The pharmacological sensitivity of a touchscreen-based visual discrimination task in the rat using simple and perceptually challenging stimuli.

RATIONALE: Cognitive testing with touchscreen-equipped operant boxes ('touchscreens') is becoming increasingly popular. Tasks, such as paired associate learning or reversal learning of visual stimuli, have the discrimination of visual stimuli as a fundamental component. However, the effect of drugs commonly used in the study of cognitive mechanisms has yet to be described in a visual discrimination. OBJECTIVE: The objective of the study was to profile a range of psychoactive agents (glutamatergic, dopaminergic, and cholinergic agonists and antagonists) known to be important in cognitive processing on visual discrimination performance using a touch sensitive computer monitor. METHODS: Male Lister Hooded rats were trained to a stable level of performance in a simple visual discrimination. In Experiment 1, the effect of MK-801, phencyclidine, memantine, dextroamphetamine sulphate (D-amphetamine) and scopolamine was assessed. In Experiment 2, the stimuli were blended together resulting in a perceptually more demanding discrimination and a reduction in accuracy. The rats used in Experiment 1 were then retested with these 'morphed' stimuli under the influence of the above compounds. RESULTS: MK-801, PCP, and D-amphetamine induced selective deficits in accuracy in both versions of the task. In contrast, scopolamine and memantine produced non-selective deficits in accuracy. Morphing the stimuli reduced accuracy, but did not alter the observed behavioural profile after compound administration. CONCLUSION: These data improve our understanding of the basic neuropharmacology of a visual discrimination in cognitive tests employing touchscreens and will aid in the interpretation of pharmacological studies with more cognitively demanding methodologies.

Job exposure matrices in industry.

Job exposure matrices (JEM) are designed to link information on occupation with information on exposure to specific workplace hazards. In spite of some limitations, JEM are particularly useful in large retrospective epidemiological studies. The development of JEM designed for a company or an industrial sector have a more specific field of application than JEM used in population-based studies, and can therefore be based on a more detailed classification of occupations and better exposure information. This article reviews on-going research related to the design of JEM in support of industry-based studies. The review covers design aspects related to the structure of JEM, and specially the four main axes that may produce differences on exposure characteristics: agent (exposure), job, time and place. Attention has also been given to the different sources of information on exposure, the characteristics of the exposure and the validation of exposure estimates.

Development and use of a welding process exposure matrix in a historical prospective study of lung cancer risk in European welders.

A welding process exposure matrix has been developed relating 13 welding process-welded metal combinations to average exposure levels for total welding fumes, total chromium, chromium (VI) and nickel. Quantitative estimates were derived from consultation of literature sources and of some company data. This matrix was applied to the welding histories of 11,092 welders in the framework of an IARC multicentre study. When detailed welding history was not available at the individual level the average company welding practice profile was applied. No dose-response relationship emerged for lung cancer risk with cumulative dose of the carcinogens chromium (VI) and nickel for stainless steel welders. Dilution of the dose-response relationship could result from between-plant and within-plant variability, and exposure in jobs not accounted for in the study, but not from the partial use of company versus individual data. It is also possible that there is no increased risk related to chromium and nickel exposure in this group of workers. Matrix exposure estimates would need to be validated and the matrix possibly refined by comparison with a variety of comprehensive welding exposure data sets.

The risk of lung cancer from asbestos among Swedish construction workers: self-reported exposure and a job exposure matrix compared.

A total of 719 lung cancers were identified in a follow-up of 135,000 Swedish construction workers interviewed during 1971-1974 by occupational health nurses as part of a routine health check-up. These were analysed in a matched case-control study nested within this cohort, to compare different methods of characterizing exposure to asbestos. Self-reported exposure was contrasted with a job exposure matrix (JEM) of five levels of exposure intensity, applied to the job at the time of health check-up. Smoking adjusted odds ratios were computed and the JEM performed better than self-reported exposure, in being able to discriminate high risk subgroups. The same pattern was evident in a parallel analysis of 41 mesotheliomas. However both measures appeared subject to misclassification, and the question put seemed to pick up the use of asbestos cement products more effectively than asbestos insulation products. It is concluded that a simple JEM can be more reliable than a simple question, but that both should be much more detailed, to take account of different types of asbestos exposure and their variation over time.

Lung cancer mortality among workers in the European production of man-made mineral fibers--a Poisson regression analysis.

One hundred and eighty-one lung cancer deaths among workers during 301,085 person-years in European man-made mineral fiber production between 1930-1955 and 1982 were analyzed according to Poisson regression models including age, calendar period, country, and exposure variables. Time since first employment was the variable most strongly associated with lung cancer risk in both the rock-slag wool and glass wool subcohorts. Workers in the early technological phase were at higher risk than those in other categories, particularly in rock-slag wool production. No clear trend with duration of employment was suggested. No major changes occurred in the interpretation of the results when workers with less than one year of employment or less than 20 years since first exposure were excluded. The original results, based on analyses for standardized mortality ratios, were confirmed, and workers with a short duration of employment or a short time since first employment did not need to be excluded from the analysis.

A historical prospective study of European stainless steel, mild steel, and shipyard welders.

A multicentre cohort of 11,092 male welders from 135 companies located in nine European countries has been assembled with the aim of investigating the relation of potential cancer risk, lung cancer in particular, with occupational exposure. The observation period and the criteria for inclusion of welders varied from country to country. Follow up was successful for 96.9% of the cohort and observed numbers of deaths (and for some countries incident cancer cases) were compared with expected numbers calculated from national reference rates. Mortality and cancer incidence ratios were analysed by cause category, time since first exposure, duration of employment, and estimated cumulative dose to total fumes, chromium (Cr), Cr VI, and nickel (Ni). Overall a statistically significant excess was reported for mortality from lung cancer (116 observed v 86.81 expected deaths, SMR = 134). When analysed by type of welding an increasing pattern with time since first exposure was present for both mild steel and stainless steel welders, which was more noticeable for the subcohort of predominantly stainless steel welders. No clear relation was apparent between mortality from lung cancer and duration of exposure to or estimated cumulative dose of Ni or Cr. Whereas the patterns of lung cancer mortality in these results suggest that the risk of lung cancer is higher for stainless steel than mild steel welders the different level of risk for these two categories of welding exposure cannot be quantified with precision. The report of five deaths from pleural mesothelioma unrelated to the type of welding draws attention to the risk of exposure to asbestos in welding activities.

A mortality follow-up study of pottery workers: preliminary findings on lung cancer.

The possible association between exposure to low levels of silica and lung cancer was investigated by following up pottery workers included in a survey conducted in 1970-71 of respiratory disease among such workers. The initial results show that, among men under the age of 60 at the time of the original survey, mortality has been similar to that expected, but that there was an excess of lung cancer of over 30% even after allowance had been made for cigarette smoking and place of residence. There were no particular excesses of lung cancer by product group or job group. However, there was some indication that lung cancer risk increased with estimated cumulative exposure to respirable quartz. These findings do suggest an association between lung cancer and the low levels of silica found in potteries, and the follow-up will therefore be continued and a more detailed analysis of the data carried out.

Lung cancer among glass fibre production workers: a case-control study.

A cohort study among 4734 employees at an English glass fibre plant previously reported no excess of lung cancer mortality either overall or when examined in broad occupational groups. To investigate occupation in more detail, and to test the hypothesis that processes producing or using finer (respirable) fibres may be related to a higher risk of lung cancer, a nested case-control study has now been carried out. Included are 73 cases of lung cancer and 506 matched controls, for whom jobs held and processes worked on have been blindly recorded in more detail than for the cohort study. Workers known to have been employed on processes containing respirable fibres had a relative risk of lung cancer of 1.2 (95% confidence interval 0.7-2.0) compared with other workers. There was no evidence of a relationship of lung cancer to fibre diameter, duration of exposure, or time since first exposure. The results by broad occupational group were similar to those of the cohort study, and although some of the many detailed occupational categories examined had significantly raised relative risks, these did not appear to be related to exposure to respirable glass fibre. Although the study has not indicated a differential risk of lung cancer among workers exposed to finer diameter glass fibres, the exposure levels were low and the number of cases small.

Estimates of the proportion of lung cancer attributable to occupational exposure.

The proportion of lung cancer due to occupational exposure has been estimated by computing the attributable risk in the population (ARp) from various case-control studies. Different criteria have been used in including occupational exposures from published studies: (i) exposure to lung carcinogens according to a job-exposure matrix approach; (ii) occupations in which an increased risk of lung cancer has been established; (iii) occupations in which an increased risk of lung cancer has been suggested; and (iv) occupations associated with a statistically significant increase of lung cancer. Only studies in which the confounding effect of smoking was controlled for have been included. We found a wide variability of ARp estimates, mainly due to the different geographical locations of the studies, while they seem to be only moderately affected by the different criteria of inclusion of the relevant occupational exposures. Studies using job-exposure matrices gave ARps ranging from 0.6% to 35%. When a list of recognized carcinogenic exposures was used for the selection of the relevant occupations, the estimates varied between 2.4% and 40%. From the studies reviewed it also appears that tobacco smoking has a very limited confounding effect. Various limitations of the exercise are discussed.

Updating lung cancer mortality among a cohort of man-made mineral fibre production workers in seven European countries.

A historical cohort of 21,967 workers ever employed in 13 European factories manufacturing various types of man-made mineral fibres (MMMF) was observed until 1982. Overall there were 2719 deaths (standardised mortality ratio (SMR) = 111) of which 189 were from lung cancer (SMR = 125). For the glasswool and rockwool/slagwool production subcohorts the lung cancer SMRs rose with time since first exposure, exceeding 170 for the period of 30 or more years. Adjustment for regional variations in mortality substantially reduced the excess in the glasswool group, but not in the rockwool/slagwool. In neither subgroup was there any relationship of lung cancer mortality with length of employment. During the early years of rockwool/slagwool production there was the potential for much higher fibrous dust exposure than at present, because of the absence of dust suppressing oil and/or the use of a batch production process. In addition slag was widely used as a raw material. Amongst workers employed during the early phase, there were 10 lung cancer deaths giving SMRs of 270 and 244 for the periods 20-29 and 30 or more years since first exposure. This group accounts for most of the absolute excess of lung cancer for the rockwool/slagwool plants.

The man-made mineral fiber European historical cohort study. Extension of the follow-up.

The study concentrated on 21,967 workers producing rock wool/slag wool, glass wool or continuous filament in 13 European factories. The expected deaths and incident cancer cases were derived from multiplying the accumulated person-years by national reference rates across sex, age, and calendar-year strata, correction factors for regional lung cancer mortality also being used. Exposure assessment was based on the results of a historical environmental investigation reported elsewhere. There were 189 deaths (151.2 expected), and for rock-wool/slag-wool and glass-wool workers the standardized mortality ratios for lung cancer showed a pattern of increasing mortality with time since first exposure but not duration of employment. There was an excess of lung cancer among rock-wool/slag-wool workers employed during an early technological phase before the introduction of dust-suppressing agents, and fiber exposure, either alone on in combination with other exposures, may have contributed to the elevated risk. No excess of the same magnitude was evident for glass-wool production, and the follow-up of the continuous filament cohort was too short to allow for an evaluation of possible long-term effects. There was no evidence of an increased risk for pleural tumors or nonmalignant respiratory diseases.

Lung cancer mortality in a cohort of English foundry workers.

A cohort of males who started work between 1946 and 1965 inclusive in nine English steel foundries and who worked in these foundries at least one year has been followed prospectively until 1978. Mortality from lung cancer was significantly raised among workers employed in the foundry and fettling shop areas (standardized mortality ratios 142 and 173, respectively). Most occupational categories in these two areas had more lung cancer deaths than expected, but the standardized mortality ratios were the largest for the furnace bricklayers, fettlers, and heat treatment furnacemen. There was some evidence of risk increasing with length of employment. There were marked differences in the standardized mortality ratio for lung cancer between study foundries. By year of entry the lung cancer risk was fairly constant, in contrast to the improvement in mortality from diseases of the respiratory system over the same period.

The impact of government insurance on a psychiatric clinic.

This paper considers the impact of a state medical insurance system on the structure of psychiatric services. The tendency of the upper socioeconomic classes to use private practitioners, and the lower classes to use public clinics, is examined before and after the imposition of the medical insurance system in Quebec in 1970. Data from one public clinic reveal a significant rise in the socioeconomic status of patients after Medicare. Alternative interpretations for the change in the clinic population are explored.