Dapagliflozin – do we need it registered for type 2 diabetes?

INTRODUCTION: Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) promote the excretion of glucose to reduce glycated hemoglobin (HbA1c) levels. Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved. AREAS COVERED: We evaluated a recent Phase III clinical trial with dapagliflozin. EXPERT OPINION: Dapagliflozin was studied as add-on therapy to sitagliptin with or without metformin, and was shown to lower HbA1c levels and body weight. The incidence of hypoglycaemia was low with dapagliflozin, but it did increase the incidence of urogenital infections. As no clear benefits have been identified for dapagliflozin over canagliflozin, which was the first gliflozin registered by the FDA, we do not fully understand why it was necessary to register dapagliflozin. Given that there are no completed cardiovascular/clinical outcome studies with dapagliflozin, and therefore no evidence of beneficial effect, it also seems premature to be using it extensively or considering it as an alternative to the clinically proven metformin.

A new look at the restrictions on the speed and magnitude of train loads for bridge management

In current bridge management systems (BMSs), load and speed restrictions are applied on unhealthy bridges to keep the structure safe and serviceable for as long as possible. But the question is, whether applying these restrictions will always decrease the internal forces in critical components of the bridge and enhance the safety of the unhealthy bridges. To find the answer, this paper for the first time in literature, looks into the design aspects through studying the changes in demand by capacity ratios of the critical components of a bridge under the train loads. For this purpose, a structural model of a simply supported bridge, whose dynamic behaviour is similar to a group of real railway bridges, is developed. Demand by capacity ratios of the critical components of the bridge are calculated, to identify their sensitivity to increase of speed and magnitude of live load. The outcomes of this study are very significant as they show that, on the contrary to what is expected, by applying restriction on speed, the demand by capacity ratio of components may increase and make the bridge unsafe for carrying live load. Suggestions are made to solve the problem.

Incorporation of road safety into road management systems

Road collisions negatively affect the lives of hundreds of Canadians per year. Unfortunately, safety has been typically neglected from management systems. It is common to find that a great deal of effort has been devoted to develop and implement systems capable of achieving and sustaining good levels of condition. It is relatively recent that road safety has become an important objective. Managing a network of roads is not an easy task; it requires long, medium and short term plans to maintain, rehabilitate and upgrade aging assets, reduce and mitigate accident exposure, likelihood and severity. This thesis presents a basis for incorporating road safety into road management systems; two case studies were developed; one limited by available data and another from sufficient information. A long term analysis was used to allocate improvements for condition and safety of roads and bridges, at the network level. It was confirmed that a safety index could be used to obtain a first cut model; meanwhile potential for improvement which is a difference between observed and predicted number of accidents was capable of capturing the degree of safety of individual segments. It was found that the completeness of the system resulted in savings because of the economies obtained from trade-off optimization. It was observed that safety improvements were allocated at the beginning of the analysis in order to reduce the extent of issues, which translated into a systematic reduction of potential for improvement up to a point of near constant levels, which were hypothesized to relate to those unavoidable collisions from human error or vehicle failure.

Non-monetised multi-objective decision making system for road management

This paper presents a performance-based optimisation approach for conducting trade-off analysis between safety (roads) and condition (bridges and roads). Safety was based on potential for improvement (PFI). Road condition was based on surface distresses and bridge condition was based on apparent age per subcomponent. The analysis uses a non-monetised optimisation that expanded upon classical Pareto optimality by observing performance across time. It was found that achievement of good results was conditioned by the availability of early age treatments and impacted by a frontier effect preventing the optimisation algorithm from realising of the long-term benefits of deploying actions when approaching the end of the analysis period. A disaggregated bridge condition index proved capable of improving levels of service in bridge subcomponents.

Lifecycle optimization and tradeoff analysis among competing objectives for a road corridor

While the philosophical motivation behind Civil Infrastructure Management Systems is to achieve optimal level of service at a minimum cost, the allocation of scarce resources among competing alternatives is still a matter of debate. It appears to be widely accepted that results from tradeoff analysis can be measured by the degree of accomplishment of the objectives. Road management systems not only deal with different asset types but also with conflicting objectives. This paper presents a case study of lifecycle optimization with tradeoff analysis for a road corridor in New Brunswick. Objectives of the study included condition of bridge and roads and road safety. A road safety index was created based on potential for improvement. Road condition was based on roughness, rutting and cracking. Initial results show lack of sustainability in bridge performance. Therefore, bridges where broken by components: deck, superstructure and substructure. Visual inspections, in addition to construction age of each bridge, were combined to generate a surrogate apparent age. Two life cycle analysis were conducted; one aimed to minimize overall cost while achieving sustainable results and another one purely for optimization. -used to identify required levels of budget. Such analyses were used to identify the minimum required budget and to demonstrate that with the same amount of money it was possible to achieve better levels of performance. Dominance and performance driven criteria were combined to identify and select an optimal result. It was found that achievement of optimally sustained results is conditioned by the availability of treatments for all asset classes at across their life spans. For the case study a disaggregated bridge condition index was introduced to the original algorithm to attempt to achieve sustainability in all bridges components, however lack of early stage treatments for substructures produce declining trends for such a component.

Finite element modeling of carbon fibre reinforced polymer (CFRP) strengthened steel tubes under axial impact

Steel hollow sections used in structures such as bridges, buildings and space structures involve different strengthening techniques according to their structural purpose and shape of the structural member. One such technique is external bonding of CFRP sheets to steel tubes. The performance of CFRP strengthening for steel structures has been proven under static loading while limited studies have been conducted on their behaviour under impact loading. In this study, a comprehensive numerical investigation is carried out to evaluate the response of CFRP strengthened steel tubes under dynamic axial impact loading. Impact force, axial deformation impact velocities are studied. The results of the numerical investigations are validated by experimental results. Based on the developed finite element (FE) model several output parameters are discussed. The results show that CFRP wrapping is an effective strengthening technique to increase the axial dynamic load bearing capacity by increasing the stiffness of the steel tube.

Estimating the burden of disease attributable to urban outdoor air pollution in South Africa in 2000

Objectives To quantify the mortality burden attributed to urban outdoor air pollution in South Africa in 2000. Design The study followed comparative risk assessment (CRA) methodology developed by the World Heath Organization (WHO). In most urban areas, annual mean concentrations of particulate matter (PM) with diameters less than 10 μum (PM10) from monitoring network data and PM with diameters less than 2.5 μm (PM2.5) derived using a ratio method were weighted according to population size. PM10 and PM2.5 data from air-quality assessment studies in areas not covered by the network were also included. Population-attributable fractions calculated using risk coefficients presented in the WHO study were weighted by the proportion of the total population (33%) in urban environments, and applied to revised estimates of deaths and years of life lost (YLLs) for South Africa in 2000. Setting South Africa. Subjects Children under 5 years and adults 30 years and older. Outcome measures Mortality and YLLs from lung cancer and cardiopulmonary disease in adults (30 years and older), and from acute respiratory infections (ARIs) in children aged 0 - 4 years. Results Outdoor air pollution in urban areas in South Africa was estimated to cause 3.7% of the national mortality from cardiopulmonary disease and 5.1% of mortality attributable to cancers of the trachea, bronchus and lung in adults aged 30 years and older, and 1.1% of mortality from ARIs in children under 5 years of age. This amounts to 4 637 or 0.9% (95% uncertainty interval 0.3 - 1.5%) of all deaths and about 42 000 YLLs, or 0.4% (95% uncertainty interval 0.1 - 0.7%) of all YLLs in persons in South Africa in 2000. Conclusion Urban air pollution has under-recognised public health impacts in South Africa. Fossil fuel combustion emissions and traffic-related air pollution remain key targets for public health in South Africa.

The BAD project: data mining, database and prediction of protein adsorption on surfaces

Protein adsorption at solid-liquid interfaces is critical to many applications, including biomaterials, protein microarrays and lab-on-a-chip devices. Despite this general interest, and a large amount of research in the last half a century, protein adsorption cannot be predicted with an engineering level, design-orientated accuracy. Here we describe a Biomolecular Adsorption Database (BAD), freely available online, which archives the published protein adsorption data. Piecewise linear regression with breakpoint applied to the data in the BAD suggests that the input variables to protein adsorption, i.e., protein concentration in solution; protein descriptors derived from primary structure (number of residues, global protein hydrophobicity and range of amino acid hydrophobicity, isoelectric point); surface descriptors (contact angle); and fluid environment descriptors (pH, ionic strength), correlate well with the output variable-the protein concentration on the surface. Furthermore, neural network analysis revealed that the size of the BAD makes it sufficiently representative, with a neural network-based predictive error of 5% or less. Interestingly, a consistently better fit is obtained if the BAD is divided in two separate sub-sets representing protein adsorption on hydrophilic and hydrophobic surfaces, respectively. Based on these findings, selected entries from the BAD have been used to construct neural network-based estimation routines, which predict the amount of adsorbed protein, the thickness of the adsorbed layer and the surface tension of the protein-covered surface. While the BAD is of general interest, the prediction of the thickness and the surface tension of the protein-covered layers are of particular relevance to the design of microfluidics devices.

On the topic of competency and excellence of our graduate engineers

Problem solving is an essential element of civil engineering education. It has been I observed that students are best able to understand civil engineering theory when there is a ' practical application of it. Teaching theory alone has led to lower levels of comprehension and motivation and a correspondingly higher rate of failure and "drop-out". This paper analyses the effectiveness of introducing practical design projects at an early stage within a civil engineering undergraduate program at Queensland University of Technology. In two of the essential basic subjects, Engineering Mechanics and Steel Structures, model projects which simulate realistic engineering exercises were introduced. Students were required to work in small groups to analyse, design and build the lightest I most efficient model bridges made of specific materials such as spaghetti, drinking straw, paddle pop sticks and balsa wood and steel columns for a given design loading/target capacity. The paper traces the success of the teaching strategy at each stage from its introduction through to the final student and staff evaluation.

Project-based civil engineering courses

Problem solving is an essential element of civil engineering education. It has been observed that students are best able to understand civil engineering theory when there is a practical application of it. Teaching theory alone has led to lower levels of comprehension and motivation and a correspondingly higher rate of failure and “drop-out”. This paper analyses the effectiveness of introducing practical design projects at an early stage within a civil engineering undergraduate program at Queensland University of Technology. In two of the essential basic subjects, Engineering Mechanics and Steel Structures, model projects which simulate realistic engineering exercises were introduced. Students were required to work in small groups to analyse, design and build the lightest / most efficient model bridges made of specific materials such as spaghetti, drinking straw, paddle pop sticks and balsa wood and steel columns for a given design loading/target capacity. The paper traces the success of the teaching strategy at each stage from its introduction through to the final student and staff evaluation.

History, status and future of Australia's native Sydney rock oyster industry

The Sydney rock oyster (Saccostrea glomerata) (SRO) is an oyster species that only occurs in estuaries along Australia's east coast. The SRO industry evolved from commercial gathering of oyster in the 1790s to a high production volume aquaculture industry in the 1970s. However, since the late 1970s the SRO industry has experienced a significant and continuous decline in production quantities and the industry's future commercial viably appears to be uncertain. The aim of this study was to review the history and the status of the SRO industry and to discuss the potential future prospects of this industry. This study summarised findings of the existing literature about the industry and defined development stages of the industry. Particular focus was put on the more recent development within the industry (1980s-present) which has not been covered adequately in the existing literature. The finding from this study revealed that major issues of the industry are linked to the management of prevailing diseases, the handling of water quality impairments from increasing coastal development, increasing competition from Australia's Pacific oyster (Crassostrea gigas) industry and the current socio-economic profile of the industry. The study also found that policy makers are currently confronted by the dilemma of saving a "dying art". Findings from this industry review may be vital for current and future fisheries managers and stakeholders as a basis for reviewing industry management and development strategies. This review may also be of interest for other aquaculture industries and fisheries who are dealing with similar challenges as the SRO industry.

Synthetic rating system for railway bridge management

This thesis developed a condition assessment and rating method to identify those bridges in a network which are in most need of repair for an effective life cycle management. The method estimates the contribution of critical factors towards bridge deterioration and uses structural analysis to overcome the subjectivity of traditional current condition assessment methods. This research was a part of the CRC project titled 'Life Cycle Management of Railway Bridges'. Efficient usage of resources and enhancing the safety and serviceability of railway bridges are the significant outcomes of using the proposed method.

Combustion enhancement in a scramjet engine using oxygen enrichment and porous fuel injection

This paper reports on the experimental testing of oxygen-enriched porous fuel injection in a scramjet engine. Fuel was injected via inlet mounted, oxide-based ceramic matrix composite (CMC) injectors on both flow path surfaces that covered a total of 9.2 % of the intake surface area. All experiments were performed at an enthalpy of 3.93−4.25±3.2% MJ kg−1, flight Mach number 9.2–9.6 and an equivalence ratio of 0.493±3%. At this condition, the engine was shown to be on the verge of achieving appreciable combustion. Oxygen was then added to the fuel prior to injection such that two distinct enrichment levels were achieved. Combustion was found to increase, by as much as 40 % in terms of combustion-induced pressure rise, over the fuel-only case with increasing oxygen enrichment. Further, the onset of combustion was found to move upstream with increasing levels of oxygen enrichment. Thrust, both uninstalled and specific, and specific impulse were found to be improved with oxygen enrichment. Enhanced fuel–air mixing due to the pre-mixing of oxygen with the fuel together with the porous fuel injection are believed to be the main contributors to the observed enhanced performance of the tested engine.

Are we there yet? Australian road safety targets and road traffic crash fatalities

Background Road safety targets are widely used and provide a basis for evaluating progress in road safety outcomes against a quantified goal. In Australia, a reduction in fatalities from road traffic crashes (RTCs) is a public policy objective: a national target of no more than 5.6 fatalities per 100,000 population by 2010 was set in 2001. The purpose of this paper is to examine the progress Australia and its states and territories have made in reducing RTC fatalities, and to estimate when the 2010 target may be reached by the jurisdictions. Methods Following a descriptive analysis, univariate time-series models estimate past trends in fatality rates over recent decades. Data for differing time periods are analysed and different trend specifications estimated. Preferred models were selected on the basis of statistical criteria and the period covered by the data. The results of preferred regressions are used to determine out-of-sample forecasts of when the national target may be attained by the jurisdictions. Though there are limitations with the time series approach used, inadequate data precluded the estimation of a full causal/structural model. Results Statistically significant reductions in fatality rates since 1971 were found for all jurisdictions with the national rate decreasing on average, 3% per year since 1992. However the gains have varied across time and space, with percent changes in fatality rates ranging from an 8% increase in New South Wales 1972-1981 to a 46% decrease in Queensland 1982-1991. Based on an estimate of past trends, it is possible that the target set for 2010 may not be reached nationally, until 2016. Unsurprisingly, the analysis indicated a range of outcomes for the respective state/territory jurisdictions though these results should be interpreted with caution due to different assumptions and length of data. Conclusions Results indicate that while Australia has been successful over recent decades in reducing RTC mortality, an important gap between aspirations and achievements remains. Moreover, unless there are fairly radical ("trend-breaking") changes in the factors that affect the incidence of RTC fatalities, deaths from RTCs are likely to remain above the national target in some areas of Australia, for years to come.