Pharmacokinetic profile and quantitation of protection against soman poisoning by the antinicotinic compound MB327 in the guinea-pig

Current organophosphorus nerve agent medical countermeasures do not directly address the nicotinic effects of poisoning. A series of antinicotinic bispyridinium compounds has been synthesized in our laboratory and screened in vitro. Their actions can include open-channel block at the nicotinic receptor which may contribute to their efficacy. The current lead compound from these studies, MB327 1,1′-(propane-1,3-diyl)bis(4-tert-butylpyridinium) as either the diiodide (I2) or dimethanesulfonate (DMS) has been examined in vivo for efficacy against nerve agent poisoning. MB327 I2 (0–113 mg kg−1) or the oxime HI-6 DMS (0–100 mg kg− 1), in combination with atropine and avizafone (each at 3 mg kg−1) was administered to guinea-pigs 1 min following soman poisoning. Treatment increased the LD50 of soman in a dose-dependent manner. The increase was statistically significant (p < 0.01) at the 33.9 mg kg−1 (MB327) or 30 mg kg−1 (HI-6) dose with a comparable degree of protection obtained for both compounds. Following administration of 10 mg kg−1 (i.m.), MB327 DMS reached plasma Cmax of 22 μM at 12 min with an elimination t1/2 of 22 min. In an adverse effect study, in the absence of nerve agent poisoning, a dose of 100 mg kg−1 or higher of MB327 DMS was lethal to the guinea-pigs. A lower dose of MB327 DMS (30 mg kg−1) caused flaccid paralysis accompanied by respiratory impairment. Respiration normalised by 30 min, although the animals remained incapacitated to 4 h. MB327 or related compounds may be of utility in treatment of nerve agent poisoning as a component of therapy with atropine, anticonvulsant and oxime, or alternatively as an infusion under medical supervision

European regulatory agenices should employ full time statisticians

No abstract available

The instability of non-Newtonian boundary-layer flows over rough rotating disks

We are concerned with the local linear convective instability of the incompressible boundary-layer flows over rough rotating disks for non-Newtonian fluids. Using the Carreau model for a range of shear-thinning and shear-thickening fluids, we determine, for the first time, steady-flow profiles under the partial-slip model for surface roughness. The subsequent linear stability analyses of these flows (to disturbances stationary relative to the disk) indicate that isotropic and azimuthally-anisotropic (radial grooves) surface roughness leads to the stabilisation of both shear-thinning and -thickening fluids. This is evident in the behaviour of the critical Reynolds number and growth rates of both Type I (inviscid cross flow) and Type II (viscous streamline curvature) modes of instability. The underlying physical mechanisms are clarified using an integral energy equation

Extensive Air Shower Simulations at the Highest Energies

Air shower simulation programs are essential tools for the analysis of data from cosmic ray experiments and for planning the layout of new detectors. They are used to estimate the energy and mass of the primary particle. Unfortunately the model uncertainties translate directly into systematic errors in the energy and mass determination. Aiming at energies $> 10^{19}$ eV, the models have to be extrapolated far beyond the energies available at accelerators. On the other hand, hybrid measurement of ground particle densities and calorimetric shower energy, as will be provided by the Pierre Auger Observatory, will strongly constrain shower models. While the main uncertainty of contemporary models comes from our poor knowledge of the (soft) hadronic interactions at high energies, also electromagnetic interactions, low-energy hadronic interactions and the particle transport influence details of the shower development. We review here the physics processes and some of the computational techniques of air shower models presently used for highest energies, and discuss the properties and limitations of the models.Comment: 32 pages, 18 figures, accepted by Astroparticle Physic

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

Effects of mineralogy, chemistry and physical properties of basalts on carbon capture potential and plant-nutrient element release via enhanced weathering

Mafic igneous rocks, such as basalt, are composed of abundant calcium- and magnesium-rich silicate minerals widely proposed to be suitable for scalable carbon dioxide removal (CDR) by enhanced rock weathering (ERW). Here, we report a detailed characterization of the mineralogy, chemistry, particle size and surface area of six mined basalts being used in large-scale ERW field trials. We use 1-D reactive transport modelling (RTM) of soil profile processes to simulate inorganic CDR potential via cation flux (Mg2+, Ca2+, K+ and Na+) and assess the release of the essential plant nutrients phosphorus (P) and potassium (K) for a typical clay-loam agricultural soil. The basalts are primarily composed of pyroxene and plagioclase feldspar (up to 71 wt%), with accessory olivine, quartz, glass and alkali feldspar. Mean crushed particle size varies by a factor of 10, owing to differences in the mining operations and grinding processes. RTM simulations, based on measured mineral composition and N2-gas BET specific surface area (SSA), yielded potential CDR values of between c. 1.3 and 8.5 t CO2 ha−1 after 15 years following a baseline application of 50 t ha−1 basalt. The RTM results are comparative for the range of inputs that are described and should be considered illustrative for an agricultural soil. Nevertheless, they indicate that increasing the surface area for slow-weathering basalts through energy intensive grinding prior to field application in an ERW context may not be warranted in terms of additional CDR gains. We developed a function to convert CDR based on widely available and easily measured rock chemistry measures to more realistic determinations based on mineralogy. When applied to a chemistry dataset for >1300 basalt analyses from 25 large igneous provinces, we simulated cumulative CDR potentials of up to c. 8.5 t CO2 ha−1 after 30 years of weathering, assuming a single application of basalt with a SSA of 1 m2 g−1. Our RTM simulations suggest that ERW with basalt releases sufficient phosphorus (P) to substitute for typical arable crop P-fertiliser usage in Europe and the USA offering potential to reduce demand for expensive rock-derived P

Emotional intelligence and British expatriates’ cross-cultural adjustment in international construction projects

© 2016 Informa UK Limited, trading as Taylor & Francis Group. Today’s internationalized business demands global mindset, intercultural sensitivity and the ability to skilfully negotiate through cross-cultural interactions. Therefore, the overall aim was to investigate the influence of emotional intelligence (EI) on cross-cultural adjustment (CCA) of British expatriates working on International Architectural, Engineering and Construction assignments in Sub-Saharan Africa, China, Middle East and Indian Sub-Continent. Specifically, the causal relationship between EI and three facets of CCA i.e. work, general and interaction adjustment was explored. A sequential exploratory mixed methods design was adopted. These include extensive review of existing literature, eighteen unstructured interviews, and questionnaire survey of 191 British expatriates operating in 29 different countries from the four regions under investigation. Structural equation modelling was used to assess the causal relationship between EI and CCA. Results show that EI accounted for 91, 64 and 24% of the variance in work, interaction and general adjustment respectively. Overall, the model was able to explain 60% variance in CCA, suggesting that EI competencies play a huge role in facilitating an expatriate understand and adapt to host country culture. The findings would help decision-makers (HR managers) during expatriate selection process, in understanding that along with technical skills, it is the emotional competencies that are crucial in assisting expatriates adjust to foreign way of life