Retrospective evaluation of landslide susceptibility maps and review of validation practice

Despite the widespread application of landslide susceptibility analyses, there is hardly any information about whether or not the occurrence of recent landslide events was correctly predicted by the relevant susceptibility maps. Hence, the objective of this study is to evaluate four landslide susceptibility maps retrospectively in a landslide-prone area of the Swabian Alb (Germany). The predictive performance of each susceptibility map is evaluated based on a landslide event triggered by heavy rainfalls in the year 2013. The retrospective evaluation revealed significant variations in the predictive accuracy of the analyzed studies. Both completely erroneous as well as very precise predictions were observed. These differences are less attributed to the applied statistical method and more to the quality and comprehensiveness of the used input data. Furthermore, a literature review of 50 peer-reviewed articles showed that most landslide susceptibility analyses achieve very high validation scores. 73% of the analyzed studies achieved an area under curve (AUC) value of at least 80%. These high validation scores, however, do not reflect the high uncertainty in statistical susceptibility analysis. Thus, the quality assessment of landslide susceptibility maps should not only comprise an index-based, quantitative validation, but also an additional qualitative plausibility check considering local geomorphological characteristics and local landslide mechanisms. Finally, the proposed retrospective evaluation approach cannot only help to assess the quality of susceptibility maps and demonstrate the reliability of such statistical methods, but also identify issues that will enable the susceptibility maps to be improved in the future

Update of the European Landslide Susceptibility Map (ELSUS Version 2)

We present an update of the initial version of the European Landslide Susceptibility Map (ELSUS Version 1) that was released in 2012 through the EU Joint Research Centre (JRC) European Soil Data Centre (ESDAC). The susceptibility evaluation methodology employed for the updated map ELSUS Version 2 presented in this paper is identical to the previous approach, and comprises the differentiation of the analyzed European area into seven climate-physiographical model zones, the use of a reduced set of spatial susceptibility predictors (shallow subsurface lithology, slope angle, and land cover), and model zone-specific heuristic spatial multicriteria evaluations (SMCE) for susceptibility mapping. The most important improvement for ELSUS version 2 is the replacement of the original “lithology” data set consisting of soil parent material information derived from the European Soil Database (ESDB) by new information derived from the digital version of the International Hydrogeological Map of Europe at scale 1:1.5 Million (IHME 1500). IHME lithology describes both consolidated and unconsolidated shallow geological materials over Europe and can be shown to have a higher significance for landslide susceptibility evaluation than the soil parent material derived from ESDB. Other improvements consist in the change of the mapping unit from 1 km to 200 m grid size and the incorporation of terrains not covered by ELSUS version 1 (e.g., Iceland, the Faroers, the Shetlands, and Cyprus). Additionally, the new ELSUS version 2 was calibrated and validated with an updated pan-European landslide inventory now containing more than 155,000 landslides (30% more than used for ELSUS version 1). The enhanced and updated landslide inventory and the higher quality of the “lithology” data enabled us to establish more consistent SMCE-schemes for the individual model zones. The enhancements of ELSUS Version 2 result in an overall increase of the predictive power of the map for about 10%, as indicated by ROC curve metrics obtained with the updated landslide inventory. However, the assessment still suffers from missing landslide information in many European terrains. It can be suspected that more distributed landslides information in specific model zones will further enhance the accuracy of ELSUS in the future.JRC.H.5-Land Resources Managemen

A decrease in rockfall probability under climate change conditions in Germany

The effect of climate change on rockfalls in the German low mountain regions is investigated following two different approaches. The first approach uses a logistic regression model that describes the combined effect of precipitation, freeze–thaw cycles, and fissure water on rockfall probability. The climate change signal for the past 6 decades is analysed by applying the model to meteorological observations. The possible effect of climate change until the end of the century is explored by applying the statistical model to the output of a multi-model ensemble of 23 regional climate scenario simulations. It is found that the number of days per year exhibiting an above-average probability for rockfalls has mostly been decreasing during the last few decades. Statistical significance is, however, present at only a few sites. A robust and statistically significant decrease can be seen in the Representative Concentration Pathway (RCP) climate scenario 8.5 (RCP8.5) simulations for Germany and neighbouring regions, locally falling below −10 % when comparing the last 30 years of the 20th century to the last 30 years of the 21st century. The most important factor determining the projected decrease in rockfall probability is a reduction in the number of freeze–thaw cycles expected under future climate conditions. For the second approach four large-scale meteorological patterns that are associated with enhanced rockfall probability are identified from reanalysis data. The frequency of all four patterns exhibits a seasonal cycle that maximises in the cold half of the year (winter and spring). Trends in the number of days that can be assigned to these patterns are determined both in meteorological reanalysis data and in climate simulations. In the reanalysis no statistically significant trend is found. For the future scenario simulations all climate models show a statistically significant decrease in the number of rockfall-promoting weather situations

Thermoregulatory Requirements Shape Mating Opportunities of Male Proboscis Bats

The spatiotemporal distribution of females is a major factor affecting animal social systems. Predation risk and the distribution of feeding resources often determine where females are found, but abiotic factors (e.g., temperature) can also shape the distribution of females and therefore variation in social organization and mating systems. Given the predicted future changes in climatic variation, it is vital to understand how animal mating systems and the sexual selection process may be altered by temperature. In bats, female distribution is tightly linked to roosting ecology and particularly to the microclimatic conditions at the roost. Proboscis bats (Rhynchonycteris naso) form cohesive and stable multi-male-multi-female groups and inhabit exposed day roosts (e.g., tree trunks, vines, buildings). Strong selection to remain inconspicuous to visually oriented predators in the exposed day roosts has been suggested to promote a rather rare male mating strategy termed site-specific dominance where males defend females directly but are successful in doing so only in their own territory. The choice of open-roost structures can result in the bats roosting under direct sunlight, making individuals susceptible to overheating. Here we investigate whether regular relocations of R. naso social groups among male territories are a mechanism of behavioral thermoregulation. Our results suggest that in general R. naso choose the warmest suitable roost sites within a roost, possibly to minimize the energetic costs of thermoregulation. However, on days with high midday temperatures at the primary roost site, bats commonly relocate to alternative, cooler sites within their roosts. These thermoregulatory relocations entail that a social group regularly switches among the territories of several males. Thus, the need for behavioral thermoregulation determines the spatial distribution of females and shapes the mating opportunities of males during the day. This is supported by our result that territorial males defending primary roost sites are reproductively more successful than territorial males of alternate roost sites. In line with other studies, our findings suggest that the increase in ambient temperatures associated with climate change has the potential to affect the intensity of sexual selection in bat species and may have far-reaching behavioral, demographic, and evolutionary consequences for their populations

Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel

Light transmission aggregometry (LTA) is used worldwide for the investigation of heritable platelet function disorders (PFDs), but interpretation of results is complicated by the feedback effects of ADP and thromboxane A(2) (TxA(2)) and by the overlap with the response of healthy volunteers. Over 5 years, we have performed lumi-aggregometry on 9 platelet agonists in 111 unrelated research participants with suspected PFDs and in 70 healthy volunteers. Abnormal LTA or ATP secretion test results were identified in 58% of participants. In 84% of these, the patterns of response were consistent with defects in Gi receptor signaling, the TxA(2) pathway, and dense granule secretion. Participants with defects in signaling to Gq-coupled receptor agonists and to collagen were also identified. Targeted genotyping identified 3 participants with function-disrupting mutations in the P2Y(12) ADP and TxA(2) receptors. The results of the present study illustrate that detailed phenotypic analysis using LTA and ATP secretion is a powerful tool for the diagnosis of PFDs. Our data also enable subdivision at the level of platelet-signaling pathways and in some cases to individual receptors. We further demonstrate that most PFDs can be reliably diagnosed using a streamlined panel of key platelet agonists and specified concentrations suitable for testing in most clinical diagnostic laboratories

European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death.

Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome

BACKGROUND: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. METHODS: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. RESULTS: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P&lt;5×10-8) near NOS1AP, KCNQ1, and KLF12, and 1 missense variant in KCNE1(p.Asp85Asn) at the suggestive threshold (P&lt;10-6). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (rg=0.40; P=3.2×10-3). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P&lt;10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P&lt;0.005). CONCLUSIONS: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.</p

Phospholipase D signaling: orchestration by PIP2 and small GTPases

Hydrolysis of phosphatidylcholine by phospholipase D (PLD) leads to the generation of the versatile lipid second messenger, phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be dramatically stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and, particularly, by the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 is well known as substrate for the generation of second messengers by phospholipase C, but is now also understood to recruit and/or activate a variety of actin regulatory proteins, ion channels and other signaling proteins, including PLD, by direct interaction. The synthesis of PIP2 by phosphoinositide 5-kinase (PIP5K) isoforms is tightly regulated by small GTPases and, interestingly, by PA as well, and the concerted formation of PIP2 and PA has been shown to mediate receptor-regulated cellular events. This review highlights the regulation of PLD by membrane receptors, and describes how the close encounter of PLD and PIP5K isoforms with small GTPases permits the execution of specific cellular functions

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK