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Jim Vincent was truly a modern-day Renaissance man. An accomplished jazz and classical pianist and composer, who performed with some of Europe's top improvisers, making appearances at major jazz festivals and in BBC broadcast concerts. However, his legacy lies elsewhere. He graduated in physics at the University of Durham with first-class honours in 1962, proceeding to a PhD in 1966. After jobs in academia and industry, in 1979 he became Head of Physics at the Institute of Occupational Medicine (IOM) in Edinburgh. He took over a research team that had been working on sampling of dusts for studies of the risks of lung disease in coal miners and other workers. Jim’s team defined the sampling criteria for the aerosol that can be inhaled into the nose or mouth, in collaboration with other European scientists and, in 1986, published the description and experimental characterisation of the IOM Inhalable Dust sampler. This sampler has been recommended for measuring dust exposure in workplaces around the world. Its design, which the IOM patented, has remained essentially unchanged for almost 40 years. Jim’s academic and professional achievements spanned an enormous breadth, but his legacy is his contribution to the way we sample hazardous aerosols.

Wearing a respirator is generally the most convenient individual intervention against ambient particulate matter (PM), and therefore there has been considerable research into its effectiveness. However, the effects of respirator intervention under different PM concentration settings have been insufficiently elucidated. We conducted a randomized, blinded, crossover intervention study in four representative cities in China in which 128 healthy university students spent 2 h walking along a busy road wearing either a real or a sham respirator and then spent the next 5 h indoors away from traffic pollution. Lung function, blood pressure, and heart rate variability were continuously measured throughout the visit. Linear mixed-effect models were fitted to evaluate the protective effects of respirator intervention on the cardiopulmonary indicators. Results showed that the beneficial effects of respirator intervention were only occasionally significant at specific time points or in specific cities or in selected parameters. Overall, respirator intervention was associated with reduced SBP (6.2 vs. 11.5 mmHg compared to baseline, p

Background People increase their risk of melanoma unless they are protected from the harmful effects of sun exposure during childhood and adolescence. We aimed to assess the feasibility of a three-component sun protection intervention- presentation, booklet, and text messages - and trial parameters. Methods This feasibility wait-list controlled trial was conducted in the United Kingdom in 2018. Students aged 13-15 years were eligible. Feasibility outcomes were collected for recruitment rates; data availability rates for objective measurements of melanin and erythema using a Mexameter and self-reported sunburn occurrences, severity and body location, tanning, sun protection behaviours and SSE collected before (baseline) and after the school summer holidays (follow-up); intervention reach, adherence, perceived impact and acceptability. Quantitative data were analysed using descriptive statistics; qualitative data were analysed thematically. Results Five out of eight schools expressing an interest in participating with four allocated to act as intervention and one control. Four parents/carers opted their child out of the study. 487 out of 724 students on the school register consented to the study at baseline (67%). 385 were in intervention group schools. Objective skin measurements were available for 255 (66%) of the intervention group at baseline and 237 (61%) of the group at follow up. Melanin increased; erythema decreased. Complete self-report data were available for 247 (64%) students in the intervention group. The number of students on the school register who attended the presentation and given the booklet was 379 (98%) and gave their mobile phone number was 155 (40%). No intervention component was perceived as more impactful on sun protection behaviours. Adolescents did not see the relevance of sun protection in the UK or for their age group. Conclusions This is the first study to use a Mexameter to measure skin colour in adolescents. Erythema (visible redness) lasts no more than three days and its measurement before and after a six week summer holiday may not yield relevant or meaningful data. A major challenge is that adolescents do not see the relevance of sun protection and SSE.

Through the APIC-ESTEE (Air Pollution Impacts on Cardiopulmonary Disease in Beijing: An integrated study of Exposure Science, Toxicogenomics and Environmental Epidemiology) project, we have develop...

Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations.

To evaluate its toxicity and clinical efficacy in children with relapsed or refractory leukemia, we performed a phase I trial of 2-chloro-2'-deoxy-adenosine (2-chlorodeoxyadenosine; 2-CDA) given as a continuous 5-day infusion at doses of 3 to 10.7 mg/m2/d. In this study of 31 children with acute leukemia, the only dose-limiting toxicity was myelosuppression. At the highest dose level, three of seven patients developed fatal systemic bacterial or fungal infections. At dose levels above 6.2 mg/m2/d, significant oncolytic responses occurred in all patients. In addition, there was a significant correlation between both the responsiveness by cell type and dose of 2-CDA, such that more oncolytic responses were noted in acute myeloid leukemia (AML) patients than acute lymphoblastic leukemia (ALL) patients (P = .02). Although this was a phase I trial in heavily pretreated patients with refractory disease, two AML patients treated at 5.2 and 10.7 mg/m2/d, respectively, had complete hematologic responses, and one patient treated at 10.7 mg/m2/d had a partial response. In addition, there was a dose-response relationship in all patients with improved cytoreduction of peripheral blast cells at higher doses of 2-CDA. In vitro evaluation of 2-CDA uptake and anabolism by leukemic blast cells from 22 patients demonstrated that 2-chloro-2'-deoxyadenosine (Cld-AMP) and 2-chloro-2'-deoxyadenosine 5'-striphosphate (CldATP) reached concentrations close to steady-state levels within 1 hour. Intracellular nucleotide disappearance rates were high with half-lives of 1.29 and 2.47 hours for CldAMP and CldATP, respectively. This suggests that continuous infusion is necessary to maintain the desired plasma concentration. The results of this study confirm the antileukemic activity of 2-CDA and the lack of prohibitive nonhematologic toxicity. Phase II trials in patients with AML and ALL are warranted.

This chapter provides a general introduction to the assessment of dermal exposure in occupational and environmental epidemiological studies. It describes models that could be used for the assessment. It provides various examples and references.

Our objective was to determine whether there are differences in debrisoquin hydroxylase (P450IID6) activity between American black subjects and white subjects. Phenotype was assigned in a group of 586 unrelated white and black children with use of dextromethorphan as the substrate probe. Restriction fragment length polymorphism analysis of genomic deoxyribonucleic acid (DNA) was performed in a subset of subjects by use of a full length complementary DNA for P450IID6. Thirty-seven of 480 (7.7%) white children were poor metabolizers compared with 2 of 106 (1.9%) black children (p = 0.03). Among 41 white subjects and 18 black subjects, there were significant differences (p < 0.05) in two Xbal DNA restriction fragments; the 44 kb fragment was more common and the 29 kb fragment was less common in black versus white extensive metabolizers. There is a lower prevalence of the debrisoquin poor metabolizer phenotype among American black persons, which could have implications for efficacy or toxicity of drugs metabolized by this enzyme, as well as for racial differences in the prevalence of diseases associated with the debrisoquin oxidative phenotype. Clinical Pharmacology and Therapeutics (1991) 50, 308–313; doi:10.1038/clpt.1991.141

A system that combines the ease of use of a job-exposure matrix while taking into account job-specific data is needed. This study aimed to produce a detailed method for combining interview data with expert assessments for a large population-based case-control study of Parkinson's disease.An interview-administered core questionnaire with a series of questions that triggers substance-specific questionnaires to gather information on key parameters is administered. Using a job-exposure matrix to generate base estimates, assessors can modify this estimate of exposure intensity using worker-specific data such as the use of control measures, reports of substance-specific acute symptoms, and the quantity of material being processed. Detailed guidance for making adjustments to exposure estimates for these modifiers is presented.The method has been partially validated through the use of a comparison of estimates for a separate cohort with previously validated exposure reconstructions. Agreement was high, with a Spearman's rho of 0.89 (P0.01). The results from a quality assurance system employed as part of the methodology show a high degree of repeatability in generated exposure values both over time (Spearman's rho 0.98, P0.01) and between different assessors (Spearman's rho 0.88, P0.01).The method provides detailed quantitative exposure indices for occupational epidemiology. It has particular strengths both in terms of ease and speed of use. It is hoped that it will provide a useful structure for future epidemiologic work.

OBJECTIVE: To study mortality from non-neoplastic diseases among European workers who produce man made vitreous fibres (MMVF). METHODS: 11,373 male workers were studied, who were employed for at least 1 year in the production of rock or slag wool (RSW), glass wool (GW), and continuous filament (CF) in 13 factories from seven European countries. Workers were followed up from the beginning of production, between 1933 and 1950 to 1990-2 and contributed 256,352 person-years of observation. Standardised mortality ratios (SMRs) were calculated with national mortalities for reference; an internal exposure-response analyses based on multivariate Poisson regression models was also conducted. RESULTS: Mortality from bronchitis, emphysema, and asthma was not increased (SMR 1.03, 95% confidence interval (95% CI) 0.82 to 1.28). In RSW workers, there was no overall increase in mortality from non-malignant renal diseases (SMR 0.97, 95% CI 0.36 to 2.11), although there was the suggestion of an increase in risk with duration of employment. Mortality from ischaemic heart disease was not increased overall (SMR 1.03, 95% CI 0.96 to 1.11), but RSW and CF workers with > or = 30 years since first employment had a higher risk. RSW and CF workers showed an increased mortality from external causes, mainly motor vehicle accidents and suicide, which was higher among workers with a short duration of employment. CONCLUSIONS: Mortality from most non-neoplastic diseases does not seem to be related to employment in the MMVF industry. The results on mortality from ischaemic heart disease and non- malignant renal diseases, however, warrant further investigations.

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.