Parenteral and mucosal delivery of a novel multi-epitope M protein-based group A streptococcal vaccine construct: investigation of immunogenicity in mice

Primary vaccine strategies against group A streptococci (GAS) have focused on the M protein-the target of opsonic antibodies important for protective immunity. We have previously reported protection of mice against GAS infection following parenteral delivery of a multi-epitope vaccine construct, referred to as a heteropolymer. This current report has assessed mucosal (intranasal (i.n.) and oral) delivery of the heteropolymer in mice with regard to the induction and specificity of mucosal and systemic antibody responses, and compared this to parenteral delivery. GAS-specific IgA responses were detected in saliva and gut upon i.n. and oral delivery of the heteropolymer co-administered with cholera toxin B subunit, respectively. High titre serum IgG responses were elicited to the heteropolymer following all routes of delivery when administered with adjuvant. Moreover, as with parenteral delivery, serum IgG antibodies were detected to the individual heteropolymer peptides following i.n. but not oral delivery. These data support the potential of the i.n. route in the mucosal delivery of a GAS vaccine. (C) 2002 Elsevier Science Ltd. All rights reserved.

Diabetes detection in Australian general practice: a comparison of diagnostic criteria

Objectives: To study the influence of different diagnostic criteria on the prevalence of diabetes mellitus and characteristics of those diagnosed. Design and setting: Retrospective analysis of data from the general-practice-based Australian Diabetes Screening Study (January 1994 to June 1995). Participants: 5911 people with no previous diagnosis of diabetes, two or more symptoms or risk factors for diabetes, a random venous plasma glucose (PG) level > 5.5 mmol/L and a subsequent oral glucose tolerance test (OGTT) result. Main outcome measure: Prevalence of undiagnosed diabetes based on each of three sets of criteria: 1997 criteria of the American Diabetes Association (ADA), 1996 two-step screening strategy of the Australian Diabetes Society (ADS) (modified according to ADA recommendations about lowered diagnostic fasting PG level), and 1999 definition of the World Health Organization (WHO). Results: Prevalence estimates for undiagnosed diabetes using the American (ADA), Australian (ADS) and WHO criteria (95% CI) were 9.4% (8.7%-10.1%), 16.0% (15.3%-16.7%) and 18.1% (17.1%-19.1%), respectively. People diagnosed with diabetes by fasting PG level (common to all sets of criteria) were more likely to be male and younger than those diagnosed only by 2 h glucose challenge PG level (Australian and WHO criteria only). The Australian (ADS) stepwise screening strategy detected 88% of those who met the WHO criteria for diabetes, including about three-quarters of those with isolated post-challenge hyperglycaemia. Conclusion: The WHO criteria (which include an OGTT result) are preferable to the American (ADA) criteria (which rely totally on fasting PG level), as the latter underestimated the prevalence of undiagnosed diabetes by almost a half. The Australian (ADS) strategy identified most of those diagnosed with diabetes by WHO criteria.

Ecological criteria for evaluating candidate sites for marine reserves

Several schemes have been developed to help select the locations of marine reserves. All of them combine social, economic, and biological criteria, and few offer any guidance as to how to prioritize among the criteria identified. This can imply that the relative weights given to different criteria are unimportant. Where two sites are of equal value ecologically; then socioeconomic criteria should dominate the choice of which should be protected. However, in many cases, socioeconomic criteria are given equal or greater weight than ecological considerations in the choice of sites. This can lead to selection of reserves with little biological value that fail to meet many of the desired objectives. To avoid such a possibility, we develop a series of criteria that allow preliminary evaluation of candidate sites according to their relative biological values in advance of the application of socioeconomic criteria. We include criteria that,. while not strictly biological, have a strong influence on the species present or ecological processes. Out scheme enables sites to be assessed according to their biodiversity, the processes which underpin that diversity, and the processes that support fisheries and provide a spectrum of other services important to people. Criteria that capture biodiversity values include biogeographic representation, habitat representation and heterogeneity, and presence of species or populations of special interest (e.g., threatened species). Criteria that capture sustainability of biodiversity and fishery values include the size of reserves necessary to protect viable habitats, presence of exploitable species, vulnerable life stages, connectivity among reserves, links among ecosystems, and provision of ecosystem services to people. Criteria measuring human and natural threats enable candidate sites to be eliminated from consideration if risks are too great, but also help prioritize among sites where threats can be mitigated by protection. While our criteria can be applied to the design of reserve networks, they also enable choice of single reserves to be made in the context of the attributes of existing protected areas. The overall goal of our scheme is to promote the development of reserve networks that will maintain biodiversity and ecosystem functioning at large scales. The values of eco-system goods and services for people ultimately depend on meeting this objective.

Outcome variables for osteoarthritis clinical trials: the OMERACT-OARSI set of responder criteria

Improvement in analysis and reporting results of osteoarthritis (OA) clinical trials has been recently obtained because of harmonization and standardization of the selection of outcome variables (OMERACT 3 and OARSI). Moreover, OARSI has recently proposed the OARSI responder criteria. This composite index permits presentation of results of symptom modifying clinical trials in OA based on individual patient responses (responder yes/no). The 2 organizations (OMERACT and OARSI) established. a task force aimed at evaluating: (1) the variability of observed placebo and active treatment effects using the OARSI responder criteria; and (2) the possibility of proposing a simplified set of criteria. The conclusions of the task force were presented and discussed during the OMERACT 6 conference, where a simplified set of responder criteria (OMERACT-OARSI set of criteria) was proposed.

Critical comparison of Julius Kruttschnitt Mineral Research Centre (JKMRC) blast fragmentation models

Blast fragmentation can have a significant impact on the profitability of a mine. An optimum run of mine (ROM) size distribution is required to maximise the performance of downstream processes. If this fragmentation size distribution can be modelled and controlled, the operation will have made a significant advancement towards improving its performance. Blast fragmentation modelling is an important step in Mine to Mill™ optimisation. It allows the estimation of blast fragmentation distributions for a number of different rock mass, blast geometry, and explosive parameters. These distributions can then be modelled in downstream mining and milling processes to determine the optimum blast design. When a blast hole is detonated rock breakage occurs in two different stress regions - compressive and tensile. In the-first region, compressive stress waves form a 'crushed zone' directly adjacent to the blast hole. The second region, termed the 'cracked zone', occurs outside the crush one. The widely used Kuz-Ram model does not recognise these two blast regions. In the Kuz-Ram model the mean fragment size from the blast is approximated and is then used to estimate the remaining size distribution. Experience has shown that this model predicts the coarse end reasonably accurately, but it can significantly underestimate the amount of fines generated. As part of the Australian Mineral Industries Research Association (AMIRA) P483A Mine to Mill™ project, the Two-Component Model (TCM) and Crush Zone Model (CZM), developed by the Julius Kruttschnitt Mineral Research Centre (JKMRC), were compared and evaluated to measured ROM fragmentation distributions. An important criteria for this comparison was the variation of model results from measured ROM in the-fine to intermediate section (1-100 mm) of the fragmentation curve. This region of the distribution is important for Mine to Mill™ optimisation. The comparison of modelled and Split ROM fragmentation distributions has been conducted in harder ores (UCS greater than 80 MPa). Further work involves modelling softer ores. The comparisons will be continued with future site surveys to increase confidence in the comparison of the CZM and TCM to Split results. Stochastic fragmentation modelling will then be conducted to take into account variation of input parameters. A window of possible fragmentation distributions can be compared to those obtained by Split . Following this work, an improved fragmentation model will be developed in response to these findings.

Selecting methods to solve multi-well master equations

There are several competing methods commonly used to solve energy grained master equations describing gas-phase reactive systems. When it comes to selecting an appropriate method for any particular problem, there is little guidance in the literature. In this paper we directly compare several variants of spectral and numerical integration methods from the point of view of computer time required to calculate the solution and the range of temperature and pressure conditions under which the methods are successful. The test case used in the comparison is an important reaction in combustion chemistry and incorporates reversible and irreversible bimolecular reaction steps as well as isomerizations between multiple unimolecular species. While the numerical integration of the ODE with a stiff ODE integrator is not the fastest method overall, it is the fastest method applicable to all conditions.

Actively shielded multi-layer gradient coil designs with improved cooling properties

In standard cylindrical gradient coils consisting of a single layer of wires, a limiting factor in achieving very large magnetic field gradients is the rapid increase in coil resistance with efficiency. This is a particular problem in small-bore scanners, such as those used for MR microscopy. By adopting a multi-layer design in which the coil wires are allowed to spread out into multiple layers wound at increasing radii, a more favourable scaling of resistance with efficiency is achieved, thus allowing the design of more powerful gradient coils with acceptable resistance values. Previously this approach has been applied to the design of unshielded, longitudinal, and transverse gradient coils. Here, the multi-layer approach has been extended to allow the design of actively shielded multi-layer gradient coils, and also to produce coils exhibiting enhanced cooling characteristics. An iterative approach to modelling the steady-state temperature distribution within the coil has also been developed. Results indicate that a good level of screening can be achieved in multi-layer coils, that small versions of such coils can yield higher efficiencies at fixed resistance than conventional two-layer (primary and screen) coils, and that performance improves as the number of layers of increases. Simulations show that by optimising multi-layer coils for cooling it is possible to achieve significantly higher gradient strengths at a fixed maximum operating temperature. A four-layer coil of 8 mm inner diameter has been constructed and used to test the steady-state temperature model. (C) 2003 Elsevier Inc. All rights reserved.

Experimental investigation of criteria for continuous variable entanglement

We generate a pair of entangled beams from the interference of two amplitude squeezed beams. The entanglement is quantified in terms of EPR paradox and inseparability criteria, with both results clearly beating the standard quantum limit. We experimentally analyze the effect of decoherence on each criterion and demonstrate qualitative differences. We also characterize the number of required and excess photons present in the entangled beams and provide contour plots of the efficacy of quantum information protocols in terms of these variables.