Modelling grouped survival times in toxicological studies using generalized additive models

A method for combining a proportional-hazards survival time model with a bioassay model where the log-hazard function is modelled as a linear or smoothing spline function of log-concentration combined with a smoothing spline function of time is described. The combined model is fitted to mortality numbers, resulting from survival times that are grouped due to a common set of observation times, using Generalized Additive Models (GAMs). The GAM fits mortalities as conditional binomials using an approximation to the log of the integral of the hazard function and is implemented using freely-available, general software for fitting GAMs. Extensions of the GAM are described to allow random effects to be fitted and to allow for time-varying concentrations by replacing time with a calibrated cumulative exposure variable with calibration parameter estimated using profile likelihood. The models are demonstrated using data from a studies of a marine and a, previously published, freshwater taxa. The marine study involved two replicate bioassays of the effect of zinc exposure on survival of an Antarctic amphipod, Orchomenella pinguides. The other example modelled survival of the daphnid, Daphnia magna, exposed to potassium dichromate and was fitted by both the GAM and the process-based DEBtox model. The GAM fitted with a cubic regression spline in time gave a 61 % improvement in fit to the daphnid data compared to DEBtox due to a non-monotonic hazard function. A simulation study using each of these hazard functions as operating models demonstrated that the GAM is overall more accurate in recovering lethal concentration values across the range of forms of the underlying hazard function compared to DEBtox and standard multiple endpoint probit analyses.

Insights into the evolution of a cryptic radiation of bats: dispersal and ecological radiation of Malagasy Miniopterus (Chiroptera: Miniopteridae)

The past decade has seen a proliferation of new species of Miniopterus bats (family Miniopteridae) recognized from Madagascar and the neighboring Comoros archipelago. The interspecific relationships of these taxa, their colonization history, and the evolution of this presumed adaptive radiation have not been sufficiently explored. Using the mitochondrial cytochrome-b gene, we present a phylogeny of the Malagasy members of this widespread Old World genus, based on 218 sequences, of which 82 are new and 136 derived from previous studies. Phylogenetic analyses recovered 18 clades, which divide into five primary lineages: (1) M. griveaudi; (2) M. mahafaliensis, M. sororculus and X3; (3) M. majori, M. gleni and M. griffithsi; (4) M. brachytragos; M. aelleniA, and M. aelleniB; and (5) M. manavi and M. petersoni recovered as sister species, which were in turn linked to a group comprising M. egeri and five genetically distinct populations referred to herein as P3, P4, P5, P6 and P7. Beast analysis indicated that the initial divergence within the Malagasy Miniopterus radiation took place 4.5 Myr; most species diverged between 4 and 2.5 Myr, and a secondary period was between 1.25 and 1 Myr. DNA K2P-distances between recognized taxa ranged from 12.9% to 2.5% and intraspecific variation was less than 1.8%. Of the 18 identified clades, Latin binomials are only associated with 11, which indicates much greater differentiation than currently recognized for Malagasy Miniopterus. These data are placed in a context of the dispersal history of this genus on the island and patterns of ecological diversity.