Possible Effects of Volcanic Eruptions on the Modern Atmosphere of Venus

This work reviews possible signatures and potential detectability of present-day volcanically emitted material in the atmosphere of Venus. We first discuss the expected composition of volcanic gases at present time, addressing how this is related to mantle composition and atmospheric pressure. Sulfur dioxide, often used as a marker of volcanic activity in Earth’s atmosphere, has been observed since late 1970s to exhibit variability at the Venus’ cloud tops at time scales from hours to decades; however, this variability may be associated with solely atmospheric processes. Water vapor is identified as a particularly valuable tracer for volcanic plumes because it can be mapped from orbit at three different tropospheric altitude ranges, and because of its apparent low background variability. We note that volcanic gas plumes could be either enhanced or depleted in water vapor compared to the background atmosphere, depending on magmatic volatile composition. Non-gaseous components of volcanic plumes, such as ash grains and/or cloud aerosol particles, are another investigation target of orbital and in situ measurements. We discuss expectations of in situ and remote measurements of volcanic plumes in the atmosphere with particular focus on the upcoming DAVINCI, EnVision and VERITAS missions, as well as possible future missions

LRAD – A Radiometer for the Lunar South Ppole Hopper µNOVA

The Lunar Prospector discovery of areas of neutron suppression and the subsequent interpretation of hydrogen enrichment near the lunar poles brought the possibility of volatile resources sequestered at the poles to the forefront of the lunar science community. Subsequently the LCROSS experiment showed that water ice is present within at least one permanently shadowed region (PSR) near the south pole and that it can be stable over geological timescales inside permanently shadowed regions (PSRs). Analysis of UV observations gathered by the Lunar Reconnaissance Orbiter Diviner instrument are consistent with the presence of surface frost in some PSRs with temperatures below 110 K. Further, the depth-to-diameter ratios of simple craters as determined from Lunar Orbiter Laser Altimeter (LOLA) altimetric measurements indicate that deposits of water ice in these cold traps may be up to 50 m thick. Moreover, water ice may be present in small PSRs at scales down to, and below 10 meters [5]. Such small-scale cold traps could significantly increase water inventory estimates and eventually simplify extraction

Performance of the ESC 0/1-h and 0/3-h Algorithm for the Rapid Identification of Myocardial Infarction Without ST-Elevation in Patients With Diabetes

Patients with diabetes mellitus (DM) have elevated levels of high-sensitivity cardiac troponin (hs-cTn). We investigated the diagnostic performance of the European Society of Cardiology (ESC) algorithms to rule out or rule in acute myocardial infarction (AMI) without ST-elevation in patients with DM.; We prospectively enrolled 3,681 patients with suspected AMI and stratified those by the presence of DM. The ESC 0/1-h and 0/3-h algorithms were used to calculate negative and positive predictive values (NPV, PPV). In addition, alternative cutoffs were calculated and externally validated in 2,895 patients.; In total, 563 patients (15.3%) had DM, and 137 (24.3%) of these had AMI. When the ESC 0/1-h algorithm was used, the NPV was comparable in patients with and without DM (absolute difference [AD] -1.50 [95% CI -5.95, 2.96]). In contrast, the ESC 0/3-h algorithm resulted in a significantly lower NPV in patients with DM (AD -2.27 [95% CI -4.47, -0.07]). The diagnostic performance for rule-in of AMI (PPV) was comparable in both groups: 0/1-h (AD 6.59 [95% CI -19.53, 6.35]) and 0/3-h (AD 1.03 [95% CI -7.63, 9.7]). Alternative cutoffs increased the PPV in both algorithms significantly, while improvements in NPV were only subtle.; Application of the ESC 0/1-h algorithm revealed comparable safety to rule out AMI comparing patients with and without DM, while this was not observed with the ESC 0/3-h algorithm. Although alternative cutoffs might be helpful, patients with DM remain a high-risk population in whom identification of AMI is challenging and who require careful clinical evaluation

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction

Background: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cardiac troponin (cTn) assays. However, it remains to be determined how to diagnose, risk stratify and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. Methods: Patients presenting to the Emergency Department with chest pain, enrolled in the CHOPIN study, were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic (ROC) curve analysis. The biomarkers analyzed were cTnI, copeptin, mid-regional pro-atrial natriuretic peptide (MRproANP), C-terminal pro-endothelin-1 (CT-proET1), mid-regional pro-adrenomedullin (MRproADM) and procalcitonin. Prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (MACE: a composite of acute MI, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. Results: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, while those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the ROC curve (AUC) for the diagnosis of T2MI was higher for CT-proET1, MRproADM and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, p = 0.294). Addition of biomarkers to the clinical model yielded the highest AUC (0.917). Other biomarkers, but not cTnI, were associated with mortality and MACE at 180-day among all patients, with no interaction between the diagnosis of T1MI or T2MI. Conclusions: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. Additionally, all biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of type of MI

Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. METHODS We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). RESULTS We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). CONCLUSIONS Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage

Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB-driven inflammation and cardiovascular risk

Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-kappa B-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-kappa B regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-kappa B. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-kappa B through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-kappa B signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities

Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-kappa B-driven inflammation and cardiovascular risk

Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-kappa B-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-kappa B regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-kappa B. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-kappa B through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-kappa B signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.Peer reviewe

Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution

Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach of immunomagnetic cell sorting after in vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect the cellular allocation of PET signals in the TME. In mice with implanted glioblastoma, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs), validated by protein levels. Translation of in vitro scRadiotracing to patients with glioma immediately after tumor resection confirmed higher single-cell TSPO tracer uptake of tumor cells compared to immune cells. Across species, cellular radiotracer uptake explained the heterogeneity of individual TSPO-PET signals. In consideration of cellular tracer uptake and cell type abundance, tumor cells were the main contributor to TSPO enrichment in glioblastoma;however, proteomics identified potential PET targets highly specific for TAMs. Combining cellular tracer uptake measures with 3D histology facilitates precise allocation of PET signals and serves to validate emerging novel TAM-specific radioligands

Evaluation of the HadGEM3-A simulations in view of detection and attribution of human influence on extreme events in Europe

A detailed analysis is carried out to assess the HadGEM3-A global atmospheric model skill in simulating extreme temperatures, precipitation and storm surges in Europe in the view of their attribution to human influence. The analysis is performed based on an ensemble of 15 atmospheric simulations forced with observed Sea Surface Temperature of the 54 year period 1960-2013. These simulations, together with dual simulations without human influence in the forcing, are intended to be used in weather and climate event attribution. The analysis investigates the main processes leading to extreme events, including atmospheric circulation patterns, their links with temperature extremes, land-atmosphere and troposphere-stratosphere interactions. It also compares observed and simulated variability, trends and generalized extreme value theory parameters for temperature and precipitation. One of the most striking findings is the ability of the model to capture North Atlantic atmospheric weather regimes as obtained from a cluster analysis of sea level pressure fields. The model also reproduces the main observed weather patterns responsible for temperature and precipitation extreme events. However, biases are found in many physical processes. Slightly excessive drying may be the cause of an overestimated summer interannual variability and too intense heat waves, especially in central/northern Europe. However, this does not seem to hinder proper simulation of summer temperature trends. Cold extremes appear well simulated, as well as the underlying blocking frequency and stratosphere-troposphere interactions. Extreme precipitation amounts are overestimated and too variable. The atmospheric conditions leading to storm surges were also examined in the Baltics region. There, simulated weather conditions appear not to be leading to strong enough storm surges, but winds were found in very good agreement with reanalyses. The performance in reproducing atmospheric weather patterns indicates that biases mainly originate from local and regional physical processes. This makes local bias adjustment meaningful for climate change attribution