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Recent research on the bivariate flood peak/volume frequency analysis has mainly focused on the statistical aspects of the use of various copula models. The interplay of climatic and catchment processes in discriminating among these models has attracted less interest. In the paper we analyse the influence of climatic and hydrological controls on flood peak and volume relationships and their models, which are based on the concept of comparative hydrology in the catchments of a selected region in Austria. Independent flood events have been isolated and assigned to one of the three types of flood processes: synoptic floods, flash floods and snowmelt floods. First, empirical copulas are regionally compared in order to verify whether any flood processes are discernible in terms of the corresponding bivariate flood-peak relationships. Next the types of copulas, which are frequently used in hydrology are fitted, and their goodness-of-fit is examined in a regional scope. The spatial similarity of copulas and their rejection rate, depending on the flood type, region, and sample size are examined, too. In particular, the most remarkable difference is observed between flash floods and the other two types of flood. It is concluded that treating flood processes separately in such an analysis is beneficial, both hydrologically and statistically, since flood processes and the relationships associated with them are discernible both locally and regionally in the pilot region. However, uncertainties inherent in the copula-based bivariate frequency analysis itself (caused, among others, also by the relatively small sample sizes for consistent copula model selection, upper tail dependence characterization and reliable predictions) may not be overcome in the scope of such a regional comparative analysis.

The work aims at analyzing the bivariate relationship between flood peaks and flood volumes, with a particular focus on the type and seasonality of flood generation processes. Instead of the usual approach that deals with an analysis of the annual maxima of flood events, the current analysis includes all independent flood events in a catchment. Flood events are considered independent when they originate from distinguishably different synoptic/meteorological situations. The target region is located in the northern part of Austria, and consists of 72 small and mid-sized catchments. On the basis of the discharge measurements with a time resolution of 1 h from the period 1976–2007, independent flood events were identified and were assigned to one of the three following flood generation type categories: synoptic floods, flash floods and snowmelt floods. These were subsequently divided into two seasons, thereby separating predominantly rainfall-fed and snowmelt-fed floods. Nine frequently-used copula types were locally fitted to the samples of the flood type and seasonal data. Their goodness-of-fit was examined locally as well as analyzed in a regional scope. It was concluded that (i) treating flood processes separately is beneficial for the statistical analysis; (ii) suitability patterns of acceptable copula types are distinguishably different for the seasons/flood types considered, (iii) the Clayton and Joe copulas shows an unacceptable performance for all the seasons/flood types in the region; (iv) the rejection rate of the other copula types depends on the season/flood type and also on the sample size; (v) given that usually more than one statistically suitable dependence model exists, an uncertainty analysis of the design values in the engineering studies resulting from the choice of model seems unavoidable; (vi) reducing uncertainty in the choice of model could be attempted by a deeper hydrological analysis of the dependence structure between flood peaks and volumes in order to give hydrological support to the decision on model's suitability in specific regions and for typical flood generation mechanisms.

The current work addresses one of the key building blocks towards an improved understanding of flood processes and associated changes in flood characteristics and regimes in Europe: the development of a comprehensive, extensive European flood database. The presented work results from ongoing cross-border research collaborations initiated with data collection and joint interpretation in mind. A detailed account of the current state, characteristics and spatial and temporal coverage of the European Flood Database, is presented. At this stage, the hydrological data collection is still growing and consists at this time of annual maximum and daily mean discharge series, from over 7000 hydrometric stations of various data series lengths. Moreover, the database currently comprises data from over 50 different data sources. The time series have been obtained from different national and regional data sources in a collaborative effort of a joint European flood research agreement based on the exchange of data, models and expertise, and from existing international data collections and open source websites. These ongoing efforts are contributing to advancing the understanding of regional flood processes beyond individual country boundaries and to a more coherent flood research in Europe.

Extreme precipitation is thought to increase with warming at rates similar to or greater than the water vapour holding capacity of the air at ~ 7% °C−1, the so-called Clausius–Clapeyron (CC) rate. We present an empirical study of the variability in the rates of increase in precipitation intensity with air temperature using 30 years of 10 min and 1 h data from 59 stations in Switzerland. The analysis is conducted on storm events rather than fixed interval data, and divided into storm type subsets based on the presence of lightning which is expected to indicate convection. The average rates of increase in extremes (95th percentile) of mean event intensity computed from 10 min data are 6.5% °C−1 (no-lightning events), 8.9% °C−1 (lightning events) and 10.7% °C−1 (all events combined). For peak 10 min intensities during an event the rates are 6.9% °C−1 (no-lightning events), 9.3% °C−1 (lightning events) and 13.0% °C−1 (all events combined). Mixing of the two storm types exaggerates the relations to air temperature. Doubled CC rates reported by other studies are an exception in our data set, even in convective rain. The large spatial variability in scaling rates across Switzerland suggests that both local (orographic) and regional effects limit moisture supply and availability in Alpine environments, especially in mountain valleys. The estimated number of convective events has increased across Switzerland in the last 30 years, with 30% of the stations showing statistically significant changes. The changes in intense convective storms with higher temperatures may be relevant for hydrological risk connected with those events in the future.

This paper presents a method to identify intense warm season storms with convective character based on intensity thresholds and the presence of lightning, and analyzes their statistical properties. Long records of precipitation and lightning data at 4 stations and 10 min resolution in different climatological regions in Switzerland are used. Our premise is that thunderstorms associated with lightning generate bursts of high rainfall intensity. We divided all recorded storms into those accompanied by lightning and those without lightning and found the threshold I* that separates intense events based on peak 10 min intensity Ip ≥ I* for a chosen misclassification rate α. The performance and robustness of the selection method was tested by investigating the inter-annual variability of I* and its relation to the frequency of lightning strikes. The probability distributions of the main storm properties (rainfall depth R, event duration D, average storm intensity Ia and peak 10 min intensity Ip) for the intense storm subsets show that the event average and peak intensities are significantly different between the stations. Non-parametric correlations between the main storm properties were estimated for intense storms and all storms including stratiform rain. The differences in the correlations between storm subsets are greater than those between stations, which indicates that care must be exercised not to mix events of different origin when they are sampled for multivariate analysis, for example, copula fitting to rainfall data.

In this paper, we implement the region-of-influence (ROI) approach for modelling probabilities of heavy 1-day and 5-day precipitation amounts in the Czech Republic. The pooling groups are constructed according to (i) the regional homogeneity criterion (assessed by a built-in regional homogeneity test), which requires that in a pooling group the distributions of extremes are identical after scaling by the at-site mean; and (ii) the 5T rule, which sets the minimum number of stations to be included in a pooling group for estimation of a quantile corresponding to return period T. The similarity of sites is evaluated in terms of climatological and geographical site characteristics. We carry out a series of sensitivity analyses by means of Monte Carlo simulations in order to explore the importance of the individual site attributes, including hybrid pooling schemes that combine both types of the site attributes with different relative weights. We conclude that in a dense network of precipitation stations in the Czech Republic (on average 1 station in a square of about 20×20 km), the actual distance between the sites plays the most important role in determining the similarity of probability distributions of heavy precipitation. There are, however, differences between the optimum pooling schemes depending on the duration of the precipitation events. While in the case of 1-day precipitation amounts the pooling scheme based on the geographical proximity of sites outperforms all hybrid schemes, for multi-day amounts the inclusion of climatological site characteristics (although with much lower weights compared to the geographical distance) enhances the performance of the pooling schemes. This finding is in agreement with the climatological expectation since multi-day heavy precipitation events are more closely linked to some typical precipitation patterns over central Europe (related e.g. to the varied roles of Atlantic and Mediterranean influences) while the dependence of 1-day extremes on climatological characteristics such as mean annual precipitation is much weaker. The findings of the paper show a promising perspective for an application of the ROI methodology in evaluating outputs of regional climate models with high resolution: the pooling schemes might serve for defining weighting functions, and the large spatial variability in the grid-box estimates of high quantiles of precipitation amounts may efficiently be reduced.

The paper compares different approaches to regional frequency analysis with the main focus on the implementation of the region-of-influence (ROI) technique for the modelling of probabilities of heavy precipitation amounts in the area of the Western Carpathians. Unlike the conventional regional frequency analysis where the at-site design values are estimated within a fixed pooling group (region), the ROI approach as a specific alternative to focused pooling techniques makes use of flexible pooling groups, i.e. each target site has its own group of sufficiently similar sites. In this paper, various ROI pooling schemes are constructed as combinations of different alternatives of sites' similarity (pooling groups defined according to climatological characteristics and geographical proximity of sites, respectively) and pooled weighting factors. The performance of the ROI pooling schemes and statistical models of conventional (regional and at-site) frequency analysis is assessed by means of Monte Carlo simulation studies for precipitation annual maxima for the 1-day and 5-day durations in Slovakia. It is demonstrated that a) all the frequency models based on the ROI method yield estimates of growth curves that are superior to the standard regional and at-site estimates at most individual sites, and b) the selection of a suitable ROI pooling scheme should be adjusted to the dominant character of the formation of heavy precipitation.

Introduction: Acute myeloid leukemia (AML) is a hematological malignancy with high mortality rate. The treatment is especially challenging in patients older than 65 years, which is the large majority of those. For patients unfit for intensive chemotherapy regimens, only palliative cytoreduction and basic supportive care used to be the options in our unit. However, from 2018, the azacitidine-venetoclax combination has been a new therapeutic alternative. This treatment resulted in marked survival benefit in clinical trials, however, its impact on the daily clinical practice and the entire patient population is unclear., Objective: Our goal was to evaluate how the application of azacitidine-venetoclax changed the treatment and survival of AML patients in our practice., Method: We retrospectively analyzed the available clinical data of all AML patients treated consecutively between January 1, 2011 and December 31, 2021 at the 3rd Department of Internal Medicine (from 2020 onward called Department of Internal Medicine and Hematology), examining their treatment depending on the time period of therapy (2011-2017 and 2018-2021). Patients with acute promyelocytic leukemia were excluded., Results: 423 patients were diagnosed during this period. The number of cases showed a marked increase: in the first 7 years of our study, 184 patients were diagnosed, while this rose to 239 during the subsequent 4 years. The median age of patients was 67.6 years, with more than 60% of patients aged over 65. An improving trend can be observed in the overall survival: between 2011 and 2017, the median overall survival was 4.8 ± 0.9 months, while between 2018 and 2021, it was 8.3 ± 1.4 months (p = 0.051). Moreover, in the case of patients over 65 there was a significant overall survival improvement: 3.1 ± 0.5 vs. 4.9 ± 0.6 months (p = 0,01). The main factor behind this improvement could be that a large proportion of over 65 patients previously only fit for supportive care could now be treated with azacitidine-venetoclax: the percentage of actively treated patients grew from 57.1% to 75.3% in the second period., Conclusion: The survival of patients unfit for curative therapy and older than 65 showed a steady increase which can be attributed to the introduction of new therapeutic alternatives. Orv Hetil. 2023; 164(45): 1787-1794.

Introduction: Multiple myeloma is one of the most common hematologic malignancies, with approximately 400 patients diagnosed in Hungary annually. Novel therapies emerging in the last decade have made a great impact on most patients' survival, however, those responding poorly to standard first-line therapy and failing to proceed to stem cell transplantation face a dire prognosis. Venetoclax, a selective Bcl-2 inhibitor has been shown very effective in the treatment of relapsed/refractory t(11;14) patients, but there are only a few studies about its safety and efficacy when used as salvage in the second line., Objective: The aim of our study was to analyze the data of t(11;14) patients treated with venetoclax salvage at our clinic and to evaluate its efficacy., Method: Between 2017 and 2021, 13 patients received venetoclax therapy at our clinic after suboptimal response to frontline treatment, whose data we analyzed retrospectively., Results: Adverse prognostic markers were very prevalent in our group, 4 of our patients had del(17p), 5 had amp(1q21) and 6 had stage 3. Nevertheless, all 13 patients responded well to venetoclax therapy, with 6 reaching very good partial response and 7 complete response. All eligible patients (10) could proceed to transplantation. After median 38 months follow up, neither median progression-free, nor median overall survival was reached, since only 3 patients progressed and 1 died., Conclusion: We have shown that when salvage is needed for t(11;14) patients who respond suboptimally to standard frontline therapy, venetoclax is a remarkably good option. Orv Hetil. 2023; 164(23): 894-899.

The Single Europe Sky Air Traffic Management Research (SESAR) program develops and implements innovative technological and operational solutions to modernize European air traffic management and to eliminate the negative environmental impacts of aviation activity. This article presents our developments within the SESAR Solution "Safety Support Tools for Avoiding Runway Excursions". This SESAR Solution aims to mitigate the risk of runway excursion, to optimize airport operation management by decreasing the number of runway inspections, to make chemical treatment effective with respect to the environment, and to increase resilience, efficiency and safety in adverse weather situations. The proposed approach is based on the enhancement of runway surface condition awareness by integrating data from various sources. Dangerous windy conditions based on Lidar measurements are also discussed as another relevant factor in relation to runway excursions. The paper aims to explore four different data mining methods to obtain runway conditions from the available input data sources, examines their performance and discusses their pros and cons in comparison with a rule-based algorithm approach. The output of the SESAR Solution is developed in compliance with the new Global Reporting Format of the International Civil Aviation Organization for runway condition description to be valid from 2020. This standard is expected to provide concerned stakeholders with more precise information to enhance flight safety and environmental protection., Competing Interests: The authors declare no conflict of interest.

Low-level wind shear, i.e., sudden changes in wind speed and/or wind direction up to altitudes of 1600 ft (500 m) above-ground is a hazardous meteorological phenomenon in aviation. It may radically change the aerodynamic circumstances of the flight, particularly during landing and take-off and consequently, it may threaten human lives and the health of passengers, people at the airport and its surrounding areas. The Bratislava Airport, the site of this case study, is one of the few airports worldwide and the first in Central Europe that is equipped with a Doppler lidar system, a perspective remote sensing tool for detecting low-level wind shear. The main objective of this paper was to assess the weather events collected over a period of one year with the occurrences of low-level wind shear situations, such as vertical discontinuities in the wind field, frontal passages and gust fronts to increase the level of flight safety and protect human lives and health. The lidar data were processed by a computer algorithm with the main focus on potential wind shear alerts and microburst alerts, guided by the recommendations of the International Civil Aviation Organisation. In parallel, the selected weather events were analyzed by the nearby located meteorological radar to utilize the strengths of both approaches. Additionally, an evaluation of the lidar capability to scan dynamics of aerosol content above the airport is presented.

There has been a surprisingly large number of major floods in the last years around the world, which suggests that floods may have increased and will continue to increase in the next decades. However, the realism of such changes is still hotly discussed in the literature. This overview article examines whether floods have changed in the past and explores the driving processes of such changes in the atmosphere, the catchments and the river system based on examples from Europe. Methods are reviewed for assessing whether floods may increase in the future. Accounting for feedbacks within the human-water system is important when assessing flood changes over lead times of decades or centuries. It is argued that an integrated flood risk management approach is needed for dealing with future flood risk with a focus on reducing the vulnerability of the societal system. WIREs Water 2015, 2:329-344. doi: 10.1002/wat2.1079 For further resources related to this article, please visit the WIREs website.

Purpose: Optimized therapy in epilepsy should include individual care for cognitive functions. Here we introduce a computerized screening instrument, called "Computerized Cognitive Testing in Epilepsy" (CCTE), which allows for time-efficient repetitive assessment of the patient's cognitive profile regarding the domains of memory and attention, which are frequently impaired due to side effects of antiepileptic medication., Methods: The CCTE battery takes 30min and covers tasks of verbal and figural memory, cognitive speed, attention and working memory. The patient's results are displayed immediately in comparison to age-related normative data. For evaluation of psychometrics and clinical correlations, data from patients of a tertiary referral epilepsy center (n=240) and healthy subjects (n=83) were explored., Results: CCTE subtests show good reliability and concurrent validity compared to standard neuropsychological tests (p<0.01). Adverse cognitive effects of antiepileptic medication can be detected (p<0.05), e.g. significant negative effects of increasing drug load. Specific epilepsy subgroups, e.g. focal versus primary generalized epilepsy or right versus left mesial temporal lobe epilepsy, showed different CCTE profiles., Conclusion: CCTE appears valuable for early detection of individual cognitive alterations related to medication. In addition, it displays interesting differences between epilepsy syndromes. The CCTE battery provides a standardized, time- and personnel-efficient assessment of cognitive functions open to a large number of patients and applicable for clinical and scientific use in epilepsy., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The effect of medial septal lesion on long-term potentiation (LTP) and the action of four cognition enhancers were studied in rat dentate gyrus, in vivo. The medial septum was partially lesioned by a radiofrequency lesion generator. The effect of lesion was studied on hippocampal function measuring two parameters; the amplitude of the maximal population spikes and the increase in population spikes evoked by high frequency stimulation of the perforant path (LTP). Both parameters were found to be significantly lower in the lesioned group than in the non-lesioned one. Four drugs (physostigmine, piracetam, vinpocetine and Hydergine), known to be effective in dementia and/or in cognitive impairments, were administered 1 h after the lesion procedure and thereafter once a day for 6 days after the operation. LTP was induced and measured at day 7. All drugs produced a complete restoration of the measured parameters affected by the lesion. These findings provided further evidence that the medial septum plays an important role in the induction of LTP in the dentate gyrus. This experimental model might be useful for studying new drugs against dementia.

The effect of four drugs considered as cognition enhancers on the amplitude of the population spikes and on the long-term potentiation (LTP) evoked by perforant path stimulation was investigated in rat dentate gyrus in vivo. LTP was characterized by the absolute increase in the amplitude of the population spikes, which were expressed in mV, contrary to the widely used percentage value, because the absolute increase was independent of the pretetanus level, whereas the percentage increase was found to be negatively correlated with it. Intravenous administration of the drugs (piracetam 500 mg/kg, hydergine 2 mg/kg, vinpocetine 0.1 and 5 mg/kg and physostigmine 0.01 and 0.1 mg/kg) did not influence the amplitude of the population spikes itself. Piracetam and hydergine did not have an effect on LTP, while vinpocetine and physostigmine altered LTP in a similar manner. The higher doses of the two latter drugs, administered 5 min before tetanic stimulation, induced a significant potentiation of LTP, whereas a significant inhibition of LTP was obtained when the drugs were administered 30 min before tetanic stimulation. Based on the results obtained from guinea pig hippocampal slices, an LTP-potentiating effect of all compounds tested could have been anticipated, but this was not supported by our data. The apparent contradiction between the in vivo and in vitro results is discussed.

GYKI 52466 is a specific antagonist of the neuronal excitation mediated by the non-NMDA type excitatory amino acid receptors, at several sites in the central nervous system. The experiments presented here show that the drug has a dose-dependent, slowly developing, long-lasting and reversible inhibitory action on the field potentials recorded from the CA1 region of the rat hippocampus, in vitro. Its action is similar to that of the well-known non-NMDA receptor blocker, CNQX. When the stimulus intensity-dependence of the population spikes was investigated, both drugs shifted the input-output curves in a parallel manner, while the maximum responses were only slightly depressed at the doses applied. With i.v. application, GYKI 52466 also inhibited the hippocampal field potentials recorded from the CA1 region of anesthetized rats dose-dependently. The inhibition was relatively weak compared to the effect found in earlier studies in the spinal cord, by the same doses. Four mg/kg i.v., a doses which is able to block spinal reflexes completely, caused an only about 20% depression of the recorded responses in the hippocampal CA1 area.

Conventional extracellular single unit recordings were used to investigate the effect of vinpocetine on locus coeruleus noradrenergic neurons in chloral hydrate-anesthetized rats. Vinpocetine produced a significant and dose-dependent increase in the firing rate of locus coeruleus neurons (ED30 = 0.75 mg/kg i.v.) up to 1 mg/kg i.v., followed by a complete blockade of spiking activity at doses higher than this. The effective dose range was in very good agreement with the dose range corresponding to the memory-enhancing effects of the compound. Our results supplied direct electrophysiological evidence that vinpocetine increases the activity of ascending noradrenergic pathways. This effect can be related to the cognitive-enhancing characteristics of the compound.