Estimating the proportion cured of cancer: Some practical advice for users

BackgroundCure models can provide improved possibilities for inference if used appropriately, but there is potential for misleading results if care is not taken. In this study, we compared five commonly used approaches for modelling cure in a relative survival framework and provide some practical advice on the use of these approaches.Patients and methodsData for colon, female breast, and ovarian cancers were used to illustrate these approaches. The proportion cured was estimated for each of these three cancers within each of three age groups. We then graphically assessed the assumption of cure and the model fit, by comparing the predicted relative survival from the cure models to empirical life table estimates.ResultsWhere both cure and distributional assumptions are appropriate (e.g., for colon or ovarian cancer patients aged <75 years), all five approaches led to similar estimates of the proportion cured. The estimates varied slightly when cure was a reasonable assumption but the distributional assumption was not (e.g., for colon cancer patients ≥75 years). Greater variability in the estimates was observed when the cure assumption was not supported by the data (breast cancer).ConclusionsIf the data suggest cure is not a reasonable assumption then we advise against fitting cure models. In the scenarios where cure was reasonable, we found that flexible parametric cure models performed at least as well, or better, than the other modelling approaches. We recommend that, regardless of the model used, the underlying assumptions for cure and model fit should always be graphically assessed.     

Fagus sylvatica trunk epicormics in relation to primary and secondary growth

Background and Aims

European beech epicormics have received far less attention than epicormics of other species, especially sessile oak. However, previous work on beech has demonstrated that there is a negative effect of radial growth on trunk sprouting, while more recent investigations on sessile oak proved a strong positive influence of the presence of epicormics. The aims of this study were, first, to make a general quantification of the epicormics present along beech stems and, secondly, to test the effects of both radial growth and epicormic frequency on sprouting.

Methods

In order to test the effect of radial growth, ten forked individuals were sampled, with a dominant and a dominated fork of almost equal length for every individual. To test the effects of primary growth and epicormic frequency, on the last 17 annual shoots of each fork arm, the number of axillary buds, shoot length, ring width profiles, epicormic shoots and other epicormics were carefully recorded.

Key Results

The distribution of annual shoot length, radial growth profiles and parallel frequencies of all epicormics are presented. The latter frequencies were parallel to the annual shoot lengths, nearly equivalent for both arms of each tree, and radial growth profiles included very narrow rings in the lowest annual shoots and even missing rings in the dominated arms alone. The location of the latent buds and the epicormics was mainly at branch base, while epicormic shoots, bud clusters and spheroblasts were present mainly in the lowest annual shoots investigated. Using a zero-inflated mixed model, sprouting was shown to depend positively on epicormic frequency and negatively on radial growth.

Conclusions

Support for a trade-off between cambial activity and sprouting is put forward. Sprouting mainly depends on the frequency of epicormics. Between- and within-tree variability of the epicormic composition in a given species may thus have fundamental and applied implications.     

CD1d-restricted NKT cells modulate placental and uterine leukocyte populations during chlamydial infection in mice

Invariant CD1d-restricted natural killer T cells play an important immunoregulatory role and can influence a broad spectrum of immunological responses including against bacterial infections. They are present at the fetal–maternal interface and although it has been reported that experimental systemic iNKT cell activation can induce mouse abortion, their role during pregnancy remain poorly understood. In the present work, using a physiological Chlamydia muridarum infection model, we have shown that, in vaginally infected pregnant mice, C. muridarum is cleared similarly in C57BL/6 wild type (WT) and CD1d^−/− mice. We have also shown that infected- as well as uninfected-CD1d^−/− mice have the same litter size as WT counterparts. Thus, CD1d-restricted cells are required neither for the resolution of chlamydial infection of the lower-genital tract, nor for the maintenance of reproductive capacity. However, unexpected differences in T cell populations were observed in uninfected pregnant females, as CD1d^−/− placentas contained significantly higher percentages of CD4⁺ and CD8⁺ T cells than WT counterparts. However, infection triggered a significant decrease in the percentages of CD4⁺ T cells in CD1d^−/− mice. In infected WT pregnant mice, the numbers of uterine CD4⁺ and CD8⁺ T cells, monocytes and granulocytes were greatly increased, changes not observed in infected CD1d^−/− mice. An increase in the percentage of CD8⁺ T cells seems independent of CD1d-restricted cells as it occurred in both WT and CD1d^−/− mice. Thus, in the steady state, the lack of CD1d-restricted NKT cells affects leukocyte populations only in the placenta. In Chlamydia-infected pregnant mice, the immune response against Chlamydia is dampened in the uterus. Our results suggest that CD1d-restricted NKT cells play a role in the recruitment or homeostasis of leukocyte populations at the maternal–fetal interface in the presence or absence of Chlamydia infection.     

Elements of episodic-like memory in animal models

Representations of unique events from one’s past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer’s disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.     

Pervasive selection or is it…? why are FST outliers sometimes so frequent?

It is now common for population geneticists to estimate F_ST for a large number of loci across the genome, before testing for selected loci as being outliers to the F_ST distribution. One surprising result of such F_ST scans is the often high proportion (>1% and sometimes >10%) of outliers detected, and this is often interpreted as evidence for pervasive local adaptation. In this issue of Molecular Ecolog, Fourcade et al. ( 2013 ) observe that a particularly high rate of F_ST outliers has often been found in river organisms, such as fishes or damselflies, despite there being no obvious reason why selection should affect a larger proportion of the genomes of these organisms. Using computer simulations, Fourcade et al. ( 2013 ) show that the strong correlation in co‐ancestry produced in long one‐dimensional landscapes (such as rivers, valleys, peninsulas, oceanic ridges or coastlines) greatly increases the neutral variance in F_ST, especially when the landscape is further reticulated into fractal networks. As a consequence, outlier tests have a high rate of false positives, unless this correlation can be taken into account. Fourcade et al.'s study highlights an extreme case of the general problem, first noticed by Robertson ( 1975a , b ) and Nei & Maruyama ( 1975 ), that correlated co‐ancestry inflates the neutral variance in F_ST when compared to its expectation under an island model of population structure. Similar warnings about the validity of outlier tests have appeared regularly since then but have not been widely cited in the recent genomics literature. We further emphasize that F_ST outliers can arise in many different ways and that outlier tests are not designed for situations where the genetic architecture of local adaptation involves many loci.     

Same species,same habitat preferences? The distribution of aquatic plants is not explained by the same predictors in lakes and streams

1. Studying the geographical distribution of species can reveal conditions and processes that may drive species presence and abundance. Organism distribution has frequently been explained by climate, but the relative role of local environmental predictors is not fully understood. Moreover, in the freshwater realm, intrinsic differences existing between different categories of water bodies can lead to significant differences in species–environment relationships. Here, we tested the relative importance of broad-scale climate and local environmental predictors in explaining plant species distributions in freshwater lakes and streams.
2. We built species distribution models to investigate which predictors best explain aquatic plant distribution in two categories of water bodies. We used species inventories and records of three climate and eight local environmental predictors for 150 lakes and 150 streams in Finland.
3. We found that sets of predictors that explain the distribution of macrophyte species are unique depending on if species are in a lake or a stream. Overall, air temperature and ecosystem size were essential to predict aquatic plant species presence in both water body categories. Broad-scale climate predictors were always very important in explaining species distribution, while local environmental conditions such as water chemistry were of variable influence, depending on species and water body category.
4. These results are probably due to high spatial and temporal variability and range of water physico-chemical parameters, especially in streams. Nonetheless, despite a lower relative importance than climatic factors, local environmental predictors also strongly affected species distributions.
5. Our findings highlight that incorporating local environmental conditions to species distribution models in addition to climate predictors is necessary to improve predictions, particularly for distribution of stream flora. Considering the species-specific responses of aquatic plants to their environment, studying species individually with species distribution models represents a useful analysis.