Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions

The intermediate stage of hepatocellular carcinoma (HCC) comprises a highly heterogeneous patient population and therefore poses unique challenges for therapeutic management, different from the early and advanced stages. Patients classified as having intermediate HCC by the Barcelona Clinic Liver Cancer (BCLC) staging system present with varying tumor burden and liver function. Transarterial chemoembolization (TACE) is currently recommended as the standard of care in this setting, but there is considerable variation in the clinical benefit patients derive from this treatment.In April 2012, a panel of experts convened to discuss unresolved issues surrounding the application of current guidelines when managing patients with intermediate HCC. The meeting explored the applicability of a subclassification system for intermediate HCC patients to tailor therapeutic interventions based on the evidence available to date and expert opinion. The present report summarizes the proposal of the expert panel: four substages of intermediate HCC patients, B1 to B4.

Strong Dynamical Heterogeneity and Universal Scaling in Driven Granular Fluids

Large-scale simulations of two-dimensional bidisperse granular fluids allow us to determine spatial correlations of slow particles via the four-point structure factor S-4 (q, t). Both cases, elastic (epsilon = 1) and inelastic (epsilon < 1) collisions, are studied. As the fluid approaches structural arrest, i.e., for packing fractions in the range 0.6 <= phi <= 0.805, scaling is shown to hold: S-4 (q, t)/chi(4)(t) = s(q xi(t)). Both the dynamic susceptibility chi(4)(tau(alpha)) and the dynamic correlation length xi(tau(alpha)) evaluated at the alpha relaxation time tau(alpha) can be fitted to a power law divergence at a critical packing fraction. The measured xi(tau(alpha)) widely exceeds the largest one previously observed for three-dimensional (3d) hard sphere fluids. The number of particles in a slow cluster and the correlation length are related by a robust power law, chi(4)(tau(alpha)) approximate to xi(d-p) (tau(alpha)), with an exponent d - p approximate to 1.6. This scaling is remarkably independent of epsilon, even though the strength of the dynamical heterogeneity at constant volume fraction depends strongly on epsilon.

Effect of Methodological and Ecological Approaches on Heterogeneity of Nest-Site Selection of a Long-Lived Vulture

The application of scientific-based conservation measures requires that sampling methodologies in studies modelling similar ecological aspects produce comparable results making easier their interpretation. We aimed to show how the choice of different methodological and ecological approaches can affect conclusions in nest-site selection studies along different Palearctic meta-populations of an indicator species. First, a multivariate analysis of the variables affecting nest-site selection in a breeding colony of cinereous vulture (Aegypius monachus) in central Spain was performed. Then, a meta-analysis was applied to establish how methodological and habitat-type factors determine differences and similarities in the results obtained by previous studies that have modelled the forest breeding habitat of the species. Our results revealed patterns in nesting-habitat modelling by the cinereous vulture throughout its whole range: steep and south-facing slopes, great cover of large trees and distance to human activities were generally selected. The ratio and situation of the studied plots (nests/random), the use of plots vs. polygons as sampling units and the number of years of data set determined the variability explained by the model. Moreover, a greater size of the breeding colony implied that ecological and geomorphological variables at landscape level were more influential. Additionally, human activities affected in greater proportion to colonies situated in Mediterranean forests. For the first time, a meta-analysis regarding the factors determining nest-site selection heterogeneity for a single species at broad scale was achieved. It is essential to homogenize and coordinate experimental design in modelling the selection of species' ecological requirements in order to avoid that differences in results among studies would be due to methodological heterogeneity. This would optimize best conservation and management practices for habitats and species in a global context.

Spatial heterogeneity of soil nutrients and plant species in herb-dominated communities of contrasting land use

Recent interest in spatial pattern in terrestrial ecosystems has come from an awareness of theintimate relationship between spatial heterogeneity of soil resources and maintenance of plant species diversity. Soil and vegetation can vary spatially inresponse to several state factors of the system. In this study, we examined fine-scale spatial variability of soil nutrients and vascular plant species in contrasting herb-dominated communities (a pasture and an oldfield) to determine degree of spatial dependenceamong soil variables and plant community characteristics within these communities by sampling at 1-m intervals. Each site was divided into 25 1-m 2 plots. Mineral soil was sampled (2-cm diameter, 5-cm depth) from each of four 0.25-m2 quarters and combined into a single composite sample per plot. Soil organic matter was measured as loss-on-ignition. Extractable NH4 and NO3 were determined before and after laboratory incubation to determine potential net N mineralization and nitrification. Cations were analyzed using inductively coupled plasma emission spectrometry. Vegetation was assessed using estimated percent cover. Most soiland plant variables exhibited sharp contrasts betweenpasture and old-field sites, with the old field having significantly higher net N mineralization/nitrification, pH, Ca, Mg, Al, plant cover, and species diversity, richness, and evenness. Multiple regressions revealedthat all plant variables (species diversity, richness,evenness, and cover) were significantly related to soil characteristics (available nitrogen, organic matter,moisture, pH, Ca, and Mg) in the pasture; in the old field only cover was significantly related to soil characteristics (organic matter and moisture). Both sites contrasted sharply with respect to spatial pattern of soil variables, with the old field exhibiting a higher degree of spatial dependence. These results demonstrate that land-use practices can exert profound influence on spatial heterogeneity of both soil properties and vegetation in herb-dominated communities.

Designed Extension of Survival Studies: Application to Clinical Trials with Unrecognized Heterogeneity

It is well known that unrecognized heterogeneity among patients, such as is conferred by genetic subtype, can undermine the power of randomized trial, designed under the assumption of homogeneity, to detect a truly beneficial treatment. We consider the conditional power approach to allow for recovery of power under unexplained heterogeneity. While Proschan and Hunsberger (1995) confined the application of conditional power design to normally distributed observations, we consider more general and difficult settings in which the data are in the framework of continuous time and are subject to censoring. In particular, we derive a procedure appropriate for the analysis of the weighted log rank test under the assumption of a proportional hazards frailty model. The proposed method is illustrated through application to a brain tumor trial.