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Gaffney, E. A.

Publications and source records attributed to Gaffney, E. A..

2 recordsLinked to original sources

Computer-assisted beat-pattern analysis and the flagellar waveforms of bovine spermatozoa

Plagued by hurdles in information extraction, handling, and processing, computer-assisted sperm analysis (CASA) systems have typically neglected the complex flagellar waveforms of spermatozoa, despite their defining role in cell motility. Recent developments in imaging techniques and data processing have produced significantly-improved methods of waveform digitisation. Here, we utilise these improvements to demonstrate that near-complete flagellar capture is realisable on the scale of hundreds of cells, and, further, that meaningful statistical comparisons of flagellar waveforms may be readily performed with widely-available tools. Representing the advent of high-fidelity computer-assisted beat-pattern analysis (CABA), we show how such a statistical approach can distinguish between samples using complex flagellar beating patterns rather than crude summary statistics. Dimensionality-reduction techniques applied to entire samples also reveal qualitatively-distinct components of the beat, and a novel data-driven methodology for the generation of representative synthetic waveform data is proposed.

microbiology

Comparative Anatomical Limits of CART-Cell Delivery to Tumours in Mice and Men

BackgroundCART-cells have demonstrated clinical success for the treatment of multiple different lymphomas and leukaemias. However, comparable clinical efficacy has not been observed for various solid tumours in human clinical trials, despite promising data from murine cancer models. Lower effective CART-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent clinical outcomes, requiring the development of quantitative methods to calculate effective dosing in the clinic and models. MethodsWe used anatomical and physiological data for human and rodent circulatory systems to calculate the typical value and expected variation of the perfusion of healthy and tumour tissues, and used these to estimate the upper limits of immune cell delivery rates (maximum possible under optimal conditions) across different organs, tumours types and species. ResultsEstimated maximum delivery rates were up to order 10,000-fold greater in mice than humans yet reported CART-cell doses are typically only 10-100-fold lower in mice, suggesting that the effective delivery rates of CART-cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were compared to published PET data and found to be consistent. ConclusionsThe results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models. These increased doses raise safety and manufacturing concerns. We posit that quantitation of species and organ-specific delivery and homing of engineered T-cells will be key to unlocking their potential for solid tumours.

cancer biology