Organismal functional strategies form a continuum from slow- to fast-growing organisms, in response to common drivers such as resource availability and disturbance. However, whether there is ...synchronisation of these strategies at the entire community level is unclear. Here, we combine trait data for >2800 above- and belowground taxa from 14 trophic guilds spanning a disturbance and resource availability gradient in German grasslands. The results indicate that most guilds consistently respond to these drivers through both direct and trophically mediated effects, resulting in a 'slow-fast' axis at the level of the entire community. Using 15 indicators of carbon and nutrient fluxes, biomass production and decomposition, we also show that fast trait communities are associated with faster rates of ecosystem functioning. These findings demonstrate that 'slow' and 'fast' strategies can be manifested at the level of whole communities, opening new avenues of ecosystem-level functional classification.
VTE‐BLEED is a validated score for identification of patients at increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE). It is unknown whether VTE‐BLEED ...high‐risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score.
This was a post hoc analysis of the randomized, double‐blind, placebo‐controlled PADIS‐PE trial that randomized patients with a first unprovoked pulmonary embolism (PE) initially treated during 6 months to receive an additional 18‐month of warfarin vs. placebo. The primary outcome of this analysis was recurrent VTE during 2‐year follow‐up after anticoagulant discontinuation, that is, after the initial 6‐month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted for study treatment allocation, was compared between patients in the high‐ vs. low‐risk VTE‐BLEED group.
In complete case analysis (n = 308; 82.4% of total population), 89 (28.9%) patients were classified as high risk; 44 VTE events occurred after anticoagulant discontinuation during 668 patient‐years. The cumulative incidence of recurrent VTE was 16.4% (95% confidence interval CI, 10.0%‐26.1%; 14 events) and 14.6% (95% CI, 10.4%‐20.3%; 30 events) in the high‐risk and low‐risk VTE‐BLEED groups, respectively, for an adjusted hazard ratio of 1.16 (95% CI, 0.62‐2.19).
In this study, patients with unprovoked PE classified at high risk of major bleeding by VTE‐BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.
The seasonal effect is the most significant external source of variation affecting vascular cambial activity and the development of newly divided cells, and hence wood properties. Here, the effect of ...edapho-climatic conditions on the phenotypic and molecular plasticity of differentiating secondary xylem during a growing season was investigated. Wood-forming tissues of maritime pine (Pinus pinaster) were collected from the beginning to the end of the growing season in 2003. Data from examination of fibre morphology, Fourier-transform infrared spectroscopy (FTIR), analytical pyrolysis, and gas chromatography/mass spectrometry (GC/MS) were combined to characterize the samples. Strong variation was observed in response to changes in edapho-climatic conditions. A genomic approach was used to identify genes differentially expressed during this growing season. Out of 3512 studied genes, 19% showed a significant seasonal effect. These genes were clustered into five distinct groups, the largest two representing genes over-expressed in the early- or late-wood-forming tissues, respectively. The other three clusters were characterized by responses to specific edapho-climatic conditions. This work provides new insights into the plasticity of the molecular machinery involved in wood formation, and reveals candidate genes potentially responsible for the phenotypic differences found between early- and late-wood.
Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) ...with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.
Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan IRI: LV5FU2–irinotecan or simplified LV5FU2–irinotecan (FOLFIRI). The CLASSIC arm was defined as LV5FU2 or LV5FU2–irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).
From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2–irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75–92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66–1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67–1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75–1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55–0.92). More patients presented grade 3–4 toxicities in IRI (52.2% versus 76.3%).
In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.
NCT00303771.
A global ocean model has been developed within the context of TOPEX/Poseidon (T/P) on the basis of a finite element hydrodynamic modeling approach combined with data assimilation based on the ...representer method. The solution produced at global scale represents a spectacular improvement over what was available before the era of T/P. Typically, the mean discrepancy between the main tidal components and a hundred in situ tide gauges is 1.7 cm for M2 and 1 cm or less for the other components. However, the accuracies of this solution and of that produced by different authors within the T/P tide working group are all worse near coastlines and over continental shelves. This is the case for our finite element solution (FES) FES94.1 solution over the Yellow Sea and the East China Sea (YS‐ECS) where the discrepancy is 33 cm for the M2 tide and 9 cm for the K1 tide when compared to a set of 192 tide gauges distributed along the coastlines. This is due largely to the complex geometry of the basin and the limited knowledge of the bathymetry. The aim of this paper is to investigate how our FES model can be improved with a dedicated application focused on one of the most energetic coastal basins: the YS‐ECS (∼180 Gigawatts for M2, i.e. 8% of the global energy dissipated in the whole ocean). For this application, a finite grid was implemented with a resolution down to 5 km along the coasts and over the continental shelf break. Particular attention was paid to bathymetry by complementing the ETOP05 database with regional maps. Sensitivity tests to the tuning of the bottom friction and the nonlinear interactions between the diurnal and semidiurnal components allow us to investigate the impact of dissipation parameterization and to produce an optimal solution, without any data assimilation, for nine main components of the tidal spectrum (improvement by a factor of 2). M2 distance to the observations is now ∼17.5 cm (global variance of 92 cm), and K1 is 4 cm (global variance of 21 cm). As nonlinear components are significant over these basins, the two main quarterdiurnal components are calculated. The improvements are explained by five points: (1) the choice of a mixed friction, (2) a refinement of the mesh, (3) a choice of reliable boundary conditions, (4) a refined topography and, (5) the use of a specific friction coefficient 1.5×10−3. Surprisingly, the energy budget for the M2 component leads to a dissipation similar to the value estimated by the global FES94.1. This is a major result of this study, which leads us to the conclusion that when forcing a regional model with sea level boundary conditions along the open limits, the simulated velocity field adjusts to the tuning of friction coefficients in order to dissipate the same amount of energy made available at its open boundaries.
The biological function of the Prion protein remains largely unknown but recent data revealed its implication in early zebrafish and mammalian embryogenesis. To gain further insight into its ...biological function, comparative transcriptomic analysis between FVB/N and FVB/N Prnp knockout mice was performed at early embryonic stages. RNAseq analysis revealed the differential expression of 73 and 263 genes at E6.5 and E7.5, respectively. The related metabolic pathways identified in this analysis partially overlap with those described in PrP1 and PrP2 knockdown zebrafish embryos and prion-infected mammalian brains and emphasize a potentially important role for the PrP family genes in early developmental processes.
A prototype detection unit of the KM3NeT deep-sea neutrino telescope has been installed at 3500m depth 80km offshore the Italian coast. KM3NeT in its final configuration will contain several hundreds ...of detection units. Each detection unit is a mechanical structure anchored to the sea floor, held vertical by a submerged buoy and supporting optical modules for the detection of Cherenkov light emitted by charged secondary particles emerging from neutrino interactions. This prototype string implements three optical modules with 31 photomultiplier tubes each. These optical modules were developed by the KM3NeT Collaboration to enhance the detection capability of neutrino interactions. The prototype detection unit was operated since its deployment in May 2014 until its decommissioning in July 2015. Reconstruction of the particle trajectories from the data requires a nanosecond accuracy in the time calibration. A procedure for relative time calibration of the photomultiplier tubes contained in each optical module is described. This procedure is based on the measured coincidences produced in the sea by the 40K background light and can easily be expanded to a detector with several thousands of optical modules. The time offsets between the different optical modules are obtained using LED nanobeacons mounted inside them. A set of data corresponding to 600 hours of livetime was analysed. The results show good agreement with Monte Carlo simulations of the expected optical background and the signal from atmospheric muons. An almost background-free sample of muons was selected by filtering the time correlated signals on all the three optical modules. The zenith angle of the selected muons was reconstructed with a precision of about 3{\deg}.
Abstract Chemical warfare agents (nerve agents) are still available and present a real threat to the population. Numerous in vitro and in vivo studies showed that various nerve agents, e.g. tabun and ...cyclosarin, are resistant towards standard therapy with atropine and oxime. Based on these facts we applied a modified biological assay for the easy, semi-quantitative testing of the detoxifying properties of the β-cyclodextrin derivative CD-IBA. Cyclosarin, sarin, tabun and VX were incubated with CD-IBA for 1–50 min at 37 °C, then an aliquot was added to erythrocyte acetylcholinesterase (AChE) and the percentage of AChE inhibition was determined. The validity of the assay was confirmed by concomitant quantification of tabun by GC–MS. Different concentrations of cyclosarin were detoxified by CD-IBA in a concentration-dependent velocity. The ability to detoxify various nerve agents decreased in the order cyclosarin > sarin > tabun ≫ VX. Hereby, no detoxification of VX could be detected. Sarin was detoxified in a biphasic reaction with a fast reduction of inhibitory potential in the first phase and a slower detoxification in the second phase. CD-IBA detoxified tabun in a one phase decay and, compared to cyclosarin and sarin, a longer half-life was determined with tabun. The modified biological assay is appropriate for the initial semi-quantitative screening of candidate compounds for the detoxification of nerve agents. The β-cyclodextrin derivative CD-IBA demonstrated its ability to detoxify different nerve agents.
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