The low-affinity site of the β1-adrenoceptor and its relevance to cardiovascular pharmacology

β-Adrenoceptor blocking agents (β-blockers) that at low concentrations antagonize cardiostimulant effects of catecholamines, but at high concentrations also cause cardiostimulation, have been appearing since the late 1960s. These cardiostimulant β-blockers, coined non-conventional partial agonists, antagonize the effects of catecholamines through a high-affinity site (β1HAR), but cause cardiostimulation mainly through a low-affinity site (β1LAR) of the myocardial β1-adrenoceptor. The experimental non-conventional partial agonist (−)-CGP12177 increases cardiac L-type Ca2+ current density and Ca2+ transients, shortens action potential duration but augments action potential plateau, increases heart rate and force, as well as causes arrhythmic Ca2+ transients and arrhythmic cardiocyte contractions. Other β-blockers, which do not cause cardiostimulation, consistently have lower affinity for β1LAR than β1HAR. These sites were verified and the cardiac pharmacology of non-conventional partial agonists confirmed on recombinant β1-adrenoceptors and on β1-adrenoceptors overexpressed into the heart. A targeted mutation of Asp138 to Glu138 virtually abolished the pharmacology of β1HAR but left intact the pharmacology of β1LAR. Non-conventional partial agonists may be beneficial for the treatment of peripheral autonomic neuropathy but probably due to their arrhythmic propensities, may be harmful for the treatment of chronic heart failure.

Test and evaluation of non conventional instrument transformers and sampled value process bus on Powerlink's transmission network

IEC 61850 Process Bus technology has the potential to improve cost, performance and reliability of substation design. Substantial costs associated with copper wiring (designing, documentation, construction, commissioning and troubleshooting) can be reduced with the application of digital Process Bus technology, especially those based upon international standards. An IEC 61850-9-2 based sampled value Process Bus is an enabling technology for the application of Non-Conventional Instrument Transformers (NCIT). Retaining the output of the NCIT in its native digital form, rather than conversion to an analogue output, allows for improved transient performance, dynamic range, safety, reliability and reduced cost. In this paper we report on a pilot installation using NCITs communicating across a switched Ethernet network using the UCAIug Implementation Guideline for IEC 61850-9-2 (9-2 Light Edition or 9-2LE). This system was commissioned in a 275 kV Line Reactor bay at Powerlink Queensland’s Braemar substation in 2009, with sampled value protection IEDs 'shadowing' the existing protection system. The results of commissioning tests and twelve months of service experience using a Fibre Optic Current Transformer (FOCT) from Smart Digital Optics (SDO) are presented, including the response of the system to fault conditions. A number of remaining issues to be resolved to enable wide-scale deployment of NCITs and IEC 61850-9-2 Process Bus technology are also discussed.

Social network market : storytelling on a Web 2.0 original literature site

This article looks at a Chinese Web 2.0 original literature site, Qidian, in order to show the coevolution of market and non-market initiatives. The analytic framework of social network markets (Potts et al., 2008) is employed to analyse the motivations of publishing original literature works online and to understand the support mechanisms of the site, which encourage readers’ willingness to pay for user-generated content. The co-existence of socio-cultural and commercial economies and their impact on the successful business model of the site are illustrated in this case. This article extends the concept of social network markets by proposing the existence of a ripple effect of social network markets through convergence between PC and mobile internet, traditional and internet publishing, and between publishing and other cultural industries. It also examines the side effects of social network markets, and the role of market and non-market strategies in addressing the issues.

Test and evaluation system for multi-protocol sampled value protection schemes

Proposed transmission smart grids will use a digital platform for the automation of substations operating at voltage levels of 110 kV and above. The IEC 61850 series of standards, released in parts over the last ten years, provide a specification for substation communications networks and systems. These standards, along with IEEE Std 1588-2008 Precision Time Protocol version 2 (PTPv2) for precision timing, are recommended by the both IEC Smart Grid Strategy Group and the NIST Framework and Roadmap for Smart Grid Interoperability Standards for substation automation. IEC 61850-8-1 and IEC 61850-9-2 provide an inter-operable solution to support multi-vendor digital process bus solutions, allowing for the removal of potentially lethal voltages and damaging currents from substation control rooms, a reduction in the amount of cabling required in substations, and facilitates the adoption of non-conventional instrument transformers (NCITs). IEC 61850, PTPv2 and Ethernet are three complementary protocol families that together define the future of sampled value digital process connections for smart substation automation. This paper describes a specific test and evaluation system that uses real time simulation, protection relays, PTPv2 time clocks and artificial network impairment that is being used to investigate technical impediments to the adoption of SV process bus systems by transmission utilities. Knowing the limits of a digital process bus, especially when sampled values and NCITs are included, will enable utilities to make informed decisions regarding the adoption of this technology.

Evolutionary biology of Gondwanan non-biting midges (Diptera: Chironomidae)

The potential restriction to effective dispersal and gene flow caused by habitat fragmentation can apply to multiple levels of evolutionary scale; from the fragmentation of ancient supercontinents driving diversification and speciation on disjunct landmasses, to the isolation of proximate populations as a result of their inability to cross intervening unsuitable habitat. Investigating the role of habitat fragmentation in driving diversity within and among taxa can thus include inferences of phylogenetic relationships among taxa, assessments of intraspecific phylogeographic structure and analyses of gene flow among neighbouring populations. The proposed Gondwanan clade within the chironomid (non-biting midge) subfamily Orthocladiinae (Diptera: Chironomidae) represents a model system for investigating the role that population fragmentation and isolation has played at different evolutionary scales. A pilot study by Krosch et al (2009) indentified several highly divergent lineages restricted to ancient rainforest refugia and limited gene flow among proximate sites within a refuge for one member of this clade, Echinocladius martini Cranston. This study provided a framework for investigating the evolutionary history of this taxon and its relatives more thoroughly. Populations of E. martini were sampled in the Paluma bioregion of northeast Queensland to investigate patterns of fine-scale within- and among-stream dispersal and gene flow within a refuge more rigorously. Data was incorporated from Krosch et al (2009) and additional sites were sampled up- and downstream of the original sites. Analyses of genetic structure revealed strong natal site fidelity and high genetic structure among geographically proximate streams. Little evidence was found for regular headwater exchange among upstream sites, but there was distinct evidence for rare adult flight among sites on separate stream reaches. Overall, however, the distribution of shared haplotypes implied that both larval and adult dispersal was largely limited to the natal stream channel. Patterns of regional phylogeographic structure were examined in two related austral orthoclad taxa – Naonella forsythi Boothroyd from New Zealand and Ferringtonia patagonica Sæther and Andersen from southern South America – to provide a comparison with patterns revealed in their close relative E. martini. Both taxa inhabit tectonically active areas of the southern hemisphere that have also experienced several glaciation events throughout the Plio-Pleistocene that are thought to have affected population structure dramatically in many taxa. Four highly divergent lineages estimated to have diverged since the late Miocene were revealed in each taxon, mirroring patterns in E. martini; however, there was no evidence for local geographical endemism, implying substantial range expansion post-diversification. The differences in pattern evident among the three related taxa were suggested to have been influenced by variation in the responses of closed forest habitat to climatic fluctuations during interglacial periods across the three landmasses. Phylogeographic structure in E. martini was resolved at a continental scale by expanding upon the sampling design of Krosch et al (2009) to encompass populations in southeast Queensland, New South Wales and Victoria. Patterns of phylogeographic structure were consistent with expectations and several previously unrecognised lineages were revealed from central- and southern Australia that were geographically endemic to closed forest refugia. Estimated divergence times were congruent with the timing of Plio-Pleistocene rainforest contractions across the east coast of Australia. This suggested that dispersal and gene flow of E. martini among isolated refugia was highly restricted and that this taxon was susceptible to the impacts of habitat change. Broader phylogenetic relationships among taxa considered to be members of this Gondwanan orthoclad group were resolved in order to test expected patterns of evolutionary affinities across the austral continents. The inferred phylogeny and estimated divergence times did not accord with expected patterns based on the geological sequence of break-up of the Gondwanan supercontinent and implied instead several transoceanic dispersal events post-vicariance. Difficulties in appropriate taxonomic sampling and accurate calibration of molecular phylogenies notwithstanding, the sampling regime implemented in the current study has been the most intensive yet performed for austral members of the Orthocladiinae and unsurprisingly has revealed both novel taxa and phylogenetic relationships within and among described genera. Several novel associations between life stages are made here for both described and previously unknown taxa. Investigating evolutionary relationships within and among members of this clade of proposed Gondwanan orthoclad taxa has demonstrated that a complex interaction between historical population fragmentation and dispersal at several levels of evolutionary scale has been important in driving diversification in this group. While interruptions to migration, colonisation and gene flow driven by population fragmentation have clearly contributed to the development and maintenance of much of the diversity present in this group, long-distance dispersal has also played a role in influencing diversification of continental biotas and facilitating gene flow among disjunct populations.

Using a social networking site such as Facebook, to enhance the feeling of belonging, within a first year nursing cohort of a large university

Recently I asked a first year student how he was coping with the transition from high school to university. The young fellow looked at me and said, “Man, everything is so different!” I smiled and said “like what?” with which he seriously replied, “Well for one thing, no one tells you that you have to wear a hat at lunch time.” I have to admit I was a little amused and surprised by this student’s response, as so often the focus, is placed on getting first year students to engage academically, when it is obvious at times, that even the mere transition in to university life and the culture itself, can be a hurdle. While teaching, within a large first year unit for over 10 years, it has become apparent that students want more connection with not only the peers that they study with, but also with the University as a whole. Dr Krause pointed out in her keynote paper, On Being Strategic about the First Year (2006), that this “sense of belonging is conducive to enhancing engagement, satisfaction with learning and commitment to study”. It has also become evident, that the way in which students want to be able to communicate has changed, with the advent of capabilities such as Instant Messaging via a network and Short Message Service SMS texting via their hand held mobile phones. To be able to chat and feel connected on social networking sites such as Bebo, Facebook and Twitter is not only a way of the future, it is here now and it is here to stay.

Interactional competence in a paired speaking test : features salient to raters

Paired speaking tests are now commonly used in both high-stakes testing and classroom assessment contexts. The co-construction of discourse by candidates is regarded as a strength of paired speaking tests, as candidates have the opportunity to display a wider range of interactional competencies, including turn taking, initiating topics and engaging in extended discourse with a partner, rather than an examiner. However, the impact of the interlocutor in such jointly negotiated discourse and the implications for assessing interactional competence are areas of concern. This article reports on the features of interactional competence that were salient to four trained raters of 12 paired speaking tests through the analysis of rater notes, stimulated verbal recalls and rater discussions. Findings enabled the identification of features of the performance noted by raters when awarding scores for interactional competence, and the particular features associated with higher and lower scores. A number of these features were seen by the raters as mutual achievements, which raises the issue of the extent to which it is possible to assess individual contributions to the co-constructed performance. The findings have implications for defining the construct of interactional competence in paired speaking tests and operationalising this in rating scales.

Development and pilot test of a peer-support based Cardiac-Diabetes Self-Management program : a study protocol

Background: People with cardiac disease and type 2 diabetes have higher hospital readmission rates (22%)compared to those without diabetes (6%). Self-management is an effective approach to achieve better health outcomes; however there is a lack of specifically designed programs for patients with these dual conditions. This project aims to extend the development and pilot test of a Cardiac-Diabetes Self-Management Program incorporating user-friendly technologies and the preparation of lay personnel to provide follow-up support. Methods/Design: A randomised controlled trial will be used to explore the feasibility and acceptability of the Cardiac-Diabetes Self-Management Program incorporating DVD case studies and trained peers to provide follow-up support by telephone and text-messaging. A total of 30 cardiac patients with type 2 diabetes will be randomised, either to the usual care group, or to the intervention group. Participants in the intervention group will received the Cardiac-Diabetes Self-Management Program in addition to their usual care. The intervention consists of three faceto- face sessions as well as telephone and text-messaging follow up. The face-to-face sessions will be provided by a trained Research Nurse, commencing in the Coronary Care Unit, and continuing after discharge by trained peers. Peers will follow up patients for up to one month after discharge using text messages and telephone support. Data collection will be conducted at baseline (Time 1) and at one month (Time 2). The primary outcomes include self-efficacy, self-care behaviour and knowledge, measured by well established reliable tools. Discussion: This paper presents the study protocol of a randomised controlled trial to pilot evaluates a Cardiac- Diabetes Self-Management program, and the feasibility of incorporating peers in the follow-ups. Results of this study will provide directions for using such mode in delivering a self-management program for patients with both cardiac condition and diabetes. Furthermore, it will provide valuable information of refinement of the intervention program.

Spatial population genetic structure reveals strong natal site fidelity in Echinocladius martini (Diptera: Chironomidae) in northeast Queensland, Australia

1. A diverse array of patterns has been reported regarding the spatial extent of population genetic structure and effective dispersal in freshwater macroinvertebrates. In river systems, the movements of many taxa can be restricted to varying degrees by the natural stream channel hierarchy. 2. In this study, we sampled populations of the non-biting freshwater midge Echinocladius martini in the Paluma bioregion of tropical northeast Queensland to investigate fine scale patterns of within- and among-stream dispersal and gene flow within a purported historical refuge. We amplified a 639 bp fragment of mitochondrial COI and analysed genetic structure using pairwise ΦST, hierarchical AMOVA, Mantel tests and a parsimony network. Genetic variation was partitioned among stream sections using Streamtree to investigate the effect of potential instream dispersal barriers. 3. The data revealed strong natal site fidelity and significant differentiation among neighbouring, geographically proximate streams. We found evidence for only episodic adult flight among sites on separate stream reaches. Overall, however, our data suggested that both larval and adult dispersal was largely limited to within a stream channel. 4. This may arise from a combination of the high density of riparian vegetation physically restricting dispersal and from the joint effects of habitat stability and large population sizes. Together these may mitigate the requirement for movement among streams to avoid inbreeding and local extinction due to habitat change and may thus enable persistence of upstream populations in the absence of regular compensatory upstream flight. Taken together, these data suggest that dispersal of E. martini is highly restricted, to the scale of only a few kilometres, and hence occurs predominantly within the natal stream.

Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice

Background Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors. Objectives To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care. Methods This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories. Results Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥50years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise. Conclusions More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care.

HyperCard test engine using Rasch Analysis

This paper will focus on the development of an interactive test engine using Rasch analysis of item responses for question selection and reporting of results. The Rasch analysis is used to determine student ability and question difficulty. This model is widely used in the preparation of paper-based tests and has been the subject of particular use and development at the Australian Council for Education Research (ACER). This paper presents an overview of an interactive implementation of the Rasch analysis model in HyperCard, where student ability estimates are generated 'on the fly' and question difficulty values updated from time to time. The student ability estimates are used to determine question selection and are the basis of scoring and reporting schemes.