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Wave transmission in Hostun sand:multiaxial experiments
No full textLaboratory geophysical techniques using waves transmitted by piezoceramic elements have become popular for estimating the very small strain stiffness of soils. Piezoceramic Bender/Extender elements have been installed in a multiaxial cubical cell which is being used to study the multiaxial stiffness of dry Hostun sand. The elements can be used to track wave transmission in both shear and compression modes both across from one side to the opposite side of the cube and diagonally from one side to an adjacent side and thus to deduce the elements of the cross-anisotropic stiffness matrix of the sand. Practicalities of the bender installation reduce the degree of redundancy in these deductions. An assessment of the evolution of elastic anisotropy under axially symmetric stress conditions is presented
Can the Dragon and Bear drink from the same well?:Examining Sino-Russian Cooperation on Transboundary Rivers through a Legal Lens. Part 1
No full textThe management and survival of patients with advanced germ-cell tumours:improving outcome in intermediate and poor prognosis patients
No full textThe survival of germ-cell tumours (GCT) was transformed after the introduction of cisplatin-based therapy. Previous trials have indicated BEP (bleomycin, etoposide and cisplatin) as the optimum treatment, although some centres including our own advocate the use of the alternating regimen POMB-ACE (cisplatin, vincristine, methotrexate, bleomycin and dactinomycin, cyclophosphamide and etoposide) for men with intermediate or poor prognosis disease. We analysed the survival and management of GCT patients treated at a specialist cancer centre in relation to internationally recognised prognostic groupings
Factors associated with uptake of pandemic influenza vaccine among general practitioners and practice nurses in Shropshire, UK
No full textBACKGROUND: At the time of the 2009-10 influenza pandemic there was considerable unease about vaccination. Early surveys suggested that the intention to be vaccinated amongst healthcare workers was low. AIMS: To determine what influenced vaccination uptake among general practice healthcare workers in Shropshire County Primary Care Trust in the UK. METHODS: A cross-sectional survey was distributed to all frontline healthcare workers in Shropshire County's general practices in June 2010. All 45 practices participated. Questionnaires were distributed by practice managers to frontline staff and returned by post. Practices with the lowest return rates were reminded by telephone after 3 months. RESULTS: 205 valid replies were received, giving a response rate of 48.0%. 10.0% reported being infected with the pandemic H1N1 strain by the time they received the questionnaire. 172 (83.9%) respondents reported that they had been vaccinated against H1N1. Influenza infection prior to vaccination had a negative impact on uptake (adjusted OR 0.17, 95% CI 0.05 to 0.56) and previous vaccination against seasonal influenza was associated with increased uptake (adjusted OR 4.07, 95% CI 1.62 to 10.24). Those who received the pandemic vaccine were seven times more likely to accept future vaccines (adjusted OR 7.04, 95% CI 2.70 to 18.37). CONCLUSIONS: Vaccination uptake was significantly higher than the national (40.3%), regional (40.9%), and county averages (49.3%). Motivation for and against vaccination was very similar to that for seasonal vaccination, with previous vaccination having the greatest influence. Ensuring healthcare workers receive vaccination early in their career is likely to set a precedent for future vaccination. This is the first detailed study purely in general practice in England
Improving the primary prevention of cardiovascular events by using biomarkers to identify individuals with silent heart disease
No full textObjectives The aim of this study was to examine whether biomarkers can identify silent cardiac target organ damage (cTOD) in a primary prevention population. Background One possible way to improve primary prevention of cardiovascular events is to identify those patients who already harbor silent cTOD (i.e., myocardial ischemia, left ventricular hypertrophy, systolic dysfunction, diastolic dysfunction, or left atrial enlargement). This might be possible by screening with a biomarker (e.g. high sensitivity cardiac troponin T [hs-cTnT] or B-type natriuretic peptide [BNP]). Methods We prospectively recruited 300 asymptomatic individuals already receiving primary prevention therapy. Transthoracic echocardiography, stress echocardiography, and/or myocardial perfusion imaging were performed to identify silent cTOD. Results One hundred two (34%) patients had evidence of cTOD. Left ventricular hypertrophy was the most prevalent (29.7%) form of cTOD, followed by diastolic dysfunction (21.3%), left atrial enlargement (15.3%), systolic dysfunction (6.3%), and ischemia (6.3%). The area under the curve (AUC) for BNP to identify any form of silent cTOD was 0.78 overall and 0.82 in men. The equivalent figures for hs-cTnT were 0.70 and 0.75 in women. The AUC for BNP and hs-cTnT together was 0.81 and 0.82 in men. However, the discrimination power of other markers was poor, with AUCs of 0.61 for microalbuminuria, 0.49 for uric acid, and 0.58 for eGFR. Conclusions In asymptomatic treated primary prevention patients, BNP screening is able to identify existing silent cTOD. The performance of hs-cTnT was not as good as that of BNP. B-type natriuretic peptide plus hs-cTnT together performed best. Prescreening with BNP +/- cTnT followed by targeted phenotyping is worth exploring further as a possible way to improve primary prevention. (J Am Coll Cardiol 2012;60:960-8) (C) 2012 by the American College of Cardiology Foundation</p
Design, Synthesis and Biological Evaluation of Novel Inhibitors of Trypanosoma brucei Pteridine Reductase 1
No full textGenetic studies indicate that the enzyme pteridine reductase 1 (PTR1) is essential for the survival of the protozoan parasite Trypanosoma brucei. Herein, we describe the development and optimisation of a novel series of PTR1 inhibitors, based on benzo[d]imidazol-2-amine derivatives. Data are reported on 33 compounds. This series was initially discovered by a virtual screening campaign (J. Med. Chem., 2009, 52, 4454). The inhibitors adopted an alternative binding mode to those of the natural ligands, biopterin and dihydrobiopterin, and classical inhibitors, such as methotrexate. Using both rational medicinal chemistry and structure-based approaches, we were able to derive compounds with potent activity against T. brucei PTR1 (K-i(app) = 7 nm), which had high selectivity over both human and T. brucei dihydrofolate reductase. Unfortunately, these compounds displayed weak activity against the parasites. Kinetic studies and analysis indicate that the main reason for the lack of cell potency is due to the compounds having insufficient potency against the enzyme, which can be seen from the low K-m to K-i ratio (K-m = 25 nm and K-i = 2.3 nm, respectively).</p
Inhibitors of the kinase IspE:structure-activity relationships and co-crystal structure analysis
No full textEnzymes of the non-mevalonate pathway for isoprenoid biosynthesis are therapeutic targets for the treatment of important infectious diseases. Whereas this pathway is absent in humans, it is used by plants, many eubacteria and apicomplexan protozoa, including major human pathogens such as Plasmodium falciparum and Mycobacterium tuberculosis. Herein, we report on the design, preparation and biological evaluation of a new series of ligands for IspE protein, a kinase from this pathway. These inhibitors were developed for the inhibition of IspE from Escherichia coli, using structure-based design approaches. Structure-activity relationships (SARs) and a co-crystal structure of Aquifex aeolicus IspE bound to a representative inhibitor validate the proposed binding mode. The crystal structure shows that the ligand binds in the substrate-rather than the adenosine 5'-triphosphate (ATP)-binding pocket. As predicted, a cyclopropyl substituent occupies a small cavity not used by the substrate. The optimal volume occupancy of this cavity is explored in detail. In the co-crystal structure, a diphosphate anion binds to the Gly-rich loop, which normally accepts the triphosphate moiety of ATP. This structure provides useful insights for future structure-based developments of inhibitors for the parasite enzymes.</p
Covert collusion? American and South African relations during the Angolan civil war, 1974-1976
No full textThe traditional focus regarding the Angolan Civil War, 1974 – 1976, has been on the nature of Soviet and Cuban involvement, the American response to communist activities, and South Africa’s invasion. A point often mentioned, but rarely elaborated upon in the literature, is the degree to which the USA encouraged South Africa to intervene in the Angolan conflict. This paper investigates the extent and nature of American collusion with South Africa in the civil war, and the degree of complicity of senior American officials. The paper argues that on balance, the evidence suggests that senior elements of the United States executive branch, covertly and informally, colluded with South Africa. South African politicians overestimated the depth and extent of American support for its intervention, and when the USA ceased its assistance, they felt betrayed by Kissinger
Interpreting transient photocurrents as a signature of the density of states distribution:the profound importance of the short-time decay
No full textWe present a study exploring the fidelity of recovery of the density of states from transient photocurrents for different distributions of traps based on computer simulation of transient photocurrent decay (TPC). The most important result of the work is that much of the information on the form of the density of states (DOS) over an energy range of up to 0.5 eV depth, is contained in the detailed form of the initial decay of the photocurrent on a timescale <10-10 s in which we might expect only the shallowest traps to have an affect. To illustrate this point, we demonstrate that substantially different DOS distributions (exponential, Gaussian, rectangular) can be made to give apparently identical TPC decays over several orders of magnitude of time after an initial trapping phase in which there are only small differences in the shape of the response. Recombination effects may also be included. Nevertheless, using a Fourier transform TPC analytical method we can make a distinction between such DOS distributions, provided the short-time initial decay is included
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