Evaluating Australia's National Medicines Policy using geographical mapping

Background: There has been a proliferation of quality use of medicines activities in Australia since the 1990s. However, knowledge of the nature and extent of these activities was lacking. A mechanism was required to map the activities to enable their coordination. Aims: To develop a geographical mapping facility as an evaluative tool to assist the planning and implementation of Australia's policy on the quality use of medicines. Methods: A web-based database incorporating geographical mapping software was developed. Quality use of medicines projects implemented across the country was identified from project listings funded by the Quality Use of Medicines Evaluation Program, the National Health and Medical Research Council, Mental Health Strategy, Rural Health Support, Education and Training Program, the Healthy Seniors Initiative, the General Practice Evaluation Program and the Drug Utilisation Evaluation Network. In addition, projects were identified through direct mail to persons working in the field. Results: The Quality Use of Medicines Mapping Project (QUMMP) was developed, providing a Web-based database that can be continuously updated. This database showed the distribution of quality use of medicines activities by: (i) geographical region, (ii) project type, (iii) target group, (iv) stakeholder involvement, (v) funding body and (vi) evaluation method. At September 2001, the database included 901 projects. Sixty-two per cent of projects had been conducted in Australian capital cities, where approximately 63% of the population reside. Distribution of projects varied between States. In Western Australia and Queensland, 36 and 73 projects had been conducted, respectively, representing approximately two projects per 100 000 people. By comparison, in South Australia and Tasmania approximately seven projects per 100 000 people were recorded, with six per 100 000 people in Victoria and three per 100 000 people in New South Wales. Rural and remote areas of the country had more limited project activity. Conclusions: The mapping of projects by geographical location enabled easy identification of high and low activity areas. Analysis of the types of projects undertaken in each region enabled identification of target groups that had not been involved or services that had not yet been developed. This served as a powerful tool for policy planning and implementation and will be used to support the continued implementation of Australia's policy on the quality use of medicines.

In vivo DNA electrotransfer

The use of electrotransfer for DNA delivery to prokaryotic cells, and eukaryotic cells in vitro, has been well known and widely used for many years. However, it is only recently that electric fields have been used to enhance DNA transfer to animal cells in vivo, and this is known as DNA electrotransfer or in vivo DNA electroporation. Some of the advantages of this method of somatic cell gene transfer are that it is a simple method that can be used to transfer almost any DNA construct to animal cells and tissues in vivo; multiple constructs can be co-transfected; it is equally applicable to dividing and nondividing cells; the DNA of interest does not need to be subeloned into a specific viral transfer vector and there is no need for the production of high titre viral stocks; and, as no viral genes are expressed there is less chance of an adverse immunologic reaction to vector sequences. The ease with which efficient in vivo gene transfer can be achieved with in vivo DNA electrotransfer is now allowing genetic analysis to be applied to a number of classic animal model systems where transgenic and embryonic stem cell techniques are not well developed, but for which a wealth of detailed descriptive embryological information is available, or surgical manipulation is much more feasible. As well as exciting applications in developmental biology, in vivo DNA electrotransfer is also being used to transfer genes to skeletal muscle and drive expression of therapeutically active proteins, and to examine exogenous gene and protein function in normal adult cells situated within the complex environment of a tissue and organ system in vivo. Thus, in effect providing the in vivo equivalent of the in vitro transient transfection assay. As the widespread use of in vivo electroporation has really only just begun, it is likely that the future will hold many more applications for this technology in basic research, biotechnology and clinical research areas.

Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a

Voltage-gated sodium channels drive the initial depolarization phase of the cardiac action potential and therefore critically determine conduction of excitation through the heart. In patients, deletions or loss-of-function mutations of the cardiac sodium channel gene, SCN5A, have been associated with a wide range of arrhythmias including bradycardia (heart rate slowing), atrioventricular conduction delay, and ventricular fibrillation. The pathophysiological basis of these clinical conditions is unresolved. Here we show that disruption of the mouse cardiac sodium channel gene, Scn5a, causes intrauterine lethality in homozygotes with severe defects in ventricular morphogenesis whereas heterozygotes show normal survival. Whole-cell patch clamp analyses of isolated ventricular myocytes from adult Scn5a(+/-) mice demonstrate a approximate to50% reduction in sodium conductance. Scn5a(+/-) hearts have several defects including impaired atrioventricular conduction, delayed intramyocardial conduction, increased ventricular refractoriness, and ventricular tachycardia with characteristics of reentrant excitation. These findings reconcile reduced activity of the cardiac sodium channel leading to slowed conduction with several apparently diverse clinical phenotypes, providing a model for the detailed analysis of the pathophysiology of arrhythmias.

Structural ordering of coal char during heat treatment and its impact on reactivity

The effect of heat treatment on the structure of an Australian semi-anthracite char was studied in detail in the 850-1150degreesC temperature range using XRD, HRTEM, and electrical resistivity techniques. It was found that the carbon crystallite size in the char does not change significantly during heat treatment in the temperature range studied, for both the raw coal and its ash-free derivative obtained by acid treatment. However, the fraction of the organized carbon in the raw coal chars, determined by XRD, increased with increase of heat treatment time and temperature, while that for the ash-free coal chars remained almost unchanged. This suggests the occurrence of catalytic ordering during heat treatment, supported by the observation that the electrical resistivity of the raw coal chars decreased with heat treatment, while that of the ash-free coal chars did not vary significantly. Further confirmatory evidence was provided by high resolution transmission electron micrographs depicting well-organized carbon layers surrounding iron particles. It is also found that the fraction of organized carbon does not reach unity, but attains an apparent equilibrium value that increases with increase in temperature, providing an apparent heat of ordering of 71.7 kJ mol(-1) in the temperature range studied. Good temperature-independent correlation was found between the electrical resistivity and the organized carbon fraction, indicating that electrical resistivity is indeed structure sensitive. Good correlation was also found between the electrical resistivity and the reactivity of coal char. All these results strongly suggest that the thermal deactivation is the result of a crystallite-perfecting process, which is effectively catalyzed by the inorganic matter in the coal char. Based on kinetic interpretation of the data it is concluded that the process is diffusion controlled, most likely involving transport of iron in the inter-crystallite nanospaces in the temperature range studied. The activation energy of this transport process is found to be very low, at about 11.8 kJ mol(-1), which is corroborated by model-free correlation of the temporal variation of organized carbon fraction as well as electrical resistivity data using the superposition method, and is suggestive of surface transport of iron. (C) 2002 Elsevier Science Ltd. All rights reserved.

Assessing clinical reasoning: a method to monitor its development in a PBL curriculum

The aim of this study was to develop and trial a method to monitor the evolution of clinical reasoning in a PBL curriculum that is suitable for use in a large medical school. Termed Clinical Reasoning Problems (CRPs), it is based on the notion that clinical reasoning is dependent on the identification and correct interpretation of certain critical clinical features. Each problem consists of a clinical scenario comprising presentation, history and physical examination. Based on this information, subjects are asked to nominate the two most likely diagnoses and to list the clinical features that they considered in formulating their diagnoses, indicating whether these features supported or opposed the nominated diagnoses. Students at different levels of medical training completed a set of 10 CRPs as well as the Diagnostic Thinking Inventory, a self-reporting questionnaire designed to assess reasoning style. Responses were scored against those of a reference group of general practitioners. Results indicate that the CRPs are an easily administered, reliable and valid assessment of clinical reasoning, able to successfully monitor its development throughout medical training. Consequently, they can be employed to assess clinical reasoning skill in individual students and to evaluate the success of undergraduate medical schools in providing effective tuition in clinical reasoning.

Thermolysin activates equine lamellar hoof matrix metalloproteinases

Cultured equine lamellar hoof explants secrete the pro-enzymes matrix metalloproteinse-2 (MMP-2, 72 kDa) and MMP-2 (92 kDa). Untreated explants remained intact tested on a calibrated force transducer, but when treated with an NIMP activator, developed in-vitro laminitis, separating at the dermal-epidermal junction. Explants treated with the bacterial protease thermolysin separated dose-dependently; this was accompanied by activation of both MMP-2 and -9. Thermolysin-mediated NIP activation did not occur in a cell-free system and was not inhibited by the addition of the MMP inhibitor and batimastat. These findings suggest that thermolysin-mediated gelatinase activation is not dependent on membrane-bound matrix metalloproteinase (MT-MMP) activation, providing further evidence that bacteria can produce potent MMP activators that probably facilitate host invasion. (C) 2002 Harcourt Publishers Ltd.

Infusing the use of seasonal climate forecasting into crop management practice in North East Australia using discussion support software

Seasonal climate forecasting offers potential for improving management of crop production risks in the cropping systems of NE Australia. But how is this capability best connected to management practice? Over the past decade, we have pursued participative systems approaches involving simulation-aided discussion with advisers and decision-makers. This has led to the development of discussion support software as a key vehicle for facilitating infusion of forecasting capability into practice. In this paper, we set out the basis of our approach, its implementation and preliminary evaluation. We outline the development of the discussion support software Whopper Cropper, which was designed for, and in close consultation with, public and private advisers. Whopper Cropper consists of a database of simulation output and a graphical user interface to generate analyses of risks associated with crop management options. The charts produced provide conversation pieces for advisers to use with their farmer clients in relation to the significant decisions they face. An example application, detail of the software development process and an initial survey of user needs are presented. We suggest that discussion support software is about moving beyond traditional notions of supply-driven decision support systems. Discussion support software is largely demand-driven and can compliment participatory action research programs by providing cost-effective general delivery of simulation-aided discussions about relevant management actions. The critical role of farm management advisers and dialogue among key players is highlighted. We argue that the discussion support concept, as exemplified by the software tool Whopper Cropper and the group processes surrounding it, provides an effective means to infuse innovations, like seasonal climate forecasting, into farming practice. Crown Copyright (C) 2002 Published by Elsevier Science Ltd. All rights reserved.

Hand-assisted laparoscopic adrenalectomy: An alternative minimal invasive surgical technique for the adrenal gland

Background: Presently the surgical approach to the adrenal gland is in a state of flux. While the traditional approach to the adrenal gland has been the open transabdominal technique, more recently laparoscopic approaches, particularly via the transabdominal route, have increasingly been utilized. However, laparoscopic intervention for the adrenal gland can be problematic in certain circumstances, particularly for large adrenal masses and in instances of adrenal malignancies. Methods: In this report we describe the use of hand-assisted laparoscopic adrenalectomy as an alternative minimal invasive surgical approach to the adrenal gland. Hand-assisted laparoscopic adrenalectomy using the HandPort system (Smith & Nephew, Sydney, Australia) was undertaken in three patients requiring adrenalectomy for mass lesions including one patient with Conn's syndrome. Results: In all three cases, surgery proceeded promptly and uneventfully. In the present paper, the details of the technique of hand-assisted adrenalectomy are described. This is the first report in the world literature of this new technique for the adrenal gland. Conclusions: Hand-assisted laparoscopic adrenalectomy is an easily performed technique, which can be completed within a short operative time span and which has the advantage of providing intraoperative tactile localization for the adrenal gland. It may be particularly applicable for large adrenal tumours, yet only involves the performance of a small abdominal incision. Postoperative recovery is comparable with that reported for the laparoscopic-only technique. Hand-assisted adrenalectomy is a new technique which has great potential and which warrants further evaluation.

Communicating with the community about grieving: A description and review of the foundations of a broken leg analogy of grieving

With loss permeating the lives of all people throughout the entire life span and its potential for serious long-term deleterious effects, providing effective care for those experiencing situations of loss would be an important element of any preventive community-based mental health promotion approach. The low use of mental health services by those confronted with loss, and the lack of such services in many areas, makes it imperative to enhance the competency of the broader community to provide appropriate care during times of loss. Contributory to such care is a sound knowledge of the literature concerning loss and grieving. The broken leg analogy of grief presented in this article integrates the traditional and emerging grief theories and empirical evidence into an analogy of grieving that can be easily communicated to the general community, is relevant to many losses. and vet upholds the differing positions concerning grieving held by various schools of psychiatric thought.

Modelling activated sludge flocculation using population balances

Activated sludge flocculation was modelled using population balances. The model followed the dynamics of activated sludge flocculation providing a good approximation of the change in mean floe size with time. Increasing the average velocity gradient decreased the final floe size. The breakage rate coefficient and collision efficiency also varied with the average velocity gradient. A power law relationship was found for the increase in breakage rate coefficient with increasing average velocity gradient. Further investigation will be conducted to determine the relationship between the collision efficiency and particle size to provide a better approximation of dynamic changes in the floe size distribution during flocculation. (C) 2002 Published by Elsevier Science B.V.

The scourge of scabies

Scabies ('Itch Mite') is truly a Great Neglected Disease that inflicts misery on millions. Molecular approaches, while still in their infancy, are providing a better understanding of the parasite and will have important implications for control and prevention. It has long been thought that dogs may act as a reservoir for human infections. However, genetic studies cast doubt over this supposition.

The E(NK) model: extending the NK model to incorporate gene-by-environment interactions and epistasis for diploid genomes

The haploid NK model developed by Kauffman can be extended to diploid genomes and to incorporate gene-by-environment interaction effects in combination with epistasis. To provide the flexibility to include a wide range of forms of gene-by-environment interactions, a target population of environment types (TPE) is defined. The TPE consists of a set of E different environment types, each with their own frequency of occurrence. Each environment type conditions a different NK gene network structure or series of gene effects for a given network structure, providing the framework for defining gene-by-environment interactions. Thus, different NK models can be partially or completely nested within the E environment types of a TPE, giving rise to the E(NK) model for a biological system. With this model it is possible to examine how populations of genotypes evolve in context with properties of the environment that influence the contributions of genes to the fitness values of genotypes. We are using the E(NK) model to investigate how both epistasis and gene-by-environment interactions influence the genetic improvement of quantitative traits by plant breeding strategies applied to agricultural systems. © 2002 Wiley Periodicals, Inc.

Stress correlation function evolution in lattice solid elasto-dynamic models of shear and fracture zones and earthquake prediction

It has been argued that power-law time-to-failure fits for cumulative Benioff strain and an evolution in size-frequency statistics in the lead-up to large earthquakes are evidence that the crust behaves as a Critical Point (CP) system. If so, intermediate-term earthquake prediction is possible. However, this hypothesis has not been proven. If the crust does behave as a CP system, stress correlation lengths should grow in the lead-up to large events through the action of small to moderate ruptures and drop sharply once a large event occurs. However this evolution in stress correlation lengths cannot be observed directly. Here we show, using the lattice solid model to describe discontinuous elasto-dynamic systems subjected to shear and compression, that it is for possible correlation lengths to exhibit CP-type evolution. In the case of a granular system subjected to shear, this evolution occurs in the lead-up to the largest event and is accompanied by an increasing rate of moderate-sized events and power-law acceleration of Benioff strain release. In the case of an intact sample system subjected to compression, the evolution occurs only after a mature fracture system has developed. The results support the existence of a physical mechanism for intermediate-term earthquake forecasting and suggest this mechanism is fault-system dependent. This offers an explanation of why accelerating Benioff strain release is not observed prior to all large earthquakes. The results prove the existence of an underlying evolution in discontinuous elasto-dynamic, systems which is capable of providing a basis for forecasting catastrophic failure and earthquakes.

Social rules for managing attempted interpersonal domination in the workplace: Influence of status and gender.

The present study utilized a social rules approach to investigate the relative influence of gender and status on managers' self-evaluations of their effectiveness in handling a dominating subordinate. In the first study 84 White middle-class participants identified the prescriptive and proscriptive rules for socially appropriate responding to a stimulus situation involving a pushy subordinate. Four rule sets were identified for female and male managers and subordinates, respectively. Rule-sets shared a number of common rules and showed some variation according to gender roles. In the second study, 91 White middle-class participants rated the individual rules for importance and also rated their personal and managerial effectiveness when responding to the stimulus situation using gender- and status-consistent and gender-and status-inconsistent response strategies. Both men and women rated the female gender and status- consistent strategy as most effective, and rated the status-inconsistent strategy as less effective than a gender-inconsistent response. Results were interpreted as providing more support for a situational gender-related theory of workplace behavior, rather than a traditional gender role perspective.

Progressive Age-Related Changes Similar to Age-Related Macular Degeneration in a Transgenic Mouse Model

Age-related macular degeneration (AMD) is the major cause of blindness in the developed world. its pathomechanism is unknown and its late onset, complex genetics and strong environmental components have all hampered investigations. Here we demonstrate the development of an animal model for AMD that reproduces features associated with geographic atrophy, a transgenic mouse line (mcd/mcd) expressing a mutated form of cathepsin D that is enzymatically inactive thus impairing processing of phagocytosed photoreceptor outer segments in the retinal pigment epithelial (RPE) cells. Pigmentary changes indicating RPE cell atrophy and a decreased response to flash electroretinograms were observed in 11- to 12-month-old mcd/mcd mice. Histological studies showed RPE cell proliferation, photoreceptor degeneration, shortening of photoreceptor outer segments, and accumulation of immunoreactive photoreceptor breakdown products in the RPE cells. An accelerated photoreceptor cell death was detected in 12-month-old mcd/mcd mice. Transmission electron microscopy demonstrated presence of basal laminar and linear deposits that are considered to be the hallmarks of AMD. Small hard drusen associated with human age-related maculopathy were absent in the mcd/mcd mouse model at the ages analyzed. in summary, this model presents several features of AMD, thus providing a valuable tool for investigating the underlying biological processes and pathomechanism of AMD.