Statistical model specification and power: recommendations on the use of test-qualified pooling in analysis of experimental data

Common approach to the analysis of experimental data across much of the biological sciences is test-qualified pooling. Here non-significant terms are dropped from a statistical model, effectively pooling the variation associated with each removed term with the error term used to test hypotheses (or estimate effect sizes). This pooling is only carried out if statistical testing on the basis of applying that data to a previous more complicated model provides motivation for this model simplification; hence the pooling is test-qualified. In pooling, the researcher increases the degrees of freedom of the error term with the aim of increasing statistical power to test their hypotheses of interest. Despite this approach being widely adopted and explicitly recommended by some of the most widely cited statistical textbooks aimed at biologists, here we argue that (except in highly specialized circumstances that we can identify) the hoped-for improvement in statistical power will be small or non-existent, and there is likely to be much reduced reliability of the statistical procedures through deviation of type I error rates from nominal levels. We thus call for greatly reduced use of test-qualified pooling across experimental biology, more careful justification of any use that continues, and a different philosophy for initial selection of statistical models in the light of this change in procedure.PostprintPeer reviewe

Assessing personality in San Joaquin kit fox in situ: efficacy of field-based experimental methods and implications for conservation management

Utilisation of animal personality has potential benefit for conservation management. Due to logistics of robust behavioural evaluation in situ, the majority of studies on wild animals involve taking animals into captivity for testing, potentially compromising results. Three in situ tests for evaluation of boldness in San Joaquin kit fox (Vulpes macrotis mutica) were developed (ENOT: extended novel object test; RNOT: rapid novel object test; TH: trap/handling test). Each test successfully identified variation in boldness within its target age class(es). The TH test was suitable for use across all age classes. Tests were assessed for in situ suitability and for quantity/quality of data yielded. ENOT was rated as requiring high levels of time, cost and labour with greater likelihood of failure. However, it was rated highly for data quantity/quality. The TH test was rated as requiring little time, labour and cost, but yielding lower quality data. RNOT was rated in the middle. Each test had merit and could be adapted to suit project or species constraints. We recommend field-based evaluation of personality, reducing removal of animals from the wild and facilitating routine incorporation of personality assessment into conservation projects

Fatty Acid Concentration and Phase Transitions Modulate Aβ Aggregation Pathways

Abstract Aggregation of amyloid β (Aβ) peptides is a significant event that underpins Alzheimer disease (AD) pathology. Aβ aggregates, especially the low-molecular weight oligomers, are the primary toxic agents in AD and hence, there is increasing interest in understanding their formation and behavior. Aggregation is a nucleation-dependent process in which the pre-nucleation events are dominated by Aβ homotypic interactions. Dynamic flux and stochasticity during pre-nucleation renders the reactions susceptible to perturbations by other molecules. In this context, we investigate the heterotypic interactions between Aβ and fatty acids (FAs) by two independent tool-sets such as reduced order modelling (ROM) and ensemble kinetic simulation (EKS). We observe that FAs influence Aβ dynamics distinctively in three broadly-defined FA concentration regimes containing non-micellar, pseudo-micellar or micellar phases. While the non-micellar phase promotes on-pathway fibrils, pseudo-micellar and micellar phases promote predominantly off-pathway oligomers, albeit via subtly different mechanisms. Importantly off-pathway oligomers saturate within a limited molecular size, and likely with a different overall conformation than those formed along the on-pathway, suggesting the generation of distinct conformeric strains of Aβ, which may have profound phenotypic outcomes. Our results validate previous experimental observations and provide insights into potential influence of biological interfaces in modulating Aβ aggregation pathways