Effect-Directed Analysis of Municipal Landfill Soil Reveals Novel Developmental Toxicants in the Zebrafish Danio rerio

Effect-directed analysis (EDA) is an approach used to identify (unknown) contaminants in complex samples which cause toxicity, using a combination of biology and chemistry. The goal of this work was to apply EDA to identify developmental toxicants in soil samples collected from a former municipal landfill site. Soil samples were extracted, fractionated, and tested for developmental effects with an embryotoxicity assay in the zebrafish Danio rerio. Gas chromatograph mass selective detection (GC-MSD) chemical screening was used to reveal candidate developmental toxicants in fractions showing effects. In a parallel study, liquid chromatography-hybrid linear ion trap Orbitrap mass spectrometry was also applied to one polar subfraction (Hoogenboom et al. J. Chromatogr. A2009, 1216, 510-519). EDA resulted in the identification of a number of previously unknown developmental toxicants, which were confirmed to be present in soil by GC-MS. These included 11H-benzo[b]fluorene, 9-methylacridine, 4-azapyrene, and 2-phenylquinoline, as well as one known developmental toxicant (retene). This work revealed the presence of novel contaminants in the environment that may affect vertebrate development, which are not subject to monitoring or regulation under current soil quality assessment guidelines. © 2011 American Chemical Society

Testing Consumer Rationality using Perfect Graphs and Oriented Discs

Given a consumer data-set, the axioms of revealed preference proffer a binary test for rational behaviour. A natural (non-binary) measure of the degree of rationality exhibited by the consumer is the minimum number of data points whose removal induces a rationalisable data-set.We study the computational complexity of the resultant consumer rationality problem in this paper. This problem is, in the worst case, equivalent (in terms of approximation) to the directed feedback vertex set problem. Our main result is to obtain an exact threshold on the number of commodities that separates easy cases and hard cases. Specifically, for two-commodity markets the consumer rationality problem is polynomial time solvable; we prove this via a reduction to the vertex cover problem on perfect graphs. For three-commodity markets, however, the problem is NP-complete; we prove thisusing a reduction from planar 3-SAT that is based upon oriented-disc drawings

Is mindfulness Buddhist? (and why it matters).

Modern exponents of mindfulness meditation promote the therapeutic effects of "bare attention"--a sort of non-judgmental, non-discursive attending to the moment-to-moment flow of consciousness. This approach to Buddhist meditation can be traced to Burmese Buddhist reform movements of the first half of the 20th century, and is arguably at odds with more traditional Theravāda Buddhist doctrine and meditative practices. But the cultivation of present-centered awareness is not without precedent in Buddhist history; similar innovations arose in medieval Chinese Zen (Chan) and Tibetan Dzogchen. These movements have several things in common. In each case the reforms were, in part, attempts to render Buddhist practice and insight accessible to laypersons unfamiliar with Buddhist philosophy and/or unwilling to adopt a renunciatory lifestyle. In addition, these movements all promised astonishingly quick results. And finally, the innovations in practice were met with suspicion and criticism from traditional Buddhist quarters. Those interested in the therapeutic effects of mindfulness and bare attention are often not aware of the existence, much less the content, of the controversies surrounding these practices in Asian Buddhist history

S. aureus MscL Is a Pentamer In Vivo but of Variable Stoichiometries In Vitro: Implications for Detergent-Solubilized Membrane Proteins

Detergent-induced rearrangements of membrane-protein subunits explain why two MscL channel stoichiometries have been resolved by X-ray crystallography - but S. aureus MscL is truly a pentamer in vivo

MicroRNA and mRNA profiling in the idiopathic inflammatory myopathies

Background The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease. Methods mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis and 5 non-myositis controls was profiled using next generation RNA sequencing. Gene ontology and pathway analyses were performed using GOseq and Ingenuity Pathway Analysis. Dysregulation of miRNAs and opposite dysregulation of predicted target mRNAs in IIM subgroups was validated using RTqPCR and investigated by transfecting human skeletal muscle cells with miRNA mimic. Results Analysis of differentially expressed genes showed that interferon signalling, and anti-viral response pathways were upregulated in PM and DM compared to controls. An anti-Jo1 autoantibody positive subset of PM and DM (n = 5) had more significant upregulation and predicted activation of interferon signalling and highlighted T-helper (Th1 and Th2) cell pathways. In miRNA profiling miR-96-5p was significantly upregulated in PM, DM and the anti-Jo1 positive subset. RTqPCR replicated miR-96-5p upregulation and predicted mRNA target (ADK, CD28 and SLC4A10) downregulation. Transfection of a human skeletal muscle cell line with miR-96-5p mimic resulted in significant downregulation of ADK. Conclusion MiRNA and mRNA profiling identified dysregulation of interferon signalling, anti-viral response and T-helper cell pathways, and indicates a possible role for miR-96-5p regulation of ADK in pathogenesis of IIM

Long working hours and risk of coronary heart disease and stroke : a systematic review and meta-analysis of published and unpublished data for 603 838 individuals

Background Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. Methods We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. Findings We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603 838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528 908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5.1 million person-years (mean 8.5 years), in which 4768 events were recorded, and for stroke was 3.8 million person-years (mean 7.2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (>= 55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1.13, 95% CI 1.02-1.26; p=0.02) and incident stroke (1.33, 1.11-1.61; p=0.002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1.30-1.42). We recorded a dose-response association for stroke, with RR estimates of 1.10 (95% CI 0.94-1.28; p=0.24) for 41-48 working hours, 1.27 (1.03-1.56; p=0.03) for 49-54 working hours, and 1.33 (1.11-1.61; p=0.002) for 55 working hours or more per week compared with standard working hours (p(trend) Interpretation Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours. Copyright (C) Kivimaki et al. Open Access article distributed under the terms of CC BY.Peer reviewe

The development of instruments to measure the work disability assessment behaviour of insurance physicians

<p>Abstract</p> <p>Background</p> <p>Variation in assessments is a universal given, and work disability assessments by insurance physicians are no exception. Little is known about the considerations and views of insurance physicians that may partly explain such variation. On the basis of the Attitude - Social norm - self Efficacy (ASE) model, we have developed measurement instruments for assessment behaviour and its determinants.</p> <p>Methods</p> <p>Based on theory and interviews with insurance physicians the questionnaire included blocks of items concerning background variables, intentions, attitudes, social norms, self-efficacy, knowledge, barriers and behaviour of the insurance physicians in relation to work disability assessment issues. The responses of 231 insurance physicians were suitable for further analysis. Factor analysis and reliability analysis were used to form scale variables and homogeneity analysis was used to form dimension variables. Thus, we included 169 of the 177 original items.</p> <p>Results</p> <p>Factor analysis and reliability analysis yielded 29 scales with sufficient reliability. Homogeneity analysis yielded 19 dimensions. Scales and dimensions fitted with the concepts of the ASE model. We slightly modified the ASE model by dividing behaviour into two blocks: behaviour that reflects the assessment process and behaviour that reflects assessment behaviour.</p> <p>The picture that emerged from the descriptive results was of a group of physicians who were motivated in their job and positive about the Dutch social security system in general. However, only half of them had a positive opinion about the Dutch Work and Income (Capacity for Work) Act (WIA). They also reported serious barriers, the most common of which was work pressure. Finally, 73% of the insurance physicians described the majority of their cases as 'difficult'.</p> <p>Conclusions</p> <p>The scales and dimensions developed appear to be valid and offer a promising basis for future research. The results suggest that the underlying ASE model, in modified form, is suitable for describing the assessment behaviour of insurance physicians and the determinants of this behaviour. The next step in this line of research should be to validate the model using structural equation modelling. Finally, the predictive value should be tested in relation to outcome measurements of work disability assessments.</p

A review of combined advanced oxidation technologies for the removal of organic pollutants from water

Water pollution through natural and anthropogenic activities has become a global problem causing short-and long-term impact on human and ecosystems. Substantial quantity of individual or mixtures of organic pollutants enter the surface water via point and nonpoint sources and thus affect the quality of freshwater. These pollutants are known to be toxic and difficult to remove by mere biological treatment. To date, most researches on the removal of organic pollutants from wastewater were based on the exploitation of individual treatment process. This single-treatment technology has inherent challenges and shortcomings with respect to efficiency and economics. Thus, application of two advanced treatment technologies characterized with high efficiency with respect to removal of primary and disinfection by-products in wastewater is desirable. This review article focuses on the application of integrated technologies such as electrohydraulic discharge with heterogeneous photocatalysts or sonophotocatalysis to remove target pollutants. The information gathered from more than 100 published articles, mostly laboratories studies, shows that process integration effectively remove and degrade recalcitrant toxic contaminants in wastewater better than single-technology processing. This review recommends an improvement on this technology (integrated electrohydraulic discharge with heterogeneous photocatalysts) viz-a-vis cost reduction in order to make it accessible and available in the rural and semi-urban settlement. Further recommendation includes development of an economic model to establish the cost implications of the combined technology. Proper monitoring, enforcement of the existing environmental regulations, and upgrading of current wastewater treatment plants with additional treatment steps such as photocatalysis and ozonation will greatly assist in the removal of environmental toxicants