Bile acid sequestrants in poor healing after endoscopic therapy of Barrett’s esophagus

Background/Aims Endoscopic therapy for neoplastic Barrett’s esophagus (BE) has become the standard of care over the past two decades. In clinical practice, we regularly encounter patients who fail to achieve complete squamous epithelialization of the esophagus. Although the therapeutic strategies in the individual stages of BE, dysplasia, and esophageal adenocarcinoma are well studied and largely standardized, the problem of inadequate healing after endoscopic therapy is only marginally considered. This study aimed to shed light on the variables influencing inadequate wound healing after endoscopic therapy and the effect of bile acid sequestrants (BAS) on healing. Methods Retrospective analysis of endoscopically treated neoplastic BE in a single referral center. Results In 12.1% out of 627 patients, insufficient healing was present 8 to 12 weeks after previous endoscopic therapy. The average follow-up duration was 38.8±18.4 months. Complete healing was achieved in 13 patients already after intensifying proton pump inhibitor therapy. Out of 48 patients under BAS, 29 patients (60.4%) showed complete healing. An additional eight patients (16.7%) improved, but only partial healing was achieved. Eleven (22.9%) patients showed no response to BAS augmented therapy. Conclusions In cases of insufficient healing even under exhaustion of proton pump inhibitors, treatment with BAS can be an option as an ultimate healing attempt

The vascular gene Apold1 is dispensable for normal development but controls angiogenesis under pathological conditions

The molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role of Apold1 (Apolipoprotein L domain containing 1) in angiogenesis in vivo and in vitro. Single-cell analyses reveal that - across tissues - the expression of Apold1 is restricted to the vasculature and that Apold1 expression in endothelial cells (ECs) is highly sensitive to environmental factors. Using Apold1$^{-/-}$ mice, we find that Apold1 is dispensable for development and does not affect postnatal retinal angiogenesis nor alters the vascular network in adult brain and muscle. However, when exposed to ischemic conditions following photothrombotic stroke as well as femoral artery ligation, Apold1$^{-/-}$ mice display dramatic impairments in recovery and revascularization. We also find that human tumor endothelial cells express strikingly higher levels of Apold1 and that Apold1 deletion in mice stunts the growth of subcutaneous B16 melanoma tumors, which have smaller and poorly perfused vessels. Mechanistically, Apold1 is activated in ECs upon growth factor stimulation as well as in hypoxia, and Apold1 intrinsically controls EC proliferation but not migration. Our data demonstrate that Apold1 is a key regulator of angiogenesis in pathological settings, whereas it does not affect developmental angiogenesis, thus making it a promising candidate for clinical investigation

Meteorological, impact and climate perspectives of the 29 June 2017 heavy precipitation event in the Berlin metropolitan area

Extreme precipitation is a weather phenomenon with tremendous damaging potential for property and human life. As the intensity and frequency of such events is projected to increase in a warming climate, there is an urgent need to advance the existing knowledge on extreme precipitation processes, statistics and impacts across scales. To this end, a working group within the Germany-based project, ClimXtreme, has been established to carry out multidisciplinary analyses of high-impact events. In this work, we provide a comprehensive assessment of the 29 June 2017 heavy precipitation event (HPE) affecting the Berlin metropolitan region (Germany), from the meteorological, impacts and climate perspectives, including climate change attribution. Our analysis showed that this event occurred under the influence of a mid-tropospheric trough over western Europe and two shortwave surface lows over Britain and Poland (Rasmund and Rasmund II), inducing relevant low-level wind convergence along the German–Polish border. Over 11 000 convective cells were triggered, starting early morning 29 June, displacing northwards slowly under the influence of a weak tropospheric flow (10 m s−1 at 500 hPa). The quasi-stationary situation led to totals up to 196 mm d−1, making this event the 29 June most severe in the 1951–2021 climatology, ranked by means of a precipitation-based index. Regarding impacts, it incurred the largest insured losses in the period 2002 to 2017 (EUR 60 million) in the greater Berlin area. We provide further insights on flood attributes (inundation, depth, duration) based on a unique household-level survey data set. The major moisture source for this event was the Alpine–Slovenian region (63 % of identified sources) due to recycling of precipitation falling over that region 1 d earlier. Implementing three different generalised extreme value (GEV) models, we quantified the return periods for this case to be above 100 years for daily aggregated precipitation, and up to 100 and 10 years for 8 and 1 h aggregations, respectively. The conditional attribution demonstrated that warming since the pre-industrial era caused a small but significant increase of 4 % in total precipitation and 10 % for extreme intensities. The possibility that not just greenhouse-gas-induced warming, but also anthropogenic aerosols affected the intensity of precipitation is investigated through aerosol sensitivity experiments. Our multi-disciplinary approach allowed us to relate interconnected aspects of extreme precipitation. For instance, the link between the unique meteorological conditions of this case and its very large return periods, or the extent to which it is attributable to already-observed anthropogenic climate change.</p

Meteorological, impact and climate perspectives of the 29 June 2017 heavy precipitation event in the Berlin metropolitan area

Extreme precipitation is a weather phenomenon with tremendous damaging potential for property and human life. As the intensity and frequency of such events is projected to increase in a warming climate, there is an urgent need to advance the existing knowledge on extreme precipitation processes, statistics and impacts across scales. To this end, a working group within the Germany-based project, ClimXtreme, has been established to carry out multidisciplinary analyses of high-impact events. In this work, we provide a comprehensive assessment of the 29 June 2017 heavy precipitation event (HPE) affecting the Berlin metropolitan region (Germany), from the meteorological, impacts and climate perspectives, including climate change attribution. Our analysis showed that this event occurred under the influence of a mid-tropospheric trough over western Europe and two shortwave surface lows over Britain and Poland (Rasmund and Rasmund II), inducing relevant low-level wind convergence along the German–Polish border. Over 11 000 convective cells were triggered, starting early morning 29 June, displacing northwards slowly under the influence of a weak tropospheric flow (10 m s$^{−1}$ at 500 hPa). The quasi-stationary situation led to totals up to 196 mm d$^{−1}$, making this event the 29 June most severe in the 1951–2021 climatology, ranked by means of a precipitation-based index. Regarding impacts, it incurred the largest insured losses in the period 2002 to 2017 (EUR 60 million) in the greater Berlin area. We provide further insights on flood attributes (inundation, depth, duration) based on a unique household-level survey data set. The major moisture source for this event was the Alpine–Slovenian region (63 % of identified sources) due to recycling of precipitation falling over that region 1 d earlier. Implementing three different generalised extreme value (GEV) models, we quantified the return periods for this case to be above 100 years for daily aggregated precipitation, and up to 100 and 10 years for 8 and 1 h aggregations, respectively. The conditional attribution demonstrated that warming since the pre-industrial era caused a small but significant increase of 4 % in total precipitation and 10 % for extreme intensities. The possibility that not just greenhouse-gas-induced warming, but also anthropogenic aerosols affected the intensity of precipitation is investigated through aerosol sensitivity experiments. Our multi-disciplinary approach allowed us to relate interconnected aspects of extreme precipitation. For instance, the link between the unique meteorological conditions of this case and its very large return periods, or the extent to which it is attributable to already-observed anthropogenic climate change

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution