The two-stage clonal expansion model in occupational cancer epidemiology: Results from three cohort studies

Copyright © 2010 by the BMJ Publishing Group Ltd. All rights reserved.Objectives: The objective of this work was to apply the two-stage clonal expansion model, with the intention to expand the literature on epidemiological applications of the model and demonstrate the feasibility of incorporating biologically based modelling methods into the widely used retrospective cohort study. Methods: The authors fitted the two-stage clonal expansion model model to three occupational cohort studies: (1) a cohort of textile workers exposed to asbestos and followed for lung cancer mortality; (2) a cohort of diatomaceous earth workers exposed to silica and also followed for lung cancer mortality; and (3) a cohort of automotive manufacturing workers exposed to straight metalworking fluid (MWF) and followed for larynx cancer incidence. The model allowed the authors to estimate exposure effects in three stages: cancer initiation (early effects), promotion or malignant transformation (late effects). Results: In the first cohort, the authors found strong evidence for an early effect of asbestos on lung cancer risk. Findings from analyses of the second cohort suggested early and less evidently late effects of silica on lung cancer risk. In the MWF (third) cohort, there was only weak evidence of straight MWF exposure effects on both early and late stages. The authors also observed a late birth cohort effect on larynx cancer risk. Conclusions: The findings for asbestos and silica were essentially confirmatory, supporting evidence for their early effects on lung cancer from a large body of literature. The effect of straight MWF on larynx cancer was less clear.This work was supported by a grant from the US National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention,R01-OH03575, and a grant from the Centers for Disease Control and Prevention/ Association of Teachers of Preventive Medicine number TS 0699

The symmetry spectrum in a hybridising, tropical group of rhododendrons

Many diverse plant clades possess bilaterally symmetrical flowers and specialised pollination syndromes, suggesting that these traits may promote diversification. We examined the evolution of diverse floral morphologies in a species‐rich tropical radiation of Rhododendron. We used restriction‐site associated DNA sequencing on 114 taxa from Rhododendron sect. Schistanthe to reconstruct phylogenetic relationships and examine hybridisation. We then captured and quantified floral variation using geometric morphometric analyses, which we interpreted in a phylogenetic context. We uncovered phylogenetic conflict and uncertainty caused by introgression within and between clades. Morphometric analyses revealed flower symmetry to be a morphological continuum without clear transitions between radial and bilateral symmetry. Tropical Rhododendron species that began diversifying into New Guinea c. 6 million years ago expanded into novel floral morphological space. Our results showed that the evolution of tropical Rhododendron is characterised by recent speciation, recurrent hybridisation and the origin of floral novelty. Floral variation evolved via changes to multiple components of the corolla that are only recognised in geometric morphometrics with both front and side views of flowers

The Cardiorespiratory Response of Qigong Performed at Different Intensities

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Charge Modulation at the Surface of High-T_c Superconductors

It is shown here that surfaces of high-temperature superconductors are covered by dipole layers. The charge density modulation is induced by the local suppression of the gap function at the surface. This effect is studied in the framework of the Ginzburg-Landau theory and crucially depends on the appropriate boundary conditions. Those are derived from Gor'kov's equations for a d-wave pairing symmetry. Within this framework the structure of the surface dipole layer is determined. The contribution of this charging to a lens-effect of superconducting films with holes, which has been studied in recent experiments, is discussed.Comment: 10 pages, RevTeX, 5 postscript figure

The precautionary principle in environmental science.

Environmental scientists play a key role in society's responses to environmental problems, and many of the studies they perform are intended ultimately to affect policy. The precautionary principle, proposed as a new guideline in environmental decision making, has four central components: taking preventive action in the face of uncertainty; shifting the burden of proof to the proponents of an activity; exploring a wide range of alternatives to possibly harmful actions; and increasing public participation in decision making. In this paper we examine the implications of the precautionary principle for environmental scientists, whose work often involves studying highly complex, poorly understood systems, while at the same time facing conflicting pressures from those who seek to balance economic growth and environmental protection. In this complicated and contested terrain, it is useful to examine the methodologies of science and to consider ways that, without compromising integrity and objectivity, research can be more or less helpful to those who would act with precaution. We argue that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results. There is a complicated feedback relation between the discoveries of science and the setting of policy. While maintaining their objectivity and focus on understanding the world, environmental scientists should be aware of the policy uses of their work and of their social responsibility to do science that protects human health and the environment. The precautionary principle highlights this tight, challenging linkage between science and policy

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

Multimodal freight transportation: sustainability challenges

Due to globalization in trade, the development of multimodal cargo shipments and the related transport needs have created a range of challenges. Interestingly, sustainability of multimodal freight transportation is still subject to minor consideration, on the grounds that economic interests are frequently positioned much higher than social or environmental objectives. This proposed research plan is needed to assess whether and to what extent the multimodal freight system is achieving the results in the sustainability dimensions: economic, social and environmental. Thus, it will carry out a critical appraisal of the multimodal freight transportation sector to provide an up-to-date knowledge on the sustainability challenges and the potential solutions through doctoral research. This paper structured to present a review of existing literature on freight transportation and multimodal freight transport highlighting the sustainability concerns with multimodal freight transport systems. It also highlights the gaps in knowledge with a justification on the need to address these gaps for the system to function optimally. It also covers the methodology that would be applied and the sources of data that would be reviewed to ensure the aim and objectives are clearly addressed. The paper concludes by discussing the significance of the expected findings in the light of sustainability in multimodal freight transport to the academia, policy makers and the freight transportation industry

A hazardous substance exposure prevention rating method for intervention needs assessment and effectiveness evaluation: the Small Business Exposure Index

Aims This paper describes the refinement and adaptation to small business of a previously developed method for systematically prioritizing needs for intervention on hazardous substance exposures in manufacturing worksites, and evaluating intervention effectiveness. Methods We developed a checklist containing six unique sets of yes/no variables organized in a 2 × 3 matrix of exposure potential versus exposure protection at three levels corresponding to a simplified hierarchy of controls: materials, processes, and human interface. Each of the six sets of indicator variables was reduced to a high/moderate/low rating. Ratings from the matrix were then combined to generate an exposure prevention \u27Small Business Exposure Index\u27 (SBEI) Summary score for each area. Reflecting the hierarchy of controls, material factors were weighted highest, followed by process, and then human interface. The checklist administered by an industrial hygienist during walk-through inspection (N = 149 manufacturing processes/areas in 25 small to medium-sized manufacturing worksites). One area or process per manufacturing department was assessed and rated. A second hygienist independently assessed 36 areas to evaluate inter-rater reliability. Results The SBEI Summary scores indicated that exposures were well controlled in the majority of areas assessed (58% with rating of 1 or 2 on a 6-point scale), that there was some room for improvement in roughly one-third of areas (31% of areas rated 3 or 4), and that roughly 10% of the areas assessed were urgently in need of intervention (rated as 5 or 6). Inter-rater reliability of EP ratings was good to excellent (e.g., for SBEI Summary scores, weighted kappa = 0.73, 95% CI 0.52–0.93). Conclusion The SBEI exposure prevention rating method is suitable for use in small/medium enterprises, has good discriminatory power and reliability, offers an inexpensive method for intervention needs assessment and effectiveness evaluation, and complements quantitative exposure assessment with an upstream prevention focus