A dynamic extreme value model with applications to volcanic eruption forecasting

Extreme events such as natural and economic disasters leave lasting impacts on society and motivate the analysis of extremes from data. While classical statistical tools based on Gaussian distributions focus on average behaviour and can lead to persistent biases when estimating extremes, extreme value theory (EVT) provides the mathematical foundations to accurately characterise extremes. In this paper, we adapt a dynamic extreme value model recently introduced to forecast financial risk from high frequency data to the context of natural hazard forecasting. We demonstrate its wide applicability and flexibility using a case study of the Piton de la Fournaise volcano. The value of using EVT-informed thresholds to identify and model extreme events is shown through forecast performance.Comment: Math Geosci (2023

COVID-19 and MIS-C treatment in children—results from an international survey

Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. In addition, access to COVID-19 therapeutics remains limited. Collecting physicians’ experiences with off-label use of therapeutics is important to inform global prioritization processes and better target pediatric research and development. A standardized questionnaire was designed to explore the use of therapeutics used to treat COVID-19 and multisystem inflammatory syndrome in children (MIS-C) in pediatric patients globally. Seventy-three physicians from 29 countries participated. For COVID-19, steroids were used by 75.6% of respondents; remdesivir and monoclonal antibodies were prescribed by 48.6% and 27.1% of respondents, respectively. For MIS-C, steroids were prescribed by 79.1% of respondents and intravenous immunoglobulins by 69.6%. The use of these products depended on their pediatric approval and the limited availability of antivirals and most monoclonal antibodies in Africa, South America, Southeast Asia, and Eastern Europe. Off-label prescription resulted widespread due to the paucity of clinical trials in young children at the time of the survey; though, based on our survey results, it was generally safe and led to clinical benefits. Conclusion: This survey provides a snapshot of current practice for treating pediatric COVID-19 worldwide, informing global prioritization efforts to better target pediatric research and development for COVID-19 therapeutics. Off-label use of such medicines is widespread for the paucity of clinical trials under 12 years and 40 kg, though appears to be safe and generally results in clinical benefits, even in young children. However, access to care, including medicine availability, differs widely globally. Clinical development of COVID-19 antivirals and monoclonal antibodies requires acceleration to ensure pediatric indication and allow worldwide availability of therapeutics that will enable more equitable access to COVID-19 treatment. What is Known: • Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. • Access to care differs widely globally, so because of the diversity of national healthcare systems; the unequal availability of medicines for COVID-19 treatment represents an obstacle to the pediatric population's universal right to health care. What is New: • Off-label COVID-19 drug prescription is widespread due to the lack of clinical trials in children younger than 12 years and weighing less than 40 kg, but relatively safe and generally leading to clinical benefit. • The application of the GAP-f framework to COVID-19 medicines is crucial, ensuring widespread access to all safe and effective drugs, enabling the rapid development of age-appropriate formulations, and developing specific access plans (including stability, storage, packaging, and labeling) for distribution in low- and middle-income countries (LMICs). Antivirals and monoclonal antibodies may benefit from the acceleration to reach widespread and equal diffusion

NanTroSEIZE Stage 1 expeditions: introduction and synthesis of key results

Integrated Ocean Drilling Program Expeditions 314, 315, and 316 were carried out as a unified program of drilling collectively known as Stage 1 of the Nankai Trough Seismogenic Zone Experiment, a multistage complex drilling project. A transect of eight sites was selected for riserless drilling to target the frontal thrust region, midslope megasplay fault region, and Kumano forearc basin region. Two of these sites are preparatory pilot holes for planned deep riser drilling operations, whereas the others targeted fault zone material in the shallow, presumed aseismic zone. Expedition 314 was dedicated to in situ measurement of physical properties and borehole imaging through logging while drilling in holes dedicated to that purpose. Expedition 315 was devoted to core sampling and downhole temperature measurements at one site in the megasplay region and one site in the forearc basin. Expedition 316 targeted the frontal and out-of-sequence megasplay fault region in the mid-slope environment. Results on accretionary complex structure, lithology and age, physical properties, and state of stress, which are documented in full in the site chapters of this volume, are here synthesized across the expeditions

Abacavir pharmacokinetics in African children living with HIV: A pooled analysis describing the effects of age, malnutrition and common concomitant medications

AIMS: Abacavir is part of WHO-recommended regimens to treat HIV in children under 15 years of age. In a pooled analysis across four studies, we describe abacavir population pharmacokinetics to investigate the influence of age, concomitant medications, malnutrition and formulation. METHODS: A total of 230 HIV-infected African children were included, with median (range) age of 2.1 (0.1-12.8) years and weight of 9.8 (2.5-30.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed-effects modelling. RESULTS: Abacavir pharmacokinetics was best described by a two-compartment model with first-order elimination, and absorption described by transit compartments. Clearance was predicted around 54% of its mature value at birth and 90% at 10 months. The estimated typical clearance at steady state was 10.7 L/h in a child weighing 9.8 kg co-treated with lopinavir/ritonavir, and was 12% higher in children receiving efavirenz. During co-administration of rifampicin-based antituberculosis treatment and super-boosted lopinavir in a 1:1 ratio with ritonavir, abacavir exposure decreased by 29.4%. Malnourished children living with HIV had higher abacavir exposure initially, but this effect waned with nutritional rehabilitation. An additional 18.4% reduction in clearance after the first abacavir dose was described, suggesting induction of clearance with time on lopinavir/ritonavir-based therapy. Finally, absorption of the fixed dose combination tablet was 24% slower than the abacavir liquid formulation. CONCLUSION: In this pooled analysis we found that children on lopinavir/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super-boosted lopinavir gave significantly reduced abacavir concentrations

Towards Regional Scale Stormwater Flood Management Strategies through Rapid Preliminary Intervention Screening

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Data underpinning this study is available upon reasonable request through contacting the authors.his paper presents the advantages and opportunities for rapid preliminary intervention screening to enhance inclusion of green infrastructures in regional scale stormwater management. Stormwater flooding is widely recognised as a significant and worsening natural hazard across the globe; however, current management approaches aimed at the site scale do not adequately explore opportunities for integrated management at the regional scale at which decisions are made. This research addresses this gap through supporting the development of stormwater management strategies, including green infrastructure, at a regional scale. This is achieved through upscaling a modelling approach using a spatially explicit inundation model (CADDIES) coupled with an economic model of inundation loss (OpenProFIA) to support widescale evaluation of green infrastructure during the informative early-stage development of stormwater management strategies. This novel regional scale approach is demonstrated across a case study of the San Francisco Bay Area, spanning 8300 sq km. The main opportunity from this regional approach is to identify spatial and temporal trends which are used to inform regional planning and direct future detailed modelling efforts. The study highlights several limitations of the new method, suggesting it should be applied as part of a suite of landscape management approaches; however, highlights that it has the potential to complement existing stormwater management toolkitsNatural Capital ProjectEngineering and Physical Sciences Research Council (EPSRC)Natural Environment Research Council (NERC)Betty and Gordon Moore FoundationNanyang Technological University and National Research Foundation, Prime Minister’s Office, SingaporeEngineering School, Universidad de Buenos Aire

Slab segmentation controls the interplate slip motion in the SW Hellenic subduction: New insight from the 2008Mw 6.8 Methoni interplate earthquake

We present an integrated approach of the seismic structure and activity along the offshore SW Hellenic subduction from combined observations of marine and land seismic stations. Our imaging of the slab top topography from teleseismic receiver function analysis at ocean bottom seismometers supports a trenchward continuation of the along-dip slab faults beneath the Peloponnesus. We further show that their morphostructural control accounts for the backstepping of the thrust contact of the Mediterranean Ridge accretionary wedge over the upper plate. Local seismic activity offshore SW Peloponnesus constrained by ocean bottom seismometer observations reveals a correlation with specific features of the forearc: the Matapan Troughs. We study the Mw6.8 14.02.2008 interplate earthquake offshore SW Peloponnesus and show that its nucleation, rupture zone, and aftershocks sequence are confined to one slab panel between two adjacent along-dip faults and are thus controlled by not only the offshore slab top segmentation but also the upper plate sea-bottom morphology