1. Results are presented of palatability tests and chronic toxicity tests with five anti-coagulant rodenticides at a variety of concentrations against wild Rattus norvegicus, R. rattus and Mus musculus. These results are compared with similar data for warfarin. Estimates are also given of the acute oral toxicity of two of the five, fumarin and diphacinone, to white rats.

2. The toxicity of the compounds vis-à-vis warfarin is examined from the standpoint of the risks to domestic animals involved in their use as rodenticides.

3. Coumachlor, 2-isovaleryl-1, 3-indandione and 2-naphthyl-1, 3-indandione are considered to be less effective than warfarin against R. norvegicus. Their effectiveness against R. rattus remains to be demonstrated.

4. Fumarin appears to be about as good as warfarin against R. norvegicus and R. rattus at similar concentrations. It appears to be slightly less effective against M. musculus.

5. Diphacinone at 0·0025% is regarded as a good alternative to 0·005% warfarin against R. norvegicus. At 0·0125% it is probably more effective against R. rattus than is 0·025% warfarin. The two poisons are about equally effective at this strength against M. musculus, but diphacinone is probably slightly more dangerous for domestic animals.

6. The results of a small number of field trials with fumarin and diphacinone are briefly summarized.

So many of our colleagues and others have helped at some stage or other of our investigations that it would be tedious to mention them all by name. We must, however, single out for our special thanks Mrs M. Rowe and Miss E. Taylor who carried out a large number of the laboratory tests, Mr A. Taylor on whose chemical experience and facilities we have freely drawn and Mr C. H. B. Worrall, Miss B. Jones, Mr S. R. Surtees and Mr J. H. Cuthbert (Department of Agriculture for Scotland) who carried out the field trials.

The variables operating in respect of the risk of provoking paralytic poliomyelitis by inoculating children with different prophylactic reagents have been analysed.

It is concluded that the use of combined diphtheria fluid toxoid and pertussis vaccine, administered in early infancy, incurs a minimal risk and is to be recommended because of its immunological effciency, its unquestionable value in helping to maintain a high immunization rate against diphtheria in the child community and for its marked administrative convenience.

The fermentation of mannitol by coagulase-positive staphylococci has been studied. It was found difficult to obtain reproducible results by methods which could be conveniently used in a routine department.

A method of grading based on the fermentation of mannitol has been examined. Organisms of the supposedly most dangerous grade (Grade A) were isolated slightly more frequently from lesions than from carriers, but from all sources a high proportion of strains belonged to this grade.

It was not possible to correlate the grades to which staphylococci were assigned with their production of diffusible antigens.

In this hospital it seems that the proportion of strains assigned to Grade A has become very much higher than it was 15 years ago.

We thank Prof. R. Knox, Mr J. B. Blaikley, Dr W. H. H. Merivale, and Dr R. H. Gorrill for the help and advice they have given us in the course of this investigation and numerous members of the nursing staff of Guy's Hospital for their co-operation in checking records and answering questions.

Experiments were made with five pathogenic serotypes and five non-pathogenic Esch. coli strains to study the competitive growth of mixed coli cultures in nutrient broth. In associations incubated at either 37 or 44°C. the organism inoculated in smallest numbers increased proportionately after 18 or more hours' incubation. The greater the initial disparity, the greater was the increase. Broth culture favoured the pathogenic strains only when these were numerically inferior in the inoculum. The tendency to numerical equation increased with increasing length of incubation.

A study was made of the use of nutrient broth as an aid to the isolation of pathogenic Esch. coli strains from the faeces of infants. 120 positive specimens were examined. Nutrient broth incubated at 44° C. was the most successful method, and when used as a complement to direct plating resulted in an additional 19·6% of positive specimens. The main value of nutrient broth as an enrichment method is in the examination of the faeces of suspected carriers and convalescent patients, in which the pathogen is likely to be outnumbered by non-pathogenic Esch. coli strains.

I wish to thank Prof. Scott Thomson for his advice and helpful criticism, and Dr R. W. S. Harvey for his interest and encouragement.

Five media—MacConkey broth, lactose broth, Teepol broth, lauryl sulphate broth and glucose glutamic acid medium—have been compared as primary media for the isolation of coliform organisms from 1691 samples of water received for examination during a period of 18 months.

Of these samples 1043 (61·7%) gave an identical result in all five media. In the other 648 (38·3%) samples there were differences either in the types of coliform organism isolated or in the rapidity with which the reactions appeared in the different media. The differences in the final yields of coliform organisms and Escherichia coli in the five media are not statistically significant.

There were differences in the number of false presumptive positive reactions given by the different media—lactose broth giving many more false presumptive positive reactions than any of the other media and nearly six times as many as MacConkey broth, which gave the smallest number.

All the reactions tended to appear rather more slowly in glucose glutamic acid medium than in the other media.

Glucose glutamic acid medium has the advantages of being a chemically defined medium and of not containing any substances which are likely to be inhibitory to coliform organisms. Other glutamic acid media may be found on further investigation to give better results than the present glucose glutamic acid medium, but those presented here suggest that media containing glutamic acid are worthy of further investigation.

I am indebted to Dr Ian Sutherland of the M.R.C. Statistical Research Unit for statistical advice and to Dr R. D. Gray of the Public Health Laboratory, Newport (Mon.) and to Dr A. H. Tomlinson of the Public Health Laboratory, Oxford, for much helpful criticism.

Studies on reproduction in a colony of albino mice before and after length of daylight was made constant show no change in litter size. However, there was an increase in the number of post-partum pregnancies after light was made constant and, during the first month thereafter, females were older at first parturition than in previous months.

Calculations have been carried out which suggest that as few as 6 × 104 molecules of anti-poliovirus antibody per millilitre of serum may be sufficient to prevent the clinical disease under certain epidemic conditions. Other calculations have been made involving therapy of the experimental disease in monkeys and certain factors required for successful serum therapy have been discussed.

1. The influence of the thyroid gland on the production of antitoxins to two alum-precipitated bacterial exotoxins has been investigated in different animal species.

2. Rats, rabbits and mice produce more circulating antitoxin when thyroidectomized, and less when made hyperthyroid by thyroxine administration, than control animals.

3. Guinea-pigs produce slightly less antitoxin when thyroidectomized, and markedly more when thyroxine treated, than control animals.

We are grateful to Dr J. S. F. Niven for histological examination of tissues, and to Miss M. V. Mussett, B.Sc., for statistical analyses. The alum-precipitated tetanus toxoid XW 2044, and tetanus toxin XW 1322, were kindly supplied by Miss Mollie Barr, M.Sc., of the Wellcome Research Laboratories, Beckenham, Kent, and we are also grateful to Mr P. Rodican of the Lister Institute, Elstree, for a supply of tetanus toxin 829.

1. Experiments have been carried out to estimate quantitatively the survival of Sh. sonnei at various R.H.'S and two different temperature ranges.

2. A fraction may survive for 7–10 days under favourable conditions.

3. At R.H.'S of 40–60% the organism survives less well than at higher or lower values.

4. Survival is better at temperatures of 5–10°C. than at 20–30°C.

I am very grateful to Mr T. Nash for his advice during the course of this work, and also to Col. H. J. Bensted for his comments on the MS.

Guinea-pigs immunized with alum-precipitated diphtheria toxoid (APT) become hypersensitive to diphtheria toxin and toxid. This hypersensitivity is probably due to a mixture of immediate (Arthus-type) reactions and delayed (tuberculin-type) reactions, the former increasing as the level of circulating precipitating antitoxin rose and tending to mask the latter. In a hyperimmune guinea-pig the residual damage following the intradermal injection of toxin is due, at least in part, to hypersensitivity to toxin; toxicity probably contributes relatively little to the extent of the lesion in animals with a high titre of antitoxin.

The technical difficulties of proving the presence of a delayed allergic reaction in animals with an early allergic reaction are discussed.

I am grateful to Dr C. G. Pope, who has been closely associated with this work, not only for providing highly purified materials, but also for his advice.

Highly purified crystalline diphtheria toxin-protein, and toxoid prepared from it, were labelled with 131I, without change of potency, and injected intradermally into immune and allergic guinea-pigs. It is probable that actively immunized guinea-pigs localize these antigens and that localization is due to hypersensitivity of a type that cannot be transferred with serum; it is possibly of the delayed (tuberculin-type) of allergy.

It is a pleasure to acknowledge the gift of highly purified (crystalline) diphtheria toxin, and toxoid prepared from it, from Dr C. G. Pope of the Wellcome Research Laboratories, England. Dr S. P. Masouredis of the Central Blood Bank of Pittsburgh kindly labelled these antigens, using the technique he devised. Dr W. J. Kuhns generously provided the human precipitating and non-precipitating diphtheria antitoxin*.

The collimator head was made by Mr J. Nechaj of the University of Pittsburgh.

All these collaborators gave me advice on matters of which I was ignorant; for this I am grateful.

On the basis of starch synthesis and degradation by the strains three subdivisions of Group A streptococci were made. In defined cultural conditions about a third of the strains accumulated starch, the majority belonging to one subgroup. Of patients from whom starch-accumulating strains were isolated at the onset of infection, the observed numbers who developed either acute nephritis or acute rheumatic fever were more than three times the expected numbers. Of eighty-six strains, including forty-six members of Type 12, and forty belonging to several other serotypes, which were associated with either nephritis or rheumatic fever, more than 90% were starch-accumulating strains. Though 47% of all Type 12 strains accumulated starch, there was a primary association of starch-accumulating strains and the sequelae, irrespective of serotype. On the basis of type-frequency, and the starch synthesizing and degrading activities of the three most common serotypes, Types 1, 4 and 12, together with the host factor (for only 25% of patients infected with starch-accumulating strains developed the sequelae) the chances of Type 12 incidents are four to one against Types 1 and 4. The probability of the findings occurring by chance was considerably less than 0·001.

Technical assistance was paid for by grants from the Royal Free Hospital Endowment Fund, and I thank the Board of Governors of the Hospital. The drawings were made by Mrs Audrey Besterman, medical artist. For all their help and patience I wish to thank Dr R. E. O. Williams, Dr M. Patricia Jevons, Mr W. R. Maxted, Dr P. J. L. Sequeira, Dr W. J. Whelan and Dr Rebecca Lancefield.