36 resultados para Intratumoural heterogeneity

em CentAUR: Central Archive University of Reading - UK


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The s–x model of microwave emission from soil and vegetation layers is widely used to estimate soil moisture content from passive microwave observations. Its application to prospective satellite-based observations aggregating several thousand square kilometres requires understanding of the effects of scene heterogeneity. The effects of heterogeneity in soil surface roughness, soil moisture, water area and vegetation density on the retrieval of soil moisture from simulated single- and multi-angle observing systems were tested. Uncertainty in water area proved the most serious problem for both systems, causing errors of a few percent in soil moisture retrieval. Single-angle retrieval was largely unaffected by the other factors studied here. Multiple-angle retrievals errors around one percent arose from heterogeneity in either soil roughness or soil moisture. Errors of a few percent were caused by vegetation heterogeneity. A simple extension of the model vegetation representation was shown to reduce this error substantially for scenes containing a range of vegetation types.

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A simple formulation relating the L-band microwave brightness temperature detected by a passive microwave radiometer to the near surface soil moisture was developed using MICRO-SWEAT, a coupled microwave emission model and soil-vegetation-atmosphere-transfer (SVAT) scheme. This simple model provides an ideal tool with which to explore the impact of sub-pixel heterogeneity on the retrieval of soil moisture from microwave brightness temperatures. In the case of a bare soil pixel, the relationship between apparent emissivity and surface soil moisture is approximately linear, with the clay content of the soil influencing just the intercept of this relationship. It is shown that there are no errors in the retrieved soil moisture from a bare soil pixel that is heterogeneous in soil moisture and texture. However, in the case of a vegetated pixel, the slope of the relationship between apparent emissivity and surface soil moisture decreases with increasing vegetation. Therefore for a pixel that is heterogeneous in vegetation and soil moisture, errors can be introduced into the retrieved soil moisture. Generally, under moderate conditions, the retrieved soil moisture is within 3% of the actual soil moisture. Examples illustrating this discussion use data collected during the Southern Great Plains '97 Experiment (SGP97).

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1. The spatial and temporal abundance of the aphid Euceraphis betulae was investigated in relation to heterogeneity in host plant ( Betula pendula) vigour and pathogenic stress. The performance of aphids feeding on vigorous and stressed foliage was also examined. 2. The plant stress and plant vigour hypotheses have been suggested as opposing ways in which foliage quality influences herbivore abundance. In many plants, however, vigorous growing foliage co-exists with stressed or damaged foliage. 3. There was a negative correlation between branch growth ( vigour) and branch stress ( leaf chlorosis), with the most vigorous branches displaying little or no stress, and the most stressed branches achieving poor growth. There was a similar negative correlation between vigour and stress at the level of individual trees, which themselves represented a continuum in quality. 4. At the beginning of the season, E. betulae were intermittently more abundant on vigorous branches than on branches destined to become stressed, but aphids became significantly more abundant on stressed branches later in the season, when symptoms of stress became apparent. Similar patterns of aphid abundance were seen on vigorous and stressed trees in the following year. 5. Euceraphis betulae performance was generally enhanced when feeding on naturally stressed B. pendula leaves, but there was some evidence for elevated potential reproduction when feeding on vigorous leaves too. 6. Overall, plant stress probably influences E. betulae distribution more than plant vigour, but the temporal and spatial variability in plant quality suggests that plant vigour could play a role in aphid distribution early in the season.

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None of the current surveillance streams monitoring the presence of scrapie in Great Britain provide a comprehensive and unbiased estimate of the prevalence of the disease at the holding level. Previous work to estimate the under-ascertainment adjusted prevalence of scrapie in Great Britain applied multiple-list capture–recapture methods. The enforcement of new control measures on scrapie-affected holdings in 2004 has stopped the overlapping between surveillance sources and, hence, the application of multiple-list capture–recapture models. Alternative methods, still under the capture–recapture methodology, relying on repeated entries in one single list have been suggested in these situations. In this article, we apply one-list capture–recapture approaches to data held on the Scrapie Notifications Database to estimate the undetected population of scrapie-affected holdings with clinical disease in Great Britain for the years 2002, 2003, and 2004. For doing so, we develop a new diagnostic tool for indication of heterogeneity as well as a new understanding of the Zelterman and Chao’s lower bound estimators to account for potential unobserved heterogeneity. We demonstrate that the Zelterman estimator can be viewed as a maximum likelihood estimator for a special, locally truncated Poisson likelihood equivalent to a binomial likelihood. This understanding allows the extension of the Zelterman approach by means of logistic regression to include observed heterogeneity in the form of covariates—in case studied here, the holding size and country of origin. Our results confirm the presence of substantial unobserved heterogeneity supporting the application of our two estimators. The total scrapie-affected holding population in Great Britain is around 300 holdings per year. None of the covariates appear to inform the model significantly.

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In this paper we present results from two choice experiments (CE), designed to take account of the different negative externalities associated with pesticide use in agricultural production. For cereal production, the most probable impact of pesticide use is a reduction in environmental quality. For fruit and vegetable production, the negative externality is on consumer health. Using latent class models we find evidence of the presence of preference heterogeneity in addition to reasonably high willingness to pay (WTP) estimates for a reduction in the use of pesticides for both environmental quality and consumer health. To place our WTP estimates in a policy context we convert them into an equivalent pesticide tax by type of externality. Our tax estimates suggest that pesticide taxes based on the primary externality resulting from a particular mode of agricultural production are a credible policy option that warrants further consideration.

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OBJECTIVES: This contribution provides a unifying concept for meta-analysis integrating the handling of unobserved heterogeneity, study covariates, publication bias and study quality. It is important to consider these issues simultaneously to avoid the occurrence of artifacts, and a method for doing so is suggested here. METHODS: The approach is based upon the meta-likelihood in combination with a general linear nonparametric mixed model, which lays the ground for all inferential conclusions suggested here. RESULTS: The concept is illustrated at hand of a meta-analysis investigating the relationship of hormone replacement therapy and breast cancer. The phenomenon of interest has been investigated in many studies for a considerable time and different results were reported. In 1992 a meta-analysis by Sillero-Arenas et al. concluded a small, but significant overall effect of 1.06 on the relative risk scale. Using the meta-likelihood approach it is demonstrated here that this meta-analysis is due to considerable unobserved heterogeneity. Furthermore, it is shown that new methods are available to model this heterogeneity successfully. It is argued further to include available study covariates to explain this heterogeneity in the meta-analysis at hand. CONCLUSIONS: The topic of HRT and breast cancer has again very recently become an issue of public debate, when results of a large trial investigating the health effects of hormone replacement therapy were published indicating an increased risk for breast cancer (risk ratio of 1.26). Using an adequate regression model in the previously published meta-analysis an adjusted estimate of effect of 1.14 can be given which is considerably higher than the one published in the meta-analysis of Sillero-Arenas et al. In summary, it is hoped that the method suggested here contributes further to a good meta-analytic practice in public health and clinical disciplines.

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Background: Variation in carrying capacity and population return rates is generally ignored in traditional studies of population dynamics. Variation is hard to study in the field because of difficulties controlling the environment in order to obtain statistical replicates, and because of the scale and expense of experimenting on populations. There may also be ethical issues. To circumvent these problems we used detailed simulations of the simultaneous behaviours of interacting animals in an accurate facsimile of a real Danish landscape. The models incorporate as much as possible of the behaviour and ecology of skylarks Alauda arvensis, voles Microtus agrestis, a ground beetle Bembidion lampros and a linyphiid spider Erigone atra. This allows us to quantify and evaluate the importance of spatial and temporal heterogeneity on the population dynamics of the four species. Results: Both spatial and temporal heterogeneity affected the relationship between population growth rate and population density in all four species. Spatial heterogeneity accounted for 23–30% of the variance in population growth rate after accounting for the effects of density, reflecting big differences in local carrying capacity associated with the landscape features important to individual species. Temporal heterogeneity accounted for 3–13% of the variance in vole, skylark and spider, but 43% in beetles. The associated temporal variation in carrying capacity would be problematic in traditional analyses of density dependence. Return rates were less than one in all species and essentially invariant in skylarks, spiders and beetles. Return rates varied over the landscape in voles, being slower where there were larger fluctuations in local population sizes. Conclusion: Our analyses estimated the traditional parameters of carrying capacities and return rates, but these are now seen as varying continuously over the landscape depending on habitat quality and the mechanisms of density dependence. The importance of our results lies in our demonstration that the effects of spatial and temporal heterogeneity must be accounted for if we are to have accurate predictive models for use in management and conservation. This is an area which until now has lacked an adequate theoretical framework and methodology.

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None of the current surveillance streams monitoring the presence of scrapie in Great Britain provide a comprehensive and unbiased estimate of the prevalence of the disease at the holding level. Previous work to estimate the under-ascertainment adjusted prevalence of scrapie in Great Britain applied multiple-list capture-recapture methods. The enforcement of new control measures on scrapie-affected holdings in 2004 has stopped the overlapping between surveillance sources and, hence, the application of multiple-list capture-recapture models. Alternative methods, still under the capture-recapture methodology, relying on repeated entries in one single list have been suggested in these situations. In this article, we apply one-list capture-recapture approaches to data held on the Scrapie Notifications Database to estimate the undetected population of scrapie-affected holdings with clinical disease in Great Britain for the years 2002, 2003, and 2004. For doing so, we develop a new diagnostic tool for indication of heterogeneity as well as a new understanding of the Zelterman and Chao's lower bound estimators to account for potential unobserved heterogeneity. We demonstrate that the Zelterman estimator can be viewed as a maximum likelihood estimator for a special, locally truncated Poisson likelihood equivalent to a binomial likelihood. This understanding allows the extension of the Zelterman approach by means of logistic regression to include observed heterogeneity in the form of covariates-in case studied here, the holding size and country of origin. Our results confirm the presence of substantial unobserved heterogeneity supporting the application of our two estimators. The total scrapie-affected holding population in Great Britain is around 300 holdings per year. None of the covariates appear to inform the model significantly.

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We focus on the comparison of three statistical models used to estimate the treatment effect in metaanalysis when individually pooled data are available. The models are two conventional models, namely a multi-level and a model based upon an approximate likelihood, and a newly developed model, the profile likelihood model which might be viewed as an extension of the Mantel-Haenszel approach. To exemplify these methods, we use results from a meta-analysis of 22 trials to prevent respiratory tract infections. We show that by using the multi-level approach, in the case of baseline heterogeneity, the number of clusters or components is considerably over-estimated. The approximate and profile likelihood method showed nearly the same pattern for the treatment effect distribution. To provide more evidence two simulation studies are accomplished. The profile likelihood can be considered as a clear alternative to the approximate likelihood model. In the case of strong baseline heterogeneity, the profile likelihood method shows superior behaviour when compared with the multi-level model. Copyright (C) 2006 John Wiley & Sons, Ltd.

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We describe a general likelihood-based 'mixture model' for inferring phylogenetic trees from gene-sequence or other character-state data. The model accommodates cases in which different sites in the alignment evolve in qualitatively distinct ways, but does not require prior knowledge of these patterns or partitioning of the data. We call this qualitative variability in the pattern of evolution across sites "pattern-heterogeneity" to distinguish it from both a homogenous process of evolution and from one characterized principally by differences in rates of evolution. We present studies to show that the model correctly retrieves the signals of pattern-heterogeneity from simulated gene-sequence data, and we apply the method to protein-coding genes and to a ribosomal 12S data set. The mixture model outperforms conventional partitioning in both these data sets. We implement the mixture model such that it can simultaneously detect rate- and pattern-heterogeneity. The model simplifies to a homogeneous model or a rate- variability model as special cases, and therefore always performs at least as well as these two approaches, and often considerably improves upon them. We make the model available within a Bayesian Markov-chain Monte Carlo framework for phylogenetic inference, as an easy-to-use computer program.

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A critical analysis of single crystal X-ray diffraction studies on a series of terminally protected tripeptides containing a centrally positioned Aib (alpha-aminoisobutyric acid) residue has been reported. For the tripeptide series containing Boc-Ala-Aib as corner residues, all the reported peptides formed distorted type II beta-turn structures. Moreover, a series of Phe substituted analogues ( tripeptides with Boc-Phe-Aib) have also shown different beta-turn conformations. However, the Leu-modified analogues (tripeptides with Boc-Leu-Aib) disrupt the concept of beta-turn formation and adopt various conformations in the solid state. X-ray crystallography sheds some light on the conformational heterogeneity at atomic resolution. (c) 2007 Elsevier Ltd. All rights reserved.

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Williams syndrome (WS) is a rare genetic disorder resulting from a deletion on chromosome 7. A number of studies have shown that individuals with WS have a superior linguistic profile compared to their non-verbal abilities, however the evidence has been inconclusive, as many studies have disputed such a profile. The vast majority of studies on WS have assumed a single, homogeneous WS linguistic profile in order to support various theoretical viewpoints. The present study investigated the linguistic profiles of 5 individuals with WS on a number of standardized verbal measures and in conversational settings. The results indicated substantially variable performance in all aspects of the verbal domain, which supports the view that WS, linguistically, is a rather heterogeneous condition and this should be taken into consideration when referring to it in theoretical accounts of language acquisition and debates on modularity.