Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio

The impact of corporate social responsibility disclosure on financial performance : evidence from the GCC Islamic banking sector.

This paper examines the relationship between corporate social responsibility (CSR) and financial performance for Islamic banks in the Gulf Cooperation Council (GCC) region over the period 2000–2014 by generating CSR-related data through disclosure analysis of the annual reports of the sampled banks. The findings of this study indicate that there is a significant positive relationship between CSR disclosure and the financial performance of Islamic banks in the GCC countries. The results also show a positive relationship between CSR disclosure and the future financial performance of GCC Islamic banks, potentially indicating that current CSR activities carried out by Islamic banks in the GCC could have a long-term impact on their financial performance. Furthermore, despite demonstrating a significant positive relationship between the composite measure of the CSR disclosure index and financial performance, the findings show no statistically significant relationship between the individual dimensions of the CSR disclosure index and the current financial performance measure except for ‘mission and vision’ and ‘products and services’. Similarly, the empirical results detect a positive significant association only between ‘mission and vision’ dimension and future financial performance of the examined banks

Temporal allocation of foraging effort in female Australian fur seals (Arctocephalus pusillus doriferus)

Across an individual\u27s life, foraging decisions will be affected by multiple intrinsic and extrinsic drivers that act at differing timescales. This study aimed to assess how female Australian fur seals allocated foraging effort and the behavioural changes used to achieve this at three temporal scales: within a day, across a foraging trip and across the final six months of the lactation period. Foraging effort peaked during daylight hours (57% of time diving) with lulls in activity just prior to and after daylight. Dive duration reduced across the day (196 s to 168 s) but this was compensated for by an increase in the vertical travel rate (1500–1600 m•h−1) and a reduction in postdive duration (111–90 s). This suggests physiological constraints (digestive costs) or prey availability may be limiting mean dive durations as a day progresses. During short trips (<2.9 d), effort remained steady at 55% of time diving, whereas, on long trips (>2.9 d) effort increased up to 2–3 d and then decreased. Dive duration decreased at the same rate in short and long trips, respectively, before stabilising (long trips) between 4–5 d. Suggesting that the same processes (digestive costs or prey availability) working at the daily scale may also be present across a trip. Across the lactation period, foraging effort, dive duration and vertical travel rate increased until August, before beginning to decrease. This suggests that as the nutritional demands of the suckling pup and developing foetus increase, female effort increases to accommodate this, providing insight into the potential constraints of maternal investment in this specie

Laforin, a Dual Specificity Phosphatase Involved in Lafora Disease, Is Present Mainly as Monomeric Form with Full Phosphatase Activity

Lafora Disease (LD) is a fatal neurodegenerative epileptic disorder that presents as a neurological deterioration with the accumulation of insoluble, intracellular, hyperphosphorylated carbohydrates called Lafora bodies (LBs). LD is caused by mutations in either the gene encoding laforin or malin. Laforin contains a dual specificity phosphatase domain and a carbohydrate-binding module, and is a member of the recently described family of glucan phosphatases. In the current study, we investigated the functional and physiological relevance of laforin dimerization. We purified recombinant human laforin and subjected the monomer and dimer fractions to denaturing gel electrophoresis, mass spectrometry, phosphatase assays, protein-protein interaction assays, and glucan binding assays. Our results demonstrate that laforin prevalently exists as a monomer with a small dimer fraction both in vitro and in vivo. Of mechanistic importance, laforin monomer and dimer possess equal phosphatase activity, and they both associate with malin and bind glucans to a similar extent. However, we found differences between the two states' ability to interact simultaneously with malin and carbohydrates. Furthermore, we tested other members of the glucan phosphatase family. Cumulatively, our data suggest that laforin monomer is the dominant form of the protein and that it contains phosphatase activity

The health impact of remarriage behavior on chronic obstructive pulmonary disease: findings from the US longitudinal survey

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is a major disease among adults, and its deterioration was reported to be associated with psychological imbalance. Meanwhile, bereavement and divorce have proven harmful to the health status of a surviving spouse. But few studies have been conducted to evaluate the remedial effect on survivors' health outcome by remarriage after bereavement. The present study thus examined the associations between remarriage and the onset of COPD.</p> <p>Methods</p> <p>Our cohort was drawn from Health and Retirement Study participants in the United States, and consisted of 2676 subjects who were divorced or bereaved from 1992 to 2002. We then followed them for up to 11 years and assessed the incidence rate of COPD using a Cox proportional hazard model after adjusting for marital status, age, gender, education and the number of cigarettes smoked.</p> <p>Results</p> <p>Among all subjects, 224 who remarried after bereavement or divorce tended to be younger and more male dominated. Remarriage after bereavement/divorce was associated with significantly decreased risk of COPD onset for overall subjects [hazard ratio (HR): 0.51, 95% confidence interval (95% CI): 0.28-0.94], female subjects [HR: 0.36, 95% CI: 0.13-0.98], and for those under 70 years old [HR: 0.36, 95% CI: 0.17-0.79].</p> <p>Conclusion</p> <p>This study investigates the impact of remarriage on health outcome based on a large-scale population survey and indicates that remarriage significantly correlates with reduced risk of COPD incidence, even after adjusting smoking habit.</p

Correlations Between Life-Detection Techniques and Implications for Sampling Site Selection in Planetary Analog Missions

We conducted an analog sampling expedition under simulated mission constraints to areas dominated by basaltic tephra of the Eldfell and Fimmvorouhals lava fields (Iceland). Sites were selected to be homogeneous at a coarse remote sensing resolution (10-100m) in apparent color, morphology, moisture, and grain size, with best-effort realism in numbers of locations and replicates. Three different biomarker assays (counting of nucleic-acid-stained cells via fluorescent microscopy, a luciferin/luciferase assay for adenosine triphosphate, and quantitative polymerase chain reaction (qPCR) to detect DNA associated with bacteria, archaea, and fungi) were characterized at four nested spatial scales (1m, 10m, 100m, and >1km) by using five common metrics for sample site representativeness (sample mean variance, group F tests, pairwise t tests, and the distribution-free rank sum H and u tests). Correlations between all assays were characterized with Spearman's rank test. The bioluminescence assay showed the most variance across the sites, followed by qPCR for bacterial and archaeal DNA; these results could not be considered representative at the finest resolution tested (1m). Cell concentration and fungal DNA also had significant local variation, but they were homogeneous over scales of >1km. These results show that the selection of life detection assays and the number, distribution, and location of sampling sites in a low biomass environment with limited a priori characterization can yield both contrasting and complementary results, and that their interdependence must be given due consideration to maximize science return in future biomarker sampling expeditions. Key Words: AstrobiologyBiodiversityMicrobiologyIcelandPlanetary explorationMars mission simulationBiomarker. Astrobiology 17, 1009-1021

Phytogeographical patterns of dry forests sensu stricto in northern Minas Gerais State, Brazil

The Deciduous Complex that occurs in northern Minas Gerais State, Brazil, raises questions about the floristic affinities of these formations in relation to neighboring phytogeographical domains. Little is known about the identity of the seasonal forest formations that comprise this complex, or about its relationships to abiotic components, such as soils, topography and climate. This study aimed to recognize the patterns of floristic similarity of all studied fragments of dry forest of northern Minas Gerais with soil and climate attributes, based on the available database. Cluster analysis indicated the existence of two floristic groups that had clear associations with either the Koppen's BSh (semi-arid) or Aw (seasonal tropical) climates. Likewise, the subdivisions of these groups showed clear associations with the dominant soil classes in the region. The Red-Yellow Latosol is the dominant soil classes in the BSh climatic domain, seconded by alluvial areas associated with Fluvic Neosols. The Aw domain comprised a much varied set of soils: Nitosols, Argisols, Cambisols and Litholic Neosols, most derived from the Bambuí limestone/slate formation. The ecotonal nature of northern Minas Gerais State provides a complex interaction between the flora of neighboring phytogeographical domains. This, allied to pedogeomorphological factors, allowed a better understanding of the effects of late Quaternary climate changes for the Deciduous Complex evolution. We conclude that the Latosols under present-day semi-arid climates (BSh) are relicts of former wetter climates, during which humid forest (semideciduous) expansion took place. Later, these semideciduous forests were subjected to a much drier climate, when selection for deciduousness led to the present-days Deciduous Complex scenario

Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease

We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population

Of Asian Forests and European Fields: Eastern U.S. Plant Invasions in a Global Floristic Context

Background: Biogeographic patterns of species invasions hold important clues to solving the recalcitrant ‘who’, ‘where’, and ‘why ’ questions of invasion biology, but the few existing studies make no attempt to distinguish alien floras (all non-native occurrences) from invasive floras (rapidly spreading species of significant management concern), nor have invasion biologists asked whether particular habitats are consistently invaded by species from particular regions. Methodology/Principal Findings: Here I describe the native floristic provenances of the 2629 alien plant taxa of the Eastern Deciduous Forest of the Eastern U.S. (EUS), and contrast these to the subset of 449 taxa that EUS management agencies have labeled ‘invasive’. Although EUS alien plants come from all global floristic regions, nearly half (45%) have native ranges that include central and northern Europe or the Mediterranean (39%). In contrast, EUS invasive species are most likely to come from East Asia (29%), a pattern that is magnified when the invasive pool is restricted to species that are native to a single floristic region (25 % from East Asia, compared to only 11 % from northern/central Europe and 2 % from the Mediterranean). Moreover, East Asian invaders are mostly woody (56%, compared to just 23 % of the total alien flora) and are significantly more likely to invade intact forests and riparian areas than European species, which dominate managed or disturbed ecosystems. Conclusions/Significance: These patterns suggest that the often-invoked ‘imperialist dogma ’ view of global invasion

Innate Immune Responses of Pulmonary Epithelial Cells to Burkholderia pseudomallei Infection

10.1371/journal.pone.0007308PLoS ONE410