Multivariate analysis as a method to understand variability in a complex excipient, and its contribution to formulation performance

A key part of the Risk Assessment of excipients is to understand how raw material variability could (or does) contribute to differences in performance of the drug product. Here we demonstrate an approach which achieves the necessary understanding for a complex, functional, excipient. Multivariate analysis (MVA) of the certificates of analysis of an ethylcellulose aqueous dispersion (Surelease) formulation revealed low overall variability of the properties of the systems. Review of the scores plot to highlight batches manufactured using the same ethylcellulose raw material in the formulation, indicated that these batches tend to be more closely related than other randomly selected batches. This variability could result in potential differences in the quality of drug product lots made from these batches. Manufacture of a model drug product from Surelease batches coated using different lots of starting material revealed small differences in the release of a model drug, which could be detected by certain model dependent dissolution modelling techniques, but they were not observed when using model-independent techniques. This illustrates that the techniques are suitable for detecting and understanding excipient variability, but that, in this case, the product was still robust

Cryptic population decrease due to invasive species predation in a long‐lived seabird supports need for eradication

SUMMARY 1. Invasive species are one of the greatest drivers of biodiversity loss worldwide, but the eradication of invasive species from islands is a highly efficient management strategy. Because eradication operations require large financial investments, uncertainty over the magnitude of impacts of both invasive species and their removal can impede the willingness of decision makers to invest in eradication. Such uncertainty is prevalent for long-lived species that display an inherent lag between life stages affected by invasive species and those used for population status assessments. 2. Albatrosses are among the longest-living bird species and are threatened on land by invasive species and at sea by industrial fisheries. As in many seabird species, usually only a segment of the population (breeding adults) is used for status assessments, making it difficult to assess their population trends and the potential benefit of conservation action, such as the management of predatory invasive species. 3. We used population monitoring and mark-recapture data to estimate the past population trajectory of the Critically Endangered Tristan Albatross (Diomedea dabbenena) by accounting for unobservable birds at sea in an integrated population model. We then projected the future population trajectory for scenarios with or without predation by invasive house mice (Mus musculus) on their main site, Gough Island. 4. The adult breeding population remained stable between 2004 and 2021, but breeding success was low (31%) and our model indicated that the total population (including unobservable immature birds) decreased from a median estimate of 9795 to 7752 birds. Eradicating invasive mice leading to a two-fold increase in breeding success would result in a 1.8–7.6 times higher albatross population by 2050 (median estimate 10 352 individuals) than without this intervention. 5. Low reproductive output for long-lived species may lead to a cryptic population decrease, which can be obscured from readily available counts of breeding pairs by changes in the breeding population. Mouse eradication is necessary to revert the ongoing population decrease, even if this decrease is not yet apparent in the breeding population size.Copyright: © 2022 The Authors. This document is the author’s submitted version of the journal article. You are advised to consult the published version if you wish to cite from it

Mechanisms driving neural crest induction and migration in the zebrafish and Xenopus laevis

The neural crest is an evolutionary adaptation, with roots in the formation of mesoderm. Modification of neural crest behavior has been critical for the evolutionary diversification of the vertebrates and defects in neural crest underlie a range of human birth defects. There has been a tremendous increase in our knowledge of the molecular, cellular and inductive interactions that converge on defining the neural crest and determining its behavior. While there is a temptation to look for simple models to explain neural crest behavior, the reality is that the system is complex in its circuitry. In this review, our goal is to identify the broad features of neural crest origins (developmentally) and migration (cellularly) using data from the zebrafish (teleost) and Xenopus laevis (tetrapod amphibian) in order to illuminate where general mechanisms appear to be in play and, equally importantly, where disparities in experimental results suggest areas of profitable study