Carbonate and Thorium concentrations of South Atlantic sediments

Rates of sedimentation of pelagic sediments in the South Atlantic have been determined using the ionium/thorium methodology. Values of the order of several millimeters per thousand years for sediments were found in the deposits in the valleys of the mid-Atlantic ridge. The equatorial deposits showed higher rates of accumulation than the corresponding deposits at higher latitudes, probably reflecting the added influx of materials to the sea floor from tropical rivers through the equatorial current systems. The deposits in the ridge valleys showed marked changes in sedimentation rates at about 115,000 years ago, at which time the present rates changed from higher to lower values. The ridge sediments were composed primarily of continentally derived materials, and there were no indications of solid phases being derived from the weathering of the ridge itself or from volcanic activity. The equatorial samples have mineral assemblages which are distinctly different from those in deposits at higher latitudes and which probably are indicative of contributions of materials from tropical weathering processes.

Mineralogy of northern Indian Ocean surface sediments and of suspended sediments of Indian rivers (Table 2 and 5)

The solid phases from surface sediments, atmospheric dusts, and rivers of the Indian Ocean environment have been analyzed for their clay minerals and quartz. Such data have been used to delimit the transport paths and sources of the detrital minerals in the oceanic deposits. Diagnostic in distinguishing fluvial and eolian inputs to the northern Indian Ocean is a combination of the clay mineral assemblages and of their geographic distributions. River borne solids are the primary components of the Bay of Bengal deposits. The eastern part receives its continental input through the Ganges-Brahmaputra river system, while drainage of the Indian Peninsula by rivers introduces solids to the western part. The former materials are characterized by high illite and chlorite in the clay mineral assemblages; the latter by montmorillonite. The winds over the Bay bear distinctive dust burdens based upon their directions. However, their contributions to the sediments are insignificant. The eastern sector of the Arabian Sea receives major contributions of continental debris from the rivers and the high montmorillonite levels clearly indicate a source in the Indian Peninsula. The rest of the Sea appears to receive most of its land-derived materials from the north, perhaps the desert regions of northern India and West Pakistan, and they are wind-borne. These materials are also transported to the equatorial regions of the Indian Ocean. A gradient in attapulgite, just north of the equator, may indicate an eolian contribution to the Arabian Sea from the African continent. The halogenated hydrocarbon pesticides were assayed in the southwest monsoon winds and enter the Bay of Bengal at levels of a half ton per month, an amount comparable to those introduced by other wind and river systems to the marine environment.

Characteristics of hospital-treated intentional drug overdose in Ireland and Northern Ireland

OBJECTIVES This study compared the profile of intentional drug overdoses (IDOs) presenting to emergency departments in Ireland and in the Western Trust Area of Northern Ireland between 2007 and 2012. Specifically the study aimed to compare characteristics of the patients involved, to explore the factors associated with repeated IDO and to report the prescription rates of common drug types in the population. METHODS We utilised data from two comparable registries which monitor the incidence of hospital-treated self-harm, recording data from deliberate self-harm presentations involving an IDO to all hospital emergency departments for the period 1 January 2007 to 31 December 2012. RESULTS Between 2007 and 2012 the registries recorded 56,494 self-harm presentations involving an IDO. The study showed that hospital-treated IDO was almost twice as common in Northern Ireland than in Ireland (278 vs 156/100,000, respectively). CONCLUSIONS Despite the overall difference in the rates of IDO, the profile of such presentations was remarkably similar in both countries. Minor tranquillisers were the drugs most commonly involved in IDOs. National campaigns are required to address the availability and misuse of minor tranquillisers, both prescribed and non-prescribed.

Understanding the work of the city manager

The managerial behaviour approach to understanding managerial work has developed from research over the course of fifty years. The approach represents a marked departure from mainstream (and still prevalent) management approaches that depict management as a set of general composite functions. The managerial behaviour approach is distinctive in its empirical research background, object, focus and methodology. Its objective is to provide the simple answer to the complex question: what do managers do? However, the emphasis in the studies on managerial behaviour represents a limitation in so far as a context for locating and judging that behaviour is largely absent (Hales, 1986). This paper presents the results of initial research into managers operating in a different and largely neglected context - city councils. The research uses Mintzberg’s (1973) concept of behavioural roles as an analytical tool to explain and understand what city managers do. This study assesses whether these roles adequately capture the important features of managerial work in the city council. It is argued that while Mintzberg’s role framework is useful, structured observation alone does not adequately address the complexities of environments and styles of managers or the cognitive processes of managers. However, by integrating this approach with an appreciation of context and cognitive processes and how they can influence or affect managerial behaviour, we develop a more realistic description of what managers actually do and why they do it.

Development of a knowledge sharing framework for improving the testing processes in global product development

As identified by Griffin (1997) and Kahn (2012), manufacturing organisations typically improve their market position by accelerating their product development (PD) cycles. One method for achieving this is to reduce the time taken to design, test and validate new products, so that they can reach the end customer before competition. This paper adds to existing research on PD testing procedures by reporting on an exploratory investigation carried out in a UK-based manufacturing plant. We explore the organisational and managerial factors that contribute to the time spent on testing of new products during development. The investigation consisted of three sections, viz. observations and process modelling, utilisation metrics and a questionnaire-based investigation, from which a proposed framework to improve and reduce the PD time cycle is presented. This research focuses specifically on the improvement of the utilisation of product testing facilities and the links to its main internal stakeholders - PD engineers.

The Electoral Rise of Populist Radical Right Parties in Europe: Ideological Parameters and Social Motivations

Populist radical right parties have become major political actors in Europe. This paper analyses the path and the different phases that have led them from the fringes of public debate to their present signifi cance, which is based on their capacity to attract electoral support and infl uence the political agendas in their respective countries. Besides, an analysis of the core ideological beliefs of these parties, and of the topics on which their mobilization capacity rests, is provided, as well as of the type of voters that are attracted by them. Finally, the authors discuss the meaning and impact of the growing popularity of the ideas and proposals put forward by the populist radical right parties.

Gas Solubility and Vapor Pressure of Electrolytes Based on Alkylcarbonates Containing Litfsi, Lifap, and LiPF6 Lithium Salt: Measurement and Prediction

Most liquid electrolytes used in commercial lithium-ion batteries are composed by alkylcarbonate mixture containing lithium salt. The decomposition of these solvents by oxidation or reduction during cycling of the cell, induce generation of gases (CO2, CH4, C2H4, CO …) increasing of pressure in the sealed cell, which causes a safety problem [1]. The prior understanding of parameters, such as structure and nature of salt, temperature pressure, concentration, salting effects and solvation parameters, which influence gas solubility and vapor pressure of electrolytes is required to formulate safer and suitable electrolytes especially at high temperature.

We present in this work the CO2, CH4, C2H4, CO solubility in different pure alkyl-carbonate solvents (PC, DMC, EMC, DEC) and their binary or ternary mixtures as well as the effect of temperature and lithium salt LiX (X = LiPF6, LiTFSI or LiFAP) structure and concentration on these properties. Furthermore, in order to understand parameters that influence the choice of the structure of the solvents and their ability to dissolve gas through the addition of a salt, we firstly analyzed experimentally the transport properties (Self diffusion coefficient (D), fluidity (h-1), and conductivity (s) and lithium transport number (tLi) using the Stock-Einstein, and extended Jones-Dole equations [2]. Furthermore, measured data for the of CO2, C2H4, CH4 and CO solubility in pure alkylcarbonates and their mixtures containing LiPF6; LiFAP; LiTFSI salt, are reported as a function of temperature and concentration in salt. Based on experimental solubility data, the Henry’s law constant of gases in these solvents and electrolytes was then deduced and compared with values predicted by using COSMO-RS methodology within COSMOthermX software. From these results, the molar thermodynamic functions of dissolution such as the standard Gibbs energy, the enthalpy, and the entropy, as well as the mixing enthalpy of the solvents and electrolytes with the gases in its hypothetical liquid state were calculated and discussed [3]. Finally, the analysis of the CO2 solubility variations with the salt addition was then evaluated by determining specific ion parameters Hi by using the Setchenov coefficients in solution. This study showed that the gas solubility is entropy driven and can been influenced by the shape, charge density, and size of the anions in lithium salt.

References<br/>
[1] S.A. Freunberger, Y. Chen, Z. Peng, J.M. Griffin, L.J. Hardwick, F. Bardé, P. Novák, P.G. Bruce, Journal of the American Chemical Society 133 (2011) 8040-8047.

[2] P. Porion, Y.R. Dougassa, C. Tessier, L. El Ouatani, J. Jacquemin, M. Anouti, Electrochimica Acta 114 (2013) 95-104.

[3] Y.R. Dougassa, C. Tessier, L. El Ouatani, M. Anouti, J. Jacquemin, The Journal of Chemical Thermodynamics 61 (2013) 32-44.

Importance of risk factor management in diabetic patients and reduction in Stage B heart failure

BACKGROUND: A number of studies have demonstrated the presence of a diabetic cardiomyopathy, increasing the risk of heart failure development in this population. Improvements in present-day risk factor control may have modified the risk of diabetes-associated cardiomyopathy.

AIM: We sought to determine the contemporary impact of diabetes mellitus (DM) on the prevalence of cardiomyopathy in at-risk patients with and without adjustment for risk factor control.

DESIGN: A cross-sectional study in a population at risk for heart failure.

METHODS: Those with diabetes were compared to those with other cardiovascular risk factors, unmatched, matched for age and gender and then matched for age, gender, body mass index, systolic blood pressure and low density lipoprotein cholesterol.

RESULTS: In total, 1399 patients enrolled in the St Vincent's Screening to Prevent Heart Failure (STOP-HF) cohort were included. About 543 participants had an established history of DM. In the whole sample, Stage B heart failure (asymptomatic cardiomyopathy) was not found more frequently among the diabetic cohort compared to those without diabetes [113 (20.8%) vs. 154 (18.0%), P = 0.22], even when matched for age and gender. When controlling for these risk factors and risk factor control Stage B was found to be more prevalent in those with diabetes [88 (22.2%)] compared to those without diabetes [65 (16.4%), P = 0.048].

CONCLUSION: In this cohort of patients with established risk factors for Stage B heart failure superior risk factor management among the diabetic population appears to dilute the independent diabetic insult to left ventricular structure and function, underlining the importance and benefit of effective risk factor control in this population on cardiovascular outcomes.

Acoustic signalling reflects personality in a social mammal

Social interactions among individuals are often mediated through acoustic signals. If acoustic signals are consistent and related to an individual's personality, these consistent individual differences in signalling may be an important driver in social interactions. However, few studies in non-human mammals have investigated the relationship between acoustic signalling and personality. Here we show that acoustic signalling rate is repeatable and strongly related to personality in a highly social mammal, the domestic pig (Sus scrofa domestica). Furthermore, acoustic signalling varied between environments of differing quality, with males from a poor-quality environment having a reduced vocalization rate compared with females and males from an enriched environment. Such differences may be mediated by personality with pigs from a poor-quality environment having more reactive and more extreme personality scores compared with pigs from an enriched environment. Our results add to the evidence that acoustic signalling reflects personality in a non-human mammal. Signals reflecting personalities may have far reaching consequences in shaping the evolution of social behaviours as acoustic communication forms an integral part of animal societies.

Modelling responses to spatially fractionated radiation fields using preclinical image-guided radiotherapy

OBJECTIVES: Radiotherapy is planned to achieve the optimal physical dose distribution to the target tumour volume whilst minimising dose to the surrounding normal tissue. Recent in vitro experimental evidence has demonstrated an important role for intercellular communication in radiobiological responses following non-uniform exposures. This study aimed to model the impact of these effects in the context of techniques involving highly modulated radiation fields or spatially fractionated treatments such as GRID therapy.

METHODS: Using the small animal radiotherapy research platform (SARRP) as a key enabling technology to deliver precision imaged-guided radiotherapy, it is possible to achieve spatially modulated dose distributions that model typical clinical scenarios. In this work, we planned uniform and spatially fractionated dose distributions using multiple isocentres with beam sizes of 0.5 - 5 mm to obtain 50% volume coverage in a subcutaneous murine tumour model, and applied a model of cellular response that incorporates intercellular communication to assess the potential impact of signalling effects with different ranges.

RESULTS: Models of GRID treatment plans which incorporate intercellular signalling showed increased cell killing within the low dose region. This results in an increase in the Equivalent Uniform Dose (EUD) for GRID exposures compared to standard models, with some GRID exposures being predicted to be more effective than uniform delivery of the same physical dose.

CONCLUSIONS: This study demonstrates the potential impact of radiation induced signalling on tumour cell response for spatially fractionated therapies and identifies key experiments to validate this model and quantify these effects in vivo.

ADVANCES IN KNOWLEDGE: This study highlights the unique opportunities now possible using advanced preclinical techniques to develop a foundation for biophysical optimisation in radiotherapy treatment planning.

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

BACKGROUND: Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up.

METHODS: CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b-T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3-6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923.

FINDINGS: Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9-77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0-90·2) in the 74 Gy group, 90·6% (88·5-92·3) in the 60 Gy group, and 85·9% (83·4-88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68-1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99-1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported.

INTERPRETATION: Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer.

FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours

Purpose: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and to determine the optimal biological dose for subsequent trials.
Experimental design: Patients with treatment-refractory, advanced solid tumours, with adequate performance status and organ function were recruited to a dose-escalation study in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with toxicity, PK and PD guided dose-escalation with potential to explore alternative schedules.
Results: Forty-one patients with advanced solid tumours refractory to standard therapies and with adequate organ function were recruited in eight cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose-limiting toxicities were observed during the study, and a maximum tolerated dose (MTD) was not established. The highest dose cohorts demonstrated sustained inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13-acetate stimulation. There was a decrease of 70 ± 26% in mean phosphorylated (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels in the 75 mg twice a week cohort. Prolonged stable disease (>6 months) was seen in two patients, one with cervical cancer and one with ampullary carcinoma.
Conclusions: WX-554 was well tolerated, and an optimal biological dose was established for further investigation in either a once or twice weekly regimens. The recommended phase 2 dose is 75 mg twice weekly.

Novel ketone diet enhances physical and cognitive performance

Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low-carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson's disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palm oil (P < 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [(31)P]-NMR spectroscopy. The novel ketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.