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An eco-friendly method for the determination of sweeteners (aspartame, acesulfame-K) and preservatives (benzoic acid, sorbic acid, methylparaben, ethylparaben) in functional beverages and flavoured waters using thin film microextraction (TFME) and high-performance liquid chromatography with UV detection (HPLC-UV) was proposed. A series of fourteen green and renewable solidified natural deep eutectic solvents (NADESs) were prepared and tested as 'eutectosorbents' in TFME for the first time. In the proposed method, the NADES containing acetylcholine chloride and 1-docosanol at a 1:3 molar ratio was finally chosen to coat a support. Four factors, i.e., the mass of the NADES, pH of the samples, extraction time, and desorption time, were tested in the central composite design to select the optimal TFME conditions. Limits of detection were equal to 0.022 µg mL−1 for aspartame, 0.020 µg mL−1 for acesulfame-K, 0.018 µg mL−1 for benzoic acid, 0.026 µg mL−1 for sorbic acid, 0.013 µg mL−1 for methylparaben, and 0.011 µg mL−1 for ethylparaben. Satisfactory extraction recoveries between 82% and 96% were achieved with RSDs lower than 6.1% (intra-day) and 7.4% (inter-day). The proposed 'eutectosorbent' presented good stability that enabled effective extractions for 16 cycles with recovery of at least 77%. The proposed NADES-TFME/HPLC-UV method is highly sensitive and selective. However, the use of a solid NADES as a sorbent, synthesized without by-products, without the need for purification, and with good stability on a support with the possibility of reusability increases the ecological benefit of this method. The greenness aspect of the method was evaluated using the Complex modified Green Analytical Procedure Index protocol and is equal to 84/100. [ABSTRACT FROM AUTHOR]

Retention of structural elements such as deadwood and habitat trees at the level of forest stands has been promoted to integrate biodiversity conservation into multiple‐use forest management. The conservation value of habitat trees is largely determined by the presence, richness, and abundance of tree‐related microhabitats (TreMs). Since TreMs are often lacking in intensively managed forests, an important question of forest conservation is how the abundance and richness of TreMs may be effectively restored. Here, we investigated whether the strict protection of forest through cessation of timber harvesting influenced TreM occurrence at tree and stand levels. For that purpose, we compared four managed and four set‐aside stands (0.25 ha each) in the Białowieża Forest, with identical origin following clear‐cuts approximately 100 years ago. We found that the abundance and richness of TreMs on living trees were not significantly different between stands that were either conventionally managed or where active forest management ceased 52 years ago. Yet, our analysis of TreMs on tree species with contrasting life‐history traits revealed that short‐lived, fast‐growing species (pioneers) developed TreMs quicker than longer‐lived, slower‐growing species. Hence, tree species such as Populus or Betula, which supply abundant and diverse TreMs, can play an important role in accelerating habitat restoration. [ABSTRACT FROM AUTHOR]

The Covid-19 coronavirus pandemic has caused changes in all areas of human life. The field of law is no exception to this list. In particular, the issues of conducting other people's affairs without a power of attorney have become especially relevant, as social distancing and restrictions on social activity have led to a significant increase in the practical need for the application of this legal institution. The significance of this study is also important in connection with the comparative analysis of the normative aspect and the practical measurement of the application of the institute of conducting other people's affairs without a power of attorney in Ukraine and Poland. These two countries are comparable in territory, number of citizens, legal tradition, but Poland has become member of the European Union, while Ukraine has remained on the sidelines of European civilization. The dialectical method, the method of comparative analysis and system analysis were chosen as the methodological basis of the research. The authors of the article concluded that institute of conducting other people's affairs without a power of attorney is characterized by an increased level of social utility. In such cases, the one who protects the interests of others without a power of attorney, as a rule, acts not only in the interests of the individual but also in the interests of the society. Thus, it helps to protect single people, the elderly ones, disabled individuals and other groups which are socially unprotected and thus prevent the pandemic spread. [ABSTRACT FROM AUTHOR]

Growing evidence shows that alterations occurring at early developmental stages contribute to symptoms manifested in adulthood in the setting of neurodegenerative diseases. Here, we studied the molecular mechanisms causing giant axonal neuropathy (GAN), a severe neurodegenerative disease due to loss-of-function of the gigaxonin-E3 ligase. We showed that gigaxonin governs Sonic Hedgehog (Shh) induction, the developmental pathway patterning the dorso-ventral axis of the neural tube and muscles, by controlling the degradation of the Shh-bound Patched receptor. Similar to Shh inhibition, repression of gigaxonin in zebrafish impaired motor neuron specification and somitogenesis and abolished neuromuscular junction formation and locomotion. Shh signaling was impaired in gigaxonin-null zebrafish and was corrected by both pharmacological activation of the Shh pathway and human gigaxonin, pointing to an evolutionary-conserved mechanism regulating Shh signaling. Gigaxonin-dependent inhibition of Shh activation was also demonstrated in primary fibroblasts from patients with GAN and in a Shh activity reporter line depleted in gigaxonin. Our findings establish gigaxonin as a key E3 ligase that positively controls the initiation of Shh transduction, and reveal the causal role of Shh dysfunction in motor deficits, thus highlighting the developmental origin of GAN. [ABSTRACT FROM AUTHOR]

Measuring disaster resilience is a key component of successful disaster risk management and climate change adaptation. Quantitative, indicator-based assessments are typically applied to evaluate resilience by combining various indicators of performance into a single composite index. Building upon extensive research on social vulnerability and coping/adaptive capacity, we first develop an original, comprehensive disaster resilience index (CDRI) at municipal level across Italy, to support the implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030. As next, we perform extensive sensitivity and robustness analysis to assess how various methodological choices, especially the normalisation and aggregation methods applied, influence the ensuing rankings. The results show patterns of social vulnerability and resilience with sizeable variability across the northern and southern regions. We propose several statistical methods to allow decision makers to explore the territorial, social and economic disparities, and choose aggregation methods best suitable for the various policy purposes. These methods are based on linear and non-liner normalization approaches combining the OWA and LSP aggregators. Robust resilience rankings are determined by relative dominance across multiple methods. The dominance measures can be used as a decision-making benchmark for climate change adaptation and disaster risk management strategies and plans. [ABSTRACT FROM AUTHOR]

Measuring adaptive capacity as a key component of vulnerability assessments has become one of the most challenging topics in the climate change adaptation context. Numerous approaches, methodologies and conceptualizations have been proposed for analyzing adaptive capacity at different scales. Indicator-based assessments are usually applied to assess and quantify the adaptive capacity for the use of policy makers. Nevertheless, they encompass various implications regarding scale specificity and the robustness issues embedded in the choice of indicators selection, normalization and aggregation methods. We describe an adaptive capacity index developed for Italy's regional and sub-regional administrative levels, as a part of the National Climate Change Adaptation Plan, and that is further elaborated in this article. The index is built around four dimensions and ten indicators, analysed and processed by means of a principal component analysis and fuzzy logic techniques. As an innovative feature of our analysis, the sub-regional variability of the index feeds back into the regional level assessment. The results show that composite indices estimated at higher administrative or statistical levels neglect the inherent variability of performance at lower levels which may lead to suboptimal adaptation policies. By considering the intra-regional variability, different patterns of adaptive capacity can be observed at regional level as a result of the aggregation choices. Trade-offs should be made explicit for choosing aggregators that reflect the intended degree of compensation. Multiple scale assessments using a range of aggregators with different compensability are preferable. Our results show that within-region variability can be better demonstrated by bottom-up aggregation methods. [ABSTRACT FROM AUTHOR]

We describe a climate risk index that has been developed to inform national climate adaptation planning in Italy and that is further elaborated in this paper. The index supports national authorities in designing adaptation policies and plans, guides the initial problem formulation phase, and identifies administrative areas with higher propensity to being adversely affected by climate change. The index combines (i) climate change-amplified hazards; (ii) high-resolution indicators of exposure of chosen economic, social, natural and built- or manufactured capital (MC) assets and (iii) vulnerability, which comprises both present sensitivity to climateinduced hazards and adaptive capacity. We use standardized anomalies of selected extreme climate indices derived from high-resolution regional climate model simulations of the EURO-CORDEX initiative as proxies of climate change-altered weather and climate-related hazards. The exposure and sensitivity assessment is based on indicators of manufactured, natural, social and economic capital assets exposed to and adversely affected by climate-related hazards. The MC refers to material goods or fixed assets which support the production process (e.g. industrial machines and buildings); Natural Capital comprises natural resources and processes (renewable and non-renewable) producing goods and services for well-being; Social Capital (SC) addressed factors at the individual (people's health, knowledge, skills) and collective (institutional) level (e.g. families, communities, organizations and schools); and Economic Capital (EC) includes owned and traded goods and services. The results of the climate risk analysis are used to rank the subnational administrative and statistical units according to the climate risk challenges, and possibly for financial resource allocation for climate adaptation. [ABSTRACT FROM AUTHOR]

Anamniotes, fishes and amphibians, have the capacity to regenerate spinal cord tissue after injury, generating new neurons that mature and integrate into the spinal circuitry. Elucidating the molecular signals that promote this regeneration is a fundamental question in regeneration research. Model systems, such as salamanders and larval and adult zebrafish are used to analyse successful regeneration. This shows that many developmental signals, such as Notch, Hedgehog (Hh), Bone Morphogenetic Protein (BMP), Wnt, Fibroblast Growth Factor (FGF), Retinoic Acid (RA) and neurotransmitters are redeployed during regeneration and activate resident spinal progenitor cells. Here we compare the roles of these signals in spinal cord development and regeneration of the much larger and fully patterned adult spinal cord. Understanding how developmental signalling systems are reactivated in successfully regenerating species may ultimately lead to ways to reactivate similar systems in mammalian progenitor cells, which do not show neurogenesis after spinal injury. [ABSTRACT FROM AUTHOR]

This paper presents a passive concentrator for single-phase inverters with a three-phase output, which uses magnetically coupled reactors. Due to the development of renewable energy systems, the proposed systems may enable the easier integration of converters in the form of inverters with the power system. Two variants of cooperation of the concentrator with single-phase voltage inverters were considered. The first variant proposed a system topology in which three single-phase full-bridge inverters were connected to the concentrator, while the other variant proposed six half-bridge inverters. A control system of the inverters that does not use PWM was developed. A common star point was created for the supply voltages in the form of a capacitive divider covering all the inverters. An analysis of the concentrator system was presented, taking into account the cooperation with inverters. The overall power of the TDSλ system was defined and the relationship for its determination was given. Simulation studies were described, presenting the obtained voltage and current waveforms. The impact of changing the supply voltage of the inverters on the operation of the concentrator and the shape of the output voltages was assessed. The proposed systems allow you to connect 3 or 6 single-phase inverters. The use of magnetically coupled reactors enables the use of a magnetic system of lower power and size. The described concentrators enable the generation of multi-level three-phase output voltage with a low THD content. [ABSTRACT FROM AUTHOR]

Abstract: Radial glia of the mouse cerebral cortex emerge from neuroepithelial stem cells around embryonic day 11 and produce excitatory cortical neurons until a few days before birth. The molecular mechanisms that regulate the end of cortical neurogenesis remain largely unknown. Here we investigated if the Dicer-dependent microRNA (miRNA) pathway is involved. By electroporating a cre-recombinase expression vector into the cortex of E13.5 embryos carrying a conditional allele of Dicer1, we induced mosaic recombination causing Dicer1 deletion and reporter activation in a subset of radial glia. We analysed the long-term fates of their progeny. We found that mutant radial glia produced abnormally large numbers of Cux1-positive neurons, many of which populated the superficial cortical layers. Injections of the S-phase marker bromodeoxyuridine between postnatal days 3 and 14 showed that much of this population was generated postnatally. Our findings suggest a role for Dicer-dependent processes in limiting the timespan of cortical neurogenesis. [Copyright &y& Elsevier]

The aim of this study, conducted in the years 2010-2012, was to evaluate bolting and seed production of shallot depending on storage temperature of steckling bulbs with different diameters. The present study included 4 cultivars ('Toto', 'Ambition F1', 'Bonilla F1', and 'Matador F1') and one local population ('U'). Bulbs with the following diameters: 20-30 mm, 31-40 mm, 41-50 mm, and 51-60 mm, were stored from the first 10-day period of November (2010 and 2011) until the end of March (2011 and 2012) at a temperature of 0-1 °C, 4-6 °C, and 8-10 °C. After they were planted in the field (the second 10-day period of April), observations of bolting were carried out, while the weight of seed umbels and seed yield were determined only for the cultivar 'Toto' and the population 'U'. The storage temperature of steckling bulbs in the range of 4-6 °C and 8-10 °C was most conducive to bolting, in particular in plants grown from large bulbs with a diameter above 40 mm. In the cultivar 'Toto', plants from bulbs with a diameter above 40 mm and stored at a temperature of 4-6 °C were characterized by the highest weight of seed umbels. This had an effect on obtaining the highest seed yield (on average 1604.16-2300.7 g per 100 m² of area). Shallot plants from the population 'U' grown from bulbs with a diameter of 20-30 mm were characterized by a distinctly lower percentage of bolting plants compared to the cultivars studied. For this reason, this population does not promise positive effects in shallot production for seed. [ABSTRACT FROM AUTHOR]

We used a Tg( glyt2:gfp) transgenic zebrafish expressing the green fluorescent protein (GFP) under control of the glycine transporter 2 (GLYT2) regulatory sequences to study for the first time the glycinergic neurons in the brain of an adult teleost. We also performed in situ hybridization using a GLYT2 probe and glycine immunohistochemistry. This study was combined with biocytin tract tracing from the spinal cord to reveal descending glycinergic pathways. A few groups of GFP+/GLYT2− cells were observed in the midbrain and forebrain, including numerous pinealocytes. Conversely, a small nucleus of the midbrain tegmentum was GLYT2+ but GFP−. Most of the GFP+ and GLYT2+ neurons were observed in the rhombencephalon and spinal cord, and a portion of these cells showed double GLYT2/GFP labeling. In the hindbrain, GFP/GLYT2+ populations were observed in the medial octavolateral nucleus; the secondary, magnocellular, and descending octaval nuclei; the viscerosensory lobes; and reticular populations distributed from trigeminal to vagal levels. No glycinergic cells were observed in the cerebellum. Tract tracing revealed three conspicuous pairs of GFP/GLYT2+ reticular neurons projecting to the spinal cord. In the spinal cord, GFP/GLYT2+ cells were observed in the dorsal and ventral horns. GFP+ fibers were observed from the olfactory bulbs to the spinal cord, although their density varied among regions. The Mauthner neurons received very rich GFP+ innervation, mainly around the axon cap. Comparison of the zebrafish glycinergic system with the glycinergic systems of other adult vertebrates reveals shared patterns but also divergent traits in the evolution of this system. J. Comp. Neurol. 521:389-425, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Early telencephalic development involves transformation of neuroepithelial stem cells into radial glia, which are themselves neuronal progenitors, around the time when the tissue begins to generate postmitotic neurons. To achieve this transformation, radial precursors express a specific combination of proteins. We investigate the hypothesis that micro RNAs regulate the ability of the early telencephalic progenitors to establish radial glia. We ablate functional Dicer, which is required for the generation of mature micro RNAs, by conditionally mutating the Dicer1 gene in the early embryonic telencephalon and analyse the molecular specification of radial glia as well as their progeny, namely postmitotic neurons and basal progenitors. Conditional mutation of Dicer1 from the telencephalon at around embryonic day 8 does not prevent morphological development of radial glia, but their expression of Nestin, Sox9, and ErbB2 is abnormally low. The population of basal progenitors, which are generated by the radial glia, is disorganised and expanded in Dicer1-/- dorsal telencephalon. While the proportion of cells expressing markers of postmitotic neurons is unchanged, their laminar organisation in the telencephalic wall is disrupted suggesting a defect in radial glial guided migration. We found that the laminar disruption could not be accounted for by a reduction of the population of Cajal Retzius neurons. Together, our data suggest novel roles for micro RNAs during early development of progenitor cells in the embryonic telencephalon. [ABSTRACT FROM AUTHOR]

The characteristic growth features of four Welsh onion cultivars ('Parade', 'Performer', 'Siedmiolatka Zielona', and 'Siedmiolatka Czerwona') dependant on growing method (seeds sown directly in the field and from transplants) were evaluated during the three-year study (2007-2009). The following traits were determined: plant height, number of leaves on a single plant, tendency to produce laterals, plant weight, as well as length and diameter of the pseudostem. Plants of the 'Parade' cultivar were the highest (76.0 cm, on average), while those of 'Siedmiolatka Czerwona' were the shortest (mean 68.6 cm). Pseudostem length was found to be the main factor determining the height of the Welsh onion. The longest pseudostems were observed for the 'Parade' and 'Performer' cultivars, while the 'Siedmiolatka Czerwona' had the shortest. In each of the tested cultivars, those grown from a transplant resulted in larger pseudostems and a larger number of leaves. Amongst the studied cultivars, 'Siedmiolatka Czerwona' had the most numerous leaves and laterals (45.2 leaves and 14.3 laterals, on average), while 'Performer' and 'Parade' had the least (mean 11.7 and 14.8 leaves and 2.4 and 2.6 laterals, respectively). The weight of a single plant with laterals significantly differed depending on the cultivar and growing method. At the end of the vegetation period (mid-October), the 'Parade' and 'Performer' cultivars grown from transplants were characterised by the highest weights (mean 518.2 g and 631.7 g), while 'Siedmiolatka Czerwona' and 'Siedmiolatka Zielona' grown from seeds had the lowest (222 g, on average). [ABSTRACT FROM AUTHOR]

Developing decision support systems for environmental applications is an intricate, challenging task. The increasing complexity of environmental decision problems, the growing number of subjects involved and keen competition between conflicting interests make decisions and decision support difficult. Decision support systems have been developed since the 1970s to help tackle semi-structured and unstructured decision problems. Despite their popularity, the success of DSS development is uncertain and many computerised decision-support tools have failed when dealing with complex and unstructured problems. This article describes the development methodology and progress of mDSS, a decision support system for water resource management that has been developed under the European research project MULINO. The mDSS tool is designed to integrate environmental (especially hydrological) models with multiple-criteria evaluation procedures. A number of prototypes have been developed and the final version is expected at the end of the 3-year project. The system''s development is driven by the experience acquired in several case studies selected in five European countries. Although the main aim of the MULINO project and the DSS is to help with increasingly complex decisions of general water management, the concepts of sustainable river basin management introduced by the water framework directive are addressed as well. [Copyright &y& Elsevier]

Nuclear factor I (NFI) is a transcription factor that binds to the adenovirus type 5 (Ad5) origin of replication and recruits the adenovirus DNA polymerase, thereby stimulating initiation of DNA replication in vitro. Using scanning force microscopy, we demonstrate that NFI induces a 60° bend upon binding to the origin. The A/T-rich region preceding the core recognition sequence of NFI influences the DNA bend angle, since substitution of A/T base pairs by G/C base pairs severely decreases bending. Mutations in the A/T-rich region do not affect binding of NFI to DNA. However, mutations that reduce the protein-induced bend lead to a loss of NFI-stimulated replication, indicating that DNA bending is functionally important. In contrast, basal initiation or DNA binding of the polymerase is not impaired by these origin mutations. We conclude that binding of NFI to the Ad5 origin causes structural changes in DNA that are essential for the stimulatory function of NFI in replication. We propose that NFI-induced origin bending facilitates the assembly of a functional initiation complex. [ABSTRACT FROM AUTHOR]

The human transcription factor Oct-1 can stimulate transcription from a variety of promoters by interacting with the coactivators OBF-1/OCA-B/BOB-1, SNAP190 and VP16. These proteins contact Oct-1 regions different from the DNA binding surface. Oct-1 also stimulates the DNA replication of adenovirus through its DNA binding site in the origin. The Oct-1 POU homeodomain (POUhd) binds the adenovirus precursor terminal protein pTP, which serves as the protein primer of DNA replication and recruits pTP to the origin. To map the interaction with pTP at the POUhd surface, we screened a library of randomly mutated POU domains and identified mutations that interfered with pTP interaction and DNA replication stimulation. These mutants clustered at a surface different from those recognized by OBF-1, SNAP190 and VP16. Unexpectedly, the pTP binding region largely overlapped with the DNA binding surface of POUhd. In agreement with this, pTP binding and DNA binding were mutually exclusive. We propose a model to reconcile pTP recruitment and DNA binding by Oct-1. [ABSTRACT FROM AUTHOR]

The paper presents a proposal of the multi-pulse AC/DC converter for providing supply for multilevel inverters and considerably reducing the line current distortion factor. It can be applied as a suitable source of DC voltage and is convenient to supply such inverters that need three or more voltage terminals to supply all sections of the inverter. The converter in question works as a multi-pulse rectifier supplying a three-level NPC (Neutral Point Clamped) inverter. The load introduced by the inverter is simulated as an impedance depended on a selected inverter state. All possible states are determined by using a set of three digits: 0, 1, 2. The sourcing converter is constructed from diode bridge rectifiers connected in parallel as well as the system of magnetically coupled reactors. The reactors are used to shift subsequent line voltages so that they create a multiphase voltage system supplying component rectifiers. The article presents two alternative rectifiers: A 12-pulse diode rectifier using one magnetically coupled reactor unit 3CRλ, and a 24-pulse one using three 3CRλ units. Simulation and experimental tests have been executed and selected results included. Conclusion and discussion are added. [ABSTRACT FROM AUTHOR]

The economic damage due to natural hazard risks in the EU over 1980-2016 amounted to 500 billion Euro (EEA, 2018), mostly triggered by extreme weather and climate-related events whose frequencies and/or intensities are expected to increase as a result of climate change in many regions across Europe. Floods are responsible for 40% of the recorded damage. The above estimates account only for capital lost, recovery and opportunity costs. Significant indirect economic losses generated by spill-over effects and disruption of production webs are omitted. Effective climate change adaptation and disaster risk reduction require an economic assessment of both direct- and indirect economic damages. A better understanding of natural hazard risk and ensuing economic losses is important for coordinating responses to shocks and crises within the European Economic and Monetary Union. In the absence of financial protection, the incidence of major disasters in several EU member states may exacerbate economic imbalances and deteriorate credit ratings (S&P, 2015). We estimate the direct and indirect economic losses of floods across Europe using a combination of contemporary stage-damage (Amadio et al., 2018; Huizinga et al., 2017) and computable general equilibrium (CGE) models (Carrera et al., 2015; Koks et al., 2016). CGE models are nonlinear models of circular flows of goods and services between agents, where representative households and firms choose their demand and supply following constrained optimization problems. For hazard characterisation we employ DEM-retrieved Geomorphic Flood Index (GFI, Samela et al., 2017) that has been proven useful for riverine flood-hazard mapping over large geographical regions in which information on flooding potential is limited or patchy. GFI is trained by model-based simulations (Alfieri et al., 2015; Dottori et al., 2016) to characterise the flood hazard distribution across the EU. Alfieri, L., Feyen, L., Dottori, F., Bianchi, A., 2015. Ensemble flood risk assessment in Europe under high end climate scenarios. Glob. Environ. Chang. 35, 199–212. doi:10.1016/j.gloenvcha.2015.09.004Amadio, M., Scorzini, A.R., Carisi, F., Essenfelder, A.H., Domeneghetti, A., Mysiak, J., Castellarin, A., 2018. Estimating flood damage in Italy: empirical vs expert-based modelling approach. Nat. Hazards Earth Syst. Sci. Discuss. 2018, 1–26. doi:10.5194/nhess-2018-324Carrera, L., Standardi, G., Bosello, F., Mysiak, J., 2015. Assessing direct and indirect economic impacts of a flood event through the integration of spatial and computable general equilibrium modelling. Environ. Model. Softw. doi:10.1016/j.envsoft.2014.09.016Dottori, F., Salamon, P., Bianchi, A., Alfieri, L., Hirpa, F.A., Feyen, L., 2016. Development and evaluation of a framework for global flood hazard mapping. Adv. Water Resour. 94, 87–102. doi:https://doi.org/10.1016/j.advwatres.2016.05.002Huizinga, J., De Moel, H., Szewczyk, W., 2017. Methodology and the database with guidelines Global flood depth-damage functions. doi:10.2760/16510Koks, E.E., Carrera, L., Jonkeren, O., Aerts, J.C.J.H., Husby, T.G., Thissen, M., Standardi, G., Mysiak, J., 2016. Regional disaster impact analysis: Comparing input-output and computable general equilibrium models. Nat. Hazards Earth Syst. Sci. 16. doi:10.5194/nhess-16-1911-2016S&P, 2015. The Heat Is On: How Climate Change Can Impact Sovereign Ratings (Report), RatingsDirect. Standard & Poors.Samela, C., Troy, T.J., Manfreda, S., 2017. Geomorphic classifiers for flood-prone areas delineation for data-scarce environments. Adv. Water Resour. 102, 13–28. doi:https://doi.org/10.1016/j.advwatres.2017.01.007 [ABSTRACT FROM AUTHOR]

Background. Arterial hypertension (HT) is a serious and prevalent epidemiological factor in the development of coronary artery disease (CAD). Metalloproteinases (MMPs), especially MMP-2 and MMP-9, and their natural endogenous tissue inhibitors (TIMPs) are involved in the pathogenesis of HT and its complications. MMPs are also involved in the development of diabetes (DM), a risk factor for CAD. The aim of the study was to explore the influence of CAD, HT, and DM on changes in plasma levels of MMP-2 and MMP-9 and their inhibitor TIMP-4. Methods and Results. The study involved 70 patients with stable CAD admitted for coronary angiography and 15 healthy subjects. Whole blood samples were collected prior to angiography. MMP-2, MMP-9, and TIMP-4 levels in plasma were estimated using ELISA tests. CAD patients showed a significantly increased level of TIMP-4 and decreased level of MMP-2 in comparison to healthy controls (p=0.011 and p=0.037, respectively). Concentration of MMP-2, MMP-9, and TIMP-4 did not differ in the group with and without hypertension. Patients with DM presented higher MMP-2 level than patients without DM (p<0.001). Multiple regression analysis of the influence of independent variables such as CAD stage, DM, and HT on MMP-2, MMP-9, and TIMP-4 showed that only DM was independently associated with a higher level of MMP-2 (β = 0.42, R2 = 0.17, p<0.001). Conclusion. Data showed that patients with CAD presented higher TIMP-4 and lower MMP-2 concentration regardless of HT and DM. HT had no effect on MMP-2, MMP-9, and TIMP-4 levels in serum. DM was independently associated with higher MMP-2 concentration; however, co-occurrence of CAD and DM was associated with the balance in the MMP-2 level. Concentration of MMP-9 did not change significantly in any of the analysed groups. [ABSTRACT FROM AUTHOR]

Abstract Raising interest in 'nature-based solutions' (NBS) has inspired attempts to organise their principles and qualities within comprehensive and internally consistent evaluation frameworks, so as to demonstrate the superior performance of 'working with nature'. However, the proposed frameworks stop short of taking into account the changing conditions in which NBS are set to operate. Climate change, in particular, can alter ecosystems and their services, and may undermine the performance of green solutions that rely on them. We present here a 'dynamic' assessment framework that explicitly accounts for the impact of climate change on the effectiveness of the proposed NBS. The framework is based on an innovative approach that integrates system analysis and backcasting. Although it has not yet been applied to the NBS context, backcasting is well-suited to seize the transformational character of NBS, as it encourages 'breakthrough' leaps rather than incremental improvements. Our framework factors in the multifunctional character of NBS and is designed to capture associated direct benefits/costs and co-benefits/costs. It is meant to be applied ex ante to ideally support the choice between innovative NBS and traditional options, in an effort to respond to the societal challenges identified by the EU Research & Innovation agenda on the environment. Graphical abstract Unlabelled Image Highlights • Assessment frameworks should evaluate NBS' effectiveness under future climate conditions. • We propose an assessment framework based on systems analysis and backcasting. • The framework can be applied to support the choice between NBS and traditional options. • The framework factors NBS' multifunctionality and assesses (in)direct benefits/costs. • Ecosystem disservices are explicitly factored in the assessment as co-costs. [ABSTRACT FROM AUTHOR]

Key points Neurodegenerative disorders can exhibit dysfunctional mitochondrial respiratory chain complex IV activity., Conditional deletion of cytochrome c oxidase, the terminal enzyme in the respiratory electron transport chain of mitochondria, from hippocampal dentate granule cells in mice does not affect low-frequency dentate to CA3 glutamatergic synaptic transmission., High-frequency dentate to CA3 glutamatergic synaptic transmission and feedforward inhibition are significantly attenuated in cytochrome c oxidase-deficient mice., Intact presynaptic mitochondrial function is critical for the short-term dynamics of mossy fibre to CA3 synaptic function., Abstract Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protohaem IX farnesyltransferase encoded by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV-deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term facilitation and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses with CA3 pyramidal cells via large mossy-fibre boutons, but rather to all synapses formed by dentate granule cells. Therefore, presynaptic mitochondrial function is critical for the short-term dynamics of synapse function, which may contribute to the cognitive deficits observed in pathological mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

This paper explores the role that incremental water charging (temporary levies on water use) can play in reducing the environmental costs that arise during drought events. The paper combines a multi-attribute Revealed Preference Model calibrated at a local level (Agricultural District) and a regionally-calibrated Computable General Equilibrium model to estimate the impacts of incremental water charging on water use, water withdrawals and market income. The methodology is applied to the particular case of Italy's Emilia Romagna Region. Results provide a basis for the assessment of tradeoffs in water conservation. [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: Using the results from climate models to force models that calculate the impacts of climate change can be challenging when ensembles are large. For detailed impacts models, it may not be computationally feasible to use all the data. We investigate ways to reduce the ensemble of different results down to just an ensemble of two patterns of change: one pattern for the mean, and one pattern for variations around the mean. Using these two patterns allows us to estimate the typical impact and the possible range of impacts. The pattern for variations around the mean we call a "representative deviation pattern." An ideal representative deviation pattern would capture the most relevant differences from the mean, where what defines relevance may vary according to the application. We compare simple and traditional methods for deriving the representative deviation pattern with a recently derived statistical method called Directional Component Analysis. We apply all the methods to help better understand the changes in rainfall expected in Europe due to climate change. We find robust results that show that the deviation from the mean with the greatest total rainfall consists of a pattern with more rainfall in most of Europe but less rainfall in the far North. Key Points: We show how to make climate model results easier to use by reducing large ensembles to just the ensemble mean and a single patternWe apply the methods to European rainfall in two climate model ensembles, and gain new insights into the structure of likely changesComparing ways to define the representative deviation, we find that simple compositing and a linear method give similar results [ABSTRACT FROM AUTHOR]

Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of the COVID-19 pandemic, the greatest challenge currently lies in managing the short- and long-term complications of COVID-19. We have assembled current knowledge of the broad spectrum of cardiovascular, pulmonary, and neuropsychiatric sequelae following SARS-CoV-2 infection to understand how these clinical manifestations collectively lead to a severe form of the disease. The ultimate goal would be to better understand these complications and find ways to prevent clinical deterioration. [ABSTRACT FROM AUTHOR]

Introduction: Trimethylamine N-oxide (TMAO) is an organic compound with a well-established involvement in the pathogenesis of cardiovascular disease (CVD). However, data on the links between TMAO levels and cardiovascular mortality in Polish patients are lacking. Objectives: We aimed to assess the relationship between serum TMAO levels and 5-year mortality in Polish patients with CVD. Patients and Methods: We retrospectively assessed serum TMAO levels in 1,036 consecutive patients (median age, 62 years; men, 61%) hospitalized between 2013 and 2015. Correlations between TMAO levels and 5-year mortality as well as anthropometric and biochemical parameters were assessed for the whole population and the subgroups of patients with acute coronary syndrome, stable coronary syndrome (SCS), chronic heart failure (HF), and atrial fibrillation (AF). Results: In the univariate analysis, increased TMAO levels predicted 5-year mortality without clinically significant power (hazard ratio [HR], 1.01; 95% CI: 1.006–1.018; p < 0.0001). However, even this weak effect was lost in the multivariate analysis after adjustment for age, sex, comorbidities, and laboratory parameters. In the whole study group, TMAO levels in the fourth quartile of concentration (>6.01 µM) predicted 5-year mortality only in the univariate analysis (HR: 1.55; 95% CI: 1.34–1.79; p < 0.0001). In subgroup univariate analysis, TMAO levels predicted 5-year mortality in patients with SCS, chronic HF, and AF. Conclusions: Despite the promising results of previous studies, our study shows that the level of TMAO has at most moderate value in predicting all-cause mortality. TMAO levels depend on other clinical variables, which limits the use of TMAO as an independent predictor of mortality in these patients. [ABSTRACT FROM AUTHOR]

The revised international health regulations offer a framework that can be used by host countries to organise public health activities for mass gatherings. From June 8, to July 1, 2012, Poland and Ukraine jointly hosted the Union of European Football Associations European Football Championship Finals (Euro 2012). More than 8 million people from around the world congregated to watch the games. Host countries and international public health agencies planned extensively to assess and build capacity in the host countries and to develop effective strategies for dissemination of public health messages. The effectiveness of public health services was maximised through rapid sharing of information between parties, early use of networks of experienced individuals, and the momentum of existing national health programmes. Organisers of future mass gatherings for sporting events should share best practice and their experiences through the WHO International Observer Program. Research about behaviour of large crowds is needed for crowd management and the evidence base translated into practice. A framework to measure and evaluate the legacy of Euro 2012 is needed based on the experiences and the medium-term and long-term benefits of the tournament. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we investigate an important obstacle which substantially complicates co-operation between ecologists and economists but which has received little attention so far: differences between the modelling approaches in economics and ecology. To understand these differences, 60 models addressing issues relevant to biodiversity conservation have been selected randomly from eight international economic and ecological journals. The models have been compared according to a number of criteria including the models'' level of generality; the mathematical techniques employed for formulation and solution of the models; the level of complexity and the way time, space and uncertainty are taken into account. The economic models sampled are formulated and analysed analytically, tend to be relatively simple and are mostly used to investigate general questions. Furthermore, they often ignore space, dynamics and uncertainty. Although some ecological models have similar properties, there is also a substantial number of another type of ecological models that are relatively complex and analysed by simulation. These models tend to be rather specific and often explicitly consider dynamics, space and uncertainty. The integrated ecological–economic models are observed to lie “in the middle” between ecological and economic models. An unexpected result is that they are not more complex than ecological and economic models (as one could have expected from a simple “merger” of models from both disciplines), but have an intermediate complexity. [Copyright &y& Elsevier]

Introduction: Under physiological conditions, the myocardial extracellular matrix (ECM) is maintained by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, changes in the balance between MMPs and TIMPs can lead to pathological remodeling of the ECM, which contributes to cardiovascular and kidney diseases. The aim of our study was to assess levels of MMPs and TIMP-2 in patients with myocarditis and their relationship to renal function. Materials and Methods: Forty five patients with myocarditis who underwent CMR were included, comprising 11 with concurrent chronic kidney disease (CKD). Blood samples were obtained to assess serum levels of MMP-2, MMP-3, MMP-9, and TIMP-2. Results: Serum MMP-2, MMP-3, and TIMP-2 levels negatively correlated with the ejection fraction in patients with myocarditis, while MMP-3 levels correlated with longitudinal deformation (p < 0.05). Serum MMP-2, MMP-3, and TIMP-2 levels also negatively correlated with renal function, as assessed by the estimated glomerular filtration rate (eGFR) (p < 0.05). Patients with myocarditis and concurrent CKD had higher levels of MMP-2 and TIMP-2 than those without kidney damage. Conclusions: (1) We demonstrated that MMP-2, MMP-3, and TIMP-2 concentrations were related to left-ventricular ejection fraction, and MMP-3 levels correlated with longitudinal deformation, indicating MMPs play an important role in the post-inflammatory remodeling of the myocardium. (2) A negative correlation between the eGFR and MMP-2, MMP-3, and TIMP-2 and a positive correlation between creatinine and MMP-3 levels indicate the role of MMPs and TIMP-2 in renal dysfunction. [ABSTRACT FROM AUTHOR]

Background. Platelet reactivity and response to antiplatelet drugs, acetylsalicylic acid (ASA) and clopidogrel, in patients with thrombocytopenia and thrombocythemia can have a potentially important effect on the outcome. The effectiveness and safety of antiplatelet drugs in such patients has not been well examined. Measuring the effect of ASA and clopidogrel on platelets could help guide the therapy. Nevertheless, platelet response to antiplatelet drugs is not routinely measured in platelet count disorders and relevant evidence is scarce. Aims. The study aimed to measure platelet reactivity and response to ASA and clopidogrel in patients with platelet count disorders. Materials and Methods. This was a cross-sectional study of consecutive patients hospitalized in cardiology and hematology departments in the years 2018–2019. The study included patients with thrombocytopenia (PLT < 150 G/L) and thrombocythemia (PLT > 450 G/L) on ASA or dual antiplatelet therapy (DAPT; ASA plus clopidogrel). Controls included patients on antiplatelet drugs with normal platelet count. Platelet reactivity was measured in whole blood (Multiplate aggregometer, Roche, Switzerland) using arachidonic acid (AA), adenosine-5′-diphosphate (ADP), and thrombin receptor agonist peptide-6 (TRAP) as agonists. Platelet aggregation was expressed in arbitrary units (AU). AA-induced aggregation was used as a measure of response to ASA with a cut-off above 30 AU showing high on-treatment platelet reactivity to ASA (HTPR-A). ADP-induced aggregation measured response to clopidogrel with a cut-off above 48 AU for high on-treatment platelet reactivity to clopidogrel (HTPR-C). TRAP-induced aggregation measured baseline platelet reactivity not affected by oral antiplatelet drugs. Results. The study included 174 patients. There were 64 patients with thrombocytopenia, 30 patients with chronic thrombocythemia, and 80 controls. All patients were on 75 mg of ASA and 32% of them additionally on 75 mg of clopidogrel due to a history of recent coronary artery angioplasty. AA- and ADP-induced aggregation was comparable between thrombocytopenic patients and controls (median (IQR) 19 (7–28) vs. 23 (15–38) for AA AU and 32 (16–44) vs. 50 (32–71) for ADP AU, respectively), while it was significantly higher in thrombocythemic patients (median (IQR) 80 (79–118) for AA AU and 124 (89–139) for ADP AU). TRAP-induced aggregation showed significantly lowest aggregation in thrombocytopenic (median (IQR) 41 (34–60) for TRAP AU) and highest in thrombocythemic patients (median (IQR) 137 (120–180) for TRAP AU). HTPR-A was frequent in thrombocythemic patients in comparison with thrombocytopenic patients and controls (60% vs. 4% vs. 15%, respectively; p < 0.0002). HTPR-C was highly common in thrombocythemic patients and least common in thrombocytopenic ones in comparison with controls (80% vs. 8% vs. 40%, respectively; p < 0.001). Conclusion. Chronic thrombocytopenia does not significantly affect platelet reactivity and response to ASA and clopidogrel in comparison with controls. Thrombocytosis significantly increases platelet reactivity and attenuates response to both ASA and clopidogrel. [ABSTRACT FROM AUTHOR]

Introduction: Although ticagrelor and prasugrel remain the standard antiplatelet treatments in acute coronary syndrome (ACS), numerous patients still present with indications for clopidogrel use. Aim: We aimed to assess the levels of clopidogrel active metabolite and to evaluate the effect of the drug on platelet inhibition in patients with ACS as compared with those with stable coronary disease. Patients were assessed for the presence of the most common genetic polymorphisms that reduce the absorption (ABCB1) and activation (CYP2C19*2 and CYP2C19*3) of clopidogrel to exclude the effect of genetic variability on drug concentrations and activity. Material and methods: This single-center, open-label, prospective study included 199 patients hospitalized due to ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) in Killip class I-III, who underwent percutaneous coronary intervention. The control group included 22 patients with stable coronary artery disease. Results: The mean (SD) levels of active clopidogrel were 17.1 (12.3) ng/ml in controls and 16.4 (12.0) ng/ml in the whole study group (p < 0.68). No differences were noted in clopidogrel levels between patients with STEMI and NSTEMI (mean (SD), 17.6 (2.3) ng/ml and 15.1 (11.5) ng/ml; p < 0.45) or between STEMI and NSTEMI groups and controls (p < 0.38 and p < 0.61, respectively). No effect of ABCB1 or CYP2C19 polymorphism was observed in the study subgroups. Conclusions: We concluded that ACS does not affect the levels of clopidogrel active metabolite or platelet inhibition in patients in Killip class I-III with or without CYP2C19 or ABCB1 gene polymorphisms. [ABSTRACT FROM AUTHOR]

The reported research aims at improving the quality of three-phase rectifier supply currents. An effective method consists of adding properly formed booster voltages to the fundamental supply voltages using a series active filter. In the proposed solution, the booster voltages are generated by three single-phase systems consisting of inverters, LC filters, and single-phase transformers. The application of LC couplings ensures low emission of disturbances, but may provoke compensator stability problems. The article presents the current control system for a series active filter designed to suppress the dominant harmonics in the supply currents of an 18-pulse rectifier, without interference into fundamental current components. A proportional control is proposed in combination with integral terms implemented in the orthogonal coordinate systems, which synchronically rotate with frequencies equal to those of the harmonic components to be eliminated. The use of complex gains in integral terms allows a simple phase correction of the output signals. A description is given of the method to determine controller parameters based on the mathematical model of the control object. Sample results of experimental tests performed in steady-state and transient conditions are included to illustrate the quality of performance of the series active filter as compared to the results recorded for the rectifier alone, and for the rectifier with additional line reactor. The applied control method of active filter significantly reduces harmonic distortion of the grid current, which is particularly advantageous at nonideal supply voltage and low loads. [ABSTRACT FROM AUTHOR]

The reported research aims at improving the quality of three-phase rectifier supply currents. An effective method consists of adding properly formed booster voltages to the fundamental supply voltages using a series active filter. In the proposed solution, the booster voltages are generated by three single-phase systems consisting of inverters, LC filters, and single-phase transformers. The application of LC couplings ensures low emission of disturbances, but may provoke compensator stability problems. The article presents the current control system for a series active filter designed to suppress the dominant harmonics in the supply currents of an 18-pulse rectifier, without interference into fundamental current components. A proportional control is proposed in combination with integral terms implemented in the orthogonal coordinate systems, which synchronically rotate with frequencies equal to those of the harmonic components to be eliminated. The use of complex gains in integral terms allows a simple phase correction of the output signals. A description is given of the method to determine controller parameters based on the mathematical model of the control object. Sample results of experimental tests performed in steady-state and transient conditions are included to illustrate the quality of performance of the series active filter as compared to the results recorded for the rectifier alone, and for the rectifier with additional line reactor. The applied control method of active filter significantly reduces harmonic distortion of the grid current, which is particularly advantageous at nonideal supply voltage and low loads. [ABSTRACT FROM AUTHOR]

Introduction: There are limited data on platelet reactivity and response to antiplatelet drugs in patients with cardiogenic shock. Aim: To assess platelet reactivity on dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor, a novel potent P2Y12 receptor inhibitor, in patients with cardiogenic shock in the course of acute coronary syndrome (ACS) who received invasive treatment. Material and methods: We enrolled 12 consecutive patients with ACS complicated by cardiogenic shock. To assess response to antiplatelet therapy during cardiogenic shock, only patients with symptoms persisting for at least 3 days and who completed a 5-day follow-up were included in the study. Patients received a loading dose of ASA (300 mg) and ticagrelor (180 mg), followed by a maintenance dose (ASA, 1 x 75 mg; ticagrelor, 2 x 90 mg). Blood samples for platelet function tests were collected. Platelet aggregation was assessed with a Multiplate whole-blood impedance aggregometer. Arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP) were used as aggregation agonists. Results: Response to antiplatelet therapy assessed by aggregometry showed numerically higher on-ASA platelet reactivity on day one and statistically significant higher on-ticagrelor platelet reactivity on day one in comparison with following days. There were 2 patients with high on ASA platelet reactivity and 3 with high on ticagrelor platelet reactivity, but only on the day one. Conclusions: Some patients with cardiogenic shock in the course of ACS treated invasively show a lower response to ASA and ticagrelor only on the first day after invasive treatment, with a good response on subsequent days. [ABSTRACT FROM AUTHOR]

Introduction: Platelets play a fundamental role in the pathogenesis of acute coronary syndrome (ACS). The platelet count (PC) at hospital admission is easy to obtain, but whether thrombocytopenia or/and thrombocytosis impact long-term mortality (LTM) after ACS is unclear. Objective: To evaluate the effect of PC at hospital admission on LTM in patients with ACS. Methods: This retrospective cohort study included patients with the ICD-10 codes for unstable angina (I.20) and acute myocardial infarction (I.21, I.22). Thrombocytopenia was defined as a blood PC <150 G/L and thrombocytosis as a PC >450 G/L. Additional platelet indices which were tested included plateletcrit (PCT), the mean platelet volume (MPV), the platelet distribution width (PDW), and the platelet larger cell ratio (P-LCR). Data on all-cause death were obtained from the National Health Fund database. Results: The study included 3,162 patients with a median follow-up of 27.2 months (interquartile range 12.5–46.8 months; max 68.7 months). Patients with thrombocytopenia and thrombocytosis yielded a higher maximal analyzed 5-year mortality rate in comparison with normal PC patients (45.8 and 47.7 vs. 24.2%, respectively; p < 0.00001) which was mainly driven by higher deaths at 1–2 years after ACS. The 5-year LTM was also significantly higher in patients with abnormal PCT and MPV levels in comparison with patients with PCT and MPV within the normal range. Other platelet indices (PDW, P-LCR) were not associated with a worse outcome. The Cox proportional hazards model revealed that thrombocytopenia at admission was independently associated with higher LTM after ACS (RR 1.83; 95% CI 1.1–3.0; p = 0.01). Conclusions: Both thrombocytopenia and thrombocytosis at hospital admission in post-ACS patients are associated with a significant almost two times higher 5-year mortality rate. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to discuss how, despite increasing data availability from a wide range of sources unlocks unprecedented opportunities for disaster risk reduction, data interoperability remains a challenge due to a number of barriers. As a first step to enhancing data interoperability for disaster risk reduction is to identify major barriers, this paper presents a case study on data interoperability in disaster risk reduction in Europe, linking current barriers to the regional initiative of the European Science and Technology Advisory Group. Design/methodology/approach: In support of Priority 2 ("Strengthening disaster risk governance to manage disaster risk") of the Sendai Framework and SDG17 ("Partnerships for the goals"), this paper presents a case study on barriers to data interoperability in Europe based on a series of reviews, surveys and interviews with National Sendai Focal Points and stakeholders in science and research, governmental agencies, non-governmental organizations and industry. Findings: For a number of European countries, there remains a clear imbalance between long-term disaster risk reduction and short-term preparation and the dominant role of emergency relief, response and recovery, pointing to the potential of investments in ex ante measures with better inclusion and exploitation of data. Originality/value: Modern society is facing a digital revolution. As highlighted by the International Council of Science and the Committee on Data for Science and Technology, digital technology offers profound opportunities for science to discover unsuspected patterns and relationships in nature and society, on scales from the molecular to the cosmic, from local health systems to global sustainability. It has created the potential for disciplines of science to synergize into a holistic understanding of the complex challenges currently confronting humanity; the Sustainable Development Goals are a direct reflectance of this. Interdisciplinary is obtained with integration of data across relevant disciplines. However, a barrier to realization and exploitation of this potential arises from the incompatible data standards and nomenclatures used in different disciplines. Although the problem has been addressed by several initiatives, the following challenge still remains: to make online data integration a routine. [ABSTRACT FROM AUTHOR]

Adult zebrafish, in contrast to mammals, regenerate neurons in their brain, but the extent and variability of this capacity is unclear. Here we ask whether the loss of various dopaminergic neuron populations is sufficient to trigger their functional regeneration. Both sexes of zebrafish were analyzed. Genetic lineage tracing shows that specific diencephalic ependymo-radial glial (ERG) progenitor cells give rise to new dopaminergic [tyrosine hydroxylase-positive (TH+)] neurons. Ablation elicits an immune response, increased proliferation of ERG progenitor cells, and increased addition of new TH+ neurons in populations that constitutively add new neurons (e.g., diencephalic population 5/6). Inhibiting the immune response attenuates neurogenesis to control levels. Boosting the immune response enhances ERG proliferation, but not addition of TH+ neurons. In contrast, in populations in which constitutive neurogenesis is undetectable (e.g., the posterior tuberculum and locus ceruleus), cell replacement and tissue integration are incomplete and transient. This is associated with a loss of spinal TH+ axons, as well as permanent deficits in shoaling and reproductive behavior. Hence, dopaminergic neuron populations in the adult zebrafish brain show vast differences in regenerative capacity that correlate with constitutive addition of neurons and depend on immune system activation. [ABSTRACT FROM AUTHOR]

In this technical note we describe Smart Climate Hydropower Tool, an innovativeopen-source web-cloud-based service that implements a set of data-driven methods for riverdischarge and energy forecasting. An application for two catchments in South America isdiscussed (test cases), where management of hydropower plants can benefit from knowledgeof incoming discharge forecasts up to 6 months in advance. This application has beendeveloped inside H2020 project CLARA - Climate forecast enabled knowledge service.Currently SCHT exploits several Artificial Intelligence algorithms and is continuouslyevolving by R&#x0026;D activity to test new ones for enhancing forecast. Although tangibleresults using AI have been published in the past (i.e. Callegari, et al., 2015, DeGregorio et. al 2017) challenges remain, particularly for seasonal lead times andrainfall dominated catchments, where forecast of meteorological variables playsa critical role. In this contribution we show results of application of different AIalgorithms (from supervised learning regression techniques, to artificial neuralnetworks). Each algorithm is trained over past decades datasets of recorded data,forecast performances are then evaluated using separate test sets with reference tobenchmarks (historical average of discharge values and simpler multiparametricregressions). Major operative advantages of AI with respect to mechanistic hydrological modelsinclude limited to none a priori knowledge of involved physical phenomena, high level offlexibility when managing heterogeneous sets of variables related to discharge generation,and quick setup time of the forecast system. On the other side major efforts are requested toidentity input data (features) related to target variable. Such features range from earthobservation products to on site gauging stations data, to public meteorological forecasts(either output of single models or ensembles), increasingly available from seasonal to subseasonal and daily lead time (i.e Copernicus Climate Change Service-C3S). Using AItechniques many combinations of spatially distributed and monitoring networks features canbe tested together, to predict target variable (i.e river discharge to the reservoir),choosing the best performing combination and tailoring the forecast service to thecatchment of interest. Once trained, each algorithm just needs to retrieve from onlinerepositories the required data to perform forecasts, requiring limited maintenanceoperations (i.e. annual re-training to consider new available hydrological data). Fordemonstrational purposes of such approach we implemented results of test cases in SCHTcloud-based service, for immediate visualization, through a common browser, of both pastand forecasted data, and on fly performance metrics calculation of the forecasts. [ABSTRACT FROM AUTHOR]

Münchausen syndrome can be characterized by simulated illness, pathological lying and wandering from place to place (the patient typically presents to numerous hospitals). Individuals with elevated blood pressure due to non-adherence to medication have the so-called pseudo-resistant hypertension. A 45-year-old woman was admitted to hospital on an emergency basis because of a hypertensive crisis. Despite combination antihypertensive treatment, normalization of blood pressure was not achieved and a device to produce a therapeutic arteriovenous fistula was implanted. After the procedure, a significant increase in pulmonary artery pressure was observed and closure of the fistula was performed by implantation of the stent graft. The suspicion was raised that the patient had not been taking her prescribed medications. Therefore, blood samples were taken and the serum was analyzed for presence of the prescribed drugs (atorvastatin, bisoprolol, chlorthalidone, clonidine, doxazosin, furosemide, nitrendipine, oxazepam and valsartan). The results confirmed suspected failure of the patient to take the prescribed medications. Münchausen syndrome is usually first suspected when inexplicable laboratory test results are noted. To our knowledge, this is the first reported case of Münchausen syndrome with pseudo-resistant hypertension leading to the implantation of a device to produce a therapeutic arteriovenous fistula. [ABSTRACT FROM AUTHOR]

Abstract Introduction Hypertension is prevalent in most patients after renal transplantation, and it is the main factor contributing to cardiovascular diseases that cause death of a significant number of these patients. Up to 95% of patients after transplantation have hypertension, and among them are patients with refractory hypertension. Elevated blood pressure is one of the causes of deterioration of transplant function and may accelerate transplant loss. Case Report We present the first case in the world of a patient (who was 61 years old) in whom denervation of native renal arteries was performed after renal transplantation (2004). The patient was suffering from uncontrolled refractory hypertension. Antihypertensive therapy was used but the effect was not satisfactory. The patient received amlodipine, bisoprolol, clonidine, furosemide, and doxazosin in high doses. Clinical assessments with ambulatory blood pressure monitoring revealed a predominant blood pressure 149/96 with incidents of hypertensive crises. High blood pressure is a cardiovascular risk factor and it also has a significant influence on transplant failure, which was the reason for performing the denervation. The procedure was carried out through the femoral artery with the use of a 6F guiding catheter. During a 3-year observation, significant decreases in ambulatory blood pressure monitoring systolic and diastolic blood pressures were observed after the procedure (149/96 mm Hg vs 134/91 mm Hg before and after the denervation, respectively). There was a significant regression of left ventricle mass (577 g before denervation vs 470 g after 3 years). The functioning of the renal transplant became stable after 3 years of observation (38 mL/min before denervation and 38 mL/min after 3 years). Conclusions The first case in the world of a renal transplant patient who had denervation of native renal arteries has demonstrated a positive effect in controlling blood pressure over a 3-year observation. Three years after denervation, a reduction of heart hypertrophy and stabilization of renal function were noted. The presented case shows that denervation of native renal arteries denervation may be successful and safe in kidney transplant recipients. Highlights • Refractory hypertension remains a big problem in patients after kidney transplantation. • Renal artery denervation is a method of treatment of a refractory hypertension. • Renal artery denervation is a new way to decrease heart hypertrophy. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess MMP-2 (matrix metalloproteinase-2) and TIMP-2 (tissue inhibitor of metalloproteinase-2) serum levels in patients with diverse types of heart failure (HF) and chronic kidney disease (CKD). 101 patients with chronic HF were enrolled. Each patient has assessed the serum levels of MMP-2, TIMP-2, and NT-proBNP. Patients were initially classified into 2 groups based on their LVEF. 43 patients were classified into the HFREF group (HF with Reduced Ejection Fraction) and 58 characterized as HFPEF (HF with Preserved Ejection Fraction). Next, all patients were subdivided into 4 groups according to the degree of diastolic dysfunction. 38 patients with CKD were classified into HF/CKD(+) group. The HF/CKD(-) (HF without CKD) group comprised 61 patients. This study provides original data on positive correlation between ejection fraction and MMP-2 levels in all patients with heart failure. Elevated levels of MMP-2 and TIMP-2 were found in serum from patients with chronic kidney disease; in addition, serum levels of MMP-2 were correlated with the degree of kidney failure. In all groups of patients there was positive correlation between MMP-2 and TIMP-2. Among patients with heart failure etiology was not related to MMP-2 and TIMP-2 serum levels. [ABSTRACT FROM AUTHOR]

Background. High on-aspirin treatment platelets reactivity (HPR) is a significant problem in long-term secondary prevention of cardiovascular events. We hypothesize that imbalance between platelets MMPs/TIMPs results in cardiovascular disorders. We also explored whether chronically elevated blood glucose affects MMP-2/TIMP-4 release from platelets. Materials and Methods. Seventy patients with stable coronary artery disease, supplemented with aspirin, participated in this pilot study. The presence of HPR and/or diabetes mellitus was considered as the differentiating factor. Light aggregometry, impedance aggregometry, and ELISA tests for TXB2, MMP-2, MMP-9, and TIMP-4 were performed in serum, plasma, platelet-rich plasma, and platelets-poor plasma, as appropriate. Results. Aspirin-HPR did not affect plasma MMP-2, MMP-9, and TIMP-4. Arachidonic acid-induced aggregation of platelets from aspirin-HPR patients did not lead to increased release of MMP-2, MMP-9, and TIMP-4. Studying patients at the lowest TXB2 serum concentration quartile revealed that high concentration of plasma TIMP-4 and TIMP-4 negatively correlated with TXB2 and platelet aggregation. Diabetics showed an increased plasma MMP-2 as well as an increased MMP-2 in supernatants after platelet aggregation. However, diabetes mellitus did not affect MMP-9 and TIMP-4. Conclusion. Aspirin-HPR did not affect the translocation and release of MMPs and TIMP-4 from platelets. TIMP-4 may serve as a marker of TXA2-mediated platelet aggregation. Chronically elevated plasma glucose increases plasma MMP-2, and HPR potentiates this phenomenon. [ABSTRACT FROM AUTHOR]

The European Union's Biodiversity Strategy for 2030 seeks to protect 30% of land, with 10% under strict protection, while building a transnational nature network. We explore the effects of the Biodiversity Strategy targets for land use and ecosystem services across the European land system. To do so, we propose a novel approach, combining a methodological framework for improving green network connectivity with an EU-wide land system model. We identify an improved network of EU protected areas consistent with the 2030 targets, and explore its effects under different levels of protection and in a range of paired climatic and socio-economic scenarios. The existing network of protected areas is highly fragmented, with more than one third of its nodes being isolated. We find that prioritizing connectivity when implementing new protected areas could achieve the strategy's targets without compromising the future provision of ecosystem services, including food production, in Europe. However, we also find that EU-wide distributions of land uses and ecosystem services are influenced by the protected area network, and that this influence manifests differently in different climatic and socio-economic scenarios. Varying the strength of protection of the network had limited effects. Extractive services (food and timber production) decreased in protected areas, but non-extractive services increased, with compensatory changes occurring outside the network. Changes were small where competition for land was low and scenario conditions were benign, but became far larger and more extensive where competition was high and scenario conditions were challenging. Our findings highlight the apparent achievability of the EU's protected area targets, but also the need to account for adaptation in the wider land system and its consequences for spatial and temporal patterns of ecosystem services provision now and in the future. [Display omitted] • Many policies prioritise expansion and connectivity of protected areas. • We simulate connections between areas to achieve EU biodiversity targets. • Network improvement and integrated land-system modelling show targets are achievable. • Ecosystem services are maintained but with large spatial changes in land use. • Impacts are divergent across a range of climatic and socio-economic scenarios. [ABSTRACT FROM AUTHOR]

Background: Impaired functional capacity is a hallmark of patients with heart failure with preserved ejection fraction (HFpEF). Despite the association of HFpEF with reduced myocardial compliance attributed to fibrosis, spironolactone has not been shown to alter outcomes-perhaps reflecting the heterogeneity of underlying pathological mechanisms.Objectives: The authors sought to identify improvement in exercise capacity with spironolactone in the subset of patients with HFpEF with exercise-induced increase in ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') reflecting elevation of left ventricular (LV) filling pressure.Methods: In this randomized, blinded, parallel-group, placebo-controlled trial, 150 subjects (age 67 ± 9 years) with exertional dyspnea (New York Heart Association functional class II to III, left ventricular ejection fraction >50%, diastolic dysfunction, and exertional E/e' >13), excluding those with ischemic heart disease, were recruited in a tertiary cardiology center. Patients were randomized to 6 months of oral spironolactone 25 mg/day or matching placebo. Primary outcomes were improvements in peak oxygen uptake (VO2) and exertional E/e' ratio, and secondary outcomes were improvements in exercise blood pressure response and global LV longitudinal strain.Results: At follow-up, 131 patients completed therapy-64 taking spironolactone and 67 placebo. At baseline, subjects had substantial exercise limitation (peak VO2 64 ± 17% predicted). The spironolactone group showed improvement in exercise capacity (increment in peak VO2 [2.9 ml/min/kg (95% confidence interval [CI]: 1.9 to 3.9 ml/min/kg) vs. 0.3 ml/min/kg (95% CI: -0.5 to 1.1 ml/min/kg); p < 0.001], anaerobic threshold [2.0 ml/min/kg (95% CI: 0.9 to 3.2 ml/min/kg) vs. -0.9 ml/min/kg (95% CI: -3.4 to 1.6 ml/min/kg); p = 0.03], and O2 uptake efficiency [0.19 (95% CI: 0.06 to 0.31) vs. -0.07 (95% CI: -0.17 to 0.04); p = 0.002]), with reduction in exercise-induced increase in E/e' (-3.0 [95% CI: -3.9 to -2.0] vs. 0.5 [95% CI: -0.6 to 1.6]; p < 0.001). There was a significant interaction of spironolactone and change in E/e' on VO2 (p = 0.039).Conclusions: In patients with HFpEF and abnormal diastolic response to exertion, improvement in exercise E/e' mediates the beneficial effect of spironolactone on exercise capacity. Identification of exercise-induced increase in LV filling pressure in patients with HFpEF may define a subgroup with warranting trial of spironolactone. [ABSTRACT FROM AUTHOR]

Background: Heart failure with preserved ejection fraction (HFpEF) has a complex etiology. Factors responsible for development of impaired exercise tolerance and disease progression are incompletely defined.Objectives: The authors sought to define the contributions of contractile reserve, ventriculo-arterial coupling (VAC) reserve, and chronotropic response to the progression of HFpEF.Methods: We performed echocardiography at rest and immediately post-cardiopulmonary exercise test in 207 patients (63 ± 8 years of age) with stage C heart failure (HF) (exertional dyspnea, New York Heart Association functional class II to III, exercise capacity <80% of normal, left ventricular ejection fraction >50%, and diastolic dysfunction) and 60 patients with stage B HF (normal exercise tolerance with left ventricular hypertrophy, and/or reduced global longitudinal strain, with diastolic dysfunction).Results: Symptomatic patients were grouped as stage C1 (ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity [E/e'] <13 both at rest and exercise; n = 63), C2 (E/e' >13 only at exercise; n = 118), and C3 (E/e' >13 both at rest and exercise; n = 26) HF. Exercise capacity and cardiovascular functional reserve were less impaired in stage C1 than in stages C2 and C3. Chronotropic response was more disturbed in stage C3 than C1 and C2. Changes from rest to exercise in E/e' (-0.6 ± 1.7 vs. 3.7 ± 2.8; p < 0.0001), global longitudinal strain (2.9 ± 2.0 vs. 1.6 ± 2.8; p < 0.002), VAC (-0.21 ± 0.17 vs. -0.09 ± 0.15; p < 0.0001), and in VO2-HR gradient (0.30 ± 0.07 vs. 0.26 ± 0.11; p < 0.01) were significantly different in stages B and C.Conclusions: Normal E/e' response to exertion in symptomatic HFpEF is associated with less profound impairment of exercise capacity and is accompanied by derangements of contractile state and VAC. The transition from asymptomatic to overt HFpEF is linked to diastolic, systolic, and chronotropic deficits and an increasing degree of hemodynamic disturbances in stage C HF. [ABSTRACT FROM AUTHOR]