infer the yield of ribose among all pentoses (5Cs) forming during the formose reaction. These laboratory yields are used to tune our theoretical model that can only predict the total abundance of 5Cs. We found that the calculated abundances of ribose were similar to the ones measured in carbonaceous chondrites. We discuss the possibilities of chemical decomposition and preservation of ribose and derived constraints on time and location in planetesimals. In conclusion, the aqueous formose reaction might produce most of the ribose in carbonaceous chondrites. Together with our previous studies on nucleobases, we found that life-building blocks of the RNA world could be synthesized inside parent bodies and later delivered onto the early Earth.
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Photochemistry in H2O:NH3:CO2 cosmic ice analogues was studied at temperatures of 75, 120, and 150 K, relevant to hot cores and warmer regions in protostellar envelopes and planet-forming disks. A combination of two triggers of surface chemistry in cosmic ice analogues, heat and UV irradiation, compared to using either just heat or UV irradiation, leads to a larger variety and an increased production of complex organic molecules, including potential precursors of prebiotic molecules. In addition to complex organic molecules detected in previous studies of H2O:NH3:CO2 ices, ammonium carbamate, carbamic acid, ammonium formate and formamide, we detected acetaldehyde, urea, and, tentatively, glycine, the simplest amino acid. Water ice hampers reactions at low temperature (75 K) but allows the parent molecules, CO2 and NH3, to stay in the solid state and react at higher temperatures (120 and 150 K, above their desorption temperatures). The experiments were performed on the surface of KBr substrates and amorphous silicate grains, analogs of cosmic silicate dust. The production of complex molecules on the silicate surface is decreased compared to KBr. This result suggests that the larger surface area and/or surface properties of the silicate grains play a role in controlling the chemistry, preventing it taking place to the same extent as on the flat KBr substrate. This is further evidence of the fact that cosmic dust grains play an important role in the chemistry taking place on their surface.
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Medio Ambiente Extraterrestre , Planetas , Dióxido de Carbono , Medio Ambiente Extraterrestre/química , Prebióticos , TemperaturaRESUMEN
In the widely accepted 'unified model'1 solution of the classification puzzle of active galactic nuclei, the orientation of a dusty accretion torus around the central black hole dominates their appearance. In 'type-1' systems, the bright nucleus is visible at the centre of a face-on torus. In 'type-2' systems the thick, nearly edge-on torus hides the central engine. Later studies suggested evolutionary effects2 and added dusty clumps and polar winds3 but left the basic picture intact. However, recent high-resolution images4 of the archetypal type-2 galaxy NGC 10685,6, suggested a more radical revision. The images displayed a ring-like emission feature that was proposed to be hot dust surrounding the black hole at the radius where the radiation from the central engine evaporates the dust. That ring is too thin and too far tilted from edge-on to hide the central engine, and ad hoc foreground extinction is needed to explain the type-2 classification. These images quickly generated reinterpretations of the dichotomy between types 1 and 27,8. Here we present new multi-band mid-infrared images of NGC 1068 that detail the dust temperature distribution and reaffirm the original model. Combined with radio data (J.F.G. and C.M.V.I., manuscript in preparation), our maps locate the central engine that is below the previously reported ring and obscured by a thick, nearly edge-on disk, as predicted by the unified model. We also identify emission from polar flows and absorbing dust that is mineralogically distinct from that towards the Milky Way centre.
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Planet formation occurs around a wide range of stellar masses and stellar system architectures1. An improved understanding of the formation process can be achieved by studying it across the full parameter space, particularly towards the extremes. Earlier studies of planets in close-in orbits around high-mass stars have revealed an increase in giant planet frequency with increasing stellar mass2 until a turnover point at 1.9 solar masses (Mâ), above which the frequency rapidly decreases3. This could potentially imply that planet formation is impeded around more massive stars, and that giant planets around stars exceeding 3 Mâ may be rare or non-existent. However, the methods used to detect planets in small orbits are insensitive to planets in wide orbits. Here we demonstrate the existence of a planet at 560 times the Sun-Earth distance from the 6- to 10-Mâ binary b Centauri through direct imaging. The planet-to-star mass ratio of 0.10-0.17% is similar to the Jupiter-Sun ratio, but the separation of the detected planet is about 100 times wider than that of Jupiter. Our results show that planets can reside in much more massive stellar systems than what would be expected from extrapolation of previous results. The planet is unlikely to have formed in situ through the conventional core accretion mechanism4, but might have formed elsewhere and arrived to its present location through dynamical interactions, or might have formed via gravitational instability.
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Recent observations of the potentially habitable planets TRAPPIST-1 e, f, and g suggest that they possess large water mass fractions of possibly several tens of weight percent of water, even though the host star's activity should drive rapid atmospheric escape. These processes can photolyze water, generating free oxygen and possibly desiccating the planet. After the planets formed, their mantles were likely completely molten with volatiles dissolving and exsolving from the melt. To understand these planets and prepare for future observations, the magma ocean phase of these worlds must be understood. To simulate these planets, we have combined existing models of stellar evolution, atmospheric escape, tidal heating, radiogenic heating, magma-ocean cooling, planetary radiation, and water-oxygen-iron geochemistry. We present MagmOc, a versatile magma-ocean evolution model, validated against the rocky super-Earth GJ 1132b and early Earth. We simulate the coupled magma-ocean atmospheric evolution of TRAPPIST-1 e, f, and g for a range of tidal and radiogenic heating rates, as well as initial water contents between 1 and 100 Earth oceans. We also reanalyze the structures of these planets and find they have water mass fractions of 0-0.23, 0.01-0.21, and 0.11-0.24 for planets e, f, and g, respectively. Our model does not make a strong prediction about the water and oxygen content of the atmosphere of TRAPPIST-1 e at the time of mantle solidification. In contrast, the model predicts that TRAPPIST-1 f and g would have a thick steam atmosphere with a small amount of oxygen at that stage. For all planets that we investigated, we find that only 3-5% of the initial water will be locked in the mantle after the magma ocean solidified.
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Atmósfera , Planetas , Planeta Tierra , Evolución Planetaria , Exobiología , Medio Ambiente Extraterrestre , Océanos y Mares , AguaRESUMEN
A deep understanding of the origin of life requires the physical, chemical, and biological study of prebiotic systems and the comprehension of the mechanisms underlying their evolutionary steps. In this context, great attention is paid to the class of interstellar molecules known as "Complex Organic Molecules" (COMs), considered as possible precursors of prebiotic species. Although COMs have already been detected in different astrophysical environments (such as interstellar clouds, protostars, and protoplanetary disks) and in comets, the physical-chemical mechanisms underlying their formation are not yet fully understood. In this framework, a unique contribution comes from laboratory experiments specifically designed to mimic the conditions found in space. We present a review of experimental studies on the formation and evolution of COMs in the solid state, i.e., within ices of astrophysical interest, devoting special attention to the in situ detection and analysis techniques commonly used in laboratory astrochemistry. We discuss their main strengths and weaknesses and provide a perspective view on novel techniques, which may help in overcoming the current experimental challenges.
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Surface processes on cosmic solids in cold astrophysical environments lead to gas-phase depletion and molecular complexity. Most astrophysical models assume that the molecular ice forms a thick multilayer substrate, not interacting with the dust surface. In contrast, we present experimental results demonstrating the importance of the surface for porous grains. We show that cosmic dust grains may be covered by a few monolayers of ice only. This implies that the role of dust surface structure, composition, and reactivity in models describing surface processes in cold interstellar, protostellar, and protoplanetary environments has to be reevaluated.
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A century of unsuccessful attempts to identify the neutral ethylenedione molecule combined with the results of quantum-chemical computations resulted in the conclusion on the instability of this molecule. In this article, we demonstrate that although the lowest energy isomer of ethylenedione with linear geometry is indeed unstable, a higher energy three-membered cyclic isomer can be stabilized, and at low temperature has a life-time longer than one millisecond. In our study, the ethylenedione C2O2 molecule was synthesized in the low-temperature reaction CO2 + C â C2O2 inside liquid helium nanodroplets. To study the reaction, a newly developed calorimetric technique was applied. Single pairs of reactants were incorporated into tiny helium droplets having a temperature of 0.37 K. The reaction energy was transferred to liquid helium stabilizing an intermediate gas-phase reaction product. The energy transfer also resulted in the evaporation of helium atoms. Therefore, the change of the helium droplets' size allowed precise calorimetry on a molecular scale.
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Hot gas giant exoplanets can lose part of their atmosphere due to strong stellar irradiation, and these losses can affect their physical and chemical evolution. Studies of atmospheric escape from exoplanets have mostly relied on space-based observations of the hydrogen Lyman-α line in the far ultraviolet region, which is strongly affected by interstellar absorption. Using ground-based high-resolution spectroscopy, we detected excess absorption in the helium triplet at 1083 nanometers during the transit of the Saturn-mass exoplanet WASP-69b, at a signal-to-noise ratio of 18. We measured line blueshifts of several kilometers per second and posttransit absorption, which we interpret as the escape of part of the atmosphere trailing behind the planet in comet-like form.
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Before the origin of simple cellular life, the building blocks of RNA (nucleotides) had to form and polymerize in favorable environments on early Earth. At this time, meteorites and interplanetary dust particles delivered organics such as nucleobases (the characteristic molecules of nucleotides) to warm little ponds whose wet-dry cycles promoted rapid polymerization. We build a comprehensive numerical model for the evolution of nucleobases in warm little ponds leading to the emergence of the first nucleotides and RNA. We couple Earth's early evolution with complex prebiotic chemistry in these environments. We find that RNA polymers must have emerged very quickly after the deposition of meteorites (less than a few years). Their constituent nucleobases were primarily meteoritic in origin and not from interplanetary dust particles. Ponds appeared as continents rose out of the early global ocean, but this increasing availability of "targets" for meteorites was offset by declining meteorite bombardment rates. Moreover, the rapid losses of nucleobases to pond seepage during wet periods, and to UV photodissociation during dry periods, mean that the synthesis of nucleotides and their polymerization into RNA occurred in just one to a few wet-dry cycles. Under these conditions, RNA polymers likely appeared before 4.17 billion years ago.
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Respiraderos Hidrotermales , Modelos Teóricos , Nucleótidos/química , ARN/química , Adenina/química , Polvo Cósmico , Planeta Tierra , Evolución Molecular , Meteoroides , Origen de la Vida , Polimerizacion , Uracilo/químicaRESUMEN
Reversed-phase high-performance liquid chromatography (RP-HPLC) has been carried out for a series of unsubstituted polycyclic aromatic hydrocarbons (PAHs) and the corresponding ethynyl, 1,3-butadiynyl, and 1,3,5-hexatriynyl derivatives. Theoretical values of the isotropic polarizability and several polarity descriptors have been computed for each compound by using semiempirical models and density functional theory (DFT), with the aim of evaluating linear functions as quantitative structure-retention relationships (QSRRs). The polarity has been described by using either the permanent electric dipole moment, the subpolarity, or a topological electronic index. Three types of partial atomic charges have been used to calculate the subpolarity and a topological index. The choice of the theoretical model, of the polarity descriptor, and of the partial atomic charges is discussed and the resulting QSRRs are compared. Calculating the retention times from the polarizability and the topological electronic index (AM1, PM3, or DFT-B3LYP/6-31+G(d,p)) gives the best agreement with the experimental values.
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OBJECTIVES: To describe the use of drug-eluting stents (DESs) in the largest population of statutory health insurance members in Germany, including newly developed bio-resorbable vascular scaffolds (BVSs), and to evaluate 1-year complication rates of DES as compared with bare metal stents (BMSs) in this cohort. DESIGN: Routine data analysis of statutory health insurance claims data from the years 2008 to 2014. SETTING: The German healthcare insurance Allgemeine Ortskrankenkasse covers approximately 30% of the German population and is the largest nationwide provider of statutory healthcare insurance in Germany. PARTICIPANTS AND INTERVENTIONS: We included all patients with a claims record for a percutaneous coronary intervention (PCI) with either DES or BMS and additionally, from 2013, BVS. Patients with acute myocardial infarction (AMI) were excluded. MAIN OUTCOME MEASURE: major adverse cerebrovascular and cardiovascular event (MACCE, defined as mortality, AMI, stroke and transient ischaemic attack), bypass surgery, PCI and coronary angiography) at 1 year after the intervention. RESULTS: A total of 243 581 PCI cases were included (DES excluding BVS: 143 765; BVS: 1440; BMS: 98 376). The 1-year MACCE rate was 7.42% in the DES subgroup excluding BVS and 11.29% in the BMS subgroup. The adjusted OR for MACCE was 0.72 (95% CI 0.70 to 0.75) in patients with DES excluding BVS as compared with patients with BMS. In the BVS group, the proportion of 1-year MACCE was 5.0%. CONCLUSION: The analyses demonstrate a lower MACCE rate for PCI with DES. BVSs are used in clinical routine in selected cases and seem to provide a high degree of safety, but data are still sparse.