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Introduction: Self-management interventions in patients with chronic conditions have received increasing attention over the past few years, yet the meta-analyses encountered considerable heterogeneity in results. This suggests that the effectiveness of self-management interventions must be assessed in the context of which components are responsible for eliciting the effect and in which subgroups of patients the intervention works best. The aim of the present study is to identify condition-transcending determinants of success of self-management interventions in two parallel individual patient data meta-analyses of self-management trials in patients with congestive heart failure (CHF) and in patients with chronic obstructive pulmonary disease (COPD). Methods and analysis: Investigators of 53 randomised trials (32 in CHF and 21 in COPD) will be requested to share their de-identified individual patient data. Data will be analysed using random effects models, taking clustering within studies into account. Effect modification by age, sex, disease severity, symptom status, comorbid conditions and level of education will be assessed. Sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and dissemination: The de-identified individual patient data are used only for the purpose for which they were originally collected and for which ethical approval has been obtained by the original investigators. Knowledge on the effective ingredients of self-management programmes and identification of subgroups of patients in which those interventions are most effective will guide the development of evidence-based personalised self-management interventions for patients with CHF and COPD as well as with other chronic diseases. Trial registration number: PROSPERO: CRD42013004698.

Dam building and reservoir operations alter the downstream hydrological regime, and as a result, affect the health of the river aquatic ecosystem, particularly for large-scale cascade reservoirs. This study investigated the impact of the Gezhouba Reservoir (GR) and the Three Gorges Reservoir (TGR) on the spawning conditions of two critical taxa, i.e., the endemic four major carps and the endangered Chinese sturgeon in the Yangtze River. We analyzed the flow, sediment, and thermal regime in these two taxa spawning seasons and compared their features between the predam and postdam periods. Our results revealed that the GR and the TGR had altered the frequency distributions of flow, sediment, and water temperature to different degrees, with the impact by the GR on the carps and Chinese sturgeon ranked as water temperature > water temperature. For the GR, the satisfying degree of the suitable flow and water temperature of the carps increased, whilst the suitable flow, sediment, and water temperature for the Chinese sturgeon decreased. These changes in TGR showed a significant ascending (descending) trend in the suitable flow (water temperature) for the carps, and a clear decreasing trend in the flow, sediment, and temperature for Chinese sturgeon. Both the TGR and the GR had negative impacts on the spawning of these two taxa in terms of the rising/falling flow characteristics. flow, and the effect of the TGR on these two taxa were ordered as flow > water temperature, sediment > water temperature > flow, sediment > flow >

Background: We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former.Methods: In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials.Results: We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74).Conclusions: Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done.

We present in this paper a useful strategy to solve stochastic partial differential equations (SPDEs) involving stochastic coefficients. Using the Wick-product of higher order and the Wiener-Itˆo chaos expansion, the SPDEs is reformulated as a large system of deterministic partial differential equations. To reduce the computational complexity of this system, we shall use a decomposition-coordination method. To obtain the chaos coefficients in the corresponding deterministic equations, we use a least square formulation. Once this approximation is performed, the statistics of the numerical solution can be easily evaluated.

The authors also acknowledge the support and collaboration of many other colleagues in their respective institutes, research communities and IT Infrastructures, together with the funding received by these from many different sources. These include but are not limited to the following: (i) The Worldwide LHC Computing Grid (WLCG) project is a global collaboration of more than 170 computing centres in 43 countries, linking up national and international grid infrastructures. Funding is acknowledged from many national funding bodies and we acknowledge the support of several operational infrastructures including EGI, OSG and NDGF/NeIC. (ii) EGI acknowledges the funding and support received from the European Commission and the many National Grid Initiatives and other members. EOSC-hub receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 777536. (iii) The work leading to these results has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 730941 (AARC2). (iv) Work on the development of ESGF's identity management system has been supported by The UK Natural Environment Research Council and funding from the European Union's Seventh Framework Programme for research, technological development and demonstration through projects IS-ENES (grant agreement no 228203) and IS-ENES2 (grant agreement no 312979). (v) Ludek Matyska and Michal Prochazka acknowledge funding from the RI ELIXIR CZ project funded by MEYS Czech Republic No. LM2015047. (vi) Scott Koranda acknowledges support provided by the United States National Science Foundation under Grant No. PHY-1700765. (vii) GÉANT Association on behalf of the GN4 Phase 2 project (GN4-2).The research leading to these results has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 731122(GN4-2). (viii) ELIXIR acknowledges support from Research Infrastructure programme of Horizon 2020 grant No 676559 EXCELERATE. (ix) CORBEL life science cluster acknowledges support from Horizon 2020 research and innovation programme under grant agreement No 654248. (x) Mirjam van Daalen acknowledges that the research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020. (xi) EISCAT is an international association supported by research organisations in China (CRIRP), Finland (SA), Japan (NIPR), Norway (NFR), Sweden (VR), and the United Kingdom (NERC). This white-paper expresses common requirements of Research Communities seeking to leverage Identity Federation for Authentication and Authorisation. Recommendations are made to Stakeholders to guide the future evolution of Federated Identity Management in a direction that better satisfies research use cases. The authors represent research communities, Research Services, Infrastructures, Identity Federations and Interfederations, with a joint motivation to ease collaboration for distributed researchers. The content has been edited collaboratively by the Federated Identity Management for Research (FIM4R) Community, with input sought at conferences and meetings in Europe, Asia and North America.

Key pointsKetone bodies are proposed to represent an alternative fuel source driving energy production, particularly during exercise. Biologically, the extent to which mitochondria utilize ketone bodies compared to other substrates remains unknown. We demonstratein vitrothat maximal mitochondrial respiration supported by ketone bodies is low when compared to carbohydrate-derived substrates in the left ventricle and red gastrocnemius muscle from rodents, and in human skeletal muscle. When considering intramuscular concentrations of ketone bodies and the presence of other carbohydrate and lipid substrates, biological rates of mitochondrial respiration supported by ketone bodies are predicted to be minimal. At the mitochondrial level, it is therefore unlikely that ketone bodies are an important source for energy production in cardiac and skeletal muscle, particularly when other substrates are readily available. Ketone bodies (KB) have recently gained popularity as an alternative fuel source to support mitochondrial oxidative phosphorylation and enhance exercise performance. However, given the low activity of ketolytic enzymes and potential inhibition from carbohydrate oxidation, it remains unknown if KBs can contribute to energy production. We therefore determined the ability of KBs (sodiumdl-beta-hydroxybutyrate, beta-HB; lithium acetoacetate, AcAc) to stimulatein vitromitochondrial respiration in the left ventricle (LV) and red gastrocnemius (RG) of rats, and in human vastus lateralis. Compared to pyruvate, the ability of KBs to maximally drive respiration was low in isolated mitochondria and permeabilized fibres (PmFb) from the LV (similar to 30-35% of pyruvate), RG (similar to 10-30%), and human vastus lateralis (similar to 2-10%). In PmFb, the concentration of KBs required to half-maximally drive respiration (LV: 889 mu m beta-HB, 801 mu mAcAc; RG: 782 mu m beta-HB, 267 mu mAcAc) were greater than KB content representative of the muscle microenvironment (similar to 100 mu m). This would predict low rates (similar to 1-4% of pyruvate) of biological KB-supported respiration in the LV (8-14 pmol s(-1) mg(-1)) and RG (3-6 pmol s(-1) mg(-1)) at rest and following exercise. Moreover, KBs did not increase respiration in the presence of saturating pyruvate, submaximal pyruvate (100 mu m) reduced the ability of physiological beta-HB to drive respiration, and addition of other intracellular substrates (succinate + palmitoylcarnitine) decreased maximal KB-supported respiration. As a result, product inhibition is likely to limit KB oxidation. Altogether, the ability of KBs to drive mitochondrial respiration is minimal and they are likely to be outcompeted by other substrates, compromising their use as an important energy source.

This is the accepted manuscript of the paper "Identification of Resistance Genes and Response to Arsenic in Rhodococcus aetherivorans BCP1", published as final paper in "Frontiers in Microbiology Volume 10, 07 May 2019, Pages 888 https://doi.org/10.3389/fmicb.2019.00888”. Arsenic (As) ranks among the priority metal(loid)s that are of public health concern. In the environment, arsenic is present in different forms, organic or inorganic, featured by various toxicity levels. Bacteria have developed different strategies to deal with this toxicity involving different resistance genetic determinants. Bacterial strains of Rhodococcus genus, and more in general Actinobacteria phylum, have the ability to cope with high concentrations of toxic metalloids, although little is known on the molecular and genetic bases of these metabolic features. Here we show that Rhodococcus aetherivorans BCP1, an extremophilic actinobacterial strain able to tolerate high concentrations of organic solvents and toxic metalloids, can grow in the presence of high concentrations of As(V) (up to 240 mM) under aerobic growth conditions using glucose as sole carbon and energy source. Notably, BCP1 cells improved their growth performance as well as their capacity of reducing As(V) into As(III) when the concentration of As(V) is within 30–100 mM As(V). Genomic analysis of BCP1 compared to other actinobacterial strains revealed the presence of three gene clusters responsible for organic and inorganic arsenic resistance. In particular, two adjacent and divergently oriented ars gene clusters include three arsenate reductase genes (arsC1/2/3) involved in resistance mechanisms against As(V). A sequence similarity network (SSN) and phylogenetic analysis of these arsenate reductase genes indicated that two of them (ArsC2/3) are functionally related to thioredoxin (Trx)/thioredoxin reductase (TrxR)-dependent class and one of them (ArsC1) to the mycothiol (MSH)/mycoredoxin (Mrx)-dependent class. A targeted transcriptomic analysis performed by RT-qPCR indicated that the arsenate reductase genes as well as other genes included in the ars gene cluster (possible regulator gene, arsR, and arsenite extrusion genes, arsA, acr3, and arsD) are transcriptionally induced when BCP1 cells were exposed to As(V) supplied at two different sub-lethal concentrations. This work provides for the first time insights into the arsenic resistance mechanisms of a Rhodococcus strain, revealing some of the unique metabolic requirements for the environmental persistence of this bacterial genus and its possible use in bioremediation procedures of toxic metal contaminated sites.

The Niphta Theischinger fauna of South America is revised to include 11 species, nine of which are described as new to science (N. acus Pivar, sp. nov., N. bifurcata Pivar &amp; Moulton, sp. nov., N. bispinosa Pivar &amp; Sinclair, sp. nov., N. brunnea Pivar, sp. nov., N. courtneyi Pivar, sp. nov., N. daniellae Pivar, sp. nov., N. downesi Pivar, sp. nov., N. eurydactyla Pivar, sp. nov., N. mapuche Pivar, sp. nov.). The genus Niphta is redefined, both previously described Chilean species are redescribed, N. halteralis (Edwards) and N. nudipennis (Edwards), and females are described or redescribed where possible. The first descriptions of the immature stages of South American Niphta are provided, which represent a new larval morphotype in Thaumaleidae, as larvae and pupae possess ventral adhesive structures. Furthermore, these larvae were collected from vegetation rather than rocky substrates. Illustrations and micrographs are provided for all species, and scanning electron microscopy images are included for select immatures. A key to species, distribution maps, and discussions regarding phylogenetic affinities and habitat are also included.

The success of invasive species has been explained by two contrasting but non-exclusive views: (i) intrinsic factors make some species inherently good invaders; (ii) species become invasive as a result of extrinsic ecological and genetic influences such as release from natural enemies, hybridization or other novel ecological and evolutionary interactions. These viewpoints are rarely distinguished but hinge on distinct mechanisms leading to different management scenarios. To improve tests of these hypotheses of invasion success we introduce a simple mathematical framework to quantify the invasiveness of species along two axes: (i) interspecific differences in performance among native and introduced species within a region, and (ii) intraspecific differences between populations of a species in its native and introduced ranges. Applying these equations to a sample dataset of occurrences of 1,416 plant species across Europe, Argentina, and South Africa, we found that many species are common in their native range but become rare following introduction; only a few introduced species become more common. Biogeographical factors limiting spread (e.g. biotic resistance, time of invasion) therefore appear more common than those promoting invasion (e.g. enemy release). Invasiveness, as measured by occurrence data, is better explained by inter-specific variation in invasion potential than biogeographical changes in performance. We discuss how applying these comparisons to more detailed performance data would improve hypothesis testing in invasion biology and potentially lead to more efficient management strategies.

<b><i>Background:</i></b> An international expert panel convened by the Independent Scientific Committee on Drugs developed a multi-criteria decision analysis model of the relative importance of different types of harm related to the use of nicotine-containing products. <b><i>Method:</i></b> The group defined 12 products and 14 harm criteria. Seven criteria represented harms to the user, and the other seven indicated harms to others. The group scored all the products on each criterion for their average harm worldwide using a scale with 100 defined as the most harmful product on a given criterion, and a score of zero defined as no harm. The group also assessed relative weights for all the criteria to indicate their relative importance. <b><i>Findings:</i></b> Weighted averages of the scores provided a single, overall score for each product. Cigarettes (overall weighted score of 100) emerged as the most harmful product, with small cigars in second place (overall weighted score of 64). After a substantial gap to the third-place product, pipes (scoring 21), all remaining products scored 15 points or less. <b><i>Interpretation:</i></b> Cigarettes are the nicotine product causing by far the most harm to users and others in the world today. Attempts to switch to non-combusted sources of nicotine should be encouraged as the harms from these products are much lower.