A procedure for combining evidence from different biological assays is shown to be equivalent both to generalized least-squares and to maximum-likelihood estimation. By appropriate nesting of hypotheses, the likelihood function can be used to test the agreement between the assays and to obtain probability limits for the combined estimate of potency. The properties of these limits are examined, with particular reference to the situation, unusual but not impossible in practice, in which the values of relative potency that they define consist of several disjoint segments instead of a single interval. The connexion with general theory of estimating linear functional relations is pointed out.

The following is an account of the bacteriological examinations for diphtheria bacilli made by me at the University Pathological Laboratory, from October 23, 1900 to Jan. 5, 1901; a period which includes all but the first week of the outbreak described in the preceding paper.

Systematic, national surveillance of outbreaks of intestinal infectious disease has been undertaken by Public Health England (PHE) since 1992. Between 1992 and 2002, there were 19 outbreaks linked to raw drinking milk (RDM) or products made using raw milk, involving 229 people; 36 of these were hospitalised. There followed an eleven-year period (2003–2013) where no outbreaks linked to RDM were reported. However, since 2014 seven outbreaks of Escherichia coli O157:H7 (n = 3) or Campylobacter jejuni (n = 4) caused by contaminated RDM were investigated and reported. Between 2014 and 2017, there were 114 cases, five reported hospitalisations and one death. The data presented within this review indicated that the risk of RDM has increased since 2014. Despite the labelling requirements and recommendations that children should not consume RDM, almost a third of outbreak cases were children. In addition, there has been an increase in consumer popularity and in registered RDM producers in the UK. The Food Standards Agency (FSA) continue to provide advice on RDM to consumers and have recently made additional recommendations to enhance existing controls around registration and hygiene of RDM producers.

In skim milk obtained from susceptible cows after intramammary and intravenous inoculation (primary infected milk), foot-and-mouth disease (FMD) virus type 01 was slower inactivated by heat treatment than virus that had been added to pre-exposure skim milk.

Residual virus infectivity in heated primary infected milk was more efficiently detected in bovine thyroid cell cultures than in secondary pig kidney (PK2) cell cultures.

Untreated primary infected milk was found to inhibit both FMD-virus and vesicular stomatitis virus plaque formation in PK2 cells, suggesting the presence of interferon. The results of further tests confirmed that the interfering activity in unheated primary infected milk was indeed caused by an interferon.

Interferon excretion in primary infected milk was investigated using a series of milk samples from three cows. Maximum interferon titres were found after 24 h, coinciding with or shortly after the first virus excretion peak. The results are discussed with particular reference to the use of primary infected milk in studies of the thermal inactivation of FMD-virus.

The bactericidal effect of ultra-violet radiation on dried films of β-haemolytic streptococci has been shown to be dependent both on the relative humidity and on the nature of the suspending medium from which the films are prepared. In particular, while the bactericidal action is most often more repaid under dry conditions, films prepared from suspensions in dust extract culture show a similar behaviour to that of naturally occurring dust flora and are most resistant to the effects of radiation under dry conditons.

With increasing knowledge of the effects of inhaled dusts upon the lungs has come an increase in the number of cases of Workmen's Compensation in which pulmonary disease is attributed to exposure to this form of risk during employment. Where a post-mortem examination has been made, and the opinion of a pathologist is sought, no difficulty is encountered in those cases of silicosis in which the disease is well developed, since the lesions are characteristic and easily recognised. The position, however, is by no means so easy where lesser degrees of pulmonary fibrosis are present and, in particular, where it becomes necessary to try to assess the bearing which these may have upon the susceptibility to, and the progress of, intercurrent pulmonary disease—for example lobar pneumonia. In these difficult circumstances recourse is frequently had to the chemical estimation of the quantity of silica recoverable from samples of lung. Certain standards have been set up, and the presence of silica in quantities in excess of the “normal” forms valuable corroborative evidence that a pulmonary fibrosis is attributable to its influence, where the subject in question has been exposed to this risk in his employment, and on the other hand the absence of an excess of silica is evidence that any pathological condition in the lung is due to other causes.

A detailed investigation of the possible role of wild mammals, other than badgers, in the maintenance of Mycobacterium bovis in an area on the South Downs of East Sussex was carried out over 3 years. Estimates of population sizes were made where possible and minimum sample sizes were selected to be 95 % certain of including at least one infected animal if the prevalence was at least 5 %. Samples of wild mammals were taken from populations which had the highest potential direct or indirect contact rate with known infected badgers. M. bovis was not isolated from any of the 15 species of wild mammals.

It was concluded that badgers are able to maintain M. bovis in an area independently of other species, and that in the area studied other species were not a source of infection for the cattle herds.

A single inoculation of pseudomonas vaccine protected mice against a 1 LD 100 challenge by nine different serotypes of Pseudomonas aeruginosa, 4 days after vaccination. Three inoculations of the same vaccine, given on consecutive days, protected mice for a longer time, against challenge by a wide range of Ps. aeruginosa serotypes, than the single inoculation of vaccine. The amount of vaccine inoculated only marginally influenced the non-specific response. F1 vaccines from eight serotypes of Ps. aeruginosa each induced protection against a different range of serotypes.

More than 25 years have passed since the last rubella epidemic in the United States. The rubella pandemic of 1964–5 demonstrated clearly the extraordinary teratogenic potential of the rubella virus. In the United States alone, it is estimated that more than 12500000 cases of rubella occurred during the winter and spring of 1964–5. Congenital rubella infection occurred in an estimated 30000 pregnancies, 10000 resulting in fetal death or therapeutic abortion and 20000 resulting in infants born with congenital rubella syndrome (CRS) [1]. In contrast, during 1988, only 225 cases of rubella were reported to the Centers for Disease Control (CDC) in Atlanta, the lowest annual total since rubella became a nationally notifiable disease in 1966 [2]. However, in 1989, this downward trend of reported cases was interrupted, with the number of reported rubella cases in the United States increasing nearly twofold, and in 1990, the total increased another threefold (to more than 1000 cases) [3]. Although the 1990 reports represent the highest total since 1982, the overall incidence of rubella in the United States has still declined by more than 98% since 1969, the year rubella vaccine was licensed (Fig. 1).

When samples of domestic sewage are treated with doses of chlorine lower than the chlorine demand bactericidal action depends not only on the proportion of the demand satisfied but also on the absolute size of the dose. With doses just sufficiently large to leave residual chlorine detectable by o-tolidine, reduction in the plate count of bacteria after contact for 15 min. ranged in various tests from 96·2 to 98·7%.

With domestic sewage reduction in bacterial count after addition of chlorine is followed, after an interval, by aftergrowth of survivors which rapidly brings the population to its original level or higher. For this interval to be prolonged the initial concentration of chlorine must be considerably greater than the chlorine demand. This accords with the fact that the rapid reaction of chlorine with constituents of the sewage, which occurs in the first few minutes, is followed by a slower absorption which takes place over a prolonged period, so that the initial bactericidal action of residual chlorine tends to be lost after a time. For many purposes the effectiveness of chlorination should be judged not only by the percentage of bacteria destroyed after a short period of contact but also by the interval which elapses before aftergrowth becomes appreciable.

In samples of sewage treated with doses of chlorine sufficient to destroy the protozoa, surviving bacteria eventually reached a level of population much higher than that of the untreated sewage. The majority of such bacteria were found to be Gram-negative, non-sporing rods, which included strains of Proteus and of Pseudomonas pyocyanea. Tests with a pure culture of a species of Proteus showed that the organisms surviving chlorination are not intrinsically capable of reaching a higher population than the parent culture.

When sewage contains small quantities of gas liquor or thiocyanate the bactericidal action of doses of chlorine lower than the demand is much more prolonged than the action of comparable doses in domestic sewage, owing to the formation of cyanogen chloride.

Comparative tests of the action of chlorine and of cyanogen chloride on pure cultures of Bacterium coli in peptone water and on the mixed flora of sewage showed that the bactericidal effect of cyanogen chloride was more persistent than that of a comparable dose of chlorine. With sewage and with some brands of peptone the immediate effect of the chlorine, on the other hand, was often considerable.

Coagulase-negative staphylococci isolated from blood or spinal fluid during a period of 1 year in a department of neurosurgery, were analysed by biotyping, antibiotic resistance pattern and plasmid profiles. Altogether 41 isolates from 19 patients were studied. About 90% of the isolates were Staphylococcus epidermidis. The antibiotic resistance pattern seemed to be closely related to antibiotic usage in the unit. Most common was resistance to penicillin (63%), trimethoprimsulphamethoxazole (49%) and cloxacillin (39%) while resistance to gentamicin was seen in only one strain.

In several cases species and antibiograms were identical in isolates from different patients. Plasmid pattern analysis could then be used for identification of different strains. In one instance, plasmid pattern and restriction enzyme analysis confirmed that two patients probably were infected by the same strain.

The effects of radiation from the surroundings on the impressions of freshness of 106 men and 39 women members of the staff of the Building Research Station were investigated during the first 6 months of 1948. Subjects were exposed to three types of environment: (1) where the walls were cooler than the air, (2) where the walls and air were at the same temperature, and (3) where the walls were warmer than the air. The tests were carried out in calm air.

It was found that the difference between the mean radiant temperature and the air temperature affected freshness impressions, but the effect was relatively slight. Environments which felt cool tended to feel fresh, yet a rise in the mean radiant temperature—which would increase the warmth of the environment—tended to produce an impression of greater freshness. At a given equivalent temperature, environments with the surroundings warmer than the air were found to be definitely fresher than cold- and neutral-wall environments. This was thought to be mainly due to the fact that the humidity of the air in the warm-wall environment was lower than that in the other two environments. Changes in humidity insufficient to affect sensations of warmth affect impressions of freshness. Under the conditions of these experiments, and to keep freshness impressions constant, a rise of 1° F. in the temperature of calm air must be compensated by a fall of about 5% in the relative humidity.

The subjects had a distinct preference for the warm-wall environment; 73% of them found it pleasanter than either the cold- or the neutral-wall environment.

Freshness impressions are considered to be related to transient fluctuations in the rate of heat loss from the head.

Canine influenza virus (CIV) is an emerging pathogen that causes acute respiratory disease in dogs. The aim of this study was to investigate the pathogenicity of A/canine/Jiangsu/06/2010 (H3N2) virus isolated in China. Nine dogs were inoculated intranasally with 107·95 of 50% egg infectious dose (EID50) of the virus. The onset of clinical signs and virus shedding was observed on day 1 post-infection (p.i.). The peak clinical score occurred between days 4 and 6 p.i. The experimentally infected dogs were found to shed virus not only via the respiratory tract but also via the digestive tract. Viral RNA could be detected in multiple organs including the trachea, lung, liver, spleen, kidney, brain and duodenum. All the sampled organs from infected dogs showed significant lesions and viral antigen staining. The results differed from those reporting using previous CIV strains; the Chinese isolate could induce extrapulmonary infection and cause extensive lesions in dogs.

This study aimed to confirm that vertical transmission of hepatitis B virus (HBV) can occur via the infected ovum. Specimens studied were obtained from discarded test-tube embryos from mothers with chronic HBV infection who had received in vitro fertilization treatment. Single-cell reverse transcriptase–polymerase chain reaction was used to detect HBV mRNA in the embryos. HBV mRNA was detected in the cleavage embryos of patients with chronic HBV infection, with a detection rate of 13·2% (5/38). The level of serum HBV DNA was not related to the HBV mRNA positivity rates in embryos. In this study, HBV mRNA was detected in test-tube embryos from HBV-infected mothers who had received in vitro fertilization treatment. This confirms the theory of vertical transmission of HBV via the ovum, thereby providing an important theoretical basis for further study on the mechanism of HBV vertical transmission, influencing factors and blocking measures.

Botulism has rarely been reported in Africa. In October 2008, botulism was reported in three Ugandan boarding-school students. All were hospitalized and one died. A cohort study was performed to assess food exposures among students, and clinical specimens and available food samples were tested for botulinum toxin. Three case-patients were identified; a homemade, oil-based condiment was eaten by all three. In the cohort study, no foods were significantly associated with illness. Botulinum toxin type A was confirmed in clinical samples. This is the first confirmed outbreak of foodborne botulism in Uganda. A homemade, oil-based condiment was the probable source. Consumption of homemade oil-based condiments is widespread in Ugandan schools, putting children at risk. Clinicians and public health authorities in Uganda should consider botulism when clusters of acute flaccid paralysis are seen. Additionally, schools should be warned of the hazard of homemade oil-based condiments, and take steps to prevent their use.

The RNA genome of rotaviruses consists of 11 segments in four size-classes which can be separated by polyacrylamide gel electrophoresis, although 11 separate bands are not shown by all strains. We propose a cryptogram (Rotacode) based on the relative distance of migration of adjacent bands in each size-class for coding the typical pattern of each strain of virus. This provides a shorthand for recording details of each strain and for grouping electrophoretically similar strains.

Rotacode was found to be reliable and reproducible, with identical codes being obtained for the same samples in repeated experiments under code and by various observers. Rotacode was also used to analyse 189 strains obtained over a three-year period and differentiated 13 electrophoretypes. This confirms the considerable electrophoretic variability of wild strains.

In May 2000, public health authorities in Dublin, Ireland, identified a cluster of unexplained severe illness among injecting drug users (IDUs). Similar clusters were also reported in Scotland and England. Concurrent investigations were undertaken to identify the aetiology and source of the illnesses. In Dublin, 22 IDUs were identified with injection-site inflammation resulting in hospitalization or death; eight (36%) died. Common clinical findings among patients with severe systemic symptoms included leukaemoid reaction and cardiogenic shock. Seventeen (77%) patients reported injecting heroin intramuscularly in the 2 weeks before illness. Of 11 patients with adequate specimens available for testing, two (18%) were positive by 16S rDNA PCR for Clostridium novyi. Clinical and laboratory findings suggested that histotoxic Clostridia caused a subset of infections in these related clusters. Empiric treatment for infections among IDUs was optimized for anaerobic organisms, and outreach led to increased enrolment in methadone treatment in Dublin. Many unique legal, medical, and public health challenges were encountered during the investigation of this outbreak.

Human papillomavirus (HPV) types 6 and 11 are the aetiological agent of recurrent respiratory papillomatosis (RRP). The complete genome of an HPV6 isolate with a 170 base pair (bp) duplication identified within the long control region (LCR) from a patient with aggressive recurrent respiratory papillomatosis was determined. The promoter sequence from the HPV LCR including the 170 bp duplication was placed upstream of a heterologous reporter gene and the activity of the reporter gene product determined using transfected cells. In total, mutations were observed at 157 nucleotide positions of the complete genome and included nucleotide substitutions, deletions and insertions, resulting in amino acid changes at 43 residue positions. Reporter gene activity using an HPV-derived LCR region with a 170 bp duplication was significantly higher than that using an HPV-derived LCR region with no duplication within this region. The results suggest that novel HPV variants warrant further investigation for potential biomarkers of aggressive disease.

Fourteen influenza A(H3N2) field isolates, mainly obtained during the first weeks of the 1982/83 influenza epidemic in The Netherlands, and nine influenza A(H3N2) reference strains were examined by means of haemagglutination inhibition (HI) tests with 23 potyclonal ferret sera. The resulting HI patterns were subjected to various methods of numerical taxonomy using, among others, taxonomic distance and correlation between strains for resemblance coefficients. Marked differences between distance and correlation coefficients were found in strains which differed in avidity only. The field isolates could be divided into four groups in respect of their taxonomic resemblance to the reference strains. The same grouping was found for five of the field isolates by testing these against 200 human sera.

The following paper investigates the prevalence and characteristics of asymptomatic norovirus infection in the population living around oyster farm sites. Two consecutive surveys were conducted from January 2014 to December 2014 and 4549 stool samples were screened during the same time period. The total asymptomatic infection rate was 4.04% (184/4549). Norovirus infection rate was 5.20% in oyster farming population which was significantly higher compared with non-farming population where the infection rate was 3.65% (χ2 = 5.49, P < 0.05). A total of 184 NoV positive samples were identified by real time-quantitative polymerase chain reaction (RT-qPCR) and semi-nested RT-PCR and 136 sequences were obtained. The sequences were clustered into 14 genotypes. GI strains were clustered into six genotypes, including GI.2, GI.3, GI.5, GI.6, GI.8 and GI.9; while GII strains were clustered into GII.2, GII.3, GII.4, GII.5, GII.6, GII.8 and GII.13. GI.9 and GII.17 were the predominant and most prevalent genotypes, respectively. The GII.17 genotype replaced GII.4 becoming the dominant genotype in the oyster farming area in 2014. To sum up, long-term monitoring of asymptomatic infection is crucial for the detection of new variant strains and for identifying outbreaks during the early stage.