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Biomedical subjects

N Stallard

Publications and source records attributed to N Stallard.

22 records · Page 2Linked to original sources
PubMed1995

Estimating the magnitude of carcinogenic effects in long-term animal studies.

Carcinogenicity studies seek to compare the incidence of tumours in animals exposed to the substance under investigation and animals used as controls. The conventional method of analysis is the Peto test, which assumes that tumours are either instantly fatal or have no effect on mortality and requires a judgement to be made regarding the lethality of each tumour. Such an assumption seems unrealistic and the judgement is often difficult to make and unreliable. The need for such a judgement and the assumption of extreme lethality can be removed by using parametric multi-state models. In this modelling approach the transition of animals between the states 'alive without a tumour', 'alive with a tumour' and 'dead' is modelled mathematically. This paper compares the Peto test with tests based on two parametric multi-state models in terms of the sensitivity of the tests to detect carcinogenicity. The sensitivity, or power, is shown to be low for commonly used numbers of animals, depending chiefly on the expected total number of animals with tumours. The Omar and Whitehead multi-state model is found to be slightly more powerful than the Dewanji et al. model and at least as powerful as the Peto test. Provided the parametric assumptions are appropriate, this method thus gives a test that is more sensitive than the Peto test and enables estimation of tumour onset and mortality rates without the requirement of tumour lethality judgements.

Animals↗
PubMed1995

The fixed-dose procedure and the acute-toxic-class method: a mathematical comparison.

The fixed-dose procedure (FDP), proposed by the British Toxicology Society, and the acute-toxic-class (ATC) method, proposed by the German Federal Health Authority, provide alternatives to the LD50 test for classifying substances by their acute oral toxicity. This paper presents a mathematical model that is used to compare the two procedures in terms of their classification properties and the required numbers of animals. It is found that the classification properties of the procedures depend on the dose levels used, the number of animals tested per dose and the criteria that are used to decide whether testing should continue at a higher or lower dose. For substances with steep dose-response curves, the most likely classification is determined chiefly by the choice of the dose levels whilst the number of animals and continuation criteria used are increasingly important for substances with dose-response curves with a smaller slope. The use of toxicity as a possible endpoint as in the FDP and the use of a two-stage testing procedure at each dose as in the ATC method are both found to reduce the expected numbers of animals required with little effect on the classification properties. On the strength of these findings it is indicated that a new procedure combining the dose levels and testing approach of the ATC method with the inclusion of toxicity as an endpoint as in the FDP would be more efficient than either the FDP or the ATC method.

Animal Welfare↗
PubMed1994

The effect of a new ejection seat headbox and high G garments on head mobility during air combat.

Full coverage anti-G trousers, a chest counter pressure garment for positive pressure breathing for G tolerance, and a smaller ejection seat headbox have been developed for future agile aircraft. The hypotheses that the new headbox might improve, and that the more restrictive high G garments might compromise, pilot head mobility were tested. The RAF institute of Aviation Medicine Hawk aircraft was equipped with a wide angle video camera facing the front seat pilot. Two experimental conditions were compared to the control air combat sortie: 1. standard garments and the smaller headbox; 2. high G garments and the smaller headbox. Data were recorded from five instructor pilots during three scheduled air combat training sorties. Their helmets were marked with 10-mm white dots in a standardized pattern. Software for recording helmet dot positions from single frame video images, and a trigonometric method for calculating head rotation and translation from changes in the helmet dot positions were devised. No differences were found between headboxes or garments at the three extremes of head movements analyzed. Observed neck rotations were similar to maximal seated norms. Optimal head and neck extension is impeded by the ejection seat headbox. Pilots' head movements are not restricted during air combat at moderate G levels.

Aerospace Medicine↗