The solution structure of the Zα domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA

Double-stranded RNA deaminase I (ADAR1) contains the Z-DNA binding domain Zα. Here we report the solution structure of free Zα and map the interaction surface with Z-DNA, confirming roles previously assigned to residues by mutagenesis. Comparison with the crystal structure of the (Zα)2/Z-DNA complex shows that most Z-DNA contacting residues in free Zα are prepositioned to bind Z-DNA, thus minimizing the entropic cost of binding. Comparison with homologous (α+β)helix–turn–helix/B-DNA complexes suggests that binding of Zα to B-DNA is disfavored by steric hindrance, but does not eliminate the possibility that related domains may bind to both B- and Z-DNA.

Computational cost of GNG3D algorithm for mesh simplification

In this paper we present a study of the computational cost of the GNG3D algorithm for mesh optimization. This algorithm has been implemented taking as a basis a new method which is based on neural networks and consists on two differentiated phases: an optimization phase and a reconstruction phase. The optimization phase is developed applying an optimization algorithm based on the Growing Neural Gas model, which constitutes an unsupervised incremental clustering algorithm. The primary goal of this phase is to obtain a simplified set of vertices representing the best approximation of the original 3D object. In the reconstruction phase we use the information provided by the optimization algorithm to reconstruct the faces thus obtaining the optimized mesh. The computational cost of both phases is calculated, showing some examples.

The eastern ‘partnership’ of gas. Gazprom and CNPC strike a deal on gas supplies to China. OSW COMMENTARY No. 139, 2014-06-16

The CEOs of Gazprom and China’s CNPC signed a contract concerning Russian gas supplies to China on 21 May 2014 in Shanghai. The contract had been under negotiation for many years and was signed in the presence of the two countries’ presidents. Under this 30-year deal, ultimately 38 billion m3 of natural gas will be exported annually from eastern Siberian fields (Chayandinskoye and Kovyktinskoye) via the Power of Siberia pipeline planned for construction in 2015–2019. The lengthy negotiation process (initial talks regarding this issue began back in the 1990s), the circumstances surrounding the signing of the contract (it was signed only on the second day of Vladimir Putin’s visit to Shanghai, and the Russian president’s personal engagement in the final phase of the talks turned out to be a key element) and information concerning the provisions of the contract (the clause determining the contract price has not been revealed) all indicate that the terms of the compromise are more favourable for China than for Russia. This contract is at present important to Russia mainly for political reasons (it will use the future diversification of gas export routes as an instrument in negotiations with the EU). However, the impact of this instrument seems to be limited since supplies cannot be redirected from Europe to Asia. It is unclear whether the contract will bring the anticipated long-term economic benefits to Gazprom. The gas price is likely to remain at a level of between US$350 and US$390 per 1000 m3. Given the high costs of gas field operation and production and transport infrastructure development, this may mean that supplies will be carried out at the margin of profitability. The Shanghai contract does not conclude the negotiation process since a legally binding agreement on gas pipeline construction has not been signed and not all of the financial aspects of the project have been agreed upon as yet (such as the issue of possible Chinese prepayments for gas supplies).

An Assessment of the Penalties System for Infringements of EU Competition Law: Can Personal Sanctions be the Missing Piece of the Puzzle? IES WORKING PAPER 6/2013

Competition law seeks to protect competition on the market as a means of enhancing consumer welfare and of ensuring an efficient allocation of resources. In order to be successful, therefore, competition authorities should be adequately equipped and have at their disposal all necessary enforcement tools. However, at the EU level the current enforcement system of competition rules allows only for the imposition of administrative fines by the European Commission to liable undertakings. The main objectives, in turn, of an enforcement policy based on financial penalties are two fold: to impose sanctions on infringing undertakings which reflect the seriousness of the violation, and to ensure that the risk of penalties will deter both the infringing undertakings (often referred to as 'specific deterrence') and other undertakings that may be considering anti-competitive activities from engaging in them (often referred to as 'general deterrence'). In all circumstances, it is important to ensure that pecuniary sanctions imposed on infringing undertakings are proportionate and not excessive. Although pecuniary sanctions against infringing undertakings are a crucial part of the arsenal needed to deter competition law violations, they may not be sufficient. One alternative option in that regard is the strategic use of sanctions against the individuals involved in, or responsible for, the infringements. Sanctions against individuals are documented to focus the minds of directors and employees to comply with competition rules as they themselves, in addition to the undertakings in which they are employed, are at risk of infringements. Individual criminal penalties, including custodial sanctions, have been in fact adopted by almost half of the EU Member States. This is a powerful tool but is also limited in scope and hard to implement in practice mostly due to the high standards of proof required and the political consensus that needs first to be built. Administrative sanctions for individuals, on the other hand, promise to deliver up to a certain extent the same beneficial results as criminal sanctions whilst at the same time their adoption is not likely to meet strong opposition and their implementation in practice can be both efficient and effective. Directors’ disqualification, in particular, provides a strong individual incentive for each member, or prospective member, of the Board as well as other senior executives, to take compliance with competition law seriously. It is a flexible and promising tool that if added to the arsenal of the European Commission could bring balance to the current sanctioning system and that, in turn, would in all likelihood make the enforcement of EU competition rules more effective. Therefore, it is submitted that a competition law regime in order to be effective should be able to deliver policy objectives through a variety of tools, not simply by imposing significant pecuniary sanctions to infringing undertakings. It is also clear that individual sanctions, mostly of an administrative nature, are likely to play an increasingly important role as they focus the minds of those in business who might otherwise be inclined to regard infringing the law as a matter of corporate risk rather than of personal risk. At the EU level, in particular, the adoption of directors’ disqualification promises to deliver more effective compliance and greater overall economic impact.

The Energy Performance of Buildings: Promises Still Unfulfilled. Egmont Paper No. 78, May 2015

EXECUTIVE SUMMARY All observers agree that energy efficiency must be the cornerstone of any serious EU energy strategy. In this general context, the EU building sector is critical. It represents about 40% of EU final energy consumption (residential houses, public/private offices, commercial buildings, etc.) and approximately 36% of EU CO2 emissions. This is massive. The EU has certainly not been inactive in this field. The Energy Performance in Buildings Directive 2002/91/EC (EPBD) was the first and the main instrument to address the problem of the energy performance of buildings. It has established numerous principles: a reliable methodology which enables the calculation and rating of the energy performance of buildings; minimum energy performance standards for new buildings and existing buildings under major renovation; energy performance certificates; regular inspection of heating and air-conditioning systems; and, finally, quality standards for inspections and energy performance certificates. They were strengthened in 2010 by the recast Directive 2010/31/EU. This directive also introduces a decisive concept for the development of the building sector: ‘nearly zeroenergy buildings’. In 2012, the new Energy Efficiency Directive 2012/27/EU dealt with other aspects. In the building sector, three of them are particularly important. They concern: (1) the establishment of long-term strategies for mobilizing investment in the renovation of the national building stocks; (2) the introduction of energy saving schemes for ‘designated’ energy companies with a view to reducing consumption among ‘final consumers’ by 1.5% annually; and (3), as an option, the setting up of an Energy Efficiency National Fund to support energy efficiency initiatives. This paper also briefly examines the different instruments put in place to disseminate information and consultation, and the EU funding for energy efficiency in buildings. Results, however, have remained limited until now. The improvement of the energy performance of buildings and the rhythm of renovation remain extremely weak. Member States’ unwillingness to timely and properly transpose and implement the Directives continues despite the high degree of flexibility permitted. The decentralized approach chosen for some specific aspects and the differentiation in the application of EPBD standards between Member States do not appear optimal either. Adequate financial schemes remain rare. The permanent deficit of qualified and trained personnel and the inertia of public authorities to make the public understand the stakes in this domain remain problematic. Hence the need to take new initiatives to reap the benefits that the building sector is meant to bring.

The Political Economy of Financial Crisis Policy. Bruegel Working Paper 2015/06, July 2015

Highlights • Government intervention to stabilise financial systems in times of banking crises ultimately involves political decisions. This paper sheds light on how certain political variables influence policy choices during banking crises and hence have an impact on fiscal outlays. • We employ cross-country econometric evidence from all crisis episodes in the period 1970-2011 to examine the impact political and party systems have on the fiscal cost of financial sector intervention. • Governments in presidential systems are associated with lower fiscal costs of crisis management because they are less likely to use costly bank guarantees, thus reducing the exposure of the state to significant contingent and direct fiscal liabilities. Consistent with these findings we find further evidence that these governments are less likely to use bank recapitalisation and more likely to impose losses on depositors.

The isotope composition of selenium in chondrites constrains the depletion mechanism of volatile elements in solar system materials

Solar nebula processes led to a depletion of volatile elements in different chondrite groups when compared to the bulk chemical composition of the solar system deduced from the Sun's photosphere. For moderately-volatile elements, this depletion primarily correlates with the element condensation temperature and is possibly caused by incomplete condensation from a hot solar nebula, evaporative loss from the precursor dust, and/or inherited from the interstellar medium. Element concentrations and interelement ratios of volatile elements do not provide a clear picture about responsible mechanisms. Here, the abundance and stable isotope composition of the moderately- to highly-volatile element Se are investigated in carbonaceous, ordinary, and enstatite chondrites to constrain the mechanism responsible for the depletion of volatile elements in planetary bodies of the inner solar system and to define a δ(82/78)Se value for the bulk solar system. The δ(82/78)Se of the studied chondrite falls are identical within their measurement uncertainties with a mean of −0.20±0.26‰ (2 s.d., n=14n=14, relative to NIST SRM 3149) despite Se abundance depletions of up to a factor of 2.5 with respect to the CI group. The absence of resolvable Se isotope fractionation rules out a kinetic Rayleigh-type incomplete condensation of Se from the hot solar nebula or partial kinetic evaporative loss on the precursor material and/or the parent bodies. The Se depletion, if acquired during partial condensation or evaporative loss, therefore must have occurred under near equilibrium conditions to prevent measurable isotope fractionation. Alternatively, the depletion and cooling of the nebula could have occurred simultaneously due to the continuous removal of gas and fine particles by the solar wind accompanied by the quantitative condensation of elements from the pre-depleted gas. In this scenario the condensation of elements does not require equilibrium conditions to avoid isotope fractionation. The results further suggest that the processes causing the high variability of Se concentrations and depletions in ordinary and enstatite chondrites did not involve any measurable isotope fractionation. Different degrees of element depletions and isotope fractionations of the moderately-volatile elements Zn, S, and Se in ordinary and enstatite chondrites indicate that their volatility is controlled by the thermal stabilities of their host phases and not by the condensation temperature under canonical nebular conditions.

Sedimentology at the continental margin of the southern Weddell Sea

During four expeditions with RV "Polarstern" at the continental margin of the southern Weddell Sea, profiling and geological sampling were carried out. A detailed bathymetric map was constructed from echo-sounding data. Sub-bottom profiles, classified into nine echotypes, have been mapped and interpreted. Sedimentological analyses were carried out on 32 undisturbed box grab surface samples, as well as on sediment cores from 9 sites. Apart from the description of the sediments and the investigation of sedimentary structures on X-radiographs the following characteristics were determined: grain-size distributions; carbonate and Corg content; component distibutions in different grain-size fractions; stable oxygen and carbon isotopes in planktic and, partly, in benthic foraminifers; and physical properties. The stratigraphy is based On 14C-dating, oxygen isotope Stages and, at one site, On paleomagnetic measurements and 230Th-analyses The sediments represent the period of deposition from the last glacial maximum until recent time. They are composed predominantly of terrigenous components. The formation of the sediments was controlled by glaciological, hydrographical and gravitational processes. Variations in the sea-ice coverage influenced biogenic production. The ice sheet and icebergs were important media for sediment transport; their grounding caused compaction and erosion of glacial marine sediments on the outer continental shelf. The circulation and the physical and chemical properties of the water masses controlled the transport of fine-grained material, biogenic production and its preservation. Gravitational transport processes were the inain mode of sediment movements on the continental slope. The continental ice sheet advanced to the shelf edge and grounded On the sea-floor, presumably later than 31,000 y.B.P. This ice movement was linked with erosion of shelf sediments and a very high sediment supply to the upper continental slope from the adiacent southern shelf. The erosional surface On the shelf is documented in the sub-bottom profiles as a regular, acoustically hard reflector. Dense sea-ice coverage above the lower and middle continental slope resulted in the almost total breakdown of biogenic production. Immediately in front of the ice sheet, above the upper continental slope, a <50 km broad coastal polynya existed at least periodically. Biogenic production was much higher in this polynya than elsewhere. Intense sea-ice formation in the polynya probably led to the development of a high salinity and, consequently, dense water mass, which flowed as a stream near bottom across the continental slope into the deep sea, possibly contributing to bottom water formation. The current velocities of this water mass presumably had seasonal variations. The near-bottom flow of the dense water mass, in combination with the gravity transport processes that arose from the high rates of sediment accumulation, probably led to erosion that progressed laterally from east to West along a SW to NE-trending, 200 to 400 m high morphological step at the continental slope. During the period 14,000 to 13,000 y.B.P., during the postglacial temperature and sea-level rise, intense changes in the environmental conditions occured. Primarily, the ice masses on the outer continental shelf started to float. Intense calving processes resulted in a rapid retreat of the ice edge to the south. A consequence of this retreat was, that the source area of the ice-rafted debris changed from the adjacent southern shelf to the eastern Weddell Sea. As the ice retreated, the gravitational transport processes On the continental slope ceased. Soon after the beginning of the ice retreat, the sea-ice coverage in the whole research area decreased. Simultaneously, the formation of the high salinity dense bottom water ceased, and the sediment composition at the continental slope then became influenced by the water masses of the Weddell Gyre. The formation of very cold Ice Shelf Water (ISW) started beneath the southward retreating Filchner-Ronne Ice Shelf somewhat later than 12,000 y.B.P. The ISW streamed primarily with lower velocities than those of today across the continental slope, and was conducted along the erosional step on the slope into the deep sea. At 7,500 y.B.P., the grounding line of the ice masses had retreated > 400 km to the south. A progressive retreat by additional 200 to 300 km probably led to the development of an Open water column beneath the ice south of Berkner Island at about 4,000 y.B.P. This in turn may have led to an additional ISW, which had formed beneath the Ronne Ice Shelf, to flow towards the Filcher Ice Shelf. As a result, increased flow of ISW took place over the continental margin, possibly enabling the ISW to spill over the erosional step On the upper continental slope towards the West. Since that time, there is no longer any documentation of the ISW in the sedimentary Parameters on the lower continental slope. There, recent sediments reflect the lower water masses of the Weddell Gyre. The sea-ice coverage in early Holocene time was again so dense that biogenic production was significantly restricted.

(Table 1) Comparison of three chronologies for the sapropel series of cores KC01-KC01b

The Quaternary climate of southern Europe (south Italy and Greece) is investigated by pollen analysis of the sapropels which were deposited in the deep eastern Mediterranean Sea during the last 1 million year (Ma). The time-scale of core KC01b in the Ionian Sea has been established by tuning its oxygen isotopic record to the ice volume model of Imbrie and Imbrie (1980, doi:10.1126/science.207.4434.943). For the last 250,000 year (250 ka), the previous pollen studies and astronomical tuning have been confirmed. Sapropels were deposited under a large range of Mediterranean climates: fully interglacial, fully glacial, and intermediary, as revealed mainly by the balance between the respective pollen abundances of oak (Quercus) and sage-brush (Artemisia). The high value of the oak reveals the warm and wet climate of an Interglacial, and the high value of the sage-brush, the dry and cold climate of a Glacial. Whereas the Mediterranean climate is directly related to the variation of the high-latitude ice sheets, the deposition of sapropels is not so. In contrast with the wide climatic range, sapropels were deposited only when summer insolation in the low latitudes reached its highest peaks. However, between 250 ka and 1 Ma, that stable pattern is not yet established. Only six sapropels are observed, many expected ones do not appear, even as ghosts signalled by peaks of barium abundance, that remain after the post-deposition oxidation of organic matter. The pattern of sapropel formation in stable and direct relationship to highest insolation does not seem to apply. For five of those sapropels, neither climate extremes are observed; they mainly formed during intermediary types of Mediterranean climate. In contrast, one sapropel (and one ghost) relates to a relatively low peak of insolation, and its climate is of a unique, composite type not seen later. This might suggest an unsuspected, more complex pattern linking the formation of Mediterranean sapropels to the astronomical configuration.

The economic costs of road traffic crashes: Australia, states and territories

In this paper, we obtain detailed data on road traffic crash (RTC) casualties, by severity, for each of the eight state and territory jurisdictions for Australia and use these to estimate and compare the economic impact of RTCs across these regions. We show that the annual cost of RTCs in Australia, in 2003, was approximately $17b, which is approximately 2.3% of the Gross Domestic Product (GDP). Importantly, though, there is remarkable intra-national variation in the incident rates of RTCs in Australia and costs range from approximately 0.62 to 3.63% of Gross State Product (GSP). The paper makes two fundamental contributions: (i) it provides a detailed breakdown of estimated RTC casualties, by state and territory regions in Australia, and (ii) it presents the first sub-national breakdown of RTC costs for Australia. We trust that these contributions will assist policy-makers to understand sub-national variations in the road toll better and will encourage further research on the causes of the marked differences between RTC outcomes across the states and territories of Australia. (c) 2006 Elsevier Ltd. All rights reserved.

Synthesis and characterization of Pd(II) and Pt(II) complexes with triazolopyrimidine derivatives: The crystal structure of [Pd2L2Cl4] where L=5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine

The Pd(II) and Pt(II) complexes with triazolopyrimidine C-nucleosides L-1 (5,7-dimethyl-3-(2',3',5'-tri-O-benzoyl-beta-D-ribofuranosyl-s-triazolo)[4,3-a]pyrimidine), L-2 (5,7-dimethyl-3-beta-D-ribofuranosyl-s-triazolo [4,3-a]pyrimidine) and L-3 (5,7-dimethyl[1,5-a]-s-triazolopyrimidine), [Pd(en)(L-1)](NO3)(2), (Pd(bpy)(L-1)](NO3)(2), cis-Pd(L-3)(2)Cl-2, [Pd-2(L-3)(2)Cl-4]center dot H2O, cis-Pd(L-2)(2)Cl-2 and [Pt-3(L-1)(2)Cl-6] were synthesized and characterized by elemental analysis and NMR spectroscopy. The structure of the [Pd-2(L-3)(2)Cl-4]center dot H2O complex was established by Xray crystallography. The two L-3 ligands are found in a head to tail orientation, with a (PdPd)-Pd-... distance of 3.1254(17) angstrom.L-1 coordinates to Pd(II) through N8 and N1 forming polymeric structures. L-2 coordinates to Pd(II) through N8 in acidic solutions (0.1 M HCl) forming complexes of cis-geometry. The Pd(II) coordination to L-2 does not affect the sugar conformation probably due to the high stability of the C-C glycoside bond. (c) 2006 Elsevier B.V. All rights reserved.

Studies in the anionic polymerization of methyl methacrylate

A study has been made of the anionic polymerization of methyl methacrylate using butyllithium and polystyryl lithium as initiators and using aluminium triisobutyl as a cocatalyst. The aspects of the polymerization that were examined were the effect of changing the order of addition of reagents, the temperature at which polymerization takes place and the polarity of the solvent. Trends were assessed in terms of molecular weight, molecular weight distribution and tacticity. In addition, a second monomer addition test was carried out to verify that the polymerization was truly a living one, and a kinetic study was attempted. Studies to investigate the effect of changing the order of addition of reagents showed that polymer with similar polydispersities and tacticities are produced whether the pre-mixing (mixing initiator and cocatalyst before addition of monomer) or the post-mixing (mixing monomer and cocatalyst before addition of initiator) method were used. However, polymerizations using the post-mixing mixing method demonstrated lower initiator efficiencies, possibly indicating a different initiating species. Investigations into the effect of changing the polymerization temperature show the molecular weight distribution to narrow as the temperature decreases, although a small amount of low molecular weight tailing was also observed at low temperature. A clear relationship between tacticity and temperature was observed with syndiotacticity increasing with decreasing temperature. Changes in solvent polarity were achieved by using mixtures of the standard solvent, toluene, with varying amounts of cyclohexane, tetrahydrofuran or dichloromethane. Experiments at low solvent polarity (using toluene/cyclohexane mixtures) showed problems with initiator solubility but produced polymer with lower polydispersity and higher syndiotacticity than in toluene alone. Experiments using toluene/THF mixtures yielded no polymer, thought to be owing to a side reaction between THF and aluminium triisobutyl. Increased solvent polarity, achieved using toluene/dichloromethane mixtures produced polymer with higher polydispersity and at lower yields than the conventional system, but also with higher syndiotacticity. Second monomer addition reactions demonstrated that the polymerization was 'living' since an increase in molecular weight was observed with no increase in polydispersity. Kinetic studies demonstrated the high speed of the polymerization but yielded no useful data.

Antitumour imidazotetrazines: probes for the major groove of DNA

The antitumour imidazotetrazinones are believed to act as prodrugs for the triazene series of alkylating agents, showing a marked pteference for the alkylation of the middle guanine residue in a run of three or more contiguous guanines. However, the. exact nature of the interactions of imidazotetrazinones within the micro~environment of DNA are; as yet unknown. In order to examine such interactions a three pronged approach involving molecular modelling, synthetic chemistry and biological analysis has been undertaken during the course of this project. . Molecular modelling studies have shown that for the 8-carboxamido substituted imidazotetrazinones antitumour activity is dependent upon the. presence of a free NH group which can be involved in the formation of both intramolecular and intermolecular hydrogen bonds, and the presence of a non-bulky substituent with a small negative potential . volume. Modelling studies involving the docking of .mitozolomide into the major groove of DNA in the region of a triguanine sequence has shown that a number of hydrogen bonding interactions are feasible. A series of 8-substituted carboxamide derivatives of mitozolomide have been synthesised via the 8-acid chloride and 8-carboxylic acid derivatives including a number of peptide analogues. The peptide derivatives were based upon the key structural features of the helix-turn-helix motif of DNA-binding proteins with a view to developing agents that are capable of binding to DNA with greater selectivity. An examination of the importance of intramolecular hydrogen bonding in influencing the antitumour activity:of :the imidazotetrazinones has led to the synthesis of the novel pyrimido[4',5' :4,3]pyrazolo[5,1-d]-1,2,3,5-tetrazine ring system. In general, in vitro cytotoxicity assays showed that the new derivatives were less active against the TLX5 lymphoma cell line. than the parent compound mitozolomide despite an increased potential for hydrogen bonding interactions. Due to the high reactivity of the: tetrazinone ring system it is difficult to study the interactions between the imidazotetrazinones and DNA. Consequently a number of structural analogues that are stable under physiological conditions have been. prepared based upon the 1,2,3 triazin-4(3H)-one ring system fused with both benzene and pyrazole rings. Although the 3-methylbenzotriazinones failed to antagonise the cytotoxic activity of temozolomide encouraging results with a 3-methylpyrazolotriazinone may suggest the existence of an imidazotetrazinone receptor site within DNA. The potential of guanine rich sequences to promote the alkylating selectivity of imidazotetrazinones by acting as a catalyst for ring cleavage and thereby generation of the alkylating agent was examined. Experiments involving the monitoring: of the rate of breakdown of mitozolomide incubated in the presence of synthetic oIigonucleotides did not reveal any catalytic effect resulting from the DNA. However, it was noted that the breakdown of mitozolomide was dependent upon the type of buffer used in the incubations and this may indeed mask any catalysis by the oligonucleotides.

The structural properties of glassfibre reinforced plastics

The research work described in this thesis is concerned with the development of glassfibre reinforced plastics for structural uses in Civil Engineering construction. The first stage was primarily concerned with the design of GRP lamintes with structura1 properties and method of manufacture suitable for use with relatively large structural components. A cold setting, pressure moulding technique was developed which proved to be efficient in reducing the void content in the composite and minimising the exothermic effect due to curing. The effect of fibre content and fibre arrangement on strength and stiffness of the cornposite was studied and the maximum amount of' fibre content that could be reached by the adopted type of moulding technique was determined. The second stage of the project was concerned with the introduction of steel-wire "sheets" into the GRP cornposites, to take advantage of the high modulus of steel wire to improve the GRP stiffness and to reduce deformation. The experimental observations agreed reasonably well with theoretical predictions in both first and second stages of the work. The third stage was concerned with studying the stability of GRP flat rectangular plates subjected to uniaxial compression or pure shear, to simulate compression flanges or shear webs respectively. The investigation was concentrated on the effect of fibre arrangement in the plate on buckling load. The effect of the introduction of steel-wire sheets on the plate stability in compression was also investigated. The boundary conditions were chosen to be close to those usually assumed in built-up box-sections for both compression flanges and webs. The orthotropic plate and the mid-plane symmetric were used successfully in predicting the buckling load theoretically. In determining the buckling load experimentally, two methods were used. The Southwell plot method and electrical strain gauge method. The latter proved to be more reliable in predicting the buckling load than the former, especially for plates under uniaxial compression. Sample design charts for GRP plates that yield and buckle simultaneously under compression are also presented in the thesis. The final stage of the work dealt with the design and test of GRP beams. The investigation began by finding the optimum cross-section for a GRP beam. The cross-section which was developed was a thin walled corrugated section which showed higher stiffness than other cross-sections for the same cross-sectional area (i.e. box, I, and rectangular sections). A cold setting, hand layings technique was used in manufacturing these beams wbich were of nine types depending on the type of glass reinforcement employed and the arrangement of layers in the beam. The simple bending theory was used in the beam design and proved to be satisfactory in predicting the stresses and deflections. A factor of safety of 4 was chosen for design purposes and considered to be suitable for long term use under static load. Because of its relatively low modulus, GRP beams allowable deflection was limited to 1/120th of the span which was found to be adequate for design purposes. A general discussion of the behaviour of GRP composites and their place relative to the more conventional structural material was also presented in the thesis.

What factors influence concordance with medications? Findings from the UK Asian Diabetes study

Aims: To investigate concordance with medication, as assessed at baseline and at 1- and 2-year follow-up, and to examine factors associated with non-concordance in a UK-resident South-Asian population. Methods: Data from the UK Asian Diabetes Study were analysed. Concordance with medications was assessed and recorded at three time points during the study. Multiple logistic regression was used to investigate the factors associated with non-concordance; the associations of baseline factors with year 1 concordance and baseline plus year 1 factors with year 2 concordance. Results: Data for 403 patients from seven practices participating in the UK Asian Diabetes Study were analysed. The numbers of patients who were non-concordant were: 63 (16%) at baseline 101 (25%) at year 1; and 122 (30%) at year 2. The baseline-measured variables that were significantly associated with year 1 non-concordance included diabetes duration, history of cardiovascular disease, components of the EuroQol quality of life questionnaire, the EQ-5D score, and number of medications prescribed. In multivariable analyses, the most important determinant of year 1 non-concordance was baseline non-concordance: odds ratio 13.6 (95% confidence limits 4.7, 39.9). Number of medications prescribed for blood pressure control was also significant: odds ratio 1.8 (95% confidence limits 1.4, 2.4). Similar results were observed for year 2 non-concordance. Conclusions: Non-concordance with medications was common and more likely in people prescribed more medications. The current target-driven management of risk factor levels may lead to increasing numbers and doses of medications. Considering the high cost of medications and the implications of poor health behaviours on morbidity and mortality, further investigation of prescribing behaviours and the factors affecting patient concordance are required.