12 resultados para dynamic treatment regime

em CentAUR: Central Archive University of Reading - UK


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Avian intestinal spirochaetosis (AIS) results from the colonization of the caeca and colon of poultry by pathogenic Brachyspira, notably Brachyspira pilosicoli. Following the ban on the use of antibiotic growth promoters in the European Union in 2006, the number of cases of AIS has increased, which, alongside emerging antimicrobial resistance in Brachyspira, has driven renewed interest in alternative intervention strategies. Lactobacillus-based probiotics have been shown to protect against infection with common enteric pathogens in livestock. Our previous studies have shown that Lactobacillus reuteri LM1 antagonizes aspects of the pathobiology of Brachyspira in vitro. Here, we showed that L. reuteri LM1 mitigates the clinical symptoms of AIS in chickens experimentally challenged with B. pilosicoli. Two groups of 15 commercial laying hens were challenged experimentally by oral gavage with B. pilosicoli B2904 at 18 weeks of age; one group received unsupplemented drinking water and the other received L. reuteri LM1 in drinking water from 1 week prior to challenge with Brachyspira and thereafter for the duration of the study. This treatment regime was protective. Specifically, B. pilosicoli was detected by culture in fewer birds, bird weights were higher, faecal moisture contents were significantly lower (P<0.05) and egg production as assessed by egg weight and faecal staining score was improved (P<0.05). Also, at post-mortem examination, significantly fewer B. pilosicoli were recovered from treated birds (P<0.05), with only mild–moderate histopathological changes observed. These data suggest that L. reuteri LM1 may be a useful tool in the control of AIS.

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BACKGROUND: The single nucleotide polymorphism (SNP), and consequent amino acid exchange from tyrosine to cysteine at location 139 of the vkorc1 gene (i.e. tyrosine139cysteine or Y139C), is the most widespread anticoagulant resistance mutation in Norway rats (Rattus norvegicus Berk.) in Europe. Field trials were conducted to determine incidence of the Y139C SNP at two rat infested farms in Westphalia, Germany, and to estimate the practical efficacy against them of applications, using a pulsed baiting treatment regime, of a proprietary bait (KleratTM) containing 50 ppm brodifacoum. RESULTS: DNA analysis for the Y139C mutation showed that resistant rats were prevalent at the two farms, with an incidence of 80.0% and 78.6% respectively. Applications of brodifacoum bait achieved results of 99.2% and 100.0% control at the two farms, when measured by census baiting, although the treatment was somewhat prolonged at one site due to the abundance of attractive alternative food. CONCLUSION: The study showed that 50 ppm brodifacoum bait is fully effective against the Y139C SNP at the Münsterland focus and is likely to be so elsewhere in Europe where this mutation is found. The pulsed baiting regime reduced to relatively low levels the quantity of bait required to control these two substantial resistant Norway rat infestations. Previous studies had shown much larger quantities of bromadiolone and difenacoum baits used in ineffective treatments against Y139C resistant rats in the Münsterland. These results should be considered when making decisions about the use of anticoagulant against resistant Norway rats and their potential environmental impacts.

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Background. Initial evidence suggests that the integrity of the ipsilesional corticospinal tract (CST) after stroke is strongly related to motor function in the chronic state but not the treatment gain induced by motor rehabilitation. Objective. We examined the association of motor status and treatment benefit by testing patients with a wide range of severity of hemiparesis of the left and right upper extremity. Method. Diffusion tensor imaging was performed in 22 patients beyond 12 months after onset of stroke with severe to moderate hemiparesis. Motor function was tested before and after 2 weeks of modified constraint-induced movement therapy. Results. CST integrity, but not lesion volume, correlated with the motor ability measures of the Wolf Motor Function Test and the Motor Activity Log. No differences were found between left and right hemiparesis. Motor performance improved significantly with the treatment regime, and did so equally for patients with left and right arm paresis. However, treatment benefit was not associated with either CST integrity or lesion volume. Conclusion. CST integrity correlated best in this small trial with chronic long-term status but not treatment-induced improvements. The CST may play a different role in the mechanisms mediating long-term outcome compared to those underlying practice-induced gains after a chronic plateau in motor function.

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We have investigated the dynamic mechanical behavior of two cross-linked polymer networks with very different topologies: one made of backbones randomly linked along their length; the other with fixed-length strands uniformly cross-linked at their ends. The samples were analyzed using oscillatory shear, at very small strains corresponding to the linear regime. This was carried out at a range of frequencies, and at temperatures ranging from the glass plateau, through the glass transition, and well into the rubbery region. Through the glass transition, the data obeyed the time-temperature superposition principle, and could be analyzed using WLF treatment. At higher temperatures, in the rubbery region, the storage modulus was found to deviate from this, taking a value that is independent of frequency. This value increased linearly with temperature, as expected for the entropic rubber elasticity, but with a substantial negative offset inconsistent with straightforward enthalpic effects. Conversely, the loss modulus continued to follow time-temperature superposition, decreasing with increasing temperature, and showing a power-law dependence on frequency.

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Here, we identify the Arabidopsis thaliana ortholog of the mammalian DEAD box helicase, eIF4A-III, the putative anchor protein of exon junction complex (EJC) on mRNA. Arabidopsis eIF4A-III interacts with an ortholog of the core EJC component, ALY/Ref, and colocalizes with other EJC components, such as Mago, Y14, and RNPS1, suggesting a similar function in EJC assembly to animal eIF4A-III. A green fluorescent protein (GFP)-eIF4A-III fusion protein showed localization to several subnuclear domains: to the nucleoplasm during normal growth and to the nucleolus and splicing speckles in response to hypoxia. Treatment with the respiratory inhibitor sodium azide produced an identical response to the hypoxia stress. Treatment with the proteasome inhibitor MG132 led to accumulation of GFP-eIF4A-III mainly in the nucleolus, suggesting that transition of eIF4A-III between subnuclear domains and/or accumulation in nuclear speckles is controlled by proteolysis-labile factors. As revealed by fluorescence recovery after photobleaching analysis, the nucleoplasmic fraction was highly mobile, while the speckles were the least mobile fractions, and the nucleolar fraction had an intermediate mobility. Sequestration of eIF4A-III into nuclear pools with different mobility is likely to reflect the transcriptional and mRNA processing state of the cell.

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We compare laboratory observations of equilibrated baroclinic waves in the rotating two-layer annulus, with numerical simulations from a quasi-geostrophic model. The laboratory experiments lie well outside the quasi-geostrophic regime: the Rossby number reaches unity; the depth-to-width aspect ratio is large; and the fluid contains ageostrophic inertia–gravity waves. Despite being formally inapplicable, the quasi-geostrophic model captures the laboratory flows reasonably well. The model displays several systematic biases, which are consequences of its treatment of boundary layers and neglect of interfacial surface tension and which may be explained without invoking the dynamical effects of the moderate Rossby number, large aspect ratio or inertia–gravity waves. We conclude that quasi-geostrophic theory appears to continue to apply well outside its formal bounds.

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Uncatalyzed, ring-opening polymerization of individual macrocyclic poly(arylene thioether ketone)s (1-4) and mixtures (5) under dynamic heating conditions has been demonstrated for the first time. High-molecular-weight, film-forming products were obtained after heating of the macrocycles up to 480 degreesC, with a heating rate of 10-20 degreesC /min. Depending on the macrocyclic structure and heat treatment conditions, the polymers obtained were amorphous or semicrystalline, soluble or slightly crosslinked. NMR analyses of the soluble polymers revealed their linear, highly regular structure. According to NMR, DSC, and TGA studies, the polymers obtained do not contain any residual macrocycles. The polymers with thio-p-arylene moieties in the main chain were thermally stabile. The catalyzed ring opening polymerization of 5 carried out in diphenyl sulfone solution is also reported for comparison. Using quantum mechanical calculations of the ring opening of macrocycles, a reaction mechanism is suggested. Preparation of nanosized poly(thioether ketone) fibrils by a replication method is described.

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Assessment of changes in precipitation (P) as a function of percentiles of surface temperature (T) and 500 hPa vertical velocity (ω) are presented, considering present-day simulations and observational estimates from the Global Precipitation Climatology Project (GPCP) combined with the European Centre for Medium-range Weather Forecasts Interim reanalysis (ERA Interim). There is a tendency for models to overestimate P in the warm, subsiding regimes compared to GPCP, in some cases by more than 100%, while many models underestimate P in the moderate temperature regimes. Considering climate change projections between 1980–1999 and 2080–2099, responses in P are characterised by dP/dT ≥ 4%/K over the coldest 10–20% of land points and over warm, ascending ocean points while P declines over the warmest, descending regimes (dP/dT ∼ − 4%/K for model ensemble means). The reduced Walker circulation limits this contrasting dP/dT response in the tropical wet and dry regimes only marginally. Around 70% of the global surface area exhibits a consistent sign for dP/dT in at least 6 out of a 7-member model ensemble when considering P composites in terms of dynamic regime.

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The assumption that ‘states' primary goal is survival’ lies at the heart of the neorealist paradigm. A careful examination of the assumption, however, reveals that neorealists draw upon a number of distinct interpretations of the ‘survival assumption’ that are then treated as if they are the same, pointing towards conceptual problems that surround the treatment of state preferences. This article offers a specification that focuses on two questions that highlight the role and function of the survival assumption in the neorealist logic: (i) what do states have to lose if they fail to adopt self-help strategies?; and (ii) how does concern for relevant losses motivate state behaviour and affect international outcomes? Answering these questions through the exploration of governing elites' sensitivity towards regime stability and territorial integrity of the state, in turn, addresses the aforementioned conceptual problems. This specification has further implications for the debates among defensive and offensive realists, potential extensions of the neorealist logic beyond the Westphalian states, and the relationship between neorealist theory and policy analysis.

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The suggestion is discussed that characteristic particle and field signatures at the dayside magnetopause, termed “flux transfer events” (FTEs), are, in at least some cases, due to transient solar wind and/or magnetosheath dynamic pressure increases, rather than time-dependent magnetic reconnection. It is found that most individual cases of FTEs observed by a single spacecraft can, at least qualitatively, be explained by the pressure pulse model, provided a few rather unsatisfactory features of the predictions are explained in terms of measurement uncertainties. The most notable exceptions to this are some “two-regime” observations made by two satellites simultaneously, one on either side of the magnetopause. However, this configuration has not been frequently achieved for sufficient time, such observations are rare, and the relevant tests are still not conclusive. The strongest evidence that FTEs are produced by magnetic reconnection is the dependence of their occurrence on the north-south component of the interplanetary magnetic field (IMF) or of the magnetosheath field. The pressure pulse model provides an explanation for this dependence (albeit qualitative) in the case of magnetosheath FTEs, but this does not apply to magnetosphere FTEs. The only surveys of magnetosphere FTEs have not employed the simultaneous IMF, but have shown that their occurrence is strongly dependent on the north-south component of the magnetosheath field, as observed earlier/later on the same magnetopause crossing (for inbound/outbound passes, respectively). This paper employs statistics on the variability of the IMF orientation to investigate the effects of IMF changes between the times of the magnetosheath and FTE observations. It is shown that the previously published results are consistent with magnetospheric FTEs being entirely absent when the magnetosheath field is northward: all crossings with magnetosphere FTEs and a northward field can be attributed to the field changing sense while the satellite was within the magnetosphere (but close enough to the magnetopause to detect an FTE). Allowance for the IMF variability also makes the occurrence frequency of magnetosphere FTEs during southward magnetosheath fields very similar to that observed for magnetosheath FTEs. Conversely, the probability of attaining the observed occurrence frequencies for the pressure pulse model is 10−14. In addition, it is argued that some magnetosheath FTEs should, for the pressure pulse model, have been observed for northward IMF: the probability that the number is as low as actually observed is estimated to be 10−10. It is concluded that although the pressure model can be invoked to qualitatively explain a large number of individual FTE observations, the observed occurrence statistics are in gross disagreement with this model.

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Transgenerational inheritance of abiotic stress-induced epigenetic modifications in plants has potential adaptive significance and might condition the offspring to improve the response to the same stress, but this is at least partly dependent on the potency, penetrance and persistence of the transmitted epigenetic marks. We examined transgenerational inheritance of low Relative Humidity-induced DNA methylation for two gene loci in the stomatal developmental pathway in Arabidopsis thaliana and the abundance of associated short-interfering RNAs (siRNAs). Heritability of low humidity-induced methylation was more predictable and penetrative at one locus (SPEECHLESS, entropy ≤ 0.02; χ2 < 0.001) than the other (FAMA, entropy ≤ 0.17; χ2 ns). Methylation at SPEECHLESS correlated positively with the continued presence of local siRNAs (r2 = 0.87; p = 0.013) which, however, could be disrupted globally in the progeny under repeated stress. Transgenerational methylation and a parental low humidity-induced stomatal phenotype were heritable, but this was reversed in the progeny under repeated treatment in a previously unsuspected manner.