Wetland productivity determines trade-off between biodiversity support and greenhouse gas production.

Establishing wetlands for nutrient capture and biodiversity support may introduce trade-offs between environmentally beneficial functions and detrimental greenhouse gas emissions. Investigating the interaction of nutrient capture, primary production, greenhouse gas production and biodiversity support is imperative to understanding the overall function of wetlands and determining possible beneficial synergistic effects and trade-offs. Here, we present temporally replicated data from 17 wetlands in hemi-boreal Sweden. We explored the relationship between nutrient load, primary producing algae, production of methane and nitrous oxide, and emergence rates of chironomids to determine what factors affected each and how they related to each other. Chironomid emergence rates correlated positively with methane production and negatively with nitrous oxide production, where water temperature was the main driving factor. Increasing nutrient loads reduced methanogenesis through elevated nitrogen concentrations, while simultaneously enhancing nitrous oxide production. Nutrient loads only indirectly increased chironomid emergence rates through increased chlorophyll-a concentration, via increased phosphorus concentrations, with certain taxa and food preference functional groups benefitting from increased chlorophyll-a concentrations. However, water temperature seemed to be the main driving factor for chironomid emergence rates, community composition and diversity, as well as for greenhouse gas production. These findings increase our understanding of the governing relationships between biodiversity support and greenhouse gas production, and should inform future management when constructing wetlands

Colocalization of synapsin and actin during synaptic vesicle recycling

It has been hypothesized that in the mature nerve terminal, interactions between synapsin and actin regulate the clustering of synaptic vesicles and the availability of vesicles for release during synaptic activity. Here, we have used immunogold electron microscopy to examine the subcellular localization of actin and synapsin in the giant synapse in lamprey at different states of synaptic activity. In agreement with earlier observations, in synapses at rest, synapsin immunoreactivity was preferentially localized to a portion of the vesicle cluster distal to the active zone. During synaptic activity, however, synapsin was detected in the pool of vesicles proximal to the active zone. In addition, actin and synapsin were found colocalized in a dynamic filamentous cytomatrix at the sites of synaptic vesicle recycling, endocytic zones. Synapsin immunolabeling was not associated with clathrin-coated intermediates but was found on vesicles that appeared to be recycling back to the cluster. Disruption of synapsin function by microinjection of antisynapsin antibodies resulted in a prominent reduction of the cytomatrix at endocytic zones of active synapses. Our data suggest that in addition to its known function in clustering of vesicles in the reserve pool, synapsin migrates from the synaptic vesicle cluster and participates in the organization of the actin-rich cytomatrix in the endocytic zone during synaptic activity

Common Genetic Variations in the NALP3 Inflammasome Are Associated with Delayed Apoptosis of Human Neutrophils

Background: Neutrophils are key-players in the innate host defense and their programmed cell death and removal are essential for efficient resolution of inflammation. These cells recognize a variety of pathogens, and the NOD-like receptors (NLRs) have been suggested as intracellular sensors of microbial components and cell injury/stress. Some NLR will upon activation form multi-protein complexes termed inflammasomes that result in IL-1 beta production. NLR mutations are associated with auto-inflammatory syndromes, and our previous data propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk and severity of inflammatory disease by acting as genetic susceptibility factors. These gene products are components of the NALP3 inflammasome, and approximately 6.5% of the Swedish population are heterozygote carriers of these combined gene variants. Since patients carrying the Q705K/C10X polymorphisms display leukocytosis, the aim of the present study was to find out whether the inflammatory phenotype was related to dysfunctional apoptosis and impaired clearance of neutrophils by macrophages. less thanbrgreater than less thanbrgreater thanMethods and Findings: Patients carrying the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well as microbe-induced apoptosis compared to matched controls. Western blotting revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients neutrophils. In contrast to macrophages from healthy controls, macrophages from the patients produced lower amounts of TNF; suggesting impaired macrophage clearance response. less thanbrgreater than less thanbrgreater thanConclusions: The Q705K/C10X polymorphisms are associated with delayed apoptosis of neutrophils. These findings are explained by altered involvement of different regulators of apoptosis, resulting in an anti-apoptotic profile. Moreover, the macrophage response to ingestion of microbe-induced apoptotic neutrophils is altered in the patients. Taken together, the patients display impaired turnover and clearance of apoptotic neutrophils, pointing towards a dysregulated innate immune response that influences the resolution of inflammation. The future challenge is to understand how microbes affect the activation of inflammasomes, and why this interaction will develop into severe inflammatory disease in certain individuals.Funding Agencies|Swedish Research Council||Heart-Lung Foundation||King Gustaf V Memorial Foundation||County Council of Ostergotland||Soderberg Foundation|

Charged multifluids in general relativity

The exact 1+3 covariant dynamical fluid equations for a multi-component plasma, together with Maxwell's equations are presented in such a way as to make them suitable for a gauge-invariant analysis of linear density and velocity perturbations of the Friedmann-Robertson-Walker model. In the case where the matter is described by a two component plasma where thermal effects are neglected, a mode representing high-frequency plasma oscillations is found in addition to the standard growing and decaying gravitational instability picture. Further applications of these equations are also discussed.Comment: 14 pages (example added), to appear in Class. Quantum Gra

Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction : systematic review and economic evaluation

Background The blockage of a coronary artery (coronary thrombosis) can lead to a heart attack (acute myocardial infarction). There are several ways of trying to overcome this blockage. The methods include drug treatment to dissolve the clot (thrombolysis) and physical intervention, either by passing a catheter into the affected artery [angioplasty or percutaneous coronary intervention (PCI)], or bypassing the blocked section by cardiac surgery [coronary artery bypass grafting (CABG)]. Thrombolysis can be given in the community before the patient is sent to hospital, or delayed until after admission. Prehospital thrombolysis is not common in the UK. Immediate angioplasty is not routinely available in the UK at present; it is much more common in the USA. Objectives To review the clinical evidence comparing immediate angioplasty with thrombolysis, and to consider whether it would be cost-effective. Methods This report was based on a systematic review of the evidence of clinical effectiveness and an economic analysis of cost-effectiveness based on the clinical review and on cost data from published sources and de novo data collection. Data sources The search strategy searched six electronic databases (including Medline, Cochrane Library and EMBASE), with English-language limits, for the periods up to December 2002. Bibliographies of related papers were assessed for relevant studies and experts contacted for advice and peer review, and to identify additional published and unpublished references. Study selection For clinical effectiveness, a comprehensive review of randomised controlled trials (RCTs) was used for efficacy, and a selection of observational studies such as case series or audit data for effectiveness safety in routine practice. RCTs of thrombolysis were used to assess the relative value of prehospital and hospital thrombolysis. Observational studies were used to assess the representativeness of patients in the RCTs, and to determine whether different groups have different capacity to benefit. They were used to assess the implications of wider diffusion of the technology away from major centres. Data extraction Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of systematic reviews, RCTs, controlled clinical trials and economic studies was assessed using criteria recommended by the NHS Centre for Reviews and Dissemination (University of York). Study synthesis Clinical effectiveness was synthesised through a narrative review with full tabulation of results of all included studies and a meta-analysis to provide a precise estimate of absolute clinical benefit. Consideration was given to the effect of the growing use of stents. The economic modelling adopted an NHS perspective to develop a decision-analytical model of cost-effectiveness focusing on opportunity costs over the short term (6 months). Results and conclusion Number and quality of studies, and summary of benefits There were several good-quality systematic reviews, including a Cochrane review, as well as an individual patient meta-analysis and a number of recent trials not included in the reviews. The results were consistent in showing an advantage of immediate angioplasty over hospital thrombolysis. The updated meta-analysis showed that mortality is reduced by about one-third, from 7.6% to 4.9% in the first 6 months, and by about the same in studies of up to 24 months. Reinfarction is reduced by over half, from 7.6% to 3.1%. Stroke is reduced by about two-thirds, from 2.3% with thrombolysis to 0.7% with PCI, with the difference being due to haemorrhagic stroke. The need for CABG is reduced by about one-third, from 13.2% to 8.4%. Caution is needed in interpreting the older trials, as changes such as an increase in stenting and the use of the glycoprotein IIb/IIa inhibitors may improve the results of PCI. There is little evidence comparing prehospital thrombolysis with immediate PCI. One good quality study from France showed that prehospital thrombolysis with PCI in those in whom thrombolysis failed was as good as universal PCI. Research on thrombolysis followed by PCI, known as facilitated PCI, is underway, but results are not yet available. Further caveats are needed. Trials may be done in select centres and results may not be as good in lower volume centres, or out of normal working hours. In addition, much of the marginal mortality benefit of PCI over hospital thrombolysis may be lost if door-to-balloon time were more than 1 hour longer than door-to-needle time. Conversely, within the initial 6 hours, the later patients present, the greater the relative advantage of PCI. Cost-effectiveness If both interventions were routinely available, the economic analysis favours PCI, given the assumptions of the model. Results suggest that PCI is more cost-effective than thrombolysis, providing additional benefits in health status at some extra cost and an incremental cost per unit change in health status under the £30,000 threshold in most instances. In the longer term, the cost difference is expected to be reduced because of higher recurrence and reintervention rates among those who had thrombolysis. The model is not particularly sensitive to variations in probabilities from the clinical effectiveness analysis. However, very few units in England could offer a routine immediate PCI service at present, and there would be considerable resource implications of setting up such services. Without a detailed survey of existing provision, it is not possible to quantify the implications, but they include both capital and revenue: an increase in catheter laboratory provision and running costs. The greatest problem would be staffing, and that would take some years to resolve. A gradual incrementalist approach based on clinical networks, with transfer to centres able to offer PCI, could be used. In rural areas, one option could be to promote an increase in prehospital thrombolysis, with PCI for thrombolysis failures. Need for further research There is a need for economic data on the long-term consequences of the treatment, the quality of life of patients after treatment and the effects of PCI following thrombolysis failure

2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis

Regular physical activity (PA) is increasingly promoted for people with rheumatic and musculoskeletal diseases as well as the general population. We evaluated if the public health recommendations for PA are applicable for people with inflammatory arthritis (iA; Rheumatoid Arthritis and Spondyloarthritis) and osteoarthritis (hip/knee OA) in order to develop evidence-based recommendations for advice and guidance on PA in clinical practice. The EULAR standardised operating procedures for the development of recommendations were followed. A task force (TF) (including rheumatologists, other medical specialists and physicians, health professionals, patient-representatives, methodologists) from 16 countries met twice. In the first TF meeting, 13 research questions to support a systematic literature review (SLR) were identified and defined. In the second meeting, the SLR evidence was presented and discussed before the recommendations, research agenda and education agenda were formulated. The TF developed and agreed on four overarching principles and 10 recommendations for PA in people with iA and OA. The mean level of agreement between the TF members ranged between 9.8 and 8.8. Given the evidence for its effectiveness, feasibility and safety, PA is advocated as integral part of standard care throughout the course of these diseases. Finally, the TF agreed on related research and education agendas. Evidence and expert opinion inform these recommendations to provide guidance in the development, conduct and evaluation of PA-interventions and promotion in people with iA and OA. It is advised that these recommendations should be implemented considering individual needs and national health systems.EULA

Defining "Development".

Is it possible, and in the first place is it even desirable, to define what "development" means and to determine the scope of the field called "developmental biology"? Though these questions appeared crucial for the founders of "developmental biology" in the 1950s, there seems to be no consensus today about the need to address them. Here, in a combined biological, philosophical, and historical approach, we ask whether it is possible and useful to define biological development, and, if such a definition is indeed possible and useful, which definition(s) can be considered as the most satisfactory