Environmental health science in the city by the Bay.
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Biomedical subjects
Publications and source records attributed to J Wakefield.
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Compartmental models are widely used to model the profile of drug concentrations versus time from administration in an individual subject. Observed concentrations are then modelled as noisy departures from the underlying profile, the latter characterised for each individual by a small number of 'individual parameters'. When a population of individuals is studied, inter-individual variation is modelled by assuming that the individual profile parameters are drawn from a population distribution, the latter characterised by 'population parameters' describing, in effect, a mean population profile and individual variation around it. From a Bayesian statistical perspective, such models fit exactly into the so-called hierarchical modelling framework, which provides a coherent basis for individual and population inferences and prediction, as well as for decision-making (for example, the design of dosage regimens). This paper outlines the hierarchical model framework and describes how the required computations can be carried out in a straightforward manner by a Markov chain Monte Carlo technique known as Gibbs sampling, even when models involve mean-variance relationships and outliers.
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Family physicians may spend up to 50% of their time dealing with emotional problems but will refer less than 10% of these cases for psychiatric treatment. This paper describes an approach developed at McMaster University which emphasizes the importance of understanding the needs of family physicians and helping them make optimum use of available psychiatric services. Such an approach aims at increasing the comfort and expertise of family physicians in handling the problems they see on a regular basis, involving them actively in their patient's care after a referral, and offering relevant services that supplement those of the family physician, while monitoring and correcting problems that can arise when the two specialties work together. The implications that this has on the training of family medicine and psychiatry residents are discussed as well as ways in which continuing education can be provided for family physicians in community practice.
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The incidence of invasive cervical cancer by age and marital status was examined, using census statistics and 1968--71 cancer registry data from women who lived in the Manchester Regional Hospital Board area. The relative rarity of the disease in the unmarried and its higher incidence in formerly married than in currently married women was confirmed. This higher incidence was shown to be mainly in widows under 50 and divorced women, suggesting that it is related to the association of the disease with number of sexual partners.
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The feasibility of mass population screening for breast cancer by clinical examination and x-ray mammography was studied. The results indicate that such a programme could be conducted effectively by non-medical staff and be safe from the dangers of irradiation. The response rate of women invited for screening suggests that such a service is acceptable to the general public. The additional work load produced by screening would not overburden the existing surgical services.
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A sensitive rat model has been designed to detect potential weak bladder carcinogens or co-carcinogens. The test compound is given to animals which have received a single initiating, but non-carcinogenic, dose of N-methyl-N-nitrosourea (MNU). The model has been used to investigate two compounds currently under suspicion as weak bladder carcinogens, namely sodium saccharin and sodium cyclamate, and one compound known to be cytotoxic but not carcinogenic for the bladder epithelium namely cyclophosphamide. For comparison, these three compounds were also tested as solitary carcinogens in animals not pre-treated with MNU. At the very high dose levels used, sodium saccharin and sodium cyclamate were weak solitary carcinogens producing 4/253 and 3/228 bladder tumours respectively, and the first of these tumours did not appear for more than 80 weeks. When tested in the MNU/rat model more than half the animals receiving either sodium saccharin or sodium cyclamate developed bladder tumours from 10 weeks onwards. By contrast, cyclophosphamide failed to produce any tumours when tested either as a solitary carcinogen or in the MNU/rat model. It must be emphasized that the doses of saccharin and cyclamate used were far higher than those consumed by man, including diabetics, and these results should not be directly extrapolated to man without careful consideration of many other factors including negative epidemiological findings. The theoretical basis of the model is discussed and also the relevance, in terms of environmental human exposure, of detecting compounds which have a synergistic effect with other known bladder carcinogens. It appears that this model can be used to detect a carcinogenic or co-carcinogenic potential in compounds which are organotropic for the bladder more rapidly and with fewer animals than if the compounds are tested as solitary carcinogens by more conventional methods. It is suggested that it could be used to detect those compounds which require further investigation.
Three years after a normal cervical smear, 1,007 women were followed up to see how they responded to a computer-generated recall letter. Seven women had died and 150 had had interim smears (mainly in association with regular contraceptive or postnatal examination). Of the remaining 850, low response was not related to lower social class in the way initial recruitment to screening is. Working outside the home was more obviously associated with lower response, as wass full-time compared with part-time work. Response was also related to where the first smear was taken (61% of women first examined at a local authority clinic, but only 29% of those from a mobile industrial clinic) and was related to repetition of a familial routine which favoured permanent rather than mobile facilities. Interviews with returners and non-returners showed that over 90% remembered receiving recall letters, so non-response was a conscious decision not to attend. When a first test originated at work, response to recall tended to be poor. Of the non-returners 42%, but only 24% of the returners, had found the first test unpleasant or embarrassing. One-third of non-returners claimed difficulties in finding time, which is in accord with the lower response from full-time workers. Over 90% of those interviewed gave fear or modesty as the reasons why other women had not had a repeat smear. In general, differences in response to a letter inviting women to have a repeat smear are unlike those which characterize recruitment for a first smear. Consistency of experience appears to be strongly favoured in the regular use of cytological screening.
In a sample of 1007 women from a large cervical cytology screening programme in the Manchester region, the apparent response-rate to a letter inviting women to have a second routine smear three years after their first was 47-6%. After taking account of those who had become ineligible on medical grounds, or inaccessible, a conservative estimate of the true rate of response was 65-7%. When women who had had interim smears or examinations elsewhere were included, 72-2% of the original population of women had continued to make use of facilities for cytological screening.