Chlamydial infection and spatial ascension of the female genital tract : a novel hybrid cellular automata and continuum mathematical model

Sexually transmitted chlamydial infection initially establishes in the endocervix in females, but if the infection ascends the genital tract, significant disease, including infertility, can result. Many of the mechanisms associated with chlamydial infection kinetics and disease ascension are unknown. We attempt to elucidate some of these processes by developing a novel mathematical model, using a cellular automata–partial differential equation model. We matched our model outputs to experimental data of chlamydial infection of the guinea-pig cervix and carried out sensitivity analyses to determine the relative influence of model parameters. We found that the rate of recruitment and action of innate immune cells to clear extracellular chlamydial particles and the rate of passive movement of chlamydial particles are the dominant factors in determining the early course of infection, magnitude of the peak chlamydial time course and the time of the peak. The rate of passive movement was found to be the most important factor in determining whether infection would ascend to the upper genital tract. This study highlights the importance of early innate immunity in the control of chlamydial infection and the significance of motility-diffusive properties and the adaptive immune response in the magnitude of infection and in its ascension.

Anti-metabolic effects of Galanthus nivalis agglutinin and wheat germ agglutinin on nymphal stages of the common brown leafhopper using a novel artificial diet system

The common brown leafhopper, Orosius orientalis (Matsumura) (Homoptera: Cicadellidae), previously described as Orosius argentatus (Evans), is an important vector of several viruses and phytoplasmas worldwide. In Australia, phytoplasmas vectored by O. orientalis cause a range of economically important diseases, including legume little leaf (Hutton & Grylls, 1956), tomato big bud (Osmelak, 1986), lucerne witches broom (Helson, 1951), potato purple top wilt (Harding & Teakle, 1985), and Australian lucerne yellows (Pilkington et al., 2004). Orosius orientalis also transmits Tobacco yellow dwarf virus (TYDV; genus Mastrevirus, family Geminiviridae) to beans, causing bean summer death disease (Ballantyne, 1968), and to tobacco, causing tobacco yellow dwarf disease (Hill, 1937, 1941). TYDV has only been recorded in Australia to date. Both diseases result in significant production and quality losses (Ballantyne, 1968; Thomas, 1979; Moran & Rodoni, 1999). Although direct damage caused by leafhopper feeding has been observed, it is relatively minor compared to the losses resulting from disease (P Tr E bicki, unpubl.).

The role of HPC facilies in development of a novel road safety barrier

Water-filled portable road safety barriers are a common fixture in road works, however their use of water can be problematic, both in terms of the quantity of water used and the transportation of the water to the installation site. This project aims to develop a new design of portable road safety barrier, which will make novel use of composite and foam materials in order to reduce the barrier’s reliance on water in order to control errant vehicles. The project makes use of finite element (FE) techniques in order to simulate and evaluate design concepts. FE methods and models that have previously been tested and validated will be used in combination in order to provide the most accurate numerical simulations available to drive the project forward. LS-DYNA code is as highly dynamic, non-linear numerical solver which is commonly used in the automotive and road safety industries. Several complex materials and physical interactions are to be simulated throughout the course of the project including aluminium foams, composite laminates and water within the barrier during standardised impact tests. Techniques to be used include FE, smoothed particle hydrodynamics (SPH) and weighted multi-parameter optimisation techniques. A detailed optimisation of several design parameters with specific design goals will be performed with LS-DYNA and LS-OPT, which will require a large number of high accuracy simulations and advanced visualisation techniques. Supercomputing will play a central role in the project, enabling the numerous medium element count simulations necessary in order to determine the optimal design parameters of the barrier to be performed. Supercomputing will also allow the development of useful methods of visualisation results and the production of highly detailed simulations for end-product validation purposes. Efforts thus far have been towards integrating various numerical methods (including FEM, SPH and advanced materials models) together in an efficient and accurate manner. Various designs of joining mechanisms have been developed and are currently being developed into FE models and simulations.

The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

Corneal confocal microscopy : a novel noninvasive means to diagnose neuropathy in patients with Fabry disease

ABSTRACT: Neuropathy is a cause of significant disability in patients with Fabry disease, yet its diagnosis is difficult. In this study we compared the novel noninvasive techniques of corneal confocal microscopy (CCM) to quantify small-fiber pathology, and non-contact corneal esthesiometry (NCCA) to quantify loss of corneal sensation, with established tests of neuropathy in patients with Fabry disease. Ten heterozygous females with Fabry disease not on enzyme replacement therapy (ERT), 6 heterozygous females, 6 hemizygous males on ERT, and 14 age-matched, healthy volunteers underwent detailed quantification of neuropathic symptoms, neurological deficits, neurophysiology, quantitative sensory testing (QST), NCCA, and CCM. All patients with Fabry disease had significant neuropathic symptoms and an elevated Mainz score. Peroneal nerve amplitude was reduced in all patients and vibration perception threshold was elevated in both male and female patients on ERT. Cold sensation (CS) threshold was significantly reduced in both male and female patients on ERT (P < 0.02), but warm sensation (WS)and heat-induced pain (HIP) were only significantly increased in males onERT (P<0.01). However, corneal sensation assessed withNCCAwas significantly reduced in female (P < 0.02) and male (P < 0.04) patients on ERT compared with control subjects. According to CCM, corneal nerve fiber and branch density was significantly reduced in female (P < 0.03) and male (P < 0.02) patients on ERT compared with control subjects. Furthermore, the severity of neuropathic symptoms and the neurological component of the Mainz Severity Score Index correlated significantly with QSTand CCM. This study shows that CCM and NCCA provide a novel means to detect early nerve fiber damage and dysfunction, respectively, in patients with Fabry disease.

Measuring episodic memory: A novel approach with an indefinite number of alternative forms

Both clinical practice and clinical research settings can require successive administrations of a memory test, particularly when following the trajectory of suspected memory decline in older adults. However, relatively few verbal episodic memory tests have alternative forms. We set out to create a broad based memory test to allow for the use of an essentially unlimited number of alternative forms. Four tasks for inclusion in such a test were developed. These tasks varied the requirement for recall as opposed to recognition, the need to form an association between unrelated words, and the need to discriminate the most recent list from earlier lists, all of which proved useful. A total of 115 participants completed the battery of tests and were used to show that the test could differentiate between older and younger adults; a sub-sample of 73 participants completed alternative forms of the tests to determine test-retest reliability and the amount of learning to learn.

Novel educational training program for community pharmacists

There is little evidence that workshops alone have a lasting impact on the day-to-day practice of participants. The current paper examined a strategy to increase generalization and maintenance of skills in the natural environment using pseudo-patients and immediate performance feedback to reinforce skills acquisition. A random half of pharmacies (N=30) took part in workshop training aimed at optimizing consumers' use of nonprescription analgesic products. Pharmacies in the training group also received performance feedback on their adherence to the recommended protocol. Feedback occurred immediately after a pseudo-patient visit in which confederates posed as purchasers of analgesics, and combined positive and corrective elements. Trained pharmacists were significantly more accurate at identifying people who misused the medication (P<0.001). The trained pharmacists were more likely than controls to use open-ended questions (P<0.001), assess readiness to change problematic use (P <0.001), and to deliver a brief intervention that was tailored to the person's commitment to alter his/her usage (P <0.001). Participants responded to the feedback positively. Results were consistent with the hypothesis that when workshop is combined with on-site performance feedback, it enhances practitioners' adherence to protocols in the natural setting.

The synthesis of novel isoindoline nitroxides bearing water-solubilising functionality

A range of novel tetramethyl- and tetraethylisoindolinenitroxides, possessing aryl-linked carboxylic acids, amines, alcohols and phosphonic acids were prepared. Notably, the chemistry established for the aromatic dibromination of the tetramethylisoindolines was not easily transferred to the corresponding tetraethylisoindoline system. Instead, various tetraethylisoindoline analogues were accessed by the oxidation of methyl groups attached to the aromatic ring to give the carboxylic acids. The increased steric bulk of the tetraethyl structures should limit bio-reduction and these compounds may have potential as antioxidants.

A novel nonrepudiable threshold multi-proxy multi-signature scheme with shared verification

Tzeng et al. proposed a new threshold multi-proxy multi-signature scheme with threshold verification. In their scheme, a subset of original signers authenticates a designated proxy group to sign on behalf of the original group. A message m has to be signed by a subset of proxy signers who can represent the proxy group. Then, the proxy signature is sent to the verifier group. A subset of verifiers in the verifier group can also represent the group to authenticate the proxy signature. Subsequently, there are two improved schemes to eliminate the security leak of Tzeng et al.’s scheme. In this paper, we have pointed out the security leakage of the three schemes and further proposed a novel threshold multi-proxy multi-signature scheme with threshold verification.

XCFS - a novel approach for clustering XML documents using both the structure and the content

XML document clustering is essential for many document handling applications such as information storage, retrieval, integration and transformation. An XML clustering algorithm should process both the structural and the content information of XML documents in order to improve the accuracy and meaning of the clustering solution. However, the inclusion of both kinds of information in the clustering process results in a huge overhead for the underlying clustering algorithm because of the high dimensionality of the data. This paper introduces a novel approach that first determines the structural similarity in the form of frequent subtrees and then uses these frequent subtrees to represent the constrained content of the XML documents in order to determine the content similarity. The proposed method reduces the high dimensionality of input data by using only the structure-constrained content. The empirical analysis reveals that the proposed method can effectively cluster even very large XML datasets and outperform other existing methods.

Tesofensine : a novel potent weight loss medicine

Background: The incidence of obesity is increasing; this is of major concern, as obesity is associated with cardiovascular disease, stroke, type 2 diabetes, respiratory tract disease, and cancer. Objectives/methods: This evaluation is of a Phase II clinical trial with tesofensine in obese subjects. Results: After 26 weeks, tesofensine caused a significant weight loss, and may have a higher maximal ability to reduce weight than the presently available anti-obesity agents. However, tesofensine also increased blood pressure and heart rate, and may increase psychiatric disorders. Conclusions: It is encouraging that tesofensine 0.5 mg may cause almost double the weight loss observed with sibutramine or rimonabant. As tesofensine and sibutramine have similar pharmacological profiles, it would be of interest to compare the weight loss with tesofensine in a head-to-head clinical trial with sibutramine, to properly assess their comparative potency. Also, as teso fensine 0.5 mg increases heart rate, as well as increasing the incidence of adverse effects such as nausea, drug mouth, flatulence, insomnia, and depressed mode, its tolerability needs to be further evaluated in large Phase III clinical trials.

A novel system for the measurement of body shape and construction of seating supports for patients

Patients with severe back deformities can greatly benefit from customized medical seating. Customized medical seating is made by taking measurements of each individual patient and making the seat as per these measurements. The current measuring systems employed by the industry are limited to use in clinics which are generally located only in major population centres. Patients living in remote areas are severely affected by this as the clinics could be far away and inaccessible for these patients. To provide service of customized medical seating requires a new measurement system which is portable so that the system could be transported to the patients in remote areas. The requirements for a new measurement system are analysed to suite the needs of Equipment Technology Services of the Cerebral Palsy League of Queensland. Design for a new measurement system was conceptualised by reviewing systems and technologies in various scientific disciplines. Design for a new system was finalised by optimizing each individual component. The final approach was validated by measuring difficult models and repeating the process to check for process variances. This system has now been adopted for clinical evaluation by ETS Suggestions have been made for further improvements in this new measurement approach.