Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.

Modeling the impact of potential vaccines on epidemics of sexually transmitted chlamydia trachomatis infection

Background. We investigated the likely impact of vaccines on the prevalence of and morbidity due to Chlamydia trachomatis (chlamydia) infections in heterosexual populations. Methods.An individual‐based mathematical model of chlamydia transmission was developed and linked to the infection course in chlamydia‐infected individuals. The model describes the impact of a vaccine through its effect on the chlamydial load required to infect susceptible individuals (the “critical load”), the load in infected individuals, and their subsequent infectiousness. The model was calibrated using behavioral, biological, and clinical data. Results.A fully protective chlamydia vaccine administered before sexual debut can theoretically eliminate chlamydia epidemics within 20 years. Partially effective vaccines can still greatly reduce the incidence of chlamydia infection. Vaccines should aim primarily to increase the critical load in susceptible individuals and secondarily to decrease the peak load and/or the duration of infection in vaccinated individuals who become infected. Vaccinating both sexes has a beneficial impact on chlamydia‐related morbidity, but targeting women is more effective than targeting men. Conclusions.Our findings can be used in laboratory settings to evaluate vaccine candidates in animal models, by regulatory bodies in the promotion of candidates for clinical trials, and by public health authorities in deciding on optimal intervention strategies.

Biomechanical aspects of bone microstructure in vertebrates : potential approach to paleontological investigations

The biomechanical or biophysical principles can be applied to study biological structures in their modern or fossil form. Bone is an important tissue in paleontological studies as it is a commonly preserved element in most fossil vertebrates, and can often allow its microstructures such as lacuna and canaliculi to be studied in detail. In this context, the principles of Fluid Mechanics and Scaling Laws have been previously applied to enhance the understanding of bone microarchitecture and their implications for the evolution of hydraulic structures to transport fluid. It has been shown that the microstructure of bone has evolved to maintain efficient transport between the nutrient supply and cells, the living components of the tissue. Application of the principle of minimal expenditure of energy to this analysis shows that the path distance comprising five or six lamellar regions represents an effective limit for fluid and solute transport between the nutrient supply and cells; beyond this threshold, hydraulic resistance in the network increases and additional energy expenditure is necessary for further transportation. This suggests an optimization of the size of bone’s building blocks (such as osteon or trabecular thickness) to meet the metabolic demand concomitant to minimal expenditure of energy. This biomechanical aspect of bone microstructure is corroborated from the ratio of osteon to Haversian canal diameters and scaling constants of several mammals considered in this study. This aspect of vertebrate bone microstructure and physiology may provide a basis of understanding of the form and function relationship in both extinct and extant taxa.

Website physical activity interventions : preferences of potential users

Information and communication technologies (particularly websites and e-mail) have the potential to deliver health behavior change programs to large numbers of adults at low cost. Controlled trials using these new media to promote physical activity have produced mixed results. User-centered development methods can assist in understanding the preferences of potential participants for website functions and content, and may lead to more effective programs. Eight focus group discussions were conducted with 40 adults after they had accessed a previously trialed physical activity website. The discussions were audio taped, transcribed and interpreted using a themed analysis method. Four key themes emerged: structure, interactivity, environmental context and content. Preferences were expressed for websites that include simple interactive features, together with information on local community activity opportunities. Particular suggestions included online community notice boards, personalized progress charts, e-mail access to expert advice and access to information on specific local physical activity facilities and services. Website physical activity interventions could usefully include personally relevant interactive and environmentally focused features and services identified through a user-centered development process.

Destination brand equity among the host community : a potential source of comparative advantage for DMO's

Since the emergence of the destination branding literature in 1998, there have been few studies related to performance measurement of destination brand campaigns. There has also been little interest to date in researching the extent to which a destination brand represents the host community’s sense of place. Given that local residents represent a key stakeholder group for the destination marketing organisation (DMO), research is required to examine the extent to which marketing communications have been effective in enhancing engagement with the brand, and inducing a brand image that is congruent with the brand identity. Motivated by conceptual and practical aims, this paper reports the trial of a hierarchy of consumer-based brand equity (CBBE) for a destination, from the perspective of residents as active participants of local tourism. It is proposed that strong levels of CBBE among the host community representsa strong level of CBBE among the host community represents a source of comparative advantage for a destination, for which the DMO could proactively develop into a competitive advantage.

Magnetic resonance spectroscopy in seizure disorders

Key points • The clinical aims of MR spectroscopy (MRS) in seizure disorders are to help identify, localize and characterize epileptogenic foci. • Lateralizing MRS abnormalities in temporal lobe epilepsy (TLE) may be used clinically in combination with structural and T2 MRI measurements together with other techniques such as EEG, PET and SPECT. • Characteristic metabolite abnormalities are decreased N-acetylaspartate (NAA) with increased choline (Cho) and myoinositol (mI) (short-echo time). • Contralateral metabolite abnormalities are frequently seen in TLE, but are of uncertain significance. • In extra-temporal epilepsy, metabolite abnormalities may be seen where MR imaging (MRI) is normal; but may not be sufficiently localized to be useful clinically. • MRS may help to characterize epileptogenic lesions visible on MRI (aggressive vs. indolent neoplastic, dysplasia). • Spectral editing techniques are required to evaluate specific epilepsy-relevant metabolites (e.g. -aminobutyric acid (GABA)), which may be useful in drug development and evaluation. • MRS with phosphorus (31P) and other nuclei probe metabolism of epilepsy, but are less useful clinically. • There is potential for assessing the of drug mode of action and efficacy through 13C carbon metabolite measurements, while changes in sodium homeostasis resulting from seizure activity may be detected with 23Na MRS.

Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model

This paper explores the potential therapeutic role of the naturally occurring sugar heparan sulfate (HS) for the augmentation of bone repair. Scaffolds comprising fibrin glue loaded with 5 lg of embryonically derived HS were assessed, firstly as a release-reservoir, and secondly as a scaffold to stimulate bone regeneration in a critical size rat cranial defect. We show HS-loaded scaffolds have a uniform distribution of HS, which was readily released with a typical burst phase, quickly followed by a prolonged delivery lasting several days. Importantly, the released HS contributed to improved wound healing over a 3-month period as determined by microcomputed tomography (lCT) scanning, histology, histomorphometry, and PCR for osteogenic markers. In all cases, only minimal healing was observed after 1 and 3 months in the absence of HS. In contrast, marked healing was observed by 3 months following HS treatment, with nearly full closure of the defect site. PCR analysis showed significant increases in the gene expression of the osteogenic markers Runx2, alkaline phosphatase, and osteopontin in the heparin sulfate group compared with controls. These results further emphasize the important role HS plays in augmenting wound healing, and its successful delivery in a hydrogel provides a novel alternative to autologous bone graft and growth factorbased therapies.

Unlocking the potential through Creative Commons

In November 2006, the Australian Research Council Centre of Excellence for Creative Industries and Innovation (CCi), in conjunction with the Queensland University of Technology, hosted the CCau Industry Forum, a research-focused industry engagement event. The event was run by the CCi ccClinic and CC + OCL Research projects, and aimed to evaluate understanding of and attitudes towards copyright, OCL and CC in Australia. The Forum focused on the government, education and the creative industries sectors. Unlocking the Potential Through Creative Commons: An Industry Engagement and Action Agenda evaluates and responds to the outcomes of this Forum and presents a strategy for continued research into Creative Commons in Australia.

Structural equation model of construction contract dispute potential

This paper presents the results of a structural equation model (SEM) for describing and quantifying the fundamental factors that affect contract disputes between owners and contractors in the construction industry. Through this example, the potential impact of SEM analysis in construction engineering and management research is illustrated. The purpose of the specific model developed in this research is to explain how and why contract related construction problems occur. This study builds upon earlier work, which developed a disputes potential index, and the likelihood of construction disputes was modeled using logistic regression. In this earlier study, questionnaires were completed on 159 construction projects, which measured both qualitative and quantitative aspects of contract disputes, management ability, financial planning, risk allocation, and project scope definition for both owners and contractors. The SEM approach offers several advantages over the previously employed logistic regression methodology. The final set of structural equations provides insight into the interaction of the variables that was not apparent in the original logistic regression modeling methodology.