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11.
12.
Sisse R. Ostrowski Ronan M. G. Berg Nis A. Windel?v Martin A. S. Meyer Ronni R. Plovsing Kirsten M?ller P?r I. Johansson 《PloS one》2013,8(3)
Background
Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG).Methods
Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour), with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA)) and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest) were recorded. Mixed models with Tukey post hoc tests and correlations were applied.Results
Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05). Platelet aggregation decreased (all tests, p<0.05), whereas TEG whole blood clot firmness increased (G, p = 0.05). Furthermore, during endotoxemia (4 h), whole blood fibrinolysis increased (clot lysis time (CLT), p<0.001) and Functional Fibrinogen clot strength decreased (p = 0.049). After endotoxemia (6 h), whole blood fibrinolysis was reduced (CLT, p<0.05). In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001).Conclusions
Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are critically involved in the vasculo-fibrinolytic response to acute inflammation is important given that disturbances in the vascular system contribute significantly to morbidity and mortality in critically ill patients. 相似文献13.
Ronan A. Lyons Denise Kendrick Elizabeth M. L. Towner Carol Coupland Mike Hayes Nicola Christie Judith Sleney Sarah Jones Richard Kimberlee Sarah E. Rodgers Samantha Turner Mariana Brussoni Yana Vinogradova Tinnu Sarvotham Steven Macey 《PloS one》2013,8(4)
Objective
To determine whether advocacy targeted at local politicians leads to action to reduce the risk of pedestrian injury in deprived areas.Design
Cluster randomised controlled trial.Setting
239 electoral wards in 57 local authorities in England and Wales.Participants
617 elected local politicians.Interventions
Intervention group politicians were provided with tailored information packs, including maps of casualty sites, numbers injured and a synopsis of effective interventions.Main outcome measures
25–30 months post intervention, primary outcomes included: electoral ward level: percentage of road traffic calmed; proportion with new interventions; school level: percentage with 20 mph zones, Safe Routes to School, pedestrian training or road safety education; politician level: percentage lobbying for safety measures. Secondary outcomes included politicians’ interest and involvement in injury prevention, and facilitators and barriers to implementation.Results
Primary outcomes did not significantly differ: % difference in traffic calming (0.07, 95%CI: −0.07 to 0.20); proportion of schools with 20 mph zones (RR 1.47, 95%CI: 0.93 to 2.32), Safe Routes to School (RR 1.34, 95%CI: 0.83 to 2.17), pedestrian training (RR 1.23, 95%CI: 0.95 to 1.61) or other safety education (RR 1.16, 95%CI: 0.97 to 1.39). Intervention group politicians reported greater interest in child injury prevention (RR 1.09, 95%CI 1.03 to 1.16), belief in potential to help prevent injuries (RR 1.36, 95%CI 1.16 to 1.61), particularly pedestrian safety (RR 1.55, 95%CI 1.19 to 2.03). 63% of intervention politicians reported supporting new pedestrian safety schemes. The majority found the advocacy information surprising, interesting, effectively presented, and could identify suitable local interventions.Conclusions
This study demonstrates the feasibility of an innovative approach to translational public health by targeting local politicians in a randomised controlled trial. The intervention package was positively viewed and raised interest but changes in interventions were not statistically significance. Longer term supported advocacy may be needed.Trial Registration
Current Controlled Trials ISRCTN91381117 相似文献14.
15.
Ronan Becheler Constance Xhaard Etienne K. Klein Katherine J. Hayden Pascal Frey Stéphane De Mita Fabien Halkett 《Ecology and evolution》2016,6(18):6625-6632
The genetic consequences of range expansions have generally been investigated at wide geographical and temporal scales, long after the colonization event. A unique ecological system enabled us to both monitor the colonization dynamics and decipher the genetic footprints of expansion over a very short time period. Each year an epidemic of the poplar rust (Melampsora larici‐populina) expands clonally and linearly along the Durance River, in the Alps. The colonization dynamics observed in 2004 showed two phases with different genetic outcomes. Upstream, fast colonization maintained high genetic diversity. Downstream, the colonization wave progressively faltered, diversity eroded, and differentiation increased, as expected under recurrent founder events. In line with the high dispersal abilities of rust pathogens, we provide evidence for leapfrog dispersal of clones. Our results thus emphasize the importance of colonization dynamics in shaping spatial genetic structure in the face of high gene flow. 相似文献
16.
17.
Sabrina Renaud Claire Delpine Ronan Ledevin Benoît Pisanu Jean‐Pierre Qur Emilie A. Hardouin 《Journal of Zoological Systematics and Evolutionary Research》2019,57(4):989-999
The house mouse (Mus musculus domesticus), as a successful invasive species worldwide, has to forage a variety of resources. Subantarctic mice display among the most notable diet shift from the usual omnivorous–granivorous diet, relying on a larger proportion of terrestrial animal prey. In agreement, a recent study of their mandible morphology evidenced an evolution of their mandible shape to optimize incisor biting and hence seize preys. Here, the incisors themselves are the focus of a morphometric analysis combined with a 3D study of their internal structure, aiming at a comparison between subantarctic populations (Guillou island, Kerguelen archipelago) with a range of western European continental, commensal mice. The predatory foraging behavior of Guillou mice was indeed associated with a sharper bevel of the lower incisor, which appears as an efficient morphology for piercing prey. The incisor of these mice also displays a reduced pulp cavity, suggesting slower eruption counterbalancing a reduced abrasion on such soft food material. The dynamics of the ever‐growing incisor may thus allow adaptive incisor sculpting and participate to the success of mice in foraging diverse resources. 相似文献
18.
Ronan James O'Sullivan Tutku Aykanat Susan E. Johnston Adam Kane Russell Poole Ger Rogan Paulo A. Prodhl Craig R. Primmer Philip McGinnity Thomas Eric Reed 《Ecology and evolution》2019,9(12):7096-7111
Comparing observed versus theoretically expected evolutionary responses is important for our understanding of the evolutionary process, and for assessing how species may cope with anthropogenic change. Here, we document directional selection for larger female size in Atlantic salmon, using pedigree‐derived estimates of lifetime reproductive success as a fitness measure. We show the trait is heritable and, thus, capable of responding to selection. The Breeder's Equation, which predicts microevolution as the product of phenotypic selection and heritability, predicted evolution of larger size. This was at odds, however, with the observed lack of either phenotypic or genetic temporal trends in body size, a so‐called “paradox of stasis.” To investigate this paradox, we estimated the additive genetic covariance between trait and fitness, which provides a prediction of evolutionary change according to Robertson's secondary theorem of selection (STS) that is unbiased by missing variables. The STS prediction was consistent with the observed stasis. Decomposition of phenotypic selection gradients into genetic and environmental components revealed a potential upward bias, implying unmeasured factors that covary with trait and fitness. These results showcase the power of pedigreed, wild population studies—which have largely been limited to birds and mammals—to study evolutionary processes on contemporary timescales. 相似文献
19.
Colin Clarke Clair Gallagher Ronan M. Kelly Michael Henry Paula Meleady Christopher C. Frye Matthew D. Osborne Ciaran P Brady Niall Barron Martin Clynes 《Biotechnology and bioengineering》2019,116(6):1556-1562
In this study, we report an investigation of a panel of clonally-derived Chinese hamster ovary (CHO) cell lines exhibiting variability in the proportion of full-length IgG4 Fc-fusion protein produced. The recombinant protein was found to be degraded during cell culture into four shorter “clipped” species (three of the four cleavage sites occurred at arginine residues) and preliminary analyses suggested that a host cell enzyme was responsible for proteolysis. To identify the specific enzyme responsible, RNA sequencing was used to identify gene expression differences between the cell lines with a “high” and “low” clipping phenotype. From this analysis, six protease-encoding genes were found to be significantly upregulated in those cell lines yielding the lowest proportion of full-length IgG4 Fc-fusion protein. Four of these protease candidates were deprioritized after examination of their cleavage site specificity. The remaining enzymes, Adam19 and Furin, were found to be capable of cleavage at arginine residues, and inhibitors for both proteases were added to cell-free media to determine if the product degradation could be reduced. While the Adam19 inhibitor had no impact, Furin inhibitor I (specific for the proprotein convertase family of enzymes) was found to result in a 33–39% increase in complete IgG4 Fc-fusion protein when compared with untreated samples. 相似文献