Dissection of peripheral and central endogenous opioid modulation of systemic interleukin-1 beta responses using c-fos expression in the rat brain

In opiate addicts or patients receiving morphine treatment, it has been reported that the immune system is often compromised. The mechanisms responsible for the adverse effects of opioids on responses to infection are not clear but it is possible that central and/or peripheral opioid receptors may be important. We have utilised an experimental immune challenge model in rats, the systemic administration of the human pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) to study the effects of selectively blocking peripheral opioid receptors only (using naloxone methiodide) or after blocking both central and peripheral opioid receptors (using naloxone). Pre-treatment with naloxone methiodide decreased (15%) IL-1 beta-induced Fos-immunoreactivity (Fos-IR) in medial parvocellular paraventricular nucleus (mPVN) corticotropin-releasing hormone (CRH) neurons but increased responses in the ventrolateral medulla (VLM) C1 (65%) and nucleus tractus solitarius (NTS) A2 (110%) catecholamine cell groups and area postrema (136%). However no effect of blocking peripheral opioid receptors was detected in the central nucleus of the amygdala (CeA) or dorsal bed nucleus of the stria terminalis (BNST). We next determined the effect of blocking both central and peripheral opioid receptors with naloxone and, when compared to the naloxone methiodide pre-treated group, a further 60% decrease in Fos-IR mPVN CRH neurons induced by IL-1 beta was detected, which was attributed to block of central opioid receptors. Similar comparisons also detected decreases in Fos-IR neurons induced by IL-1 beta in the VLM A1, VLM C1 and NTS A2 catecholamine cell groups, area postrema, and parabrachial nucleus. In contrast, pre-treatment with naloxone increased Fos-IR neurons in CeA (98%) and dorsal BNST (72%). These results provide novel evidence that endogenous opioids can influence central neural responses to systemic IL-1 beta and also suggest that the differential patterns of activation may arise because of actions at central and/or peripheral opioid receptors that might be important in regulating behavioural, hypothalamic-pituitary-adrenal axis and sympathetic nervous system responses during an immune challenge. (c) 2005 Elsevier Ltd. All rights reserved.

Multigradient field-active contour model for multilayer boundary detection of ultrasound rectal wall image

Extraction and reconstruction of rectal wall structures from an ultrasound image is helpful for surgeons in rectal clinical diagnosis and 3-D reconstruction of rectal structures from ultrasound images. The primary task is to extract the boundary of the muscular layers on the rectal wall. However, due to the low SNR from ultrasound imaging and the thin muscular layer structure of the rectum, this boundary detection task remains a challenge. An active contour model is an effective high-level model, which has been used successfully to aid the tasks of object representation and recognition in many image-processing applications. We present a novel multigradient field active contour algorithm with an extended ability for multiple-object detection, which overcomes some limitations of ordinary active contour models—"snakes." The core part in the algorithm is the proposal of multigradient vector fields, which are used to replace image forces in kinetic function for alternative constraints on the deformation of active contour, thereby partially solving the initialization limitation of active contour for rectal wall boundary detection. An adaptive expanding force is also added to the model to help the active contour go through the homogenous region in the image. The efficacy of the model is explained and tested on the boundary detection of a ring-shaped image, a synthetic image, and an ultrasound image. The experimental results show that the proposed multigradient field-active contour is feasible for multilayer boundary detection of rectal wall

Nonplanar distortions and strain energies of polycyclic aromatic hydrocarbons

On the basis of HF/6-31G(d) optimized structures, the nonplanar distortions of 135 polycyclic aromatic hydrocarbons (PAHs) have been classified as splitting (S-) and arching (A-) distortions. Three bay structures are proposed as the structural origin of S-distortion. Due to the limitation of sample molecules, a set of universal motifs for molecules containing A-distortions is not available; however, a set of motifs and parameters are developed for the semiquantitative estimation of the nonplanar strain energies of PAHs containing the corannulene structure, and the differences between the E, values from quantum calculations and those from these estimations vary from -5.60 to 5.51 kcal/mol. The above results are fundamentally important for the understanding of nonplanar distortion of PAHs and fullerenes, and this method can also be employed to semiquantitatively estimate strain energies of such molecules containing hundreds of carbon atoms.

A modelling approach to estimate the effect of exotic pollinators on exotic weed population dynamics: bumblebees and broom in Australia

The role of mutualisms in contributing to species invasions is rarely considered, inhibiting effective risk analysis and management options. Potential ecological consequences of invasion of non-native pollinators include increased pollination and seed set of invasive plants, with subsequent impacts on population growth rates and rates of spread. We outline a quantitative approach for evaluating the impact of a proposed introduction of an invasive pollinator on existing weed population dynamics and demonstrate the use of this approach on a relatively data-rich case study: the impacts on Cytisus scoparius (Scotch broom) from proposed introduction of Bombus terrestris. Three models have been used to assess population growth (matrix model), spread speed (integrodifference equation), and equilibrium occupancy (lattice model) for C. scoparius. We use available demographic data for an Australian population to parameterize two of these models. Increased seed set due to more efficient pollination resulted in a higher population growth rate in the density-independent matrix model, whereas simulations of enhanced pollination scenarios had a negligible effect on equilibrium weed occupancy in the lattice model. This is attributed to strong microsite limitation of recruitment in invasive C. scoparius populations observed in Australia and incorporated in the lattice model. A lack of information regarding secondary ant dispersal of C. scoparius prevents us from parameterizing the integrodifference equation model for Australia, but studies of invasive populations in California suggest that spread speed will also increase with higher seed set. For microsite-limited C. scoparius populations, increased seed set has minimal effects on equilibrium site occupancy. However, for density-independent rapidly invading populations, increased seed set is likely to lead to higher growth rates and spread speeds. The impacts of introduced pollinators on native flora and fauna and the potential for promoting range expansion in pollinator-limited 'sleeper weeds' also remain substantial risks.

Healthy waterways: Healthy catchments - An integrated research/management program to understand and reduce impacts of sediments and nutrients on waterways in Queensland, Australia

The Moreton Bay Waterways and Catchments Partnership, now branded the Healthy Waterways Partnership, has built on the experience of the past 15 years here in South East Queensland (SEQ). It focuses on water quality and the ecosystem health of our freshwater, estuarine and marine systems through the implementation of actions by individual partners and the collective oversight of a regional work program that assists partners to prioritise their investments and address emerging issues. This regional program includes monitoring, reporting, marketing and communication, development of decision support tools, research that is directed to problem solving, and maintaining extensive consultative and engagement arrangements. The Partnership has produced information-based outcomes which have led to significant cost savings in the protection of water quality and ecosystem resources by its stakeholders. This has been achieved by: – providing a clear focus for management actions that has ownership of governments, industry and community; – targeted scientific research to address issues requiring appropriate management actions; – management actions based on a sound understanding of the waterways and rigorous public consultation; and, – development and implementation of a strategy that incorporates commitments from all levels of stakeholders. While focusing on our waterways, the Partnership’s approach includes addressing catchment management issues particularly relating to the management of diffuse pollution sources in both urban and rural landscapes as well as point source loads. We are now working with other stakeholders to develop a framework for integrated water management that will link water quality and water quantity goals and priorities.

Ciguatoxins: Cyclic polyether modulators of voltage-gated Iion channel function

Ciguatoxins are cyclic polyether toxins, derived from marine dinoflagellates, which are responsible for the symptoms of ciguatera poisoning. Ingestion of tropical and subtropical fin fish contaminated by ciguatoxins results in an illness characterised by neurological, cardiovascular and gastrointestinal disorders. The pharmacology of ciguatoxins is characterised by their ability to cause persistent activation of voltage-gated sodium channels, to increase neuronal excitability and neurotransmitter release, to impair synaptic vesicle recycling, and to cause cell swelling. It is these effects, in combination with an action to block voltage-gated potassium channels at high doses, which are believed to underlie the complex of symptoms associated with ciguatera. This review examines the sources, structures and pharmacology of ciguatoxins. In particular, attention is placed on their cellular modes of actions to modulate voltage-gated ion channels and other Na+-dependent mechanisms in numerous cell types and to current approaches for detection and treatment of ciguatera.

Neuromuscular-skeletal constraints on the acquisition of skill in a discrete torque production task

The organisation of the human neuromuscular-skeletal system allows an extremely wide variety of actions to be performed, often with great dexterity. Adaptations associated with skill acquisition occur at all levels of the neuromuscular-skeletal system although all neural adaptations are inevitably constrained by the organisation of the actuating apparatus (muscles and bones). We quantified the extent to which skill acquisition in an isometric task set is influenced by the mechanical properties of the muscles used to produce the required actions. Initial performance was greatly dependent upon the specific combination of torques required in each variant of the experimental task. Five consecutive days of practice improved the performance to a similar degree across eight actions despite differences in the torques required about the elbow and forearm. The proportional improvement in performance was also similar when the actions were performed at either 20 or 40% of participants' maximum voluntary torque capacity. The skill acquired during practice was successfully extrapolated to variants of the task requiring more torque than that required during practice. We conclude that while the extent to which skill can be acquired in isometric actions is independent of the specific combination of joint torques required for target acquisition, the nature of the kinetic adaptations leading to the performance improvement in isometric actions is influenced by the neural and mechanical properties of the actuating muscles.

New descriptions and understandings of internationalisation: A tale of knowledge-intensive SMEs

This research seeks to generate and foster new descriptions and understandings of processes underlying the internationalisation experienced by small- and medium-sized, knowledge-intensive enterprises. The longitudinal study centres on the growth and internationalisation of a cluster of small- and medium-sized enterprises (SMEs) in the most southern state of Australia, of which a number were 'bom global.' It draws on both retrospective data such as corporate archives, as well as observations and interviews as events unfolded over a period of eighteen months to garner insights into processes underlying the SMEs' internationalisation. The approach to inquiry is influenced by an epistemology of social constructionism, interpretive narrative, sensemaking and dramaturgical theoretical perspectives, and elements of cultural anthropology. Exploratory in the early stages, a funnel approach characteristic of ethnographic enquiry was used whereby the study became progressively focused over time. The extended period of fieldwork led to observations and interpretations that cast the retrospective data in new light, and the use of the construct 'legitimacy' as a lens through which to view activities and events infusing the firms' internationalisation. A generic narrative scheme that offers a temporal ordering of actions, context and meaning attributions in relation to legitimation behaviours and internationalisation processes is developed. This narrative scheme is then used to garner a deeper understanding of three activities that were central to the firms' internationalisation over time: the choice of geographic export markets, strategic participation in international standard-setting committees, and portfolio entrepreneurship. In addition, the study offers a rich story of the growth and internationalisation of the cluster of knowledge-intensive SMEs. The tale of growth and internationalisation pursued by the cluster of knowledgeintensive SMEs spans the period from 1975 to mid 1997, and may prove a useful resource for the theorising of others.

The importance of collaborative frontloading in automotive supply networks

Purpose – The purpose of this paper is to investigate how research and development (R&D) collaboration takes place for complex new products in the automotive sector. The research aims to give guidelines to increase the effectiveness of such collaborations. Design/methodology/approach – The methodology used to investigate this issue was grounded theory. The empirical data were collected through a mixture of interviews and questionnaires. The resulting inducted conceptual models were subsequently validated in industrial workshops. Findings – The findings show that frontloading of the collaborative members was a major issue in managing successful R&D collaborations. Research limitations/implications – The limitation of this research is that it is only based in the German automotive industry. Practical implications – Practical implications have come out of this research. Models and guidelines are given to help make a success of collaborative projects and their potential impacts on time, cost and quality metrics. Originality/value – Frontloading is not often studied in a collaborative manner; it is normally studied within just one organisation. This study has novel value because it has involved a number of different members throughout the supplier network.

Communities of implementation

The concept of communities of practice (CoPs) has rapidly gained ground in fields such as knowledge management and organisational learning since it was first identified by Lave and Wenger (1991) and Brown and Duguid (1991). In this article, we consider a related concept that we have entitled “communities of implementation.” Communities of implementation (CoIs) are similar to communities of practice in that they offer an opportunity for a collection of individuals to support each other and share knowledge in a dynamic environment and on a topic in which they share interest. In addition, and to differentiate them from CoPs, a community of implementation extends the responsibilities of a CoP by having as its focus the implementation of a programme of change. This may well extend to designing the change programme. Thus, whereas a main purpose of a CoP is to satisfy “a real need to know what each other knows” (Skyrme, 1999) in an informal way, we argue that a main purpose of a community of implementation is to “pool individual knowledge (including contacts and ways of getting things done) to stimulate collective enthusiasm in order to take more informed purposeful action for which the members are responsible.” Individual and collective responsibility and accountability for successfully implementing the actions/change programme is a key feature of a community of implementation. Without these pressures the members might lower the priority of implementation, allowing competing priorities to dominate their attention and resources. Without responsibility and accountability, the result is likely to be (at best) an organisation which has not begun a change programme, or (at worst) an organisation which is stuck halfway through another failing initiative. To achieve these additional objectives beyond those of a CoP, the CoI needs to provide heightened support to its members. In fact often the members will collectively strategise the development and implementation of the change programme they are leading in the organisation. Other concepts similar to CoPs have appeared in the literature, for example “communities of knowing” (Boland & Tenkasi, 1995), but none have a specific focus on implementation. Perhaps the closest example of a CoI, as suggested by our definition, is reported by Karsten, Lyytinen, Hurskainen, and Koskelainen (2001) who describe a CoP in a paper machinery manufacturer which seems to have the necessary focus on implementation. The theoretical aspects of this article will explore the relationship between CoPs and CoIs, and the needs for different arrangements for a CoI. The practical aspect of this article will consist of a report on a case study of a CoI that was successful in its implementation of a programme of change that aimed to improve its organisation’s knowledge management activities. Over two years the CoI implemented a suite of complementary actions across the organisation. These actions transformed the organisation and moved it towards achieving its ‘core values’ and overall objectives. The article will explore: the activities that formed and gelled the community, the role of the community in the implementation of actions, and experiences from key members of this community on its success and potential improvements.

Quid pro quo:reflections on the value of problem structuring workshops

Attracting clients who are willing to invest in using a problem structuring method (PSM) can be particularly difficult for the emerging generation of modellers. There are many reasons for this, not least that the benefits of a problem structuring intervention are vague and evidence of benefits are often anecdotal for example, claims of constructing a deeper understanding of the problem or building the commitment of a group to implementing an outcome. This paper contributes to the evaluation of problem structuring methods by reflecting on the quid pro quo that a client and problem structuring modeller can enjoy from collaboration. The paper reflects on 21 cases, where Journey Making (a problem structuring method) was used with 16 organizations to help managers agree a suite of actions to tackle a complex strategic issue. The reflections are clustered around those benefits that pertain to: PSMs in general; PSMs that use computer-supported workshops; the Journey Making methodology.

Social and scientific issues in the acceptibility of radiation risks

Ionising radiation hazards are perhaps the most documented and regulated occupational and environmental hazard. In the radiological protection field a single expert advisory organisation has had an unusually large influence on the international standard setting process. This is the International Commission on Radiological Protection (ICRP). Two common, and opposing views, exist over the formulation of protection recommendations by the ICRP. The first, and most widely accepted, is that its recommendations are scientifically determined. The second view, is that its recommendations are politically or socially determined. Neither of these analyses adequately accounts for the complex process in which protection recommendations are formulated. A third view, provided by studies of the origins of scientific controversy, suggests that both science and social factors are important in the assessment and limitation of risk. The aim of this thesis is not simply to examine the origin of controversy. Issues of equal, if not more, importance are the resolution of controversy, the formation of consensus and the maintenance of expert authority and influence. These issues form the central focus of this thesis. The aim is to assess the process through which the ICRP formulates its radiological protection recommendations and comment on the extent that these are influenced by the affiliations of its members. This thesis concludes that the ICRP's recommendations have been shaped by a complex relationship of scientific and social considerations, in which a socio-technical commitment to nuclear energy has played a key role. The Commission has responded to new scientific data by making complex changes to its philosophy and methods of describing risk. Where reductions in numerical limits have been applied they have been accompanied by practical measures designed to limit the impact of the change and provide continuity with the old limits and flexibility in the application of the new recommendations.

The design of environmental test rigs

Product reliability and its environmental performance have become critical elements within a product's specification and design. To obtain a high level of confidence in the reliability of the design it is customary to test the design under realistic conditions in a laboratory. The objective of the work is to examine the feasibility of designing mechanical test rigs which exhibit prescribed dynamical characteristics. The design is then attached to the rig and excitation is applied to the rig, which then transmits representative vibration levels into the product. The philosophical considerations made at the outset of the project are discussed as they form the basis for the resulting design methodologies. It is attempted to directly identify the parameters of a test rig from the spatial model derived during the system identification process. It is shown to be impossible to identify a feasible test rig design using this technique. A finite dimensional optimal design methodology is developed which identifies the parameters of a discrete spring/mass system which is dynamically similar to a point coordinate on a continuous structure. This design methodology is incorporated within another procedure which derives a structure comprising a continuous element and a discrete system. This methodology is used to obtain point coordinate similarity for two planes of motion, which is validated by experimental tests. A limitation of this approach is that it is impossible to achieve multi-coordinate similarity due to an interaction of the discrete system and the continuous element at points away from the coordinate of interest. During the work the importance of the continuous element is highlighted and a design methodology is developed for continuous structures. The design methodology is based upon distributed parameter optimal design techniques and allows an initial poor design estimate to be moved in a feasible direction towards an acceptable design solution. Cumulative damage theory is used to provide a quantitative method of assessing the quality of dynamic similarity. It is shown that the combination of modal analysis techniques and cumulative damage theory provides a feasible design synthesis methodology for representative test rigs.

Evolving forms of manufacturing strategy development:evidence and implications

This paper outlines, using evidence from several case studies, the use of alternative forms of manufacturing strategy processes. Our investigation shows that the manufacturing strategy development practices of manufacturers are evolving in many directions; we found several alternatives to the formal top-down planning process. Manufacturers use one or more of the following alternatives with or without the top-down manufacturing strategy process: a coherent pattern of actions; manufacturing/process improvement programs; or the pursuit of core manufacturing capabilities. It appears that the various manufacturing strategy development processes may be tied to the strategic role of manufacturing in a company. This paper offers a framework that captures the relationship between the strategic role of manufacturing and the process of manufacturing strategy development. An in-depth case from a UK company illustrates the evolving forms of manufacturing strategy development processes.

Statnote 31:analysis of covariance

Analysis of covariance (ANCOVA) is a useful method of ‘error control’, i.e., it can reduce the size of the error variance in an experimental or observational study. An initial measure obtained before the experiment, which is closely related to the final measurement, is used to adjust the final measurements, thus reducing the error variance. When this method is used to reduce the error term, the X variable must not itself be affected by the experimental treatments, because part of the treatment effect would then also be removed. Hence, the method can only be safely used when X is measured before an experiment. A further limitation of the analysis is that only the linear effect of Y on X is being removed and it is possible that Y could be a curvilinear function of X. A question often raised is whether ANCOVA should be used routinely in experiments rather than a randomized blocks or split-plot design, which may also reduce the error variance. The answer to this question depends on the relative precision of the difference methods with reference to each scenario. Considerable judgment is often required to select the best experimental design and statistical help should be sought at an early stage of an investigation.