PubMed Health⌕ Search

Biomedical subjects

R N Curnow

Publications and source records attributed to R N Curnow.

12 recordsLinked to original sources
PubMed1992

Statistical evaluation of the fixed-dose procedure.

The fixed-dose procedure (FDP) was proposed by the British Toxicology Society in 1984 as an alternative to the LD50 study in the assessment of the acute oral toxicity of a substance. This paper presents a statistical evaluation of this procedure. A mathematical description of the FDP shows that the starting dose can affect the toxic classification of a substance. The toxic classification based on the FDP is compared with that based on an LD50 test. This shows that, in general, the FDP is likely to result in the same classification or a less toxic one than the LD50 procedure. However, for substances with very shallow dose-response slopes, the FDP is likely to result in the same classification or a more toxic one. The expected number of animals that will be tested and will die using the FDP will be reduced compared with the LD50 study. The results from the international validation study carried out in 1989 showed agreement with the results predicted from the mathematical model.

Animals↗
PubMed1990

A study of the inheritance of susceptibility to bovine spongiform encephalopathy.

A genetic study of 75 cases of bovine spongiform encephalopathy (BSE) of which 51 were confirmed by histopathology in 29 pedigree and seven non-pedigree herds of Holstein Friesian cattle revealed that 73 per cent of 60 BSE cases had first or second degree relatives also affected. All the 44 cases assigned to families could be traced back in the previous three generations to one cow and 11 bulls, which were of Canadian Holstein or Dutch Friesian heredity. No single common ancestor could be identified in the parentage of BSE-affected animals in pedigree studies up to six or more generations. The number of common ancestors and the degree of relatedness of the affected animals in a multiple-case herd was no more than would be expected from the breeding structure of the herd. The segregation ratio of affected cows in the proband generation within sire and maternal grandsire sibships in 12 pedigree herds was not inconsistent with Mendelian expectation for autosomal recessive inheritance with complete penetrance. The data analysed shows that the disease itself is not simply inherited. However, there remains a real possibility that the susceptibility of individual animals to BSE is inherited. This should be taken into account in current and future research on the aetiology and control of the disease.

Animals↗
PubMed1990

An accurate approximation to the distribution of the length of the longest matching word between two random DNA sequences.

An accurate approximation is derived to the distribution of the length of the longest matching word present between two random DNA sequences of finite length, using only elementary probability arguments. The distribution is shown to be consistent with previous asymptotic results for the mean and variance of longest common words. The application of the distribution to assessing the statistical significance of sequence similarities is considered. It is shown how the distribution can be modified to take account of non-independence of neighbouring bases in real sequences.

Computer Simulation↗
PubMed1990

Tests for the statistical significance of protein sequence similarities in data-bank searches.

A suite of tests to evaluate the statistical significance of protein sequence similarities is developed for use in data bank searches. The tests are based on the Wilbur-Lipman word-search algorithm, and take into account the sequence lengths and compositions, and optionally the weighting of amino acid matches. The method is extended to allow for the existence of a sequence insertion/deletion within the region of similarity. The accuracy of statistical distributions underlying the tests is validated using randomly generated sequences and real sequences selected at random from the data banks. A computer program to perform the tests is briefly described.

Algorithms↗
PubMed1979

A two-locus model for the inheritance of a familial disease.

A model for the inheritance of a disease involving genes at just two linked loci is presented and discussed. One of the two pairs of opposite double homozygotes is assumed to lead to the disease and death. The other genotypes are assumed to be less fit than the double heterozygote. The cause of this reduced fitness may or may not be due to the disease. Conditions for the existence of a stable equilibrium are presented. The model has a sound biological basis and could be used to explain a wide range of disease frequencies and patterns of inheritance. Mutation is not required to explain why the disease persists in the population. Recurrence risks for sibs and twin concordance rates are derived and the consequences of the relaxation of selection against those with the disease are predicted. The effects of a selection model of the kind described on the amount of linkage disequilibrium in the population and on the estimation of the frequency of recombination are discussed.

Chromosome Mapping↗
PubMed1978

On effects of relaxed selection in familial disorders.

Theoretical predictions are made of the effect of improved treatments, with consequent increase in fertility of affected individuals, on the frequency of familial disorders. Multifactorial inheritance and some two-locus models are considered. (Changes for simple Mendelian disorders have been estimated previously by many authors.) It is estimated that, with two-locus or multifactorial models, an increase in frequency per generation of not more than a few per cent of the frequency of a disorder may be expected. The greatest increase will be in the first generation following introduction of the new treatment.

Gene Frequency↗