119 research outputs found
Double Blind, Randomised Controlled Trial
Purpose Surgical patients are at high risk for developing infectious
complications and postoperative delirium. Prolonged infections and delirium
result in worse outcome. Granulocyte-macrophage colony-stimulating factor (GM-
CSF) and influenza vaccination are known to increase HLA-DR on monocytes and
improve immune reactivity. This study aimed to investigate whether GM-CSF or
vaccination reverses monocyte deactivation. Secondary aims were whether it
decreases infection and delirium days after esophageal or pancreatic resection
over time. Methods In this prospective, randomized, placebo-controlled,
double-blind, double dummy trial setting on an interdisciplinary ICU of a
university hospital 61 patients with immunosuppression (monocytic HLA-DR
[mHLA-DR] <10,000 monoclonal antibodies [mAb] per cell) on the first day after
esophageal or pancreatic resection were treated with either GM-CSF (250
μg/m2/d), influenza vaccination (Mutagrip 0.5 ml/d) or placebo for a maximum
of 3 consecutive days if mHLA-DR remained below 10,000 mAb per cell. HLA-DR on
monocytes was measured daily until day 5 after surgery. Infections and
delirium were followed up for 9 days after surgery. Primary outcome was HLA-DR
on monocytes, and secondary outcomes were duration of infection and delirium.
Results mHLA-DR was significantly increased compared to placebo (p < 0.001)
and influenza vaccination (p < 0.001) on the second postoperative day.
Compared with placebo, GM-CSF-treated patients revealed shorter duration of
infection (p < 0.001); the duration of delirium was increased after
vaccination (p = 0.003). Conclusion Treatment with GM-CSF in patients with
postoperative immune suppression was safe and effective in restoring monocytic
immune competence. Furthermore, therapy with GM-CSF reduced duration of
infection in immune compromised patients. However, influenza vaccination
increased duration of delirium after major surgery
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Historical variability and lifecycles of North Atlantic midlatitude cyclones originating in the tropics
North Atlantic tropical and post‐tropical cyclones impact midlatitude regions, but the inhomogeneous observational record of the latter stages of tropical cyclones precludes many climatological analyses. The frequency of tropical‐origin storms basin‐wide is projected to increase under anthropogenic climate change, so establishing confidence in our knowledge of their historical variability and lifecycles—against which climate model simulations may be evaluated—is important. We used a Lagrangian feature‐tracking algorithm to identify tropical cyclones that impacted Northeast North America and Europe in seven global reanalysis datasets, distinguishing systems that retained warm‐core structures or underwent warm seclusion from those that underwent extratropical transition, acquiring cold‐core, frontal structures. Over the last four decades, ∼25 % and ∼10 % of tropical‐origin cyclones made landfall across Northeast North America and Europe, respectively, as warm‐core systems, with, on average, higher wind speeds than cold‐core systems. Historical warm‐ and cold‐core landfalls also exhibit distinct tracks, likely responding to differing steering flow and midlatitude conditions
Effects of daily static stretch training over 6 weeks on maximal strength, muscle thickness, contraction properties, and flexibility
PurposeStatic stretch training (SST) with long stretching durations seems to be sufficient to increase flexibility, maximum strength (MSt) and muscle thickness (MTh). However, changes in contraction properties and effects on muscle damage remain unclear. Consequently, the objective of the study was to investigate the effects of a 6-week self-performed SST on MSt, MTh, contractile properties, flexibility, and acute response of creatine kinase (CK) 3 days after SST.MethodsForty-four participants were divided into a control (CG, n = 22) and an intervention group (IG, n = 22), who performed a daily SST for 5 min for the lower limb muscle group. While isometric MSt was measured in leg press, MTh was examined via sonography and flexibility by functional tests. Muscle stiffness and contraction time were measured by tensiomyography on the rectus femoris. Additionally, capillary blood samples were taken in the pretest and in the first 3 days after starting SST to measure CK.ResultsA significant increase was found for MSt (p < 0.001, η2 = 0.195) and flexibility in all functional tests (p < 0.001, η2 > 0.310). Scheffé post hoc test did not show significant differences between the rectus femoris muscle inter- and intragroup comparisons for MTh nor for muscle stiffness and contraction time (p > 0.05, η2 < 0.100). Moreover, CK was not significantly different between IG and CG with p > 0.05, η2 = 0.032.DiscussionIn conclusion, the increase in MSt cannot be exclusively explained by muscular hypertrophy or the increased CK-related repair mechanism after acute stretching. Rather, neuronal adaptations have to be considered. Furthermore, daily 5-min SST over 6 weeks does not seem sufficient to change muscle stiffness or contraction time. Increases in flexibility tests could be attributed to a stretch-induced change in the muscle–tendon complex
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Why do some post-tropical cyclones impact europe?
Post-tropical cyclones (PTCs) can bring high winds and extreme precipitation to Europe. Although the structure and intensity of observed Europe-impacting PTCs has been investigated in previous studies, a quantitative understanding of the factors important for PTCs to reach Europe has not been established. By tracking and identifying the full life cycle of tropical cyclones (TCs) in the ERA5 reanalysis, we investigate why some PTCs impact Europe and why others do not, using a composite analysis. We show that PTCs that impact Europe are typically ∼4–6 m s−1 stronger at their lifetime maximum intensity and throughout the extratropical transition process. They are also twice as likely to reintensify in the midlatitudes. During ET, the Europe-impacting PTCs interact more strongly with an upstream upper-level trough in a significantly more baroclinic environment. The Europe-impacting PTCs are steered on a more poleward trajectory across a midlatitude jet streak. It is during the crossing of the jet that these cyclones often undergo their reintensification. Using contingency table analysis, TC lifetime maximum intensity, and whether post-ET reintensification occurs are shown to be significantly associated with the odds that a PTC reaches Europe. This supports our composite analysis and further indicates that TC intensity and reintensification both modulate the likelihood that a PTC will impact Europe
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Impact of higher spatial atmospheric resolution on precipitation extremes over land in global climate models
Finer grids in global climate models could lead to an improvement in the simulation of precipitation extremes. We assess the influence on model performance of increasing spatial resolution by evaluating pairs of high‐ and low‐resolution forced atmospheric simulations from six global climate models (generally the latest CMIP6 version) on a common 1° × 1° grid. The differences in tuning between the lower and higher resolution versions are as limited as possible, which allows the influence of higher resolution to be assessed exclusively. We focus on the 1985–2014 climatology of annual extremes of daily precipitation over global land, and models are compared to observations from different sources (i.e., in situ‐based and satellite‐based) to enable consideration of observational uncertainty. Finally, we address regional features of model performance based on four indices characterizing different aspects of precipitation extremes. Our analysis highlights good agreement between models that precipitation extremes are more intense at higher resolution. We find that the spread among observations is substantial and can be as large as intermodel differences, which makes the quantitative evaluation of model performance difficult. However, consistently across the four precipitation extremes indices that we investigate, models often show lower skill at higher resolution compared to their corresponding lower resolution version. Our findings suggest that increasing spatial resolution alone is not sufficient to obtain a systematic improvement in the simulation of precipitation extremes, and other improvements (e.g., physics and tuning) may be required
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The giant diploid faba genome unlocks variation in a global protein crop
Publisher Copyright: © 2023, The Author(s).Increasing the proportion of locally produced plant protein in currently meat-rich diets could substantially reduce greenhouse gas emissions and loss of biodiversity1. However, plant protein production is hampered by the lack of a cool-season legume equivalent to soybean in agronomic value2. Faba bean (Vicia faba L.) has a high yield potential and is well suited for cultivation in temperate regions, but genomic resources are scarce. Here, we report a high-quality chromosome-scale assembly of the faba bean genome and show that it has expanded to a massive 13 Gb in size through an imbalance between the rates of amplification and elimination of retrotransposons and satellite repeats. Genes and recombination events are evenly dispersed across chromosomes and the gene space is remarkably compact considering the genome size, although with substantial copy number variation driven by tandem duplication. Demonstrating practical application of the genome sequence, we develop a targeted genotyping assay and use high-resolution genome-wide association analysis to dissect the genetic basis of seed size and hilum colour. The resources presented constitute a genomics-based breeding platform for faba bean, enabling breeders and geneticists to accelerate the improvement of sustainable protein production across the Mediterranean, subtropical and northern temperate agroecological zones.Peer reviewe
The Cost of Virulence: Retarded Growth of Salmonella Typhimurium Cells Expressing Type III Secretion System 1
Virulence factors generally enhance a pathogen's fitness and thereby foster transmission. However, most studies of pathogen fitness have been performed by averaging the phenotypes over large populations. Here, we have analyzed the fitness costs of virulence factor expression by Salmonella enterica subspecies I serovar Typhimurium in simple culture experiments. The type III secretion system ttss-1, a cardinal virulence factor for eliciting Salmonella diarrhea, is expressed by just a fraction of the S. Typhimurium population, yielding a mixture of cells that either express ttss-1 (TTSS-1+ phenotype) or not (TTSS-1− phenotype). Here, we studied in vitro the TTSS-1+ phenotype at the single cell level using fluorescent protein reporters. The regulator hilA controlled the fraction of TTSS-1+ individuals and their ttss-1 expression level. Strikingly, cells of the TTSS-1+ phenotype grew slower than cells of the TTSS-1− phenotype. The growth retardation was at least partially attributable to the expression of TTSS-1 effector and/or translocon proteins. In spite of this growth penalty, the TTSS-1+ subpopulation increased from <10% to approx. 60% during the late logarithmic growth phase of an LB batch culture. This was attributable to an increasing initiation rate of ttss-1 expression, in response to environmental cues accumulating during this growth phase, as shown by experimental data and mathematical modeling. Finally, hilA and hilD mutants, which form only fast-growing TTSS-1− cells, outcompeted wild type S. Typhimurium in mixed cultures. Our data demonstrated that virulence factor expression imposes a growth penalty in a non-host environment. This raises important questions about compensating mechanisms during host infection which ensure successful propagation of the genotype
Simulation vs. Reality: A Comparison of In Silico Distance Predictions with DEER and FRET Measurements
Site specific incorporation of molecular probes such as fluorescent- and nitroxide spin-labels into biomolecules, and subsequent analysis by Förster resonance energy transfer (FRET) and double electron-electron resonance (DEER) can elucidate the distance and distance-changes between the probes. However, the probes have an intrinsic conformational flexibility due to the linker by which they are conjugated to the biomolecule. This property minimizes the influence of the label side chain on the structure of the target molecule, but complicates the direct correlation of the experimental inter-label distances with the macromolecular structure or changes thereof. Simulation methods that account for the conformational flexibility and orientation of the probe(s) can be helpful in overcoming this problem. We performed distance measurements using FRET and DEER and explored different simulation techniques to predict inter-label distances using the Rpo4/7 stalk module of the M. jannaschii RNA polymerase. This is a suitable model system because it is rigid and a high-resolution X-ray structure is available. The conformations of the fluorescent labels and nitroxide spin labels on Rpo4/7 were modeled using in vacuo molecular dynamics simulations (MD) and a stochastic Monte Carlo sampling approach. For the nitroxide probes we also performed MD simulations with explicit water and carried out a rotamer library analysis. Our results show that the Monte Carlo simulations are in better agreement with experiments than the MD simulations and the rotamer library approach results in plausible distance predictions. Because the latter is the least computationally demanding of the methods we have explored, and is readily available to many researchers, it prevails as the method of choice for the interpretation of DEER distance distributions
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