Using the classical model for structured expert judgment to estimate extremes: a case study of discharges in the Meuse River

Accurate estimation of extreme discharges in rivers, such as the Meuse, is crucial for effective flood risk assessment. However, hydrological models that estimate such discharges often lack transparency regarding the uncertainty in their predictions. This was evidenced by the devastating flood that occurred in July 2021, which was not captured by the existing model for estimating design discharges. This article proposes an approach to obtain uncertainty estimates for extremes with structured expert judgment using the classical model (CM). A simple statistical model was developed for the river basin, consisting of correlated generalized extreme value (GEV) distributions for discharges from upstream tributaries. The model was fitted to seven experts' estimates and historical measurements using Bayesian inference. Results were fitted only to the measurements were solely informative for more frequent events, while fitting only to the expert estimates reduced uncertainty solely for extremes. Combining both historical observations and estimates of extremes provided the most plausible results. The classical model reduced the uncertainty by appointing the most weight to the two most accurate experts, based on their estimates of less extreme discharges. The study demonstrates that with the presented Bayesian approach that combines historical data and expert-informed priors, a group of hydrological experts can provide plausible estimates for discharges and potentially also other (hydrological) extremes with relatively manageable effort.</p

Épica, crónicas y genealogías. En torno a la historicidad de la Leyenda de los infantes de Lara

[ES] Este trabajo analiza la historicidad de la narración épica conocida como Leyenda de los Infantes de Lara. Frente a la visión tradicional, que atribuía a este relato una gran fidelidad a los hechos históricos, se sugiere una imagen más compleja, que mezcla elementos nuevos y más antiguos: 1) Un posible núcleo histórico consistente en la historia de Ruy Velázquez; 2) Una parte más compacta formada por la trama de la venganza de sangre, que enlaza la traición con la venganza de Mudarra. Frente a la idea tradicional de que la venganza es una completa ficción elaborada mucho tiempo después, se sugiere que traición y venganza constituyen una unidad lógica, aunque no se relacione con hechos históricos concretos. Es muy probable que el núcleo central de la leyenda, tal y como nos ha llegado, sea más bien un conjunto amplio de temas y motivos entretejidos con hechos históricos más o menos desfigurados. Finalmente, todas estas piezas cobran sentido en su contexto geográfico: la leyenda parece estar reflejando un conflicto entre Lara y Salas, leído desde el punto de vista de Salas, con una clara hostilidad hacia Lara.Peer reviewe

Circulating Precursor Levels of Endothelin-1 and Adrenomedullin, Two Endothelium-Derived, Counteracting Substances, in Sepsis

Plasma levels of endothelin-1 (ET-1) and adrenomedullin (ADM), two opposingly acting peptides, correlate with mortality in endotoxemia, but their measurement is cumbersome. New sandwich assays have been introduced that measure more stable precursor fragments. The objective of this study was to investigate the counterplay of their precursor peptides in septic patients and to compare them with disease severity and other biomarkers. Blood samples of an observational study in 95 consecutive critically ill patients admitted to the intensive care unit (ICU) were analyzed. CT-proET-1 and MR-proADM concentrations on admission were measured using new sandwich immunoassays. Depending on the clinical severity of the infection, both CT-proET-1 and MR-proADM levels exhibited a gradual increase from Systemic Inflammatory Response Syndrome (SIRS) to sepsis and septic shock (p < .001). Compared to the group of survivors, the group of non-survivors had higher median values of MR-proADM (5.7 nmol/L [range 0.4 to 21.0] versus 1.9 nmol/L [range 0.3 to 17.1], p < .02) and similar CT-proET-1 levels (56.0pmol/L [range 0.5 to 271.0] versus 54.1pmol/L [range 1.0 to 506.0], p = .86). Receiver operating characteristics (ROC) curve analysis showed a higher prognostic accuracy of the calculated ratio of both counteracting substances as compared to CT-proET-1 (p = 0.001) and C-reactive protein (CRP) (p = .001) and in the range of MR-proADM (p = .51), procalcitonin (p = 0.22), and the APACHE II score (p = .61). Endothelin-1 and adrenomedullin precursor peptides gradually increase with increasing severities of infection in critically ill patients. The ratio of the two counteracting peptides correlates with mortality and shows aprognostic accuracy to predict adverse outcome comparable to the APACHE II score

Diannexin Protects against Renal Ischemia Reperfusion Injury and Targets Phosphatidylserines in Ischemic Tissue

Renal ischemia/reperfusion injury (IRI) frequently complicates shock, renal transplantation and cardiac and aortic surgery, and has prognostic significance. The translocation of phosphatidylserines to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed phosphatidylserines by the annexin A5 (ANXA5) homodimer Diannexin protects against renal IRI. Protective effects of Diannexin on the kidney were studied in a mouse model of mild renal IRI. Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution and targeting. When comparing its biodistribution and elimination to ANXA5, Diannexin was found to have a distinct distribution pattern and longer blood half-life. Diannexin targeted specifically to the ischemic muscle and its affinity exceeded that of ANXA5. Targeting of both proteins was inhibited by pre-treatment with unlabeled ANXA5, suggesting that Diannexin targets specifically to ischemic tissues via phosphatidylserine-binding. This study emphasizes the importance of phosphatidylserine translocation in the pathophysiology of IRI. We show for the first time that Diannexin protects against renal IRI, making it a promising therapeutic tool to prevent IRI in a clinical setting. Our results indicate that Diannexin is a potential new imaging agent for the study of phosphatidylserine-exposing organs in vivo

Calculating flood probability in Obihiro using a probabilistic method: incorporating the probability of dike failure with uncertainty

In Japan, estimating flood risk follows a deterministic approach. A probabilistic risk method, as adapted in the Netherlands, would be better suited for the quantitative evaluation of flood damage. This study applies such a method in Obihiro, Hokkaido, northern island of Japan. We modelled dike failure with the mechanism overtopping. The probability of dike failure is calculated with a Monte Carlo simulation, considering uncertainties in water levels, critical flow velocity, and dike heights. This results in more accurate failure probabilities compared to the deterministic approach. Additionally, we corrected the dike failure probability for upstream dike failures because these reduce downstream water levels. This conditional flood probability is about 1/10th of the independent situation, indicating a significant effect of considering dike failure in dependence on upstream failures.</p

Guidelines for limiting exposure to electromagnetic fields (100 kHz to 300 GHz)

Radiofrequency electromagnetic fields (EMFs) are used to enable a number of modern devices, including mobile telecommunications infrastructure and phones, Wi-Fi, and Bluetooth. As radiofrequency EMFs at sufficiently high power levels can adversely affect health, ICNIRP published Guidelines in 1998 for human exposure to time-varying EMFs up to 300 GHz, which included the radiofrequency EMF spectrum. Since that time, there has been a considerable body of science further addressing the relation between radiofrequency EMFs and adverse health outcomes, as well as significant developments in the technologies that use radiofrequency EMFs. Accordingly, ICNIRP has updated the radiofrequency EMF part of the 1998 Guidelines. This document presents these revised Guidelines, which provide protection for humans from exposure to EMFs from 100 kHz to 300 GHz

Array-based DNA methylation profiling of primary lymphomas of the central nervous system

<p>Abstract</p> <p>Background</p> <p>Although primary lymphomas of the central nervous system (PCNSL) and extracerebral diffuse large B-cell lymphoma (DLBCL) cannot be distinguished histologically, it is still a matter of debate whether PCNSL differ from systemic DLBCL with respect to their molecular features and pathogenesis. Analysis of the DNA methylation pattern might provide further data distinguishing these entities at a molecular level.</p> <p>Methods</p> <p>Using an array-based technology we have assessed the DNA methylation status of 1,505 individual CpG loci in five PCNSL and compared the results to DNA methylation profiles of 49 DLBCL and ten hematopoietic controls.</p> <p>Results</p> <p>We identified 194 genes differentially methylated between PCNSL and normal controls. Interestingly, Polycomb target genes and genes with promoters showing a high CpG content were significantly enriched in the group of genes hypermethylated in PCNSL. However, PCNSL and systemic DLBCL did not differ in their methylation pattern.</p> <p>Conclusions</p> <p>Based on the data presented here, PCNSL and DLBCL do not differ in their DNA methylation pattern. Thus, DNA methylation analysis does not support a separation of PCNSL and DLBCL into individual entities. However, PCNSL and DLBCL differ in their DNA methylation pattern from non- malignant controls.</p