Profile likelihood-based parameter and predictive interval analysis guides model choice for ecological population dynamics

Calibrating mathematical models to describe ecological data provides important insight via parameter estimation that is not possible from analysing data alone. When we undertake a mathematical modelling study of ecological or biological data, we must deal with the trade-off between data availability and model complexity. Dealing with the nexus between data availability and model complexity is an ongoing challenge in mathematical modelling, particularly in mathematical biology and mathematical ecology where data collection is often not standardised, and more broad questions about model selection remain relatively open. Therefore, choosing an appropriate model almost always requires case-by-case consideration. In this work we present a straightforward approach to quantitatively explore this trade-off using a case study exploring mathematical models of coral reef regrowth after some ecological disturbance, such as damage caused by a tropical cyclone. In particular, we compare a simple single species ordinary differential equation (ODE) model approach with a more complicated two-species coupled ODE model. Univariate profile likelihood analysis suggests that the both models are practically identifiable. To provide additional insight we construct and compare approximate prediction intervals using a new parameter-wise prediction approximation, confirming both the simple and complex models perform similarly with regard to making predictions. Our approximate parameter-wise prediction interval analysis provides explicit information about how each parameter affects the predictions of each model. Comparing our approximate prediction intervals with a more rigorous and computationally expensive evaluation of the full likelihood shows that the new approximations are reasonable in this case. All algorithms and software to support this work are freely available as jupyter notebooks on GitHub so that they can be adapted to deal with any other ODE-based models.</p

Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents

A series of analogs with nitro or serinamide substituents at the C-2′-, C-5′-, or C-6′-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in SCID mice, and as inhibitors of tubulin polymerization. The synthesis of these analogs typically featured a Wittig reaction between a suitably functionalized arylaldehyde and an arylphosphonium salt followed by separation of the resultant E- and Z-isomers. Several of these nitrogen-modified CA4 derivatives (both amino and nitro) demonstrate significant inhibition of tubulin assembly as well as cytotoxicity and in vivo blood flow reduction. 2′-Aminostilbenoid 7 and 2′-amino-3′-hydroxystilbenoid 29 proved to be the most active in this series. Both compounds, 7 and 29, have the potential for further pro-drug modification and development as vascular disrupting agents for treatment of solid tumor cancers and certain ophthalmological diseases. © 2006 Elsevier Ltd. All rights reserved

Lack of Diagnostic Pluripotentiality in Patients at Clinical High Risk for Psychosis: Specificity of Comorbidity Persistence and Search for Pluripotential Subgroups

More than 20 years after the clinical high risk syndrome for psychosis (CHR) was first articulated, it remains controversial whether the CHR syndrome predicts onset of psychosis with diagnostic specificity or predicts pluripotential diagnostic outcomes. Recently, analyses of observational studies, however, have suggested that the CHR syndrome is not pluripotential for emergent diagnostic outcomes. The present report conducted additional analyses in previously reported samples to determine (1) whether comorbid disorders were more likely to persist in CHR patients compared to a comparison group of patients who responded to CHR recruitment efforts but did not meet criteria, termed help-seeking comparison subjects (HSC); and (2) whether clinically defined pluripotential CHR subgroups could be identified. All data were derived from 2 multisite studies in which DSM-IV structured diagnostic interviews were conducted at baseline and at 6-month intervals. Across samples we observed persistence of any nonpsychotic disorder in 80/147 CHR cases (54.4%) and in 48/84 HSC cases (57.1%, n.s.). Findings with persistence of anxiety, depressive, and bipolar disorders considered separately were similar. Efforts to discover pluripotential CHR subgroups were unsuccessful. These findings add additional support to the view that the CHR syndrome is not pluripotential for predicting various diagnostic outcomes but rather is specific for predicting emergent psychosis