Rupert G. Miller

Assay of the Immune Inhibitor in Classic Haemophilia: Application of Virus-Antibody Reaction Kinetics

The kinetics of virus neutralization by antibody are shown to apply to factor‐VIII neutralization by the immune antibody of haemophilic patients. The analysis established for virus neutralization has been used as a model for designing a general system for inhibitor assay based on mixtures in which antigen is present in excess, rather than with antibody in excess, as has been the case with systems previously proposed. The new system permits conversion of inhibitor potency results from other systems based on the use of different mixtures of factor VIII and inhibitor as long as factor VIII is in excess and as long as constant physical conditions of time and temperature of incubation are applied. It also takes account of the fact that some antibodies reveal a‘residual resistant fraction’ of antigen with which they cannot react. The procedure for converting assay data into‘Oxford units’ is described.

Jackknifing the kaplan-meier survival estimator for censored data: Simulation results and asymptotic analysis

It is shown by simulation t h a t the (arc-sine transformation of the) Kaplan-Meier survival estimator for censored data can be usefully jackknifed to give conservative confidence limits for survival probabilities when samples are small (25 and 50). Mathematical demonstration of the asymptotic, large-sample, validity of the jackknife is included.

[A THEORETICAL MODEL FOR THE STUDY OF THE EFFECTS OF NEUTRONS AND X-RAYS ON TUMOR CELL POPULATIONS].

This work deals with the mathematical formulation of a model for studying the effects of X-ray and fast-neutron irradiation on tumor cell populations, the end-effect being the inhibition of reproductive integrity. The variables considered in such a model are largely based on original work performed on trasplantable tumors and obtained in part from other published data; they regard: a) The sensitivity of the tumor cell population with respect both to the extrapolation number and to the slope of the exponential part of the survival curve. b) The type of radiation used, allowing for different RBE values under oxygenated or anoxic conditions. c) The oxygen-enhancement ratios of the radiations considered. d) Different modalities of irradiation (single and multiple doses), allowing for cell recovery in the latter case. e) Different modalities of fractionation with respect to the magnitude of the dose delivered at each fraction. f) The degree of anoxia and the percentage of anoxic cells in the tumor population. g) Possible variations in the percentage of anoxic cells at various points along the course of the radiation treatment. The results of this theoretical analysis are presented, both with regard to the shape of the survival curve of the total cell population and to dose-cure-rate tables, under each of the above-mentioned conditions. Finally, the possible advantages and limitations of the use of neutrons in clinical radiotherapy are briefly discussed.