Understanding PK/PD

Pharmacology is the science underpinning dosing, mechanisms of action and effectiveness of drugs. Central to pharmacology, are the studies of pharmacokinetics (PK) and pharmacodynamics (PD). On one hand, PK defines the time-course of drug concentrations in the body and incorporates the broad concepts of drug absorption, distribution, metabolism and elimination. On the other hand, PD describes the relationship between drug concentrations and pharmacological effects. In practice, PK is often referred as “what the body does to the drug” whilst PD as “what the drug does to the body”. Thus, PK/PD describes the relationship between drug dose and pharmacological effects with changes in drug concentrations leading to different pharmacological effects.

Saving schools from abomination and abnormal sex : a discourse analysis of online public commentary about 'queering' school spaces

Homophobic hatred: these words summarise online commentary made by people in support of a school that banned gay students from taking their same sex partners to a school formal. With the growing popularity of online news sites, it seems appropriate to critically examine how these sites are becoming a new arena in which people can express personal opinions about controversial topics. While commentators equally expressed two dominant viewpoints about the school ban (homophobic hatred and human rights), this paper focuses on homophobic hatred as a discursive position and how the comments work to confirm the legitimacy of the schools’ decision. Drawing on the work of Foucault and others, the paper examines how the comments constitute certain types of subjectivity drawing on dominant ideas about what it means to be homophobic. The analysis demonstrates the complex and competing skein of strategies that constitute queering school social spaces as a social problem.

Creative clusters and universities : the cluster concept in economics and geography

This paper considers the history of the cluster concept in urban economic geography, and its relationship to recent debates about creative cities. It then looks at the role that universities can play in the development of a creative cluster, as well as some of the potential pitfalls.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections : clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin–clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of β-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin–clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3–12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin–clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Poster Abstract : A public key technology platform for wireless sensor networks

Communication security for wireless sensor networks (WSN) is a challenge due to the limited computation and energy resources available at nodes. We describe the design and implementation of a public-key (PK) platform based on a standard Trusted Platform Module (TPM) chip that extends the capability of a standard node. The result facilitates message security services such as confidentiality, authenticity and integrity. We present results including computation time, energy consumption and cost.

Delaying mismatched field multiplications in pairing computations

Miller’s algorithm for computing pairings involves perform- ing multiplications between elements that belong to different finite fields. Namely, elements in the full extension field Fpk are multiplied by elements contained in proper subfields F pk/d , and by elements in the base field Fp . We show that significant speedups in pairing computations can be achieved by delaying these “mismatched” multiplications for an optimal number of iterations. Importantly, we show that our technique can be easily integrated into traditional pairing algorithms; implementers can exploit the computational savings herein by applying only minor changes to existing pairing code.

Children, childhood and the contemporary media

This chapter investigates and critiques the idea of the sexualization of children in the contemporary media with a focus on recent events in Australia. It begins by commenting about aspects of Corporate Paedophilia: Sexualisation of children in Australia (Rush & La Nauze, 2006a) and then investigates relevant literature about consuming bodies to provide a frame for discussing consumer culture, children and childhood. Following this, the sexualization of children in the contemporary media is explored from the perspective of moral panics and the discourses of neoliberal tolerance and intolerance. The chapter concludes that although the idea of children being sexualized in contemporary media is contested, there can be no simple explanations and that a multiplicity of factors need to be taken into account that exist outside of media discourses.

Show us your mess!

Epilogue for the edited book "Nexus: New Intersections in Internet Research"

Education for the creative economy : innovation, transdisciplinarity, and networks

The question posed in this chapter is: To what extent does current education theory and practice prepare graduates for the creative economy? We first define what we mean by the term creative economy, explain why we think it is a significant point of focus, derive its key features, describe the human capital requirements of these features, and then discuss whether current education theory and practice are producing these human capital requirements. The term creative economy can be critiqued as a shibboleth, but as a high level metaphor, it nevertheless has value in directing us away from certain sorts of economic activity and toward other kinds. Much economic activity is in no way creative. If I have a monopoly on some valued resource, I do not need to be creative. Other forms of economic activity are intensely creative. If I have no valued resources, I must create something that is valued. At its simplest and yet most profound, the idea of a creative economy suggests a capacity to compete based on engaging in a gainful activity that is different from everyone else’s, rather than pursuing the same endeavor more competitively than everyone else. The ability to differentiate on novelty is key to the concept of creative economy and key to our analysis of education for this economy. Therefore, we follow Potts and Cunningham (2008, p. 18) and Potts, Cunningham, Hartley, and Ormerod (2008) in their discussion of the economic significance of the creative industries and see the creative economy not as a sector but as a set of economic processes that act on the economy as a whole to invigorate innovation based growth. We see the creative economy as suffused with all industry rather than as a sector in its own right. These economic processes are essentially concerned with the production of new ideas that ultimately become new products, service, industry sectors, or, in some cases, process or product innovations in older sectors. Therefore, our starting point is that modern economies depend on innovation, and we see the core of innovation as new knowledge of some kind. We commence with some observations about innovation.

Recent advances in cancer therapy targeting proteins involved in DNA double-strand break repair

Damage to genetic material represents a persistent and ubiquitous threat to genomic stability. Once DNA damage is detected, a multifaceted signaling network is activated that halts the cell cycle, initiates repair, and in some instances induces apoptotic cell death. In this article, we will review DNA damage surveillance networks, which maintain the stability of our genome, and discuss the efforts underway to identify chemotherapeutic compounds targeting the core components of DNA double-strand breaks (DSB) response pathway. The majority of tumor cells have defects in maintaining genomic stability owing to the loss of an appropriate response to DNA damage. New anticancer agents are exploiting this vulnerability of cancer cells to enhance therapeutic indexes, with limited normal tissue toxicity. Recently inhibitors of the checkpoint kinases Chk1 and Chk2 have been shown to sensitize tumor cells to DNA damaging agents. In addition, the treatment of BRCA1- or BRCA2-deficient tumor cells with poly(ADP-ribose) polymerase (PARP) inhibitors also leads to specific tumor killing. Due to the numerous roles of p53 in genomic stability and its defects in many human cancers, therapeutic agents that restore p53 activity in tumors are the subject of multiple clinical trials. In this article we highlight the proteins mentioned above and catalog several additional players in the DNA damage response pathway, including ATM, DNA-PK, and the MRN complex, which might be amenable to pharmacological interventions and lead to new approaches to sensitize cancer cells to radio- and chemotherapy. The challenge is how to identify those patients most receptive to these treatments.

Queers doing theory : Australian queer student activist print media’s representations of capitalism

Queer university student print media often represents capitalism in a framework which could be classified as Marxism. However, at the same time, queer student media extensively publishes ideas which could be classified as academic queer theory. This chapter features analysis of these representations from the 2003, 2004 and 2006 editions of national queer student publication, Querelle, and from a sample of queer student media from four Australian universities. The perspectives of Marxism and academic queer theory are often argued to be contradictory (See for example, Hennessy 1994; Morton 1996b; Kirsch 2007), and thus the students’ application of these theories in tandem could be considered problematic. McKee asks ‘Who gets to be an intellectual?’ (2004) and suggests that the intellectualising undertaken by mainstream and alternative cultural creators is just as valid as that undertaken by university academics. He also raises concerns that the concept of theory is seen to be kept separate from everyday culture (McKee 2002). This chapter argues that in the construction and representation of their politics in this manner the queer student activists are creating their own version of queer theory. This analysis of queer student media contributes to research on queer communities and queer theory, demonstrating how one specific cultural subset theorises queerness and queer politics, thereby contributing to the genealogy of queer.

Pre-digital Virtuality: Early Modern Scholars and the Republic of Letters

This chapter explores the idea of virtual participation through the historical example of the republic of letters in early modern Europe (circa 1500-1800). By reflecting on the construction of virtuality in a historical context, and more specifically in a pre-digital environment, it calls attention to accusations of technological determinism in ongoing research concerning the affordances of the Internet and related media of communication. It argues that ‘the virtual’ is not synonymous with ‘the digital’ and suggests that, in order to articulate what is novel about modern technologies, we must first understand the social interactions underpinning the relationships which are facilitated through those technologies. By analysing the construction of virtuality in a pre-digital environment, this chapter thus offers a baseline from which scholars might consider what is different about the modes of interaction and communication being engaged in via modern media.