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The ECB's target was recently revised, specifying that the 2%-inflation-rate threshold must be applied sym-metrically and with a medium-term orientation. In the current phase, characterized by high inflation rates and a growing risk of stagnation in the euro area, this revision of the monetary policy strategy is crucial for explaining the recent decisions of the ECB and forecasting their possible evolution. However, monetary policy can only become one of many policy tools in the euro area. Therefore, there is room for a compelling policy mix necessary to control excessive inflation and to support the medium-term sustainable growth of the European economy. (c) 2023 Published by Elsevier Inc. on behalf of The Society for Policy Modeling.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.

The atmosphere transports energy polewards by circulation cells and eddies. To the present day, there has been a knowledge gap regarding the preferred spatial scales and physical mechanisms of eddy energy transport. To fill the gap, we separate the meridional atmospheric energy transport in the ERA5 reanalysis by spatial scales and into quasi-stationary and transient flow patterns and latent and dry components. Baroclinic instability is the major instability mechanism in the transient synoptic scales and is responsible for forming cyclones, anticyclones, and small-scale Rossby waves. At the planetary scales, circulation patterns are often induced by other mechanisms such as flow interaction with orography and land–sea heating contrasts. However, a separation between circulation patterns at the synoptic and planetary scales has yet to be established. We find that both baroclinically induced and transient energy transport is predominantly associated with eddies at wavelengths between 2000 and 8000 km. The maxima in both types of transport occur at wavelengths around 5000 km, in good agreement with linear baroclinic theory. Since these results are independent of latitude, we adapt the scale separation of the energy transport to be based on the wavelength instead of the previously used wavenumber. We define the synoptic transport by the wavelength band between 2000 and 8000 km. We analyse the annual and seasonal mean in the energy transport components and their inter-annual variability. The scale-separated transport components are fairly similar in both hemispheres. Transport by synoptic waves is the largest contributor to extra-tropical energy and moisture transport, mainly of a transient character, and is influenced little by seasonality. In contrast, transport by planetary waves depends highly on the season and has two distinct characteristics. (1) In the extra-tropical winter, planetary waves are important due to a large transport of dry energy. This planetary transport features the largest inter-annual variability of all components and is mainly quasi-stationary in the Northern Hemisphere but transient in its southern counterpart. (2) In the sub-tropical summer, quasi-stationary planetary waves are the most important transport component, mainly due to moisture transport, presumably associated with monsoons. In contrast to transport by planetary and synoptic waves, only a negligible amount of energy is transported by mesoscale eddies (< 2000 km).

Biologics are emerging as the most important class of drugs and are used to treat a large variety of pathologies. Most of biologics are proteins administered in large amounts, either by intramuscular injection or by intravenous infusion. Asparaginase is a large tetrameric protein assembly, currently used against acute lymphoblastic leukemia. Here, a gadolinium(III)-DOTA derivative has been conjugated to asparaginase, and its relaxation properties have been investigated to assess its efficiency as a possible theranostic agent. The field-dependent

In recent years, new treatments have been approved for nonmetastatic castration-resistant prostate cancer (M0CRPC). Because direct comparisons between these treatments are not available to guide treatment decisions, indirect comparisons can be of interest.Our analysis evaluated second-generation hormone treatments proposed for M0CRPC. We searched multiple databases for articles published between 2010 and 2022. Phase-III clinical trials that studied these agents in M0CRPC patients were eligible. Among these, we included trials reporting overall survival (OS) through Kaplan-Meier curves. We performed the reconstruction of individual patient data from Kaplan-Meier graphs, according to the Shiny method, to indirectly compare the efficacy of the different agents. Indirect comparisons included testing for equivalence according to FDA criteria. Confidence intervals (CI) were 95% in all analyses except equivalence testing, where 90%CIs were used.Three studies met these inclusion criteria. Apalutamide (hazard ratio [HR]: 0.75, 95% confidence interval [CI] 0.64-0.88), darolutamide (HR 0.70, 95%CI 0.58-0.84), and enzalutamide (HR 0.77, 95%CI 0.65-0.90) were all significantly more effective than the placebo. Our results showed no difference in OS between any of these three agents, and in testing for equivalence, our estimates of HR met the 0.75-1.33 level.While the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons based on mature OS demonstrated similar efficacy and substantial equivalence among these three second-generation androgen receptor inhibitors.

Biomechanical finite-element study.To directly compare the biomechanical effects of two different techniques for sagittal plane correction of adult spine deformity based on the anterior longitudinal ligament (ALL) resection and use of hyperlordotic cages, namely, the anterior column realignment (ACR) in L3-4, and ALIF in L5-S1 in terms of primary stability and rod stresses using finite-element models.A finite-element model of the thoracolumbar spine was used to perform the analysis. Starting from this "intact" model, three further models were constructed through the insertion of spinal instrumentation, i.e., pedicle screws, rods and cages: 1) posterior instrumentation between T9 and S1 (referred to as "T9-S1"); 2) posterior instrumentation T9-S1 + Hyperlordotic (26°) ALIF cage in L5-S1 ("ALIF"); 3) posterior instrumentation T9-S1 + Hyperlordotic (30°) ACR cage in L3-4 ("ACR"). These models were studied by simulations applying, alternately, a pure moment of 7.5 Nm between the three planes of motion (flexion, extension, lateral bending, and bilateral axial rotation), uniformly distributed over the upper surface of the T9 thoracic vertebra. A total of 24 simulations were performed (6 per models).All models presented a significant reduced ROM when compared to the intact model; the ROM reduction was higher both at L3-4 in the ACR model and at L5-S1 in the ALIF model. At L3-4, the ACR model had, in all cases, the lowest maximum values of Von Mises stresses on the rods, especially in flexion-extension. At L4-5, the ALIF model had the lowest stresses during flexion-extension and axial rotation, while the ACR model had the lowest stresses during lateral bending. At L5-S1, the ALIF model had, in all cases, the lowest stresses on the rods.This finite-element study showed how both ACR at L3-4 and ALIF-ACR at L5-S1 are effective in restoring lumbar lordosis (LL), stabilizing the spine and reducing stress on posterior rods at the index level when compared to a simple fixation model. Interestingly, ALIF-ACR reduces rod stress even at L4-5 in flexion-extension and axial rotation, possibly due to a better distribution of LL, especially on the lower arch, while ACR reduces the stress at L4-5 in lateral bending, possibly thanks to the larger footprint of the cage that increases the area of contact with the lateral side of the endplates.

The European regulatory framework lacks standardisation as regards the minimum requirements for shelter facilities, making defining welfare standards for dogs challenging. Dog (Canis familiaris) welfare assessments should consist of a comprehensive set of measurements that allow the calculation of an overall ‘welfare score.’ The Shelter Quality protocol was developed for the purpose of assessing shelter dog welfare. The study aims to establish a standardised system for evaluating shelter dog welfare by obtaining agreement from experts on the weighting of different measures contributing to an overall welfare score. The Delphi technique is a widely used method for establishing consensus among experts. Two Delphi procedures were implemented and we compared their effectiveness in achieving expert consensus by evaluating rounds’ numbers required to reach consensus and the response and attrition rates. Expert consensus was achieved in Delphi 1 when the standard deviation in the expert weightings was ≤ 5. This was achieved easily for the welfare score weightings of the four principles: ‘Good feeding’, ‘Good housing’, ‘Good Health’, and ‘Appropriate behaviour.’ Animal-based measures were found to reach consensus more quickly than resource-based measures. In Delphi 2, we used the coefficient of variation to determine consensus. No statistical differences were found between the two Delphi methods for attrition rate, response rate or number of participants. Continuing rounds until a consensus is reached is recommended as this method balances time and participant fatigue. A standardised scoring system is provided, using a single overall score of welfare that can be used to compare welfare standards between shelters.

Insufficient in-situ observations from the Antarctic marginal ice zone limit our understanding and description of relevant mechanical and thermodynamic processes that regulate the seasonal sea ice cycle. Here we present high-resolution thermal images of the ocean surface and complementary measurements of atmospheric variables that were acquired underway during one austral winter and one austral spring expedition in the Atlantic and Indian sectors of the Southern Ocean. Skin temperature data and ice cover images were used to estimate the partitioning of the heterogeneous surface and calculate the heat fluxes to compare with ERA5 reanalyses. The winter marginal ice zone was composed of different but relatively regularly distributed sea ice types with sharp thermal gradients. The surface-weighted skin temperature compared well with the reanalyses due to a compensation of errors between the sea ice fraction and the ice floe temperature. These uncertainties determine the dominant source of inaccuracy for heat fluxes as computed from observed variables. In spring, the sea ice type distribution was more irregular, with alternation of sea ice cover and large open water fractions even 400 km from the ice edge. The skin temperature distribution was more homogeneous and did not produce substantial uncertainties in heat fluxes. The discrepancies relative to reanalysis data are however larger than in winter and are attributed to biases in the atmospheric variables, with the downward solar radiation being the most critical.

Extreme windstorms are of considerable interest due to their potential to cause significant socio-economic damages over very large areas of land. As a result, understanding how climate change may affect the characteristics of the most severe storms is an important question for adaptation planing. However, projections of how the hazard associated with windstorms will change in the future are highly uncertain.Here, we use an efficient statistical approach that characterises individual windstorms in terms of their intensity and exposure to estimate the present-day risk from such storms. We then use a methodology used widely in detection and attribution of climate change to assess how such characteristics may change into the future. Using windstorms simulated by a diverse set of high-resolution regional climate model projections for Europe, the EURO-CORDEX ensemble, we provide projections of risk over a range of future climate scenarios. Finally, we explore how the variety of driving and regional models influence the associated uncertainties, and how considering the performance and independence of the models can improve the robustness of the projections.

Extreme events can cause severe disruption to society on many levels, and the ability to forecast these events represents a significant step towards the ability to reduce their impacts. Anomalously persistent atmospheric configurations are typically regarded to be strongly linked with temperature extremes in Europe, however, traditional methods of analysing atmospheric persistence lack a mathematically well-grounded definition. Furthermore, we are not aware of a metric which allows for quantification of instantaneous atmospheric persistence for forecasts for either an individual ensemble member or a deterministic forecast. We aim to help refine the definition of atmospheric persistence by presenting a mathematically well-grounded definition of persistence, which can potentially also be applied in a forecasting environment. We examine the link between the extremal index, an indicator for atmospheric persistence based on dynamical systems theory, and warm temperature extremes in several regions of Europe. We then consider the applicability of this technique to forecast data, in particular ECMWF extended range reforecast data, discussing its potential value as an additional forecast evaluation metric.

Terrestrial vegetation is largely mediated by vegetation-climate coupling. Growing conditions control vegetation growth, which in turn feeds back to climate through changes in biophysical and biogeochemical properties and processes, such as canopy structure and carbon and water exchanges. The vegetation-climate coupling is thus highly variable in space and time. However, little is known on how the large-scale vegetation-climate coupling varies within growing season, and how vegetation responds to climate extremes. In this contribution, we present some recent findings on seasonal and intra-seasonal vegetation-climate coupling and vegetation sensitivity to droughts using multiple remote sensing products including MODIS EVI, GIMMS3g NDVI and VIP EVI2. We account for the differences in phenological stages of growing seasons affected by both climate and landscape heterogeneity. Based on a novel analytical framework incorporating meteorological and vegetation conditions to locally defined vegetation growing seasons, we analyse vegetation-climate couplings using both local climate conditions and teleconnection indices (e.g., Jet Latitude Index). In addition, vegetation sensitivity to droughts and post-drought vegetation changes are assessed. Our results highlight the importance of considering vegetation phenology in understanding sub-seasonal land-atmosphere interaction and vegetation dynamics. The developed analytical framework is suggested to be an effective approach for evaluating vegetation and climate dynamics simulated by Earth System Models.

We examine the characteristics of North Atlantic extratropical cyclones in ERA5 data during cold air outbreaks over continental North America. Previous research has established a statistical link between occurrences of North American cold air outbreaks and an increased frequency of extreme wet and windy conditions over Europe. The theoretical understanding of cyclogenesis suggests that greater numbers of extratropical cyclones will be generated in the North Atlantic, resulting from an enhanced temperature difference between the North American continent and the Gulf Stream during cold air outbreaks. Our analysis finds that counts of extratropical cyclones in the North Atlantic storm track are no greater, or even less than climatology during periods with cold air outbreaks. We instead find anomalous jet stream activity associated with the cold air outbreaks. The jet stream acts to focus extratropical cyclones to a specific region of the North Atlantic, depending on the regional extent of the cold air outbreak, resulting in significantly higher extratropical cyclone counts for that specific region. The regions found to be experiencing higher counts of extratropical cyclones align with previously established geographical dependencies between co-occurrences of North American cold air outbreaks and wet and windy extremes over Europe. We also find that cold air outbreaks associated with an anomalously strengthened jet result in a general increase in the strength of the extratropical cyclones reaching Europe, whilst a more equatorward-displaced jet, with lower maximum speed, results in more persistent extratropical cyclones over southern Europe.

Extremes in extratropical meridional energy transports in the atmosphere are associated with the dynamics of the atmosphere at multiple spatial scales, from planetary to synoptic. This is related to the nature of amplifying baroclinic waves, that are fundamentally intermittent and sporadic, significantly affecting the net seasonal transport across latitudes. Here, we use the ERA5 reanalysis data to perform a wavenumber decomposition of meridional energy transports in the Northern Hemisphere mid-latitudes during winter and summer. Extreme transport events are linked to atmospheric circulation anomalies and dominant weather regimes, identified by clustering 500 hPa geopotential height fields. Partitioning the extreme events across zonal wavenumber highlights the different role of scales in different seasons and regions. In general, planetary-scale waves determine the strength and meridional position of the synoptic-scale baroclinic activity with their phase and amplitude. During winter, large wavenumbers (k = 2–3) are key drivers of the meridional-energy-transport extremes, and planetary- and synoptic-scale transport extremes virtually never co-occur. In summer, extremes are associated with higher wavenumbers (k = 4–6), identified as synoptic-scale motions. Focusing on recently occurred exceptionally strong summertime heat waves and wintertime cold spells, we notice that regime structures of these events are typical of extremely large poleward meridional energy transports.

The proposed drivers of wintertime North American cold spells are multifarious, including modes of climate variability, planetary wave patterns and regional-to-continental-scale weather regimes. The Arctic stratospheric polar vortex has also been reported as a potential remote driver. One proposed coupling mechanism between the stratospheric polar vortex and the troposphere is upward-propagating planetary waves being reflected downward by the polar vortex. Here, we present a physically interpretable regional stratospheric wave reflection detection metric and identify the tropospheric circulation anomalies over North America associated with prolonged periods of wave reflection. The stratospheric reflection events show a systematic evolution from a Pacific Trough regime – associated on average with positive temperature anomalies and a near-complete absence of anomalously cold temperatures in North America – to an Alaskan Ridge regime, which favours low temperatures over much of the continent. The most striking feature of the stratospheric reflection events is thus a systematic shift in the tropospheric circulation in North America, associated with a rapid, continental-scale decrease in temperatures. These emerge as continental-scale cold spells by the end of the reflection events. Stratospheric reflection events are thus highly relevant in a tropospheric predictability perspective.

Concurrent extreme events exacerbate adverse impacts on humans, economy, and environment relative to those from independent extreme events. However, while the effects of climate change on the frequency of individual extreme events have been highly researched, the impacts of climate change on the interaction, dependence and joint occurrence of these extremes have not been extensively investigated, particularly in the East African region. Here, we investigate the joint occurrence of six categories of extreme events in East Africa, namely: river floods, droughts, heatwaves, crop failures, wildfires and tropical cyclones using bias-adjusted impact simulations under past and future climate conditions. We show that the change in the probability of joint occurrence of these extreme events in the region can be explained by the effects of climate change on the frequency, spatial distribution, and dependence of these extreme events. The analysis demonstrates that there is a higher positive correlation between most co-occurring pairs of extremes in the region under end-of-century global warming conditions leading to more frequent concurrence in comparison to the early-industrial period. Our results further highlight the most affected locations in the region by these concurrent events and consequently the main driver(s) in the various co-occurring pairs of extremes. Our results overall highlight that concurrent extremes will become the norm rather than the exception in East Africa under low-end warming scenarios.

The final stage of the Proterozoic, the Ediacaran, shields fascinating insights on the development and dispersal of complex metazoans related to dramatic compositional changes in the atmosphere and hydrosphere. Alternating sequences of siliciclastic and carbonate rocks of the Namibian Nama basin record the final stage of the Ediacaran and contain a vast amount of soft-bodied fauna, as well as some of the first biocalcifying organisms. However, the sparsity of ash beds at the base of the Nama group, preclude accurate and precise constraints on the onset of the Ediacaran biota in Nama group and correlation with chemo stratigraphic records worldwide. Due to the scarcity of ash layers, we apply U-Pb dating to carbonate rocks especially from the lower stratigraphic sections of the Nama Group combining the spatial resolution of LA-ICP-MS and the high-precision ID-TIMS U-Pb dating. The combination with mineralogical and geochemical techniques (d13C, d18O, XRD, SEM, EPMA, CL imaging, LA trace element transects, Raman spectroscopy, clumped isotope thermometry, QEMSCAN, SIMS) enables us to better understand the nature of the analyzed carbonates to distinguish between more pristine and diagenetic phases.This study elaborates on the potential and limitations of carbonate U-Pb dating for improved stratigraphic correlation on these ancient pre-Cambrian marine carbonates from the Nama Group.

North American cold spells tend to co-occur with extreme wind and precipitation events over Europe, but the physical mechanisms behind such “pan-Atlantic” compound extremes have not been fully clarified yet. Rather than proposing a single mechanism, we discuss how cold spells over a single North American region can be connected with wind extremes over different European regions through separate, physically consistent dynamical pathways. The first one involves the propagation of a Rossby wave train from the Pacific Ocean, and is associated with windstorms over north-western Europe in the 5-10 days after the cold spell peak. The second one is associated with a high-latitude anticyclone over the North Atlantic and an equatorward-shifted jet, leading to windstorms over south-western Europe already in the days preceding the cold spell peak.The same dynamical pathways can be independently retrieved from a cluster analysis based on the temporal evolution of the North Atlantic circulation in the days preceding North American cold spells. Such an analysis highlights significantly different stratospheric circulation patterns between the two pathways, with cold spells of the second pathway tied to a weaker than usual stratospheric polar vortex, and an enhanced occurrence of sudden stratospheric warmings.

The propagation and the characteristics of Rossby waves are influenced by the large-scale background flow where they occur: for instance, the role of upper-level jet streams in promoting Rossby wave propagation along preferred directions (so-called “waveguidability”) is a classic problem in climate dynamics. We propose a linear framework to study barotropic Rossby waves over a spherical domain for arbitrary orographic forcing and zonal background flow configurations, including cases with localised single and double jet streams. The approach allows to analytically obtain the steady-state linear flow response to orographic forcing without performing lengthy numerical integrations, together with the flow evolution as a combination of few modes composed by the various eigensolutions of the unforced problem (thus independent of the forcing). The connection between jet strength and waveguidability noticed by previous studies is confirmed. Background flow states featuring a strong jet stream are also prone to barotropic instability.The eigenvalue analysis reveals the spatial structure of the associated Rossby modes and their growth rates, allowing to detect the presence of instabilities. We notice that, even in presence of a damping term, some background flow configurations allow wave instabilities to exist. According to the linear theory, the flow should diverge from the equilibrium state, since some waves are linearly unstable. Nonlinear simulations are performed to provide insights about the waves evolution in the unstable case. Such simulations reveal two interesting effects: 1) a damping effect operated by the nonlinear terms (i.e., the flow is unstable linearly but stable nonlinearly) for medium jet strengths; 2) a quasi-periodic behaviour around the unstable equilibrium state for the strongest jets, indicating the existence of a limit cycle. The linear analysis was still able to capture the unstable equilibrium state at the center of the limit cycle and to provide insights about the spatial structure of the dominant modes. These results indicate the usefulness of linearized approaches in the development of a reduced-order model to describe the barotropic instability mechanisms driving spherical Rossby waves.

This study investigates winter cyclones that cause extreme 10 m winds in the central North Atlantic region (30o to 60o latitude, -50o to -10o longitude) in the ERA5 dataset. We employ a bottom-up approach consisting of selection of the extreme 10 m wind events and analysis of the cyclones that caused the extremes.The 10 m wind extremes were ranked using the Klawa and Ulbrich (2003) destructiveness index, which takes into account wind exceedances over the local 98th percentiles. The top 1% of destructive events were chosen for further analysis. Cyclones were associated with the extreme winds by finding the closest sea-level pressure lows at the times of maximum wind speeds.By analyzing various meteorological fields associated with the temporal evolution of the selected cyclones, we find an important role of interactions with other pre-existing cyclones that create suitable conditions for the development of the subsequent extreme windstorms.

We present an application of quantile generalised additive models (QGAMs) to study spatially compounding climate extremes, namely extremes that occur (near-) simultaneously in geographically remote regions. We take as an example wintertime cold spells in North America and co-occurring wet or windy extremes in Western Europe, which we collectively term Pan-Atlantic compound extremes. QGAMS are largely novel in climate science applications and present a number of key advantages over conventional statistical models of weather extremes. Specifically, they remove the need for a direct identification and parametrisation of the extremes themselves, since they model all quantiles of the distributions of interest. They thus make use of all information available, and not only of a small number of extreme values. Moreover, they do not require any a priori knowledge of the functional relationship between the predictors and the dependent variable. Here, we use QGAMs to both characterise the co-occurrence statistics and investigate the role of possible dynamical drivers of the Pan-Atlantic compound extremes. We find that cold spells in North America are a useful predictor of subsequent wet or windy extremes in Western Europe, and that QGAMs can predict those extremes more accurately than conventional peak-over-threshold models.

Moisture transport within atmospheric rivers (ARs) is a complex combination of processes, with convergence of moisture with different origin and its changes over the life cycle of an AR. The water vapour budget in an AR enables us to understand the contribution of the different moisture sources and sinks (horizontal transport, local evaporation and precipitation). Here, we focus on how these contributed to the formation and development of the exceptional AR associated with storm Denis that occurred in February 2020 leading to the 3rd highest UK average daily rainfall since 18911.We use the WRF-ARW numerical limited-area atmospheric model to simulate the life-cycle of the AR in the North Atlantic basin. We use a resolution of 0.09º, and a domain covering both the AR’s formation region close to the Gulf of Mexico to the landfall region in northern and central Europe. Moreover, we performed two sets of sensitivity experiments by reducing the tropical moisture transport, and the sensible heat flux in specific areas of the oceanic basin to assess how these two main components affect the water vapour balance within the AR. We also defined a threshold to map the AR and used a centroid-based method to track its path in order to measure the shift of its location and intensity through time in the different experiments. Our findings reveal significant relationships between the reduction of tropical moisture and a change of the location of the AR. The analysis also detected regional and temporal changes in the water vapour budget due to the perturbations done in the sensitivity experiments. In addition, relative importance of moisture sources are assessed. As such, our work provides a new case study to unravel feedback processes and the influence to the AR characteristics when perturbing the water vapour balance. 1 Davies, Paul A., et al. "The wet and stormy UK winter of 2019/2020." Weather 76.12 (2021): 396-402.

Despite the progress in seasonal drought forecasting, it remains challenging to identify suitable drought indices for accurately predicting the impacts of a future drought event. In this study, we identified relationships across Europe between the forecasting skill of various drought indices and the estimated drought impacts. We calculated the indices over various accumulation periods, and assessed the forecasting skill of indices computed based on various seasonal prediction systems. An evaluation was performed by computing the same indices from the ERA5 reanalysis data and comparing them across various verification metrics. We further conducted a literature review of the studies assessing the performance of the indices in terms of estimating drought impacts across Europe. We finally performed a trade-off analysis and mapped the drought indices based on their drought forecasting and drought impact estimating skills.Overall, this analysis is a step forward to detect the most suitable drought indices for predicting drought impacts across Europe. Here, not only we present a new approach for evaluating the relationship between drought indices and impacts, we also resolve the dilemma of choosing the indices to be incorporated in the impact functions. Such scientific advancements are setting significant contributions to the emerging field of operational impact-based forecasting and operational drought early warning services.

The TRANSCEND trial1 studied a cohort of more than 250 patients with relapsed/refractory non-Hodgkin's lymphoma treated with the chimeric antigen receptor T-cell (CART) product, lisocabtagene maraleucel. This trial enrolled a high number of patients and included a relatively long follow-up (36 months). Estimating the gain in overall survival (OS) for CART patients versus non-CART controls suffers from the lack of long-term survival information for CART. One advantage of the TRANSCEND trial is the availability of survival results at 36 months; this allows us to reliably determine the survival gain. To carry out this estimation, we kept in mind that the restricted mean survival time (RMST) is recognised to be the best outcome measure for managing long-term survival …

In inoperable pleural mesothelioma, pemetrexed + cisplatin as first line is considered the standard of care, but novel treatments have been recently proposed. Our objective was to comparatively examine the information on overall survival (OS) with these new agents. The Shiny technique was employed for reconstructing individual patient data. Cox statistics was run to estimate hazard ratios (HRs). After a standard literature search, four new treatments were identified (nivolumab + ipilimumab, bevacizumab + pemetrexed + cisplatin, pembrolizumab monotherapy, and durvalumab + pemetrexed + cisplatin). Pemetrexed + ciplatin was the treatment for controls. Nivolumab + ipilimumab and bevacizumab + pemetrexed + cisplatin showed a better OS compared with controls (HR, 0.79 and 0.79, respectively; p 0.05). Pembrolizumab determined only a numerical improvement (p 0.05). In contrast, OS worsened with durvalumab + pemetrexed + cisplatin. Our analysis indicates that the novel treatments for inoperable mesothelioma have similar efficacy and, in general, provide a small though significant survival benefit compared with standard of care. Further research is needed to identify agents determining a more substantial OS improvement.

The aim of this paper is to present the ex ante Socio-Economic Impact Assessment of a European Social Science Research Infrastructure (RI) named EuroCohort that will provide, over the next 34 years, a longitudinal study of the well-being of children and young people across Europe.

Pt-Based drugs play a very important role in current cancer treatments; yet, their cellular and mechanistic aspects are not fully understood. NMR metabolomics provides a powerful tool to investigate the metabolic perturbations induced by Pt drugs in cancer cells and decipher their meaning in relation to the presumed molecular mechanisms. We have carried out a systematic and comparative

Pd compounds form a promising class of experimental anticancer drug candidates whose mechanism of action is still largely unknown; in particular, a few organopalladium compounds seem very attractive. To gain mechanistic insight into medicinal palladium compounds, we have explored here - through ESI MS analysis - the interactions of four organopalladium agents (1-4) - showing remarkable

A novel gold(I) complex inspired by the known medicinal inorganic compounds auranofin and thimerosal, namely ethylthiosalicylate(triethylphosphine)gold(I) (AFETT hereafter), was synthesized and characterised and its structure was resolved through X-ray diffraction. The solution behavior of AFETT and its interactions with two biologically relevant proteins (

The reaction of the cytotoxic compound dirhodium tetraacetate with a B-DNA double helical dodecamer was studied by X-ray crystallography and mass spectrometry.

Arsenoplatin-1 (AP-1) is an innovative dual-action anticancer agent that contains a platinum(ii) center coordinated to an arsenous acid moiety. We found that AP-1 spontaneously aggregates in aqueous solutions generating oligomeric species of increasing length. Afterward, we succeeded in solving the crystal structure of the adduct formed between the model protein lysozyme and an early AP-1 oligomer that turned out to be a trimer. Remarkably, this crystal structure traps an early stage of AP-1 aggregation offering detailed insight into the molecular process of the oligomer's growth.

Calculating impacts from climate projection ensembles can be challenging. A simple approach might consider just the ensemble mean, but this ignores much of the information in the ensemble and does not explore the range of possible impacts. A more thorough approach would consider every ensemble member, but may be computationally unfeasible for many impact models. We investigate the compromise in which we represent the ensemble by the mean and a single deviation from the mean. The deviation from the mean would ideally be representative both of variability in the ensemble, and have a significant impact, according to some impact metric. We compare methods for calculating the deviation from the mean, based on traditional compositing and a statistical method known as Directional Component Analysis (DCA). DCA is based on linearizing the impact metric around the ensemble mean. We illustrate the methods with synthetic examples, and derive new mathematical results that clarify the interpretation of DCA. We then use the methods to derive scenarios from the UKCP18 and EURO-CORDEX projections of future precipitation in Europe. We find that the worst ensemble member is not robust, but that deviations from the ensemble mean calculated using compositing and DCA are robust. They thus give robust insight into the patterns of change in the ensemble. We conclude that mean and representative deviation methods may be suitable for climate projection users who wish to explore the implications of the uncertainty around the ensemble mean without having to calculate the impacts of every ensemble member.

Metal compounds form an attractive class of ligands for a variety of nucleic acids. Five metal complexes bearing aminopyridyl-2,2'-bipyridine tetradentate ligands and possessing a quasi-planar geometry were challenged toward different types of nucleic acid molecules including RNA polynucleotides in the duplex or triplex form, an RNA Holliday four-way junction, natural double helix DNA and a DNA G-quadruplex. The binding process was monitored comparatively using different spectroscopic and melting methods. The binding preferences that emerge from our analysis are discussed in relation to the structural features of the metal complexes.

By definition, anteroposterior (AP) compression type 1 (APC-1) injury is a type of pelvic ring injury, which is widely acknowledged as ‘stable’. Unstable forms of this injury are very rare and present a challenge for diagnosis and clinical management. Detailed herein is a man in his early 30s, referred to our institution with a 2-year history of pubic symphysis pain following a road traffic accident. Radiological investigation revealed an unstable APC-1 injury. This was subsequently managed with surgical reconstruction leading to the successful return of the patient to former function and recreational activities.