What distinguishes 100-year precipitation extremes over central European river catchments from more moderate extreme events?

Historical extreme flooding events in central European river catchments caused high socioeconomic impacts. Previous studies have analysed single events in detail but have not focused on a robust analysis of the underlying extreme precipitation events in general, as historical events are too rare for a robust assessment of their generic dynamical causes. This study tries to fill this gap by analysing a set of realistic daily 100-year large-scale precipitation events over five major European river catchments with the help of operational ensemble prediction data from the ECMWF. The dynamical conditions during such extreme events are investigated and compared to those of more moderate extreme events (20 to 50 year); 100-year precipitation events are generally associated with an upper-level cutoff low over central Europe in combination with a surface cyclone southeast of the specific river catchment. The 24 h before the event is decisive for the exact location of this surface cyclone, depending on the location and velocity of the upper-level low over western Europe. The difference between 100-year and more moderate extreme events varies from catchment to catchment. Dynamical mechanisms such as an intensified upper-level cutoff low and surface cyclone are the main drivers distinguishing 100-year events in the Oder and Danube catchments, whereas thermodynamic mechanisms such as a higher moisture supply in the lower troposphere east of the specific river catchment are more relevant in the Elbe and Rhine catchments. For the Weser and Ems catchment, differences appear in both dynamical and thermodynamic mechanisms

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

Peripheral Delta Opioid Receptors Mediate Formoterol Anti-allodynic Effect in a Mouse Model of Neuropathic Pain.

Neuropathic pain is a challenging condition for which current therapies often remain unsatisfactory. Chronic administration of β2 adrenergic agonists, including formoterol currently used to treat asthma and chronic obstructive pulmonary disease, alleviates mechanical allodynia in the sciatic nerve cuff model of neuropathic pain. The limited clinical data currently available also suggest that formoterol would be a suitable candidate for drug repurposing. The antiallodynic action of β2 adrenergic agonists is known to require activation of the delta-opioid (DOP) receptor but better knowledge of the molecular mechanisms involved is necessary. Using a mouse line in which DOP receptors were selectively ablated in neurons expressing Nav1.8 sodium channels (DOP cKO), we showed that these DOP peripheral receptors were necessary for the antiallodynic action of the β2 adrenergic agonist formoterol in the cuff model. Using a knock-in mouse line expressing a fluorescent version of the DOP receptor fused with the enhanced green fluorescent protein (DOPeGFP), we established in a previous study, that mechanical allodynia is associated with a smaller percentage of DOPeGFP positive small peptidergic sensory neurons in dorsal root ganglia (DRG), with a reduced density of DOPeGFP positive free nerve endings in the skin and with increased DOPeGFP expression at the cell surface. Here, we showed that the density of DOPeGFP positive free nerve endings in the skin is partially restored and no increase in DOPeGFP translocation to the plasma membrane is observed in mice in which mechanical pain is alleviated upon chronic oral administration of formoterol. This study, therefore, extends our previous results by confirming that changes in the mechanical threshold are associated with changes in peripheral DOP profile. It also highlights the common impact on DOP receptors between serotonin noradrenaline reuptake inhibitors such as duloxetine and the β2 mimetic formoterol.journal article20192020 02 14importe

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

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p