Regression models for censored serological data.

The impact was assessed of censored serological measurements on regression equations fitted to data from panels of sera tested by different laboratories, for the purpose of standardizing serosurvey results to common units. Several methods that adjust for censoring were compared, such as deletion, simple substitution, multiple imputation and censored regression. Simulations were generated from different scenarios for varying proportions of data censored. The scenarios were based on serological panel comparisons tested by different national laboratories and assays as part of the European Sero-Epidemiology Network 2 project. The results showed that the simple substitution and deletion methods worked reasonably well for low proportions of data censored (<20 %). However, in general, the censored regression method gave estimates closer to the truth than the other methods examined under different scenarios, such as types of equations used and violation of regression assumptions. Interval-censored regression produced the least biased estimates for assay data resulting from dilution series. Censored regression produced the least biased estimates in comparison with the other methods examined. Moreover, the results suggest using interval-censored regression methods for assay data resulting from dilution series.

The results of real-time brachytherapy for the management of low- and intermediate-risk prostate cancer in patients with prostate volumes up to 100 mL.

OBJECTIVES: • To report the results of real-time brachytherapy in the management of low-risk and intermediate-risk prostate cancer in patients with prostate volumes up to 100 mL, over a 6-year period. • To prospectively determine whether prostate volume influences the ability to achieve a quality implant and therefore impact upon prostate-specific antigen (PSA) relapse-free survival, and urinary and rectal toxicity. SUBJECTS AND METHODS: • In all, 216 men with localized prostate cancer were treated with real-time prostate brachytherapy using (125) I implants between November 2003 and December 2009. • Patient selection was based upon functional parameters; International Prostate Symptom Score (IPSS) and flowmetry. • Patients had computed tomography imaging at 1 month to assess post-implant dosimetry. PSA, IPSS and Radiation Therapy Oncology Group rectal toxicity scores were recorded prospectively over the follow-up period. • Patients with prostate volumes ≤50 mL and those with volumes >50 mL were compared. RESULTS: • Overall PSA relapse-free survival was 98.8%; 97.0% for intermediate-risk patients and 100.0% for low-risk patients. By volume, 98.5% of men with standard prostates were free from PSA relapse compared with 100.0% of men with large prostates. • The mean post-implant D90 was 177.0 Gy; 175.5 Gy in standard prostates and 183.5 Gy in large prostates. • The overall acute urinary retention rate was 1.9%; 1.7% in standard prostates and 2.4% in large prostates. There were three urethral strictures, all in the standard prostate group. The mean IPSS increased to 11 and 14 at 3 months for the standard and large prostate groups, respectively, before settling to 2 above baseline for both groups at 12 months. • There were no rectovesical fistulae. Persistent rectal bleeding was reported by one (0.5%) patient in the standard prostate group. CONCLUSIONS: • Prostate brachytherapy is effective in the treatment of low-risk and intermediate-risk prostate cancer. • It is technically possible to deliver a quality implant in a large prostate using real-time brachytherapy. • The treatment itself is well tolerated. Prostate volumes up to 100 mL should not exclude patients from brachytherapy providing either flow rate ≥14 mL/s or symptom score (IPSS) ≤ 10.

A fundamental, eco-hydrological basis for niche segregation in plant communities.

• Ecologists still puzzle over how plant species manage to coexist with one another while competing for the same essential resources. The classic answer for animal communities is that species occupy different niches, but how plants do this is more difficult to determine. We previously found niche segregation along fine-scale hydrological gradients in European wet meadows and proposed that the mechanism might be a general one, especially in communities that experience seasonal saturation. • We quantified the hydrological niches of 96 species from eight fynbos communities in the biodiversity hotspot of the Cape Floristic Region, South Africa and 99 species from 18 lowland wet meadow communities in the UK. Niche overlap was computed for all combinations of species. • Despite the extreme functional and phylogenetic differences between the fynbos and wet meadow communities, an identical trade-off (i.e. specialization of species towards tolerance of aeration and/or drying stress) was found to cause segregation along fine-scale hydrological gradients. • This study not only confirms the predicted generality of hydrological niche segregation, but also emphasizes its importance for structuring plant communities. Eco-hydrological niche segregation will have implications for conservation in habitats that face changing hydrology caused by water abstraction and climate change.

A likelihood-based method for testing for nonstochastic variation of diversification rates in phylogenies.

Observed variations in rates of taxonomic diversification have been attributed to a range of factors including biological innovations, ecosystem restructuring, and environmental changes. Before inferring causality of any particular factor, however, it is critical to demonstrate that the observed variation in diversity is significantly greater than that expected from natural stochastic processes. Relative tests that assess whether observed asymmetry in species richness between sister taxa in monophyletic pairs is greater than would be expected under a symmetric model have been used widely in studies of rate heterogeneity and are particularly useful for groups in which paleontological data are problematic. Although one such test introduced by Slowinski and Guyer a decade ago has been applied to a wide range of clades and evolutionary questions, the statistical behavior of the test has not been examined extensively, particularly when used with Fisher's procedure for combining probabilities to analyze data from multiple independent taxon pairs. Here, certain pragmatic difficulties with the Slowinski-Guyer test are described, further details of the development of a recently introduced likelihood-based relative rates test are presented, and standard simulation procedures are used to assess the behavior of the two tests in a range of situations to determine: (1) the accuracy of the tests' nominal Type I error rate; (2) the statistical power of the tests; (3) the sensitivity of the tests to inclusion of taxon pairs with few species; (4) the behavior of the tests with datasets comprised of few taxon pairs; and (5) the sensitivity of the tests to certain violations of the null model assumptions. Our results indicate that in most biologically plausible scenarios, the likelihood-based test has superior statistical properties in terms of both Type I error rate and power, and we found no scenario in which the Slowinski-Guyer test was distinctly superior, although the degree of the discrepancy varies among the different scenarios. The Slowinski-Guyer test tends to be much more conservative (i.e., very disinclined to reject the null hypothesis) in datasets with many small pairs. In most situations, the performance of both the likelihood-based test and particularly the Slowinski-Guyer test improve when pairs with few species are excluded from the computation, although this is balanced against a decline in the tests' power and accuracy as fewer pairs are included in the dataset. The performance of both tests is quite poor when they are applied to datasets in which the taxon sizes do not conform to the distribution implied by the usual null model. Thus, results of analyses of taxonomic rate heterogeneity using the Slowinski-Guyer test can be misleading because the test's ability to reject the null hypothesis (equal rates) when true is often inaccurate and its ability to reject the null hypothesis when the alternative (unequal rates) is true is poor, particularly when small taxon pairs are included. Although not always perfect, the likelihood-based test provides a more accurate and powerful alternative as a relative rates test.

Nonstochastic variation of species-level diversification rates within angiosperms.

Variations in the origination and extinction rates of species over geological time often are linked with a range of factors, including the evolution of key innovations, changes in ecosystem structure, and environmental factors such as shifts in climate and physical geography. Before hypothesizing causality of a single factor, it is critical to demonstrate that the observed variation in diversification is significantly greater than one would expect due to natural stochasticity in the evolutionary branching process. Here, we use a likelihood-ratio test to compare taxonomic rate heterogeneity to a neutral birth-death model, using data on well-supported sister pairs of taxa and their species richness. We test the likelihood that the distribution of extant species among angiosperm genera and families could be the result of constant diversification rates. Results strongly support the conclusion that there is significantly more heterogeneity in diversity at the species level within angiosperms than would be expected due to stochastic processes. This result is consistent in datasets of genus pairs and family pairs and is not affected significantly by degrading pairs to simulate inaccuracy in the assumption of simultaneous origin of sister taxa. When we parse taxon pairs among higher groups of angiosperms, results indicate that a constant rates model is not rejected by rosid and basal eudicot pairs but is rejected by asterid and eumagnoliid pairs. These results provide strong support for the hypothesis that species-level rates of origination and/or extinction have varied nonrandomly within angiosperms and that the magnitude of heterogeneity varies among major groups within angiosperms.

Ecological and genetic correlates of long-term population trends in the park grass experiment.

The Park Grass Experiment (PGE) is the longest-observed set of experimental plant communities in existence. Although the gross composition of the vegetation was at equilibrium over the 60-yr period from 1920 to 1979, annual records show that individual species exhibited a range of dynamics. We tested two hypotheses to explain why some species initially increased and why subsequently some of these (the outbreak species) decreased again. The study was designed around eight phylogenetically independent contrasts (PICs), each containing related species with different dynamics. Our first hypothesis was that persistent increasers and outbreakers have higher intrinsic rates of natural increase than control species (species without trends), allowing them to spread when interspecific competition is reduced by drought. This was tested by measuring establishment and seed production of species in field experiments, with and without interspecific competition. Seed production in outbreak species responded more strongly to release from interspecific competition than it did in either of the other groups of species. Our second hypothesis was that outbreak species eventually declined because they lacked the genetic variation necessary to adapt to the novel habitats to which they had initially spread. We tested this by measuring mating systems and genetic diversity in persistent and outbreak species in the PGE. In seven out of seven PICs tested, the outbreak species was more selfing than its persistent relative. There was a significant positive correlation between outcrossing rate and gene diversity. These results support roles for both ecological and genetic traits in long-term dynamics.