An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria : implications for ex vivo drug susceptibility testing

The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

Foundations of International Climate Law : Objectives, principles and methods

This chapter explores the objectives, principle and methods of climate law. The United Nations Framework Convention on Climate Change (UNFCCC) lays the foundations of the international regime by setting out its ultimate objectives in Article 2, the key principles in Article 3, and the methods of the regime in Article 4. The ultimate objective of the regime – to avoid dangerous anthropogenic interference – is examined and assessments of the Intergovernmental Panel on Climate Change (IPCC) are considered when seeking to understand the definition of this concept. The international environmental principles of: state sovereignty and responsibility, preventative action, cooperation, sustainable development, precaution, polluter pays and common but differentiated responsibility are then examined and their incorporation within the international climate regime instruments evaluated. This is followed by an examination of the methods used by the mitigation and adaptation regimes in seeking to achieve the objective of the UNFCCC. Methods of the mitigation regime include: domestic implementation of policies, setting of standards and targets and allocation of rights, use of flexibility mechanisms, and reporting. While it is noted that methods of the adaptation regime are still evolving, the latter includes measures such as impact assessments, national adaptation plans and the provision of funding.

Review of statistical methods for disease mapping

Cancer poses an undeniable burden to the health and wellbeing of the Australian community. In a recent report commissioned by the Australian Institute for Health and Welfare(AIHW, 2010), one in every two Australians on average will be diagnosed with cancer by the age of 85, making cancer the second leading cause of death in 2007, preceded only by cardiovascular disease. Despite modest decreases in standardised combined cancer mortality over the past few decades, in part due to increased funding and access to screening programs, cancer remains a significant economic burden. In 2010, all cancers accounted for an estimated 19% of the country's total burden of disease, equating to approximately $3:8 billion in direct health system costs (Cancer Council Australia, 2011). Furthermore, there remains established socio-economic and other demographic inequalities in cancer incidence and survival, for example, by indigenous status and rurality. Therefore, in the interests of the nation's health and economic management, there is an immediate need to devise data-driven strategies to not only understand the socio-economic drivers of cancer but also facilitate the implementation of cost-effective resource allocation for cancer management...

Multi-area reliability assessment of interconnected generating systems using hybrid approach

This paper present an efficient method using system state sampling technique in Monte Carlo simulation for reliability evaluation of multi-area power systems, at Hierarchical Level One (HLI). System state sampling is one of the common methods used in Monte Carlo simulation. The cpu time and memory requirement can be a problem, using this method. Combination of analytical and Monte Carlo method known as Hybrid method, as presented in this paper, can enhance the efficiency of the solution. Incorporation of load model in this study can be utilised either by sampling or enumeration. Both cases are examined in this paper, by application of the methods on Roy Billinton Test System(RBTS).

Guerrilla research tactics: alternative research methods

This case-study explores alternative and experimental methods of research data acquisition, through an emerging research methodology, ‘Guerrilla Research Tactics’ [GRT]. The premise is that the researcher develops covert tactics for attracting and engaging with research participants. These methods range between simple analogue interventions to physical bespoke artefacts which contain an embedded digital link to a live, interactive data collecting resource, such as an online poll, survey or similar. These artefacts are purposefully placed in environments where the researcher anticipates an encounter and response from the potential research participant. The choice of design and placement of artefacts is specific and intentional. DESCRIPTION: Additional information may include: the outcomes; key factors or principles that contribute to its effectiveness; anticipated impact/evidence of impact. This case-study assesses the application of ‘Guerrilla Research Tactics’ [GRT] Methodology as an alternative, engaging and interactive method of data acquisition for higher degree research. Extending Gauntlett’s definition of ‘new creative methods… an alternative to language driven qualitative research methods' (2007), this case-study contributes to the existing body of literature addressing creative and interactive approaches to HDR data collection. The case-study was undertaken with Masters of Architecture and Urban Design research students at QUT, in 2012. Typically students within these creative disciplines view research as a taxing and boring process, distracting them from their studio design focus. An obstacle that many students face, is acquiring data from their intended participant groups. In response to these challenges the authors worked with students to develop creative, fun, and engaging research methods for both the students and their research participants. GRT are influenced by and developed from a combination of participatory action research (Kindon, 2008) and unobtrusive research methods (Kellehear, 1993), to enhance social research. GRT takes un-obtrusive research in a new direction, beyond the typical social research methods. The Masters research students developed alternative methods for acquiring data, which relied on a combination of analogue design interventions and online platforms commonly distributed through social networks. They identified critical issues that required action by the community, and the processes they developed focused on engaging with communities, to propose solutions. Key characteristics shared between both GRT and Guerrilla Activism, are notions of political issues, the unexpected, the unconventional, and being interactive, unique and thought provoking. The trend of Guerrilla Activism has been adapted to: marketing, communication, gardening, craftivism, theatre, poetry, and art. Focusing on the action element and examining elements of current trends within Guerrilla marketing, we believe that GRT can be applied to a range of research areas within various academic disciplines.

A spectroscopic comparison of YBCO superconductors synthesised by solid-state and co-precipitation methods

Raman spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) have been used to compare samples of YBa2Cu3O7 (YBCO) synthesised by the solid-state method and a novel co-precipitation technique. XRD results indicate that YBCO prepared by these two methods are phase pure, however the Raman and SEM results show marked differences between these samples.

Analytical electron microscope investigation of boron carbide microstructures at elevated temperatures

The microstructures of hot-pressed B4C were monitored during in situ heating experiments from room temperature to 1000C by analytical electron microscopy (AEM). Variations in the microstructure of B4C were not observed. However, during heating, secondary phases formed in voids and on the surfaces of the specimen.

Analytical model for fault section estimation and state identification of unobserved protective relays in power systems [电力系统故障诊断与不可观测保护状态识别的解析模型]

In recent years, some models have been proposed for the fault section estimation and state identification of unobserved protective relays (FSE-SIUPR) under the condition of incomplete state information of protective relays. In these models, the temporal alarm information from a faulted power system is not well explored although it is very helpful in compensating the incomplete state information of protective relays, quickly achieving definite fault diagnosis results and evaluating the operating status of protective relays and circuit breakers in complicated fault scenarios. In order to solve this problem, an integrated optimization mathematical model for the FSE-SIUPR, which takes full advantage of the temporal characteristics of alarm messages, is developed in the framework of the well-established temporal constraint network. With this model, the fault evolution procedure can be explained and some states of unobserved protective relays identified. The model is then solved by means of the Tabu search (TS) and finally verified by test results of fault scenarios in a practical power system.