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Relative bioavailability of lead from mining waste soil in rats.

The purposes of this study were to determine the extent of absorption of lead (Pb) in mining waste soil from Butte, Montana, and to investigate the effect of mining waste soil dose (g soil/day) on tissue lead concentrations. Young, 7- to 8-week-old male and female Sprague-Dawley rats (5/sex/group) were given mining waste soil that contained 810 or 3908 ppm lead mixed in a purified diet (AIN-76) at four different dose levels (0.2, 0.5, 2, and 5% dietary soil) for 30 consecutive days. Standard groups included untreated controls and dosed feed soluble lead acetate groups (1, 10, 25, 100, and 250 micrograms Pb/g feed). The test soil dose levels bracketed a pica child's soil exposure level and the lead acetate concentrations bracketed the test soil dose levels of lead. Liver, blood, and femur were analyzed for total lead concentration using graphite furnace atomic absorption spectroscopy. Clinical signs, body weight, food consumption, and liver weights for test soil and standard groups were similar to control. Tissue lead concentrations from test soil animals were significantly lower than the tissue concentrations for the lead acetate group. Relative percentage bioavailability values, based on lead acetate as the standard, were independent of the two different test soils, dose levels, and sex and were only slightly dependent on the tissue (blood > bone, liver). Mean relative percentage bioavailability values of lead in the Butte mining waste soil were 20% based on the blood data, 9% based on the bone data, and 8% based on the liver data. The results of this study will provide the information needed to determine the significance of lead exposure from Butte soils in assessing human health risks as part of the Superfund Remedial Investigation/Feasibility Study process.

Animals

Regulatory implications of airborne respirable free silica variability in underground coal mines.

The respirable dust standard for respirable free crystalline silica in underground coal mines is expressed as milligrams per cubic meter (mg/m3) of respirable dust and is determined by the silica content of the dust. The Mine Safety and Health Administration (MSHA) regulates silica exposure by determining and enforcing compliance with the respirable dust standard for each active mine section. The MSHA strategy for regulation is examined in the context of respirable free crystalline silica and dust data. Deficiencies of the strategy include the same enforcement efforts regardless of compliance history, inappropriate treatment of data, and emphasis on short-term variability of silica content. These deficiencies result in inadequate enforcement in chronically dusty mines, "game playing" with optional samples, and an overall approach that does not focus on the long-term impact of silica exposure on lung health. Alternative approaches include enforcement efforts proportional to compliance history, use of a moving average silica content, and more statistically sound approaches to data interpretation.

Air Pollutants, Occupational

Government regulation of occupational safety: underground coal mine accidents 1973-75.

The purpose of this paper is to determine the influence of federal mine safety inspections on underground coal mine accidents. An economic incentives model is developed to relate federal enforcement activities to accident rates. The determinants of accident rates are analyzed for 535 coal mines during the period 1973-75. Estimates based on these data when applied to the model indicate that increasing inspections by 25 per cent would have produced a 13 per cent decline in fatal accidents and an 18 per cent decline in disabling accidents.

Accident Prevention

A retrospective epidemiological study of mortality at a large western copper smelter.

In comparing the smelter with the mine, concentrator, and State of Utah, it was found that they were very similar in the percentage of deaths due to all causes except lung cancer; 7.0% of all deaths at the smelter were due to lung cancer compared to 2.2% for the mine, 2.2% for the concentrator, and 2.7% for the state. The excess at the smelter was statistically significant. Approximate age-adjusted death rates were obtained for various causes of death. The rates for the smelter are higher than for the mine and the state for lung cancer and for all causes combined. The average age at death for smelter workers is nearly the same as for mine employees, even for those who died of lung cancer. Smoking data was examined and there was no indication of a smoking synergism. Cumulative exposure indices for SO2, H2SO4 mist, As, Pb, and Cu were computed for each deceased smelter worker based n the length of time he worked in each of 12 major areas. Those who died of lung cancer had the highest average exposure index for all five constituents. Stack emission data showed much higher levels of As and SO2 prior to 1959.

Adult

Epidemiological data on US coal miners' pneumoconiosis, 1960 to 1988.

OBJECTIVES: Statistics on prevalence of pneumoconiosis among working underground coal miners based on epidemiologic data collected between 1960 and 1988 are presented. The main intent was to examine the time-related trend in prevalence, particularly after 1969, when substantially lower dust levels were mandated by federal act. METHODS: Data from studies undertaken between 1960 and 1968 were collected and compared. Information for the period 1969 to 1988 was extracted from a large ongoing national epidemiologic study. Tenure-specific prevalence rates and summary statistics derived from the latter data for four consecutive time intervals within the 19-year period were calculated and compared. RESULTS: The results indicate a reduction in pneumoconiosis over time. The trend is similar to that seen in a large radiologic surveillance program of underground miners operated concurrently. CONCLUSIONS: Although such factors as x-ray reader variation, changes in x-ray standards, and worker self-selection for examination may have influenced the findings to some extent, adjusted summary rates reveal a reduction in prevalence concurrent with reductions in coal mine dust levels mandated by federal act in 1969.

Adult

Dietary determinants of lung-cancer risk: results from a case-control study in Yunnan Province, China.

The relation between diet and lung cancer was studied among male residents of a mining community in Yunnan Province. After obtaining food frequency data from subjects or proxies, we compared diets of 428 cases, aged 35-74 years, and 1,011 age-matched controls. Cases tended to consume slightly more rice, but less protein-rich foods (i.e., bean curd, meat, eggs) and vegetables than did controls. The relative risks of lung cancer across increasing quartiles of meat (i.e., pork) consumption, for example, were 1.00, 0.67, 0.72 and 0.46 (p for trend less than 0.01). The relative risks of lung cancer across increasing quartiles of consumption of dark-green, leafy vegetables were 1.00, 0.62, 0.52 and 0.41 (p for trend less than 0.01). Although specific dietary constituent(s) responsible for the protective effect of vegetable consumption could not be identified, carotenoids other than beta-carotene, or compounds in cruciferous or Allium vegetables, are possibilities.

Animals

The assessment of health policy changes using the time-reversed crossover design.

The time-reversed crossover design is a quasi-experimental design which can be applied to evaluate the impact of a change in health policy on a large population. This design makes use of separate sampling and analysis strategies to improve the validity of conclusions drawn from such an evaluation. The properties of the time-reversed crossover design are presented including the use of stratification on outcome in the sampling stage, which is intended to improve external validity. It is demonstrated that, although this feature of the design introduces internal validity threats due to regression toward the mean in extreme-outcome strata, these effects can be measured and eliminated from the test of significance of treatment effects. Methods for within- and across-stratum estimation and hypothesis-testing are presented which are similar to those which have been developed for the traditional two-period crossover design widely used in clinical trials. The procedures are illustrated using data derived from a study conducted by the United Mine Workers of America Health and Retirement Funds to measure the impact of cost-sharing on health care utilization among members of its health plan.

Costs and Cost Analysis

Social cost of land mines in four countries: Afghanistan, Bosnia, Cambodia, and Mozambique.

OBJECTIVES: To document the effects of land mines on the health and social conditions of communities in four affected countries. DESIGN: A cross design of cluster survey and rapid appraisal methods including a household questionnaire and qualitative data from key informants, institutional reviews, and focus groups of survivors of land mines from the same communities. SETTING: 206 communities, 37 in Afghanistan, 66 in Bosnia, 38 in Cambodia, and 65 in Mozambique. SUBJECTS: 174,489 people living in 32,904 households in the selected communities. MAIN OUTCOME MEASURES: Effects of land mines on food security, residence, livestock, and land use; risk factors: extent of individual land mine injuries; physical, psychological, social, and economic costs of injuries during medical care and rehabilitation. RESULTS: Between 25% and 87% of households had daily activities affected by land mines. Based on expected production without the mines, agricultural production could increase by 88-200% in different regions of Afghanistan, 11% in Bosnia, 135% in Cambodia, and 3.6% in Mozambique. A total of 54,554 animals was lost because of land mines, with a minimum cash value of $6.5m, or nearly $200 per household. Overall, 6% of households (1964) reported a land mine victim; a third of victims died in the blast. One in 10 of the victims was a child. The most frequent activities associated with land mine incidents were agricultural or pastoral, except in Bosnia where more than half resulted from military activities, usually during patrols. Incidences have more than doubled between 1980-3 and 1990-3, excluding the incidents in Bosnia. Some 22% of victims (455/2100) were from households reporting attempts to remove land mines; in these households there was a greatly increased risk of injury (odds ratio 4.2 and risk difference 19% across the four countries). Lethality of the mines varied; in Bosnia each blast killed an average of 0.54 people and injured 1.4, whereas in Mozambique each blast killed 1.45 people and wounded 1.27. Households with a land mine victim were 40% more likely to experience difficulty in providing food for the family. Family relationships were affected for around one in every four victims and relationships with colleagues in 40%. CONCLUSIONS: Land mines seriously undermine the economy and food security in affected countries; they kill and maim civilians at an increasing rate. The expense of medical care and rehabilitation add economic disability to the physical burden. Awareness of land mines can be targeted at high risk attitudes, such as those associated with tampering with mines.

Adolescent

Demixer: a probabilistic generative model to delineate different strains of a microbial species in a mixed infection sample.

MOTIVATION: Multi-drug resistant or hetero-resistant tuberculosis (TB) hinders the successful treatment of TB. Hetero-resistant TB occurs when multiple strains of the TB-causing bacterium with varying degrees of drug susceptibility are present in an individual. Existing studies predicting the proportion and identity of strains in a mixed infection sample rely on a reference database of known strains. A main challenge then is to identify de novo strains not present in the reference database, while quantifying the proportion of known strains. RESULTS: We present Demixer, a probabilistic generative model that uses a combination of reference-based and reference-free techniques to delineate mixed infection strains in whole genome sequencing (WGS) data. Demixer extends a topic model widely used in text mining to represent known mutations and discover novel ones. Parallelization and other heuristics enabled Demixer to process large datasets like CRyPTIC (Comprehensive Resistance Prediction for Tuberculosis: an International Consortium). In both synthetic and experimental benchmark datasets, our proposed method precisely detected the identity (e.g. 91.67% accuracy on the experimental in vitro dataset) as well as the proportions of the mixed strains. In real-world applications, Demixer revealed novel high confidence mixed infections (101 out of 1963 Malawi samples analysed), and new insights into the global frequency of mixed infection (2% at the most stringent threshold in the CRyPTIC dataset) and its significant association to drug resistance. Our approach is generalizable and hence applicable to any bacterial and viral WGS data. AVAILABILITY AND IMPLEMENTATION: All code relevant to Demixer is available at https://github.com/BIRDSgroup/Demixer.

Mycobacterium tuberculosis

[Structure and dynamics of systemic organization of the cardiorespiratory function during the adaptation process of miners to occupational factors in deep coal mines].

Characteristics of the systems organization of the cardiorespiratory function were analyzed in miners of different age. The findings were compared to the data on labour turnover, work efficiency and the rate of cardiovascular diseases. It is indicated that an initial adaptation period in deep coal mines was accompanied by the stress of vegetative regulatory mechanisms, significant labour turnover and low work efficiency of miners. The stage of resistant adaptation was characterized by raising functional flexibility, decrease in labour turnover and elevation of the degree of professional work capacity. For miners aged 35 and older the process of systems restructuring of vegetative functions was followed by the decrease in labour efficiency and significant growth of cardiovascular diseases.

Adaptation, Physiological

Progression of irregular opacities in asbestos miners.

All white and mixed race men who were employed in South African asbestos mines and mills between 30 November 1970 and 30 November 1975 were studied. The men who had two radiographs available, the first taken some time between the above two dates and the latest available radiograph which had to be at least two years after the first one numbered 1454: 793 continued exposure after the first radiograph and 661 did not. The films were read by a panel of three readers. Data available included age, years of exposure to asbestos and other mining, intensity of exposure to asbestos and other dust, and smoking habit. Progression was expressed as the difference between the average readings of radiograph 2--radiograph 1 in minor categories per year of irregular opacities. Changes in pleural abnormality were also measured. No differences of progression in the profusion or change in size of the irregular opacities were found between the two groups or in the number of zones affected. "New attacks" appeared equally frequently between the two groups. No difference in the change in extent of any type of pleural change was seen. It appears that once a dose of asbestos sufficient to initiate the disease has been retained it is inexorably progressive.

Asbestos

Lung cancer mortality among U.S. uranium miners: a reappraisal.

This report examines lung cancer mortality among a cohort of white underground uranium miners in the Colorado plateau and is based on mortality follow-up through December 31, 1977. The analytic methods represent a miner's annual age-specific lung cancer mortality rate as the (unspecified) rate among nonsmoking men born at the same time and with no mining history, multiplied by the relative risk factor R. This factor depends on the miner's total exposures to radon daughters [in working level months (WLM) and to cigarettes (in packs), accumulated from start of exposure until 10 years before his current age. Among those examined, the relative risk function giving the highest likelihood of the data was R = (1 + 0.31 X 10(-2) WLM)(1 + 0.51 X 10(-3) packs). This multiplicative function specifies that ratios of mortality rates for miners versus nonminers with similar age and smoking characteristics do not depend on smoking status. By contrast, differences between miners' and nonminers' mortality rates are substantially higher for smokers than for nonsmokers. The data rejected (P = .01) several additive functions for R that specify relative risk as a sum of components due to radiation and to cigarette smoking. Cumulative exposures to both radiation and cigarettes gave better fits to the data than did average annual exposure rates. Age at start of underground mining had no effect on risk, after controlling for age at lung cancer death, year of birth, and cumulative radiation and smoking exposures.

Adult

Evidence for an amphibole asbestos threshold exposure for asbestosis assessed by autopsy in South African asbestos miners.

In an attempt to determine whether there exists a threshold asbestos dose below which asbestosis does not occur, data on 807 men who had worked on amphibole asbestos mines and undergone autopsy were analysed. When exposure was expressed as fibre-years no asbestosis was found at autopsy when exposure was up to 2 fibre-years, even after 31-45 years of residence time. In the group exposed to greater than 2-5 fibre-years asbestosis was found. When exposure was expressed as average fibre concentration asbestosis occurred below 2 fibres per ml (f ml-1) and the prevalence increased with residence time. In conclusion, if a threshold dose for asbestosis does exist it is at approximately 2 fibre-years if off-shift exposure is ignored.

Adolescent

A medical information system for the Norwegian continental shelf (MICS).

The Norwegian offshore oil industry is rapidly expanding. The health services for this industry have also developed quickly. An EDB-based medical registration system for the Norwegian continental shelf (MICS) has been planned in support of health services, health authorities and researchers. This information system will consist of an injury/disease register and a register of the population on the Norwegian continental shelf. The injury/disease register will comprise inter alia reported cases of occupational injury, occupational disease, notifiable infectious disease and summary data about rate of utilisation of ambulance transport and health services offshore. The system will be administered by the Norwegian Directorate of Health in cooperation with the Norwegian Oil Directorate. MICS will provide new possibilities for epidemiological studies of health and disease among the employees in the oil industry.

Data Collection

Target and biomarker exploration portal for drug discovery.

MOTIVATION: The discovery of novel drug targets and precision biomarkers remains a major challenge in drug development, with traditional differential expression analysis often overlooking key regulatory proteins. Here, we present a novel, web-based bioinformatics tool, the Target and Biomarker Exploration Portal (TBEP), designed to accelerate the drug discovery process by integrating large-scale biomedical data with network analysis techniques. RESULTS: TBEP harnesses machine-learning approaches to mine and combine multimodal datasets, including human genetics, functional genomics, and protein-protein interaction networks, to decode causal disease mechanisms and uncover novel therapeutic targets and precision biomarkers for specific phenotypes. A unique feature of the tool is its ability to process large-scale data in real-time, facilitated by an efficient cloud-based architecture. Additionally, the tool incorporates an integrated large language model (LLM), which assists researchers in exploring and interpreting complex biological relationships within the generated networks and multi-omics data using natural language (English). By offering an intuitive, interactive interface, the LLM enhances the exploration of biological insights, making it easier for scientists to derive actionable conclusions. This powerful integration of network analysis, multi-omics data, and LLM provides a robust framework for accelerating the identification of novel drug targets. AVAILABILITY AND IMPLEMENTATION: The tool is publicly available at https://tbep.missouri.edu. The source code, documentation and installation instructions are available at GitHub repository: https://github.com/mizzoudbl/tbep.

Drug Discovery