HUN-REN Balaton Limnological Research Institute

AIMS: Although platelet reactivity during P2Y12-inhibitors is associated with stent thrombosis (ST) and bleeding, standardized and clinically validated thresholds for accurate risk stratification after percutaneous coronary intervention (PCI) are lacking. We sought to determine the prognostic value of low platelet reactivity (LPR), optimal platelet reactivity (OPR), or high platelet reactivity (HPR) by applying uniform cut-off values for standardized devices. METHODS AND RESULTS: Authors of studies published before January 2015, reporting associations between platelet reactivity, ST, and major bleeding were contacted for a collaborative analysis using consensus-defined, uniform cut-offs for standardized platelet function assays. Based on best available evidence for each device (exploratory studies), LPR-OPR-HPR categories were defined as <95, 95-208, and >208 PRU for VerifyNow, <19, 19-46, and >46 U for the Multiplate analyser and <16, 16-50, and >50% for VASP assay. Seventeen studies including 20 839 patients were used for the analysis; 97% were treated with clopidogrel and 3% with prasugrel. Patients with HPR had significantly higher risk for ST [risk ratio (RR) and 95% CI: 2.73 (2.03-3.69), P < 0.00001], yet a slight reduction in bleeding [RR: 0.84 (0.71-0.99), P = 0.04] compared with those with OPR. In contrast, patients with LPR had a higher risk for bleeding [RR: 1.74 (1.47-2.06), P < 0.00001], without any further benefit in ST [RR: 1.06 (0.68-1.65), P = 0.78] in contrast to OPR. Mortality was significantly higher in patients with HPR compared with other categories (P < 0.05). Validation cohorts (n = 14) confirmed all results of exploratory studies (n = 3). CONCLUSIONS: Platelet reactivity assessment during thienopyridine-type P2Y12-inhibitors identifies PCI-treated patients at higher risk for mortality and ST (HPR) or at an elevated risk for bleeding (LPR).

The metacommunity concept has the potential to integrate local and regional dynamics within a general community ecology framework. To this end, the concept must move beyond the discrete archetypes that have largely defined it (e.g. neutral vs. species sorting) and better incorporate local scale species interactions and coexistence mechanisms. Here, we present a fundamental reconception of the framework that explicitly links local coexistence theory to the spatial processes inherent to metacommunity theory, allowing for a continuous range of competitive community dynamics. These dynamics emerge from the three underlying processes that shape ecological communities: (1) density-independent responses to abiotic conditions, (2) density-dependent biotic interactions and (3) dispersal. Stochasticity is incorporated in the demographic realisation of each of these processes. We formalise this framework using a simulation model that explores a wide range of competitive metacommunity dynamics by varying the strength of the underlying processes. Using this model and framework, we show how existing theories, including the traditional metacommunity archetypes, are linked by this common set of processes. We then use the model to generate new hypotheses about how the three processes combine to interactively shape diversity, functioning and stability within metacommunities.

SUMMARY 1. The effect of benthivorous bream and carp on sediment resuspension and the concentrations of nutrients and chlorophyll a were studied in sixteen experimental ponds (mean depth 1m, mean area 0.1 ha, sandy clay/clay sediment), stocked with bream or carp at densities varying from 0 to 500 kg ha −1 . Planktivorous perch ( Perca fluviatilis L.) were added to some ponds to suppress zooplankton. 2. Suspended sediment concentrations increased linearly with biomass of benthivorous fish. Bream caused an increase of 46 g sediment m −2 day −1 per 100kg bream ha −1 and a reduction of 0.38m −1 in reciprocal Secchi disc depth, corresponding to an increase in the extinction coefficient of 0.34m −1 . 3. No relationship was found between size of fish and amount of resuspension, but the effect of bream was twice as great as that of carp. Benthivorous feeding was reduced in May because alternative food (zooplankton) was available. 4. Assuming a linear relationship, chlorophyll a level increased by 9.0 μgI −1 , total P by 0.03mgl −1 and Kjeldahl‐N by 0.48mgl −1 per 100kg bream ha −1 . Silicate, chlorophyll a , total P and total N were all positively correlated with fish biomass, but orthophosphate showed no correlation.

A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.

Abstract Aim To propose a unified framework for quantifying taxon ( T β), phylogenetic ( P β) and functional ( F β) beta diversity via pairwise comparisons of communities, which allows these types of beta diversity to be partitioned into ecologically meaningful additive components. Location Global, with case studies in E urope and the A zores archipelago. Methods Using trees as a common representation for taxon, phylogenetic and functional diversity, we partition total beta diversity (β total ) into its replacement (turnover, β repl ) and richness difference (β rich ) components according to which part of a global tree was shared by or unique to communities that were being compared. We demonstrate the application of this framework using artificial and empirical examples (mammals in Europe and epigean arthropods in the Azores). Results Our empirical examples show that comparing P β and F β with the most commonly used T β revealed previously hidden patterns of beta diversity. More importantly, we demonstrate that partitioning P β total and F β total into their respective β repl and β rich components facilitates the detection of more complex patterns than using the overall coefficients alone, further elucidating the different forces operating in community assembly. Main conclusions The methods presented here allow the integration and full comparison of T β, P β and F β. They provide a tool for effectively disentangling the replacement (turnover) and richness difference components of the different biodiversity facets within the same methodological framework.

Optimizing outcomes after percutaneous coronary intervention (PCI) requires balancing between the risks of thrombotic and bleeding events in individual patients. 1 -3 However, finding the optimal balance is not always straightforward since the risks of thrombotic and bleeding complications may differ extremely between individuals. In addition, the individual effects of anticoagulant and antiplatelet drugs are not uniform in patients. ecent European guidelines 1,3 recommend the use of prasugrel or ticagrelor instead of clopidogrel in all PCI-treated acute coronary syndrome (ACS) patients without contraindication, acknowledging that laboratory assessment of P2Y 12 -receptor inhibition may be considered only in selected cases when clopidogrel is used. 1 However, there is no guidance with respect to the appropriate methodology and the suggested interpretation of results.

Hutchinson's paradox of the plankton inspired many studies on the mechanisms of species coexistence. Recent laboratory experiments showed that partitioning of white light allows stable coexistence of red and green picocyanobacteria. Here, we investigate to what extent these laboratory findings can be extrapolated to natural waters. We predict from a parameterized competition model that the underwater light colour of lakes and seas provides ample opportunities for coexistence of red and green phytoplankton species. To test this prediction, we sampled picocyanobacteria of 70 aquatic ecosystems, ranging from clear blue oceans to turbid brown peat lakes. As predicted, red picocyanobacteria dominated in clear waters, whereas green picocyanobacteria dominated in turbid waters. We found widespread coexistence of red and green picocyanobacteria in waters of intermediate turbidity. These field data support the hypothesis that niche differentiation along the light spectrum promotes phytoplankton biodiversity, thus providing a colourful solution to the paradox of the plankton.

Oxidative stress has been ascribed a role in the pathogenesis of diabetes and its complications, and stress proteins have been shown to protect organisms in vitro and in vivo against oxidative stress. To study the putative role of one of the most abundant cytoprotective stress proteins, inducible cytoplasmic 72-kDa-mass heat shock protein (Hsp-72), in the pathogenesis of diabetes, we measured its mRNA concentration in muscle biopsies from six type 2 diabetic patients and six healthy control subjects (protocol 1) as well as in 12 twin pairs discordant for type 2 diabetes and 12 control subjects undergoing a euglycemic-hyperinsulinemic clamp in combination with indirect calorimetry (protocol 2). The amount of Hsp-72 mRNA in muscle was significantly lower in type 2 diabetic patients than in healthy control subjects (in protocol 1: 5.2 +/- 2.2 vs. 53 +/- 32 million copies of Hsp-72 mRNA/microg total RNA, n = 6, P = 0.0039; in protocol 2: 3.2 +/- 3.3 vs. 43 +/- 31 million copies of Hsp-72 mRNA/microg total RNA, n = 12, P = 0.0001). Hsp-72 mRNA levels were also markedly reduced in the nondiabetic co-twins compared with healthy control subjects (5.8 +/- 5.0 vs. 43 +/- 31, n = 12, P = 0.0001), but they were also statistically significantly different from their diabetic co-twins when the difference between the pairs was compared (P = 0.0280). Heat shock protein mRNA content in muscle of examined patients correlated with the rate of glucose uptake and other measures of insulin-stimulated carbohydrate and lipid metabolism. In conclusion, the finding of decreased levels of Hsp-72 mRNA in skeletal muscle of patients with type 2 diabetes and its relationship with insulin resistance raises the question of whether heat shock proteins are involved in the pathogenesis of skeletal muscle insulin resistance in type 2 diabetes.

OBJECTIVE: To compare efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled with metformin. RESEARCH DESIGN AND METHODS: Adults with diabetes inadequately controlled (HbA1c 7-10%) with metformin were randomized to lixisenatide 20 μg once daily (n=318) or exenatide 10 μg twice daily (n=316) in a 24-week (main period), open-label, parallel-group, multicenter study. The primary objective was a noninferiority assessment of lixisenatide versus exenatide in HbA1c change from baseline to week 24. RESULTS: Lixisenatide once daily demonstrated noninferiority in HbA1c reduction versus exenatide twice daily. The least squares mean change was -0.79% (mean decrease 7.97 to 7.17%) for lixisenatide versus -0.96% (mean decrease 7.96 to 7.01%) for exenatide, and treatment difference was 0.17% (95% CI, 0.033-0.297), meeting a predefined noninferiority upper CI margin of 0.4%. Responder rate (HbA1c<7.0%) and improvements in fasting plasma glucose were comparable. Both agents induced weight loss (from 94.5 to 91.7 kg and from 96.7 to 92.9 kg with lixisenatide and exenatide, respectively). Incidence of adverse events (AEs) was similar for lixisenatide and exenatide, as was incidence of serious AEs (2.8 and 2.2%, respectively). Discontinuations attributable to AEs occurred in 33 lixisenatide (10.4%) and 41 exenatide (13.0%) patients. In the lixisenatide group, fewer participants experienced symptomatic hypoglycemia (2.5 vs. 7.9%; P<0.05), with fewer gastrointestinal events (especially nausea; 24.5 vs. 35.1%; P<0.05). CONCLUSIONS: Add-on lixisenatide once daily in type 2 diabetes inadequately controlled with metformin demonstrated noninferior improvements in HbA1c, with slightly lower mean weight loss, lower incidence of hypoglycemia, and better gastrointestinal tolerability compared with exenatide twice daily.

UNLABELLED: We examined the mechanisms of enhanced insulin sensitivity in 9 male healthy athletes (age, 25 +/- 1 yr; maximal aerobic power [VO2max], 57.6 +/- 1.0 ml/kg per min) as compared with 10 sedentary control subjects (age, 28 +/- 2 yr; VO2max, 44.1 +/- 2.3 ml/kg per min). In the athletes, whole body glucose disposal (240-min insulin clamp) was 32% (P < 0.01) and nonoxidative glucose disposal (indirect calorimetry) was 62% higher (P < 0.01) than in the controls. Muscle glycogen content increased by 39% in the athletes (P < 0.05) but did not change in the controls during insulin clamp. VO2max correlated with whole body (r = 0.60, P < 0.01) and nonoxidative glucose disposal (r = 0.64, P < 0.001). In the athletes forearm blood flow was 64% greater (P < 0.05) than in the controls, whereas their muscle capillary density was normal. Basal blood flow was related to VO2max (r = 0.63, P < 0.05) and glucose disposal during insulin infusion (r = 0.65, P < 0.05). The forearm glucose uptake in the athletes was increased by 3.3-fold (P < 0.01) in the basal state and by 73% (P < 0.05) during insulin infusion. Muscle glucose transport protein (GLUT-4) concentration was 93% greater in the athletes than controls (P < 0.01) and it was related to VO2max (r = 0.61, P < 0.01) and to whole body glucose disposal (r = 0.60, P < 0.01). Muscle glycogen synthase activity was 33% greater in the athletes than in the controls (P < 0.05), and the basal glycogen synthase fractional activity was closely related to blood flow (r = 0.88, P < 0.001). IN CONCLUSION: (a) athletes are characterized by enhanced muscle blood flow and glucose uptake. (b) The cellular mechanisms of glucose uptake are increased GLUT-4 protein content, glycogen synthase activity, and glucose storage as glycogen. (c) A close correlation between glycogen synthase fractional activity and blood flow suggests that they are causally related in promoting glucose disposal.

Although several studies have examined the functional diversity of freshwater macroinvertebrates, the variety of methodologies combined with the absence of a synthetic review make our understanding of this field incomplete. Therefore, we reviewed the current methodology for assessing functional diversity in freshwater macroinvertebrate research. Our review showed that most papers quantified functional diversity using biological traits, among which feeding habits were the most common traits probably due to the assumed links between feeding and ecosystem functions. A large number of diversity measures have been applied for quantifying functional diversity of freshwater macroinvertebrate assemblages, among which Rao’s quadratic entropy looks like the most frequent. In most papers, functional diversity was positively related to taxon richness, and functional redundancy was a key concept in explaining this correlation. Most studies detected strong influence of the environmental factors as well as human impact on functional diversity. Finally, our review revealed that functional diversity research is biased towards European running waters and is hindered by yet insufficient information on the autecology of macroinvertebrates.

1 Cylindrospermopsis raciborskii occupies a rapidly expanding geographical area. Its invasive success challenges eutrophication control in many lakes. To understand better the load-dependent behaviour of this nitrogen fixing cyanobacterium under in situ conditions, we studied P-dependent growth of a C. raciborskii strain under continuous and pulsed P supply. 2 The Droop model reasonably described P-dependent growth in the continuously supplied chemostats. Large P pulses, however, caused a delay in growth and cells subject to P pulses grew slower than their counterparts with the same P quota supplied continuously. 3 The kinetics of P uptake indicated that C. raciborskii is opportunistic with respect to P. Its high excess P storage capacity after a saturating P pulse (Qex=95 µg P [mg C]-1) and P-specific uptake capacity (Umax = Vmax/QP=150–1200) are indicative of storage adaptation. At the same time, the affinity of the P uptake system (Umax/K = 800–4000) is also high. 4 Rate of leakage exceeded that of the steady state net P uptake by one to two orders of magnitude. Growth affinity of C. raciborskii (µmax/Kµ≈ 20) was relatively low, presumably due to the substantial leakage. 5 The dynamics of the particular water body determine which trait contributes most to competitive success of C. raciborskii. In deep lakes with vertical nutrient gradients, the cyanobacterium may rely primarily on its high P storage capacity, which is coupled to a lack of short-term feedback inhibition and efficient buoyancy regulation. In lakes without such gradients, high P uptake affinity may be vitally important.

Summary A safe, clean water supply is critical for sustaining many important ecosystem services provided by freshwaters. The development of cyanobacterial blooms in lakes and reservoirs has a major impact on the provision of these services, particularly limiting their use for recreation and water supply for drinking and spray irrigation. Nutrient enrichment is thought to be the most important pressure responsible for the widespread increase in cyanobacterial blooms in recent decades. Quantifying how nutrients limit cyanobacterial abundance in lakes is, therefore, a key need for setting robust targets for the management of freshwaters. Using a data set from over 800 European lakes, we highlight the use of quantile regression modelling for understanding the maximum potential capacity of cyanobacteria in relation to total phosphorus ( TP ) and the use of a range of quantile responses, alongside World Health Organisation ( WHO ) health alert thresholds for recreational waters, for setting robust phosphorus targets for lake management in relation to water use. The analysis shows that cyanobacteria exhibit a nonlinear response to phosphorus with the sharpest increase in cyanobacterial abundance occurring in the TP range from about 20 μg L −1 up to about 100 μg L −1 . The likelihood of exceeding the World Health Organisation ( WHO ) ‘low health alert’ threshold increases from about 5% exceedance at 16 μg L −1 to 40% exceedance at 54 μg L −1 . About 50% of the studied lakes remain below this WHO health alert threshold, irrespective of high summer TP concentrations, highlighting the importance of other factors affecting cyanobacteria population growth and loss processes, such as high flushing rate. Synthesis and applications . Developing a more quantitative understanding of the effect of nutrients on cyanobacterial abundance in freshwater lakes provides important knowledge for restoring and sustaining a safe, clean water supply for multiple uses. Our models can be used to set nutrient targets to sustain recreational services and provide different levels of precaution that can be chosen dependent on the importance of the service provision.

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.

Remote sensing has the potential to provide truly synoptic views of water quality, in particular, the spatial distributions of phytoplankton. Whilst the spectral capabilities of satellites used in ocean colour work have improved significantly over recent years, the application of satellite remote sensing to lake water is constrained by the need for high spatial resolution image data and thus remains limited by spectral resolution capabilities. This becomes a significant problem when attempting to quantify chlorophyll a (Chl a) in waters characterized by high and heterogeneous suspended sediment concentrations (SSC). The SSC dominates the spectral reflectance, masking the spectral influence from other components in broad spectral band systems, making Chl a determination from remote sensing imagery difficult. This paper presents a linear mixture modelling approach to derive accurate estimates of Chl a from Landsat Thematic Mapper (TM) imagery. This approach was tested in Lake Balaton, Europe's largest shallow lake characterized by high suspended sediment and, until recently, frequent eutrophic and hypereutrophic episodes. The last significant bloom occurred in September of 2000 and a Landsat TM image was acquired for 11th September, during which ground reference data of water quality was collected. The modelled image‐derived results of Chl a demonstrate an excellent correspondence (r2 = 0.95) between the ground‐based measurements of Chl a, and yield considerable detail of lake phytoplankton distributions. The September 2000 calibration was then successfully applied to a July 1994 Landsat TM image and validated with Chl a data collected coincidently within two days of the image. The comparability between water sample data and image results demonstrates that there is temporal stability and robustness in the approach and calibration described.

Increased risk of infectious disease is assumed to be a major cost of group living, yet empirical evidence for this effect is mixed. We studied whether larger social groups are more subdivided structurally. If so, the social subdivisions that form in larger groups may act as barriers to the spread of infection, weakening the association between group size and infectious disease. To investigate this 'social bottleneck' hypothesis, we examined the association between group size and four network structure metrics in 43 vertebrate and invertebrate species. We focused on metrics involving modularity, clustering, distance and centralization. In a meta-analysis of intraspecific variation in social networks, modularity showed positive associations with network size, with a weaker but still positive effect in cross-species analyses. Network distance also showed a positive association with group size when using intraspecific variation. We then used a theoretical model to explore the effects of subgrouping relative to other effects that influence disease spread in socially structured populations. Outbreaks reached higher prevalence when groups were larger, but subgrouping reduced prevalence. Subgrouping also acted as a 'brake' on disease spread between groups. We suggest research directions to understand the conditions under which larger groups become more subdivided, and to devise new metrics that account for subgrouping when investigating the links between sociality and infectious disease risk.

The hypotheses that beta diversity should increase with decreasing latitude and increase with spatial extent of a region have rarely been tested based on a comparative analysis of multiple datasets, and no such study has focused on stream insects. We first assessed how well variability in beta diversity of stream insect metacommunities is predicted by insect group, latitude, spatial extent, altitudinal range, and dataset properties across multiple drainage basins throughout the world. Second, we assessed the relative roles of environmental and spatial factors in driving variation in assemblage composition within each drainage basin. Our analyses were based on a dataset of 95 stream insect metacommunities from 31 drainage basins distributed around the world. We used dissimilarity-based indices to quantify beta diversity for each metacommunity and, subsequently, regressed beta diversity on insect group, latitude, spatial extent, altitudinal range, and dataset properties (e.g., number of sites and percentage of presences). Within each metacommunity, we used a combination of spatial eigenfunction analyses and partial redundancy analysis to partition variation in assemblage structure into environmental, shared, spatial, and unexplained fractions. We found that dataset properties were more important predictors of beta diversity than ecological and geographical factors across multiple drainage basins. In the within-basin analyses, environmental and spatial variables were generally poor predictors of variation in assemblage composition. Our results revealed deviation from general biodiversity patterns because beta diversity did not show the expected decreasing trend with latitude. Our results also call for reconsideration of just how predictable stream assemblages are along ecological gradients, with implications for environmental assessment and conservation decisions. Our findings may also be applicable to other dynamic systems where predictability is low.

Abstract Human activities drive a wide range of environmental pressures, including habitat change, pollution and climate change, resulting in unprecedented effects on biodiversity 1,2 . However, despite decades of research, generalizations on the dimensions and extent of human impacts on biodiversity remain ambiguous. Mixed views persist on the trajectory of biodiversity at the local scale 3 and even more so on the biotic homogenization of biodiversity across space 4,5 . We compiled 2,133 publications covering 97,783 impacted and reference sites, creating an unparallelled dataset of 3,667 independent comparisons of biodiversity impacts across all main organismal groups, habitats and the five most predominant human pressures 1,6 . For all comparisons, we quantified three key measures of biodiversity to assess how these human pressures drive homogenization and shifts in composition of biological communities across space and changes in local diversity, respectively. We show that human pressures distinctly shift community composition and decrease local diversity across terrestrial, freshwater and marine ecosystems. Yet, contrary to long-standing expectations, there is no clear general homogenization of communities. Critically, the direction and magnitude of biodiversity changes vary across pressures, organisms and scales at which they are studied. Our exhaustive global analysis reveals the general impact and key mediating factors of human pressures on biodiversity and can benchmark conservation strategies.

Freshwater ecosystems are among the most threatened in the world, while providing numerous essential ecosystem services (ES) to humans. Despite their importance, research on freshwater ecosystem services is limited. Here, we examine how freshwater studies could help to advance ES research and vice versa. We summarize major knowledge gaps and suggest solutions focusing on science and policy in Europe. We found several features that are unique to freshwater ecosystems, but often disregarded in ES assessments. Insufficient transfer of knowledge towards stakeholders is also problematic. Knowledge transfer and implementation seems to be less effective towards South-east Europe. Focusing on the strengths of freshwater research regarding connectivity, across borders, involving multiple actors can help to improve ES research towards a more dynamic, landscape-level approach, which we believe can boost the implementation of the ES concept in freshwater policies. Bridging these gaps can contribute to achieve the ambitious targets of the EU's Green Deal.

A great deal of attention has been given to declining species diversity in terrestrial systems, and certainly the rate of species loss in tropical forests is staggering. Recently, increasing attention has been focused on the loss of species in aquatic ecosystems. Indeed, Ricciardi and Rasmussen (1999) report that freshwater extinctions in North America far exceed extinctions in terrestrial environments. For example, an increasing number of freshwater fish and bivalves are being added to endangered species lists In contrast to our knowledge of fish and bivalves, information on species extinctions or even inventory lists are lacking for most inhabitants of the bottom sediments of lakes, streams, ground waters and wetlands, even though these "invisible" habitats harbor diverse and abundant biota (e.g., estimated at more than 100,000 species of sediment invertebrates globally, 10,000 species of algae, and more than 20,000 species of protozoans and bacteria; Although the local and global environmental