A new species of Pareledone (Cephalopoda : Octopodidae) from Antarctic Peninsula Waters

During recent cruises aboard RV Polarstern in the Antarctic Peninsula region, a new species of benthic octopodid was discovered whose generic affinities based on morphological characteristics were uncertain. Molecular sequence analysis of six mitochondrial and nuclear genes allows this species to be placed with confidence within the genus Pareledone. The species is described herein and morphological diagnostic characters are provided for its identification.

Extent and nature of unlicensed and off-label medicine use in hospitalised children in Palestine

Objective of the study: To determine the extent and nature of unlicensed/off-label prescribing patterns in hospitalised children in Palestine. Setting: Four paediatric wards in two public health system hospitals in Palestine [Caritas children’s hospital (Medical and neonatal intensive care units) and Rafidia general hospital (Medical and surgical units)]. Method: A prospective survey of drugs administered to infants and children <18 years old was carried out over a five-week period in the four paediatric wards. Main outcome measure: Drug-licensing status of all prescriptions was determined according to the Palestinian Registered Product List and the Physician’s Desk Reference. Results: Overall, 917 drug prescriptions were administered to 387 children. Of all drug prescriptions, 528 (57.5%) were licensed for use in children; 65 (7.1%) were unlicensed; and 324 (35.3%) were used off-label. Of all children, 49.6% received off-label prescriptions, 10.1% received unlicensed medications and 8.2% received both. Seventy-two percent of off-label drugs and 66% of unlicensed drugs were prescribed for children <2 years. Multivariate analysis showed that patients who were admitted to the neonatal intensive care unit and infants aged 0–1 years were most likely to receive a greater number of off-label or unlicensed medications (OR 1.80; 95% CI 1.03–3.59 and OR 1.99; 95% CI 0.88–3.73, respectively). Conclusion: The present findings confirmed the elevated prevalence of unlicensed and off-label paediatric drugs use in Palestine and strongly support the need to perform well designed clinical studies in children.

Photospheric magnetic vortex structures

Using direct numerical magneto-hydrodynamic (MHD) simulations, we demonstrate the evidence of two physically different types of vortex motions in the solar photosphere. Baroclinic motions of plasma in non-magnetic granules are the primary source of vorticity in granular regions of the solar photosphere, however, there is a significantly more efficient mechanism of vorticity production in strongly magnetised intergranular lanes. These swirly motions of plasma in intergranular magnetic field concentrations could be responsible for the generation of different types of MHD wave modes, for example, kink, sausage and torsional Alfven waves. These waves could transport a relevant amount of energy from the lower solar atmosphere and contribute to coronal plasma heating.

RABBIT PANCREATIC-POLYPEPTIDE

1. In almost all studies involving localization or quantitation of regulatory peptides, an essential prerequisite is the generation of specific antisera in rabbits. Despite this almost universal practice, the primary structures of some established regulatory peptides, such as pancreatic polypeptide (PP), of the rabbit, remain unknown.

Assessment of sample quality in soft clay using shear wave velocity and suction measurements

The characterisation of soils for civil engineering purposes depends on removing sufficiently high-quality samples from the ground. Accurate evaluation of sample quality is therefore important if reliable design parameters are to be determined. This paper describes the use of unconfined shear wave velocity (V _s) and suction (u _r) measurements to assess sample quality rapidly in soft clay. Samples of varying quality from three well-characterised soft clay sites are initially assessed using conventional techniques, and their results compared with V _s and u _r measurements performed on the same samples. It is observed that the quality of samples indicated by these measurements is very similar to those inferred from traditional disturbance measures, with V _s being the more reliable indicator. A tentative empirically derived criterion, based on samples tested in this project, is proposed to quantify sample disturbance combining both V _s and u _r measurements. Further work using this criterion on different materials is important so as to test its usefulness.

The use of a GA to improve the postbuckling strength of stiffened composite panels susceptible to secondary instabilities

The use of genetic algorithms (GAs) for structural optimisation is well established but little work has been reported on the inclusion of damage variables within an optimisation framework. This approach is particularly useful in the optimisation of composite structures which are prone to delamination damage. In this paper a challenging design problem is presented where the objective was to delay the catastrophic failure of a postbuckling secondary-bonded stiffened composite panel susceptible to secondary instabilities. It has been conjectured for some time that the sudden energy release associated with secondary instabilities may initiate structural failure, but this has proved difficult to observe experimentally. The optimisation methodology confirmed this indirectly by evolving a panel displaying a delayed secondary instability whilst meeting all other design requirements. This has important implication in the design of thin-skinned lightweight aerostructures which may exhibit this phenomenon.

Aflatoxin Exposure May Contribute to Chronic Hepatomegaly in Kenyan School Children

BACKGROUND: Presentation with a firm type of chronic hepatomegaly of multifactorial etiology is common among school-age children in sub-Saharan Africa.

OBJECTIVE: Aflatoxin is a liver toxin and carcinogen contaminating staple maize food. In this study we examined its role in chronic hepatomegaly.

METHODS: Plasma samples collected in 2002 and again in 2004 from 218 children attending two schools in neighboring villages were assayed for aflatoxin exposure using the aflatoxin-albumin adduct (AF-alb) biomarker. Data were previously examined for associations among hepatomegaly, malaria, and schistosomiasis.

RESULTS: AF-alb levels were high in children from both schools, but the geometric mean (95% confidence interval) in year 2002 was significantly higher in Matangini [206.5 (175.5, 243.0) pg/mg albumin] than in Yumbuni [73.2 (61.6, 87.0) pg/mg; p < 0.001]. AF-alb levels also were higher in children with firm hepatomegaly [176.6 (129.6, 240.7) pg/mg] than in normal children [79.9 (49.6, 128.7) pg/mg; p = 0.029]. After adjusting for Schistosoma mansoni and Plasmodium infection, we estimated a significant 43% increase in the prevalence of hepatomegaly/hepatosplenomegaly for every natural-log-unit increase in AF-alb. In 2004, AF-alb levels were markedly higher than in 2002 [539.7 (463.3, 628.7) vs. 114.5 (99.7, 131.4) pg/mg; p < 0.001] but with no significant difference between the villages or between hepatomegaly and normal groups [539.7 (436.7, 666.9) vs. 512.6 (297.3, 883.8) pg/mg], possibly because acute exposures during an aflatoxicosis outbreak in 2004 may have masked any potential underlying relationship.

CONCLUSIONS: Exposure to aflatoxin was associated with childhood chronic hepatomegaly in 2002. These preliminary data suggest an additional health risk that may be related to aflatoxin exposure in children, a hypothesis that merits further testing.

Effects of short term increase of intraocular pressure on optic disc cupping

Aims. To evaluate the effect of acute elevation of intraocular pressure (IOP) on optic disc cupping. Methods. 10 emmetropic and 10 myopic volunteers were included in this study. The cup area (CA) and cup volume (CV) of the optic disc were determined with the Heidelberg retina tomograph (HRT). After baseline determinations, a suction cup was used to increase the intraocular pressure (IOP) to 20-25 mmHg above the baseline and HRT images were obtained. Results. Baseline IOP was 13.5 (SD 1.3) mmHg and 12.6 (2.6) mmHg in the emmetropic and myopic groups, respectively. The IOP was elevated to 35.4 (3.3) mmHg and 34.4 (2.5) mmHg in the emmetropic and myopic groups, respectively. When compared with their baseline values, the cupping variables (CA and CV) were significantly increased (p <0.05) during the suction treatment in both emmetropic and myopic subjects. Conclusion. There was a significant enlargement in the optic disc cupping during the artificial increment of intraocular pressure in both emmetropic and myopic eyes. In non-glaucomatous eyes the optic nerve head has a partially dynamic topography dependent upon the level of IOP.

Integrating Multiple Point Statistics with Aerial Geophysical Data to assist Groundwater Flow Models

The process of accounting for heterogeneity has made significant advances in statistical research, primarily in the framework of stochastic analysis and the development of multiple-point statistics (MPS). Among MPS techniques, the direct sampling (DS) method is tested to determine its ability to delineate heterogeneity from aerial magnetics data in a regional sandstone aquifer intruded by low-permeability volcanic dykes in Northern Ireland, UK. The use of two two-dimensional bivariate training images aids in creating spatial probability distributions of heterogeneities of hydrogeological interest, despite relatively ‘noisy’ magnetics data (i.e. including hydrogeologically irrelevant urban noise and regional geologic effects). These distributions are incorporated into a hierarchy system where previously published density function and upscaling methods are applied to derive regional distributions of equivalent hydraulic conductivity tensor K. Several K models, as determined by several stochastic realisations of MPS dyke locations, are computed within groundwater flow models and evaluated by comparing modelled heads with field observations. Results show a significant improvement in model calibration when compared to a simplistic homogeneous and isotropic aquifer model that does not account for the dyke occurrence evidenced by airborne magnetic data. The best model is obtained when normal and reverse polarity dykes are computed separately within MPS simulations and when a probability threshold of 0.7 is applied. The presented stochastic approach also provides improvement when compared to a previously published deterministic anisotropic model based on the unprocessed (i.e. noisy) airborne magnetics. This demonstrates the potential of coupling MPS to airborne geophysical data for regional groundwater modelling.

GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1-2 September 2014

G-protein coupled receptors (GPCRs) are the targets of over half of all prescribed drugs today. The UniProt database has records for about 800 proteins classified as GPCRs, but drugs have only been developed against 50 of these. Thus, there is huge potential in terms of the number of targets for new therapies to be designed. Several breakthroughs in GPCRs biased pharmacology, structural biology, modelling and scoring have resulted in a resurgence of interest in GPCRs as drug targets. Therefore, an international conference, sponsored by the Royal Society, with world-renowned researchers from industry and academia was recently held to discuss recent progress and highlight key areas of future research needed to accelerate GPCR drug discovery. Several key points emerged. Firstly, structures for all three major classes of GPCRs have now been solved and there is increasing coverage across the GPCR phylogenetic tree. This is likely to be substantially enhanced with data from x-ray free electron sources as they move beyond proof of concept. Secondly, the concept of biased signalling or functional selectivity is likely to be prevalent in many GPCRs, and this presents exciting new opportunities for selectivity and the control of side effects, especially when combined with increasing data regarding allosteric modulation. Thirdly, there will almost certainly be some GPCRs that will remain difficult targets because they exhibit complex ligand dependencies and have many metastable states rendering them difficult to resolve by crystallographic methods. Subtle effects within the packing of the transmembrane helices are likely to mask and contribute to this aspect, which may play a role in species dependent behaviour. This is particularly important because it has ramifications for how we interpret pre-clinical data. In summary, collaborative efforts between industry and academia have delivered significant progress in terms of structure and understanding of GPCRs and will be essential for resolving problems associated with the more difficult targets in the future.