The nature of the fluorescent iron line in V 1486 Ori

The fluorescent 6.4 keV iron line provides information on cool material in the vicinity of hard X-ray sources as well as on the characteristics of the X-ray sources themselves. First discovered in the X-ray spectra of the flaring Sun, X-ray binaries and active galactic nuclei (AGN), the fluorescent line was also observed in a number of stellar X-ray sources. The young stellar object (YSO) V1486 Ori was observed in the framework of the Chandra Ultra Deep Project (COUP) as the source COUP 331. We investigate its spectrum, with emphasis on the strength and time variability of the fluorescent iron K-alpha line, derive and analyze the light curve of COUP 331 and proceed with a time-resolved spectral analysis of the observation. The light curve of V 1486 Ori shows two major flares, the first one lasting for (approx) 20 ks with a peak X-ray luminosity of 2.6*10^{32} erg/s (dereddened in the 1-10 keV band) and the second one -- only partially observed -- for >60 ks with an average X-ray luminosity of 2.4*10^{31} erg/s (dereddened). The spectrum of the first flare is very well described by an absorbed thermal model at high temperature, with a pronounced 6.7 keV iron line complex, but without any fluorescent K-alpha line. The X-ray spectrum of the second flare is characterized by even higher temperatures (>= 10 keV) without any detectable 6.7 keV Fe XXV feature, but with a very strong fluorescent iron K-alpha line appearing predominantly in the 20 ks rise phase of the flare. Preliminary model calculations indicate that photoionization is unlikely to account for the entire fluorescent emission during the rise phase.Comment: 4 pages, letter, accepted for publication in A&

Sediment Transport Over Labyrinth Weirs

Fixed weir types are generally passive weirs and are supposed to be more prone to hold back sediments. Few model tests have been conducted for specific prototypes of labyrinth weirs which indicate that sediments will be scoured out upstream of the weir by the turbulent action. But an attempt to generalize the findings of the studies is missing. The question that arises is whether the self-cleaning is predictable in dependence of geometry, discharge and sediment properties. The main purpose of this study is to describe and to quantify the self-cleaning process at labyrinth weirs and to predict scouring in various conditions. Therefore systematic experimental tests were performed on a physical model in the laboratory of BAW. The self-cleaning performance of a rectangular and a trapezoidal labyrinth weir are compared for different sediment types. Four sediments were tested under various flow conditions: fine quartz sand, fine gravel, medium-grained gravel and polystyrene granules. In general, the present results confirm the self-cleaning ability of labyrinth weirs. The data of the tested sediments collapse to a single curve for the densimetric Froude number Fd. Accordingly Fd is the dominant parameter and mainly affects the scouring mechanism. It can be seen that self-cleaning begins at a rectangular labyrinth weir at lower discharges compared to a trapezoidal labyrinth weir

INCREASE : An updated model suite to study the INfluence of Cosmic Rays on Exoplanetary AtmoSpherEs

Exoplanets are as diverse as they are fascinating. They vary from ultrahot Jupiter-like low-density planets to presumed gas-ice-rock mixture worlds such as GJ 1214b or worlds as LHS 1140b, which features twice the Earth's bulk density. Regarding the great diversity of exoplanetary atmospheres, much remains to be explored. For a few selected objects such as GJ1214b, Proxima Centauri b, and the TRAPPIST-1 planets, the first observations of their atmospheres have already been achieved or are expected in the near future with the launch of the James Webb Space Telescope envisaged in October 2021. However, in order to interpret these observations, model studies of planetary atmospheres that account for various processes—such as atmospheric escape, outgassing, climate, photochemistry, as well as the physics of air showers and the transport of stellar energetic particles and galactic cosmic rays through the stellar astrospheres and planetary magnetic fields—are necessary. Here, we present our model suite INCREASE, a planned extension of the model suite discussed in Herbst, Grenfell, et al. (2019)

Impact of Cosmic Rays on Atmospheric Ion Chemistry and Spectral Transmission Features of TRAPPIST-1e

Ongoing observing projects like the James Webb Space Telescope and future missions offer the chance to characterize Earth-like exoplanetary atmospheres. Thereby, M dwarfs are preferred targets for transit observations, for example, due to their favorable planet–star contrast ratio. However, the radiation and particle environment of these cool stars could be far more extreme than what we know from the Sun. Thus, knowing the stellar radiation and particle environment and its possible influence on detectable biosignatures—in particular, signs of life like ozone and methane—is crucial to understanding upcoming transit spectra. In this study, with the help of our unique model suite INCREASE, we investigate the impact of a strong stellar energetic particle event on the atmospheric ionization, neutral and ion chemistry, and atmospheric biosignatures of TRAPPIST-1e. Therefore, transit spectra for six scenarios are simulated. We find that a Carrington-like event drastically increases atmospheric ionization and induces substantial changes in ion chemistry and spectral transmission features: all scenarios show high event-induced amounts of nitrogen dioxide (i.e., at 6.2 μm), a reduction of the atmospheric transit depth in all water bands (i.e., at 5.5–7.0 μm), a decrease of the methane bands (i.e., at 3.0–3.5 μm), and depletion of ozone (i.e., at ∼9.6 μm). Therefore, it is essential to include high-energy particle effects to correctly assign biosignature signals from, e.g., ozone and methane. We further show that the nitric acid feature at 11.0–12.0 μm, discussed as a proxy for stellar particle contamination, is absent in wet-dead atmospheres

Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic Melanoma—A Retrospective Multicenter ADOReg Study

The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progressionfree (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary realworld cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT

Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis

Introduction The EXIST-2 (NCT00790400) study demonstrated the superiority of everolimus over placebo for the treatment of renal angiomyolipomas associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). This post hoc analysis of EXIST-2 study aimed to assess angiomyolipoma tumor behavior among patients who submitted to continued radiographic examination following discontinuation of everolimus in the noninterventional follow-up phase. Methods For patients who discontinued everolimus at the completion of extension phase for reasons other than angiomyolipoma progression, a single CT/MRI scan of the kidney was collected after 1 year of treatment discontinuation. Changes from baseline and from the time of everolimus discontinuation in the sum of volumes of target angiomyolipoma lesions were assessed in the non-interventional follow-up phase (data cutoff date, November 6, 2015). Results Of the 112 patients who received >= 1 dose of everolimus and discontinued treatment by the end of extension phase, 34 (30.4%) were eligible for participation in the non-interventional follow-up phase. Sixteen of 34 patients were evaluable for angiomyolipoma tumor behavior as they had at least one valid efficacy assessment (i.e. kidney CT/MRI scan) after everolimus discontinuation. During the non-interventional follow-up phase, compared with baseline, two patients (12.5%) experienced angiomyolipoma progression (angiomyolipoma-related bleeding [n = 1], increased kidney volume [n = 1]). Five patients out of 16 (31.3%) experienced angiomyolipoma progression when compared with the angiomyolipoma tumor assessment at everolimus discontinuation. The median (range) percentage change in angiomyolipoma tumor volume (cm 3) from baseline was -70.56 (-88.30;-49.64) at time of everolimus discontinuation (n = 11), and -50.55 (-79.40;-23.16) at week 48 (n = 7) after discontinuation of everolimus. One patient death was reported due to angiomyolipoma hemorrhage. Conclusions Angiomyolipoma lesions displayed an increase in volume following discontinuation of everolimus in patients with renal angiomyolipoma or sporadic LAM associated with TSC, but there was no evidence of rapid regrowth

Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy

Background: Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy. Methods: 505 Caucasian stage III-IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed. Results: Among 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS (P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status (P = 0.018). Importantly, however, G12V KRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes (P = 0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P = 0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233 days; versus 175 days in the G12x group; P = 0.145). Conclusions: While KRAS mutation status per se is neither prognostic nor predictive in stage III-IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions. © 2014 The Authors