HELIOS-Retrieval: An Open-source, Nested Sampling Atmospheric Retrieval Code, Application to the HR 8799 Exoplanets and Inferred Constraints for Planet Formation

We present an open-source retrieval code named HELIOS-Retrieval (hereafter HELIOS-R), designed to obtain chemical abundances and temperature-pressure profiles from inverting the measured spectra of exoplanetary atmospheres. In the current implementation, we use an exact solution of the radiative transfer equation, in the pure absorption limit, in our forward model, which allows us to analytically integrate over all of the outgoing rays (instead of performing Gaussian quadrature). Two chemistry models are considered: unconstrained chemistry (where the mixing ratios are treated as free parameters) and equilibrium chemistry (enforced via analytical formulae, where only the elemental abundances are free parameters). The nested sampling algorithm allows us to formally implement Occam's Razor based on a comparison of the Bayesian evidence between models. We perform a retrieval analysis on the measured spectra of the HR 8799b, c, d and e directly imaged exoplanets. Chemical equilibrium is disfavored by the Bayesian evidence for HR 8799b, c and d. We find supersolar C/O, C/H and O/H values for the outer HR 8799b and c exoplanets, while the inner HR 8799d and e exoplanets have substellar C/O, substellar C/H and superstellar O/H values. If these retrieved properties are representative of the bulk compositions of the exoplanets, then they are inconsistent with formation via gravitational instability (without late-time accretion) and consistent with a core accretion scenario in which late-time accretion of ices occurred differently for the inner and outer exoplanets. For HR 8799e, we find that spectroscopy in the K band is crucial for constraining C/O and C/H. HELIOS-R is publicly available as part of the Exoclimes Simulation Platform (ESP; www.exoclime.org).Comment: 27 pages, 21 figures, 3 tables, published in A

Microlensing Results Challenge the Core Accretion Runaway Growth Scenario for Gas Giants

We compare the planet-to-star mass-ratio distribution measured by gravitational microlensing to core accretion theory predictions from population synthesis models. The core accretion theory's runaway gas accretion process predicts a dearth of intermediate-mass giant planets that is not seen in the microlensing results. In particular, the models predict $\sim10\,\times$ fewer planets at mass ratios of $10^{-4} \leq q \leq 4 \times 10^{-4}$ than inferred from microlensing observations. This tension implies that gas giant formation may involve processes that have hitherto been overlooked by existing core accretion models or that the planet-forming environment varies considerably as a function of host-star mass. Variation from the usual assumptions for the protoplanetary disk viscosity and thickness could reduce this discrepancy, but such changes might conflict with microlensing results at larger or smaller mass ratios, or with other observations. The resolution of this discrepancy may have important implications for planetary habitability because it has been suggested that the runaway gas accretion process may have triggered the delivery of water to our inner solar system. So, an understanding of giant planet formation may help us to determine the occurrence rate of habitable planets.Comment: 12 pages, 2 figures, 1 table, accepted for publication in ApJ

Natural history of carotid artery free-floating thrombus-A single center, consecutive cohort analysis.

Introduction Carotid free-floating thrombus (CFFT) is a rare cause of stroke and is thought to be associated with a high risk of recurrent cerebrovascular ischaemic events. The existing data on the natural history and optimal treatment modalities of CFFT is scanty and no clear recommendations exist. Objective A retrospective analysis, single-center cohort of consecutive patients diagnosed with CFFT was conducted, investigating the risk for recurrent cerebrovascular ischaemic events. Methods We performed a single-center retrospective analysis including all patients presenting at our tertiary center between January 2005 and December 2020 with symptoms consistent with ischaemic stroke and/or transient ischaemic attack. Digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were used to diagnose CFFT. In all included patients, CFFT was confirmed with a second imaging modality. CFFT was defined on imaging as a defect in contrast filling extending into the carotid lumen. We gathered information on vascular risk factors, diagnosis and follow-up methods, modality of treatment and neurological outcome. A survival analysis was performed, assessing the risk for recurrent cerebrovascular events. Results In total, N = 62 patients presenting with symptomatic CFFT were included. Mean age was 68 years, 69% (43/62) of patients were male, 52% (32/62) current or previous smokers, 76% (47/62) suffered from arterial hypertension, 68% (42/62) from dyslipidaemia, and 31% (19/62) from diabetes mellitus. Overall, 71% (44/62) of patients received any kind of intervention [endovascular or surgical carotid thrombo-endartectomy (CEA)] at any time point during follow-up. Sixteen percent of patients (10/62) received intervention within 48 h after diagnosis of CFFT. The survival analysis and Kaplan-Meier model censoring patients at the time of intervention or last follow-up showed that the risk for any recurrent ischaemic stroke was 19.7% within the first 7 days and 27.4% within 3 months after diagnosis. No patients experienced a new ischaemic stroke beyond 11 days after diagnosis of CFTT (n = 17). Conclusion The risk of recurrent ischaemic events in patients with CFFT is high, especially in the first week after diagnosis. Prospective studies are needed to further investigate the optimal management of these patients

Heterogeneity in the processing of ClC-5 mutants related to Dent disease

International audienceMutations in the electrogenic Cl-/H+ exchanger ClC-5 gene CLCN5 are frequently associated with Dent disease, an X-linked recessive disorder affecting the proximal tubules. Here, we investigate the consequences in X. laevis oocytes and in HEK293 cells of 9 previously reported, pathogenic, missense mutations of ClC-5, most of them which are located in regions forming the subunit interface. Two mutants trafficked normally to the cell surface and to early endosomes, and displayed complex glycosylation at the cell surface like wild-type ClC 5, but exhibited reduced currents. Three mutants displayed improper N-glycosylation, and were non-functional due to being retained and degraded at the endoplasmic reticulum. Functional characterization of four mutants allowed us to identify a novel mechanism leading to ClC-5 dysfunction in Dent disease. We report that these mutant proteins were delayed in their processing and that the stability of their complex glycosylated form was reduced, causing lower cell surface expression. The early endosome distribution of these mutants was normal. Half of these mutants displayed reduced currents, whereas the other half showed abolished currents. Our study revealed distinct cellular mechanisms accounting for ClC-5 loss-of-function in Dent disease

Diagnosis of Small Unruptured Intracranial Aneurysms : Comparison of 7 T versus 3 T MRI.

PURPOSE Differentiating normal anatomical variants such as an infundibulum or a vascular loop from true intracranial aneurysms is crucial for patient management. We hypothesize that high-resolution 7 T magnetic resonance imaging (MRI) improves the detection and characterization of normal anatomical variants that may otherwise be misdiagnosed as small unruptured aneurysms. METHODS This is a retrospective, single-center study. All patients were scanned on a clinically approved 7 T MRI scanner and on a 3 T scanner. Image analysis was performed independently by three neuroradiologists blinded to clinical information. The presence of an unruptured intracranial aneurysm (UIA) and level of diagnostic certainty were assessed and the interrater agreement was calculated. If an aneurysm was present, the anatomic location and shape were recorded and compared. RESULTS In total, 53 patients with equivocal cerebrovascular findings on 1.5 T or 3 T MRI referred for a 7T MRI examination were included. Aneurysms were suspected in 42 patients examined at 3 T and in 23 patients at 7 T (rate difference 36%, 95% confidence interval, CI, 19-53%, p-value < 0.001). Major disagreement between the field strengths was observed in the A1 segment of anterior cerebral artery/anterior communicating artery (A1/ACOM) complex. The interrater agreement among the readers on the presence of an aneurysm on 7 T MRI was higher than that for 3 T MRI (0.925, 95% CI 0.866-0.983 vs. 0.786, 95% CI 0.700-0.873). CONCLUSION Our analysis demonstrates a significantly higher interrater agreement and improved diagnostic certainty when small intracranial aneurysms are visualized on 7 T MRI compared to 3 T. In a selected patient cohort, clinical implementation of 7 T MRI may help to establish the definitive diagnosis and thus have a beneficial impact on patient management

Planetary population synthesis

In stellar astrophysics, the technique of population synthesis has been successfully used for several decades. For planets, it is in contrast still a young method which only became important in recent years because of the rapid increase of the number of known extrasolar planets, and the associated growth of statistical observational constraints. With planetary population synthesis, the theory of planet formation and evolution can be put to the test against these constraints. In this review of planetary population synthesis, we first briefly list key observational constraints. Then, the work flow in the method and its two main components are presented, namely global end-to-end models that predict planetary system properties directly from protoplanetary disk properties and probability distributions for these initial conditions. An overview of various population synthesis models in the literature is given. The sub-models for the physical processes considered in global models are described: the evolution of the protoplanetary disk, the planets' accretion of solids and gas, orbital migration, and N-body interactions among concurrently growing protoplanets. Next, typical population synthesis results are illustrated in the form of new syntheses obtained with the latest generation of the Bern model. Planetary formation tracks, the distribution of planets in the mass-distance and radius-distance plane, the planetary mass function, and the distributions of planetary radii, semimajor axes, and luminosities are shown, linked to underlying physical processes, and compared with their observational counterparts. We finish by highlighting the most important predictions made by population synthesis models and discuss the lessons learned from these predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the 'Handbook of Exoplanets', planet formation section, section editor: Ralph Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed

Temporal Trends and Risk Factors for Delayed Hospital Admission in Suspected Stroke Patients.

(1) Background: The benefit of acute ischemic stroke (AIS) treatment declines with any time delay until treatment. Hence, factors influencing the time from symptom onset to admission (TTA) are of utmost importance. This study aimed to assess temporal trends and risk factors for delays in TTA. (2) Methods: We included 1244 consecutive patients from 2015 to 2018 with suspected stroke presenting within 24 h after symptom onset registered in our prospective, pre-specified hospital database. Temporal trends were assessed by comparing with a cohort of a previous study in 2006. Factors associated with TTA were assessed by univariable and multivariable regression analysis. (3) Results: In 1244 patients (median [IQR] age 73 [60-82] years; 44% women), the median TTA was 96 min (IQR 66-164). The prehospital time delay reduced by 27% in the last 12 years and the rate of patients referred by Emergency medical services (EMS) increased from 17% to 51% and the TTA for admissions by General Practitioner (GP) declined from 244 to 207 min. Factors associated with a delay in TTA were stroke severity (beta-1.9; 95% CI-3.6 to -0.2 min per point NIHSS score), referral by General Practitioner (GP, beta +140 min, 95% CI 100-179), self-admission (+92 min, 95% CI 57-128) as compared to admission by emergency medical services (EMS) and symptom onset during nighttime (+57 min, 95% CI 30-85). Conclusions: Although TTA improved markedly since 2006, our data indicates that continuous efforts are mandatory to raise public awareness on the importance of fast hospital referral in patients with suspected stroke by directly informing EMS, avoiding contact of a GP, and maintaining high effort for fast transportation also in patients with milder symptoms

Nephron-Specific Deletion of Circadian Clock Gene Bmal1 Alters the Plasma and Renal Metabolome and Impairs Drug Disposition.

The circadian clock controls a wide variety of metabolic and homeostatic processes in a number of tissues, including the kidney. However, the role of the renal circadian clocks remains largely unknown. To address this question, we performed a combined functional, transcriptomic, and metabolomic analysis in mice with inducible conditional knockout (cKO) of BMAL1, which is critically involved in the circadian clock system, in renal tubular cells (Bmal1(lox/lox)/Pax8-rtTA/LC1 mice). Induction of cKO in adult mice did not produce obvious abnormalities in renal sodium, potassium, or water handling. Deep sequencing of the renal transcriptome revealed significant changes in the expression of genes related to metabolic pathways and organic anion transport in cKO mice compared with control littermates. Furthermore, kidneys from cKO mice exhibited a significant decrease in the NAD(+)-to-NADH ratio, which reflects the oxidative phosphorylation-to-glycolysis ratio and/or the status of mitochondrial function. Metabolome profiling showed significant changes in plasma levels of amino acids, biogenic amines, acylcarnitines, and lipids. In-depth analysis of two selected pathways revealed a significant increase in plasma urea level correlating with increased renal Arginase II activity, hyperargininemia, and increased kidney arginine content as well as a significant increase in plasma creatinine concentration and a reduced capacity of the kidney to secrete anionic drugs (furosemide) paralleled by an approximate 80% decrease in the expression level of organic anion transporter 3 (SLC22a8). Collectively, these results indicate that the renal circadian clocks control a variety of metabolic/homeostatic processes at the intrarenal and systemic levels and are involved in drug disposition

Discovery of a massive giant planet with extreme density around a sub-giant star TOI-4603

We present the discovery of a transiting massive giant planet around TOI-4603, a sub-giant F-type star from NASA's Transiting Exoplanet Survey Satellite (TESS). The newly discovered planet has a radius of $1.042^{+0.038}_{-0.035}$ $R_{J}$, and an orbital period of $7.24599^{+0.00022}_{-0.00021}$ days. Using radial velocity measurements with the PARAS {and TRES} spectrographs, we determined the planet's mass to be $12.89^{+0.58}_{-0.57}$ $M_{J}$, resulting in a bulk density of $14.1^{+1.7}_{-1.6}$ g ${cm^{-3}}$. This makes it one of the few massive giant planets with extreme density and lies in the transition mass region of massive giant planets and low-mass brown dwarfs, an important addition to the population of less than five objects in this mass range. The eccentricity of $0.325\pm0.020$ and an orbital separation of $0.0888\pm0.0010$ AU from its host star suggest that the planet is likely undergoing high eccentricity tidal (HET) migration. We find a fraction of heavy elements of $0.13^{+0.05}_{-0.06}$ and metal enrichment of the planet ($Z_{P}/Z_{star}$) of $4.2^{+1.6}_{-2.0}$. Detection of such systems will offer us to gain valuable insights into the governing mechanisms of massive planets and improve our understanding of their dominant formation and migration mechanisms.Comment: accepted for publication in A&A Letter

Benefit of Advanced 3D DSA and MRI/CT Fusion in Neurovascular Pathology.

Digital subtraction angiography provides excellent spatial and temporal resolution; however, it lacks the capability to depict the nonvascular anatomy of the brain and spinal cord.A review of the institutional database identified five patients in whom a new integrated fusion workflow of cross-sectional imaging and 3D rotational angiography (3DRA) provided important diagnostic information and assisted in treatment planning. These included two acutely ruptured brain arteriovenous malformations (AVM), a small superficial brainstem AVM after radiosurgery, a thalamic microaneurysm, and a spine AVM, and fusion was crucial for diagnosis and influenced further treatment.Fusion of 3DRA and cross-sectional imaging may help to gain a deeper understanding of neurovascular diseases. This is advantageous for planning and providing treatment and, most importantly, may harbor the potential to minimize complication rates. Integrating image fusion in the work-up of cerebrovascular diseases is likely to have a major impact on the neurovascular field in the future