Global seasonal prediction of fire danger.

The European Centre for Medium range weather forecast (ECMWF) on behalf of the Copernicus Emergency Management Service (CEMS) has recently widened the fire danger data offering in the Climate Data Store (CDS) to include a set of fire danger forecasts with lead times up to 7 months. The dataset incorporates fire danger indices for three different models developed in Canada, United States and Australia. The indices are calculated using ECMWF Seasonal Forecasting System 5 (SEAS5) and verified against the relevant reanalysis of fire danger based on the ECMWF Re-Analysis (ERA5). The data set is made openly available for the period 1981 to 2023 and will be updated regularly providing a resource to assess the predictability of fire weather at the seasonal time scale. The data set complements the availability of seasonal forecast provided by the Copernicus Emergency Management Service in real time.A preliminary analysis shows that globally anomalous conditions for fire weather can be predicted with confidence 1 month ahead. In some regions the prediction can extend to 2 months ahead. In most situations beyond this horizon, forecasts do not show more skill than climatology. However an extended predictability window, up to 6-7 months ahead is possible when anomalous fire weather is the results of large scale phenomena such as the El Niño Southern Oscillation and the Indian Ocean Dipole, often conducive of extensive fire burning in regions such as Indonesia and Australia.

Global warming is shifting the relationships between fire weather and realized fire-induced CO2 emissions in Europe.

Fire activity has significantly changed in Europe over the last decades (1980-2020s), with the emergence of summers attaining unprecedented fire prone weather conditions. Here we report a significant shift in the non-stationary relationship linking fire weather conditions and fire intensity measured in terms of CO2 emissions released during biomass burning across a latitudinal gradient of European IPCC regions. The reported trends indicate that global warming is possibly inducing an incipient change on regional fire dynamics towards increased fire impacts in Europe, suggesting that emerging risks posed by exceptional fire-weather danger conditions may progressively exceed current wildfire suppression capabilities in the next decades and impact forest carbon sinks.

ERA5-based global meteorological wildfire danger maps.

Forest fires are an integral part of the natural Earth system dynamics, however they are becoming more devastating and less predictable as anthropogenic climate change exacerbates their impacts. In order to advance fire science, fire danger reanalysis products can be used as proxy for fire weather observations with the advantage of being homogeneously distributed both in space and time. This manuscript describes a reanalysis dataset of fire danger indices based on the Canadian Fire Weather Index system and the ECMWF ERA5 reanalysis dataset, which supersedes the previous dataset based on ERA-Interim. The new fire danger reanalysis dataset provides a number of benefits compared to the one based on ERA-Interim: it relies on better estimates of precipitation, evaporation and soil moisture, it is available in a deterministic form as well as a probabilistic ensemble and it is characterised by a considerably higher spatial resolution. It is a valuable resource for forestry agencies and scientists in the field of wildfire danger modeling and beyond. The global dataset is produced by ECMWF, as the computational centre of the European Forest Fire information System (EFFIS) of the Copernicus Emergency Management Service, and it is made available free of charge through the Climate Data Store.

Cost-effectiveness and budget impact analysis of viscosupplementation with hylan G-F 20 for knee and hip osteoarthritis.

PURPOSE: To estimate the cost-effectiveness and budget impact of viscosupplementation with one intra-articular (IA) injection of 6 mL hylan G-F 20 (Synvisc-One®) and with three injections of 2 mL hylan G-F 20 (Synvisc®3×2) in knee osteoarthritis (OA) patients compared with conventional support therapy (CST - eg, NSAIDs and acetaminophen) and the cost-effectiveness of one IA injection of 2 mL hylan G-F 20 (Synvisc®1×2) in hip OA patients compared with CST from an Italian Health System perspective. METHODS: The model used was a Markov model with states for stages II-IV on the Kellgren-Lawrence scale and runs on 6-month cycles over a 5-year time horizon. A 3.5% discount was applied to both costs and utilities. Direct costs were determined from the perspective of the Italian National Health Service. A one-way and probabilistic sensitivity analysis was conducted for both comparisons. RESULTS: Hylan G-F 20 1×6 mL and hylan G-F 20 3×2 mL for knee OA were very likely to be cost-effective when compared to acetaminophen (ICER = €3,160.61 and €3,845.81 per QALY, respectively) and NSAIDs as both ICERs are below €25,000. The hip OA treatment by hylan G-F 20 1×2 mL was dominant compared to NSAIDs and very likely compared to acetaminophen. The results of the cost-effectiveness analysis were confirmed by one-way sensitivity analysis. The budget impact analysis for knee and hip OA showed a small increase in expenditure during 5 years. CONCLUSIONS: Hylan G-F 20 1×6 mL/hylan G-F 20 is a cost-effectiveness treatment compared to NSAIDs and acetaminophen in the treatment of knee/hip OA in Italy. The treatment of hip and knee OA resulted in cost-saving with hylan G-F 20 1×2 mL and economically sustainable with hylan G-F 20 1×6 mL. However, Real Word Evidence studies should be conducted in order to estimate costs associated with both prosthetics and to understand the reduction of physiotherapy and medication due to hylan G-F 20.

Mapping combined wildfire and heat stress hazards to improve evidence-based decision making.

Heat stress and forest fires are often considered highly correlated hazards as extreme temperatures play a key role in both occurrences. This commonality can influence how civil protection and local responders deploy resources on the ground and could lead to an underestimation of potential impacts, as people could be less resilient when exposed to multiple hazards. In this work, we provide a simple methodology to identify areas prone to concurrent hazards, exemplified with, but not limited to, heat stress and fire danger. We use the combined heat and forest fire event that affected Europe in June 2017 to demonstrate that the methodology can be used for analysing past events as well as making predictions, by using reanalysis and medium-range weather forecasts, respectively. We present new spatial layers that map the combined danger and make suggestions on how these could be used in the context of a Multi-Hazard Early Warning System. These products could be particularly valuable in disaster risk reduction and emergency response management, particularly for civil protection, humanitarian agencies and other first responders whose role is to identify priorities during pre-interventions and emergencies.

A 1980-2018 global fire danger re-analysis dataset for the Canadian Fire Weather Indices.

This data descriptor documents a dataset containing over 38 years of global reanalysis of wildfire danger. It consists of seven fields to assess fuel moisture as well as fire behavior. The methodology employed to generate these data is based on the Canadian Forest Fire Weather Danger Rating and utilizes weather forcing from ERA-Interim, a global reanalysis dataset produced by the European Centre for Medium-range Weather Forecasts. Global fire danger reanalysis data are used to quantify the climatological expectation of fire danger at a certain time of the year and for any location on the globe. It can be regarded as a complementary product to the fire danger forecasts issued daily by the Global Wildfire Information System (GWIS) under the umbrella of the European Copernicus program.

Dynamical Malaria Forecasts Are Skillful at Regional and Local Scales in Uganda up to 4 Months Ahead.

Malaria forecasts from dynamical systems have never been attempted at the health district or local clinic catchment scale, and so their usefulness for public health preparedness and response at the local level is fundamentally unknown. A pilot preoperational forecasting system is introduced in which the European Centre for Medium Range Weather Forecasts ensemble prediction system and seasonal climate forecasts of temperature and rainfall are used to drive the uncalibrated dynamical malaria model VECTRI to predict anomalies in transmission intensity 4 months ahead. It is demonstrated that the system has statistically significant skill at a number of sentinel sites in Uganda with high-quality data. Skill is also found at approximately 50% of the Ugandan health districts despite inherent uncertainties of unconfirmed health reports. A cost-loss economic analysis at three example sentinel sites indicates that the forecast system can have a positive economic benefit across a broad range of intermediate cost-loss ratios and frequency of transmission anomalies. We argue that such an analysis is a necessary first step in the attempt to translate climate-driven malaria information to policy-relevant decisions.

Caliver: An R package for CALIbration and VERification of forest fire gridded model outputs.

The name caliver stands for CALIbration and VERification of forest fire gridded model outputs. This is a package developed for the R programming language and available under an APACHE-2 license from a public repository. In this paper we describe the functionalities of the package and give examples using publicly available datasets. Fire danger model outputs are taken from the modeling components of the European Forest Fire Information System (EFFIS) and observed burned areas from the Global Fire Emission Database (GFED). Complete documentation, including a vignette, is also available within the package.

Impact analysis of ICH S9 on non-clinical development of anticancer drugs.

Cancer presents a major healthcare challenge worldwide, with several millions new cases a year, and represents a therapeutic area with a high need for new drugs. To respond to this, the parties of the International Conference for Harmonization agreed in 2007 to develop a guideline on nonclinical requirements for oncology therapeutics' development (ICH S9), which came into effect in early 2010. This guideline includes recommendations to facilitate and accelerate the development and marketing of cancer therapeutic agents for serious and life threatening malignancies and aims to address this need through a refinement and a reduction in the use of experimental animals, following the 3Rs principles. To assess the impact of ICH S9 on drug development and reduction of animal use, we performed an analysis of Marketing Authorization Applications at the European Medicines Agency relevant to the period in which the development of the guideline was approaching the final steps and its early implementation period. From the analysis performed, a consistent trend towards a decrease in the average number of non-clinical studies performed (-40.7%) and number of animals used per development program (-58.1%) for new chemical entities has been detected, highlighting increasing compliance by companies to the recommendations of ICH S9.

Changes and determination of dosing recommendations for medicinal products recently authorised in the European Union.

INTRODUCTION: The quantity and quality of data for determining the dose and treatment schedule of medicinal products is directly related to how safe and efficacious these medicines are and how successful they can be used to treat patients. AREAS COVERED: This review provides an analysis of dose-related label modifications of recently approved drugs. It shows which areas could benefit from a better dose-exposure-response understanding, both during initial assessment and after marketing authorisation. This analysis highlights regulators' considerations in dosage evaluations and provides reflections for drug developers on how to ensure best possible dose selection in the interest of the patients. EXPERT OPINION: Using modelling and simulation, pharmacogenomics, population pharmacokinetics, physiologically based pharmacokinetic models and drug-drug interaction studies in conjunction with well-designed clinical trials will improve the understanding of the pharmacology of medicines, of the physiology of the disease and of the dose-exposure-response relationship during drug development. More focus should be given to the investigation of dose and regimens for special populations before applying for marketing authorisation. Consequently, regulators could review dose-exposure-response data with more certainty and better define dose recommendations in the label.

Control of pH responsive peptide self-association during endocytosis is required for effective gene transfer.

Cationic amphipathic histidine rich peptides demonstrate differential nucleic acid binding capabilities at neutral and acidic pH and adopt conformations at acidic pH that enable interaction with endosomal membranes, their subsequent disordering and facilitate entry of cargo to the cell cytosol. To better understand the relative contributions of each stage in the process and consequently the structural requirements of pH responsive peptides for optimal nucleic acid transfer, we used biophysical methods to dissect the series of events that occur during endosomal acidification. Far-UV circular dichroism was used to characterise the solution conformation of a series of peptides, containing either four or six histidine residues, designed to respond at differing pH while a novel application of near-UV circular dichroism was used to determine the binding affinities of the peptides for both DNA and siRNA. The peptide induced disordering of neutral and anionic membranes was investigated using (2)H solid-state NMR. While each of these parameters models key stages in the nucleic acid delivery process and all were affected by increasing the histidine content of the peptide, the effect of a more acidic pH response on peptide self-association was most notable and identified as the most important barrier to further enhancing nucleic acid delivery. Further, the results indicate that Coulombic interactions between the histidine residues modulate protonation and subsequent conformational transitions required for peptide mediated gene transfer activity and are an important factor to consider in future peptide design.

Grooming, rank, and agonistic support in tufted capuchin monkeys.

Studies investigating the relation between allogrooming and social rank in capuchin monkeys (genus Cebus) have yielded inconsistent results. In this study, we investigated the relation between grooming, agonistic support, aggression and social rank in a captive group of tufted capuchin monkeys (C. apella). Differently from most previous studies, we based our analyses on a relatively large database and studied a group with known genealogical relationships. Tufted capuchin females did not exchange grooming for rank-related benefits such as agonistic support or reduced aggression. Coherently with this picture, they did not groom up the hierarchy and did not compete for accessing high-ranking grooming partners. It is suggested that a small group size, coupled with a strong kin bias, may make the exchange of grooming for rank-related benefits impossible or unprofitable, thus eliminating the advantages of grooming up the hierarchy. We provide several possible explanations for the heterogeneity of results across capuchin studies that have addressed similar questions.