Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8α+ dendritic cells

Although CD8+ T cells do not contribute to protection against the blood stage of Plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ECM). At present, there is no direct evidence that the CD8+ T cells mediating ECM are parasite-specific or, for that matter, whether parasite-specific CD8+ T cells are generated in response to blood-stage infection. To resolve this and to define the cellular requirements for such priming, we generated transgenic P. berghei parasites expressing model T cell epitopes. This approach was necessary as MHC class I-restricted antigens to blood-stage infection have not been defined. Here, we show that blood-stage infection leads to parasite-specific CD8+ and CD4+ T cell responses. Furthermore, we show that P. berghei-expressed antigens are cross-presented by the CD8α+ subset of dendritic cells (DC), and that this induces pathogen-specific cytotoxic T lymphocytes (CTL) capable of lysing cells presenting antigens expressed by blood-stage parasites. Finally, using three different experimental approaches, we provide evidence that CTL specific for parasite-expressed antigens contribute to ECM.

Chemical modification of timber decking: looking to the future

To help avoid conflict and even market rejection, the design and introduction of new technologies can be aided by consideration of the potential concerns of different stakeholder groups. An assessment of their desired goals for technological change may be useful for pre-empting changes in the  parameters of acceptability for technologies. As part of a research  programme evaluating the parameters of acceptability for bio-based  technologies using life cycle assessment of products and an analysis of the  perceptual frameworks of stakeholders, respondents from four stakeholder  groups in New Zealand were interviewed about the desirable and  undesirable trajectories for chemical modification technologies. Three  examples of pine decking products derived using different amounts and  types of chemical modification served to help explore the contemporary  criteria and rationale for acceptability. The responses of the 70 respondents  in those four groups indicated that new technologies need to be able to  prove their worth with regard to both tangible and intangible qualities if they  are to be accepted into the market in the place of either the existing product  or an inorganic competitor.

The role of fatty acids in satiation and satiety

Background – Satiation and satiety describe the events which lead to meal termination and the maintenance of hunger induced by physical and metabolic events following food ingestion. Fatty acids, components of dietary fat (triglyceride) may be important, if not essential components of satiation and satiety. Emerging evidence suggests fatty acid now constitutes a sixth taste modality and orally sensed fatty acids mediate unique cephalic and hormonal responses priming the body for fat digestion, and may contribute to sensory specific satiety. Once ingested, fatty acids are sensed in the gastrointestinal tract (GIT) where they cause the release of hormones, stimulate the vagus and enter the blood stream where they act a number of organs (brain, liver) to influence satiety.
Objective – To review the role of fatty acids in sensory and metabolic satiation and satiety.
Design – Literature search and review of papers from the past decade on satiety, satiation, fat taste and fatty acids.
Outcomes – The physiological significance of gustatory fat detection is still unclear, but it may signal the nutritious content of fat similar to the tastes of sweet or umami which signal the presence of carbohydrate or proteins. Like other tastants, fatty acid taste sensitivity is thought to vary in the population and differences in sensitivity may influence dietary choice and fat intake. Fatty acid taste may contribute to sensory specific satiety as foods are eaten. Animal models have observed an inverse relationship between oral fatty acid sensitivity and fat consumption, which leads to obesity. Observations that the obese have heightened preferences for, and consume more fat than lean individuals questions whether such a relationship may also be apparent in humans. At the GIT, fatty acids are sensed by enterocytes and bind to receptors, transporters or ion channels where they initiate gut-brain communication over nutrient status through the vagus and cause the release of satiety hormones which lead to meal termination. Inefficient fatty acid sensing at either or both locations is thought to accompany the aetiology of obesity.
Conclusion – Variations in sensitivity to fatty acids may alter preferences and consumption of fats or hormonal responses to fat ingestion which influence sensory-specific, metabolic and subjective satiety.

Reaching and influencing consumers in the prescription medicine market

Purpose – Celebrex became the first of a new class of drugs known as COX-2 selective non-steroidal anti-inflammatory drugs. It improves treatment for arthritis sufferers without compromising the protective lining of the stomach. The purpose of this paper is to illustrate how direct-to-consumer advertising (DTCA) of prescription medicines can be used to rebuild faith in the cyclooxygenase-2 (COX-2) product category.

Design/methodology/approach – The case is developed using published sources and no input is required from company representatives. The presentation style follows the classic comprehensive case format used in postgraduate teaching programmes.

Findings – Business executives and strategic marketing students would benefit from a discussion on how external environmental factors can suddenly impose a review of marketing strategy. The reader learns how management addresses the business dilemma using DTCA.

Research limitations/implications – A blockbuster rival drug Vioxx is withdrawn due to cardiovascular (CV) health safety concerns. A resulting dominant market situation soon becomes a business dilemma. The Federal Drug Administration calls for a “black box” warning label on Celebrex, the most serious type of warning.

Practical implications – The implications are that having a product in a class of its own is not enough. It highlights the need to communicate to different audiences, to both the medical profession and the end-user. Getting doctors to recommend the medicine and pulling the product through the channel by stimulating patient demand after a health scare are paramount.

Originality/value – This is the first pharmaceutical business case where the withdrawal of a rival product leaves the dominant competitor in a monopoly situation. Contrary to expectation, market share plummets despite the absence of competition.

High prices for generics in Australia : more competition might help

It is commonly believed that dispensed prices of medicines in Australia are substantially lower than those in other developed countries, particularly the US. This article reports the results of an analysis comparing dispensed prices for the most commonly prescribed and the highest cost items in Australia with dispensed prices in the US. Although a large majority of items are less expensive in Australia than in the US, Australian prices are higher for a substantial number of products, particularly generic drugs. This article examines various policies affecting the pricing of generics in Australia. It is postulated that the main cause for higher prices for a substantial number of generic products is the lack of price competition. This results from government policy which ensures that a price reduction by one company is communicated immediately to all competitors in that market along with an invitation to match the reduced price. The dominant strategy for all suppliers is to only reduce their price in response to a reduction in price by a competitor. The result is a lack of differentiation in pricing across brands of a medicine on the Schedule of Pharmaceutical Benefits. The government could improve the structure of the generics market and encourage greater competition by ceasing to disclose competitor firms’ offers to other competitors. The government could conduct pricing reviews of each generic product relatively infrequently (eg, only once annually or every 18 months). At the time of the pricing review, the government would request confidential offers on price for a generic from all players in the market. Brands should then all be listed under the Pharmaceutical Benefits Scheme (PBS) at the offered price. Prices offered by the individual supplier would apply until the next pricing review. The PBS would continue to subsidise up to the price of the lowest priced brand, with brand premiums applying to all brands priced higher than the benchmark price. Such an approach would provide opportunity for players in the market to capture market share by being thelowest priced brand.

Dissociations between implicit and explicit memory in children : the role of strategic processing and the knowledge base

A review of the literature shows that explicit memory develops substantially from three years of age to adulthood, while implicit memory remains stable across this age range. Previously, this developmental dissociation has been attributed to different memory systems, or to confounds with perceptual vs. conceptual processing. Prompted by an alternative developmental framework, the experiments reported here provide evidence against both interpretations. Instead, it will be argued that (a) the implicit - explicit developmental dissociation reflects differences in strategic processing (strategy use and metamemory) across childhood and (b) that implicit memory can show development if a child's knowledge base in the tested domain is developing with age.

The 1859 election on the Ovens

The Victorian general election of 1859 occurred during a time of social transition and electoral reformation, which extended the vote to previously unrepresented adult males. Gold discoveries, including those on the Ovens, triggered the miners’ insistent demands for access to land and participation in the political process. The thesis identifies issues, which emerged during the election campaign on the Ovens goldfields, surrounding Beechworth. The struggle centred on the two Legislative Assembly seats for the Ovens and the one Legislative Council seat for the Murray District. Though the declared election issue was land reform, it concealed a range of underlying tensions, which divided the electorate along lines of nationality and religion. Complicating these tensions within the European community was the Chinese presence throughout the Ovens. The thesis suggests the historical memory of the French Revolution, the European Revolutions of 1848 and the Catholic versus Protestant revivals divided the Ovens goldfield community. The competing groups formed alliances; a Beechworth-centred grouping of traders, merchants and the Constitution’s editor, ensured the existing conservative agenda triumphed over those perceived radicals who sought reform. In the process the land hungry miners did not gain any political representation in the Legislative Assembly, while a prominent Catholic squatter who advocated limited land reform was defeated for the Legislative Council seat. Two daily Beechworth papers, Ovens and Murray Advertiser and its fierce competitor, the Constitution and Ovens Mining Intelligencer are the major primary sources for the thesis.

A note on work-related values, budget emphasis and managers’ organisational commitment

Managers’ work-related values (WRVs) have important implications for designing appropriate management accounting systems (MAS) in organisations. This paper examines the effect of the interaction between managers’ WRV for innovation and budget emphasis (an integral part of MAS) on their organisational commitment. The sample consisted of 109 managers from production, marketing and support departments within Australian manufacturing firms. Hypotheses were tested using both quantitative and qualitative data collected by a questionnaire survey and post-survey interviews. The results indicate that the adoption of low budget emphasis led to high organisational commitment when managers’ WRV for innovation was high, but not when managers’ WRV for innovation was low. The results also indicate that marketing managers held higher WRV for innovation than production managers. The post-survey interviews provide further insight into how a more customer- and competitor-focused subculture of marketing managers and a more technical- and efficiency-focused subculture of production managers may promote the difference in their WRV for innovation, and affect their attitudes towards budget emphasis. The findings of the study have implications for design of performance evaluation systems for managers in functionally differentiated organisations.

Determinants of demand for Fiji's exports : an empirical investigation

Fiji is no exception to the rule that exports are an important source of growth and development. In this light, it is important to know the determinants of exports. However, there is no empirical study on Fiji's export demand. This paper uses the modern econometric techniques—in particular, the autoregressive distributed lag approach to cointegration—to investigate whether the standard export demand variables, viz., trading partner income, export price, and competitor price, have a long-run cointegration relationship with Fiji's real exports for the period 1970 to 1999. In addition, the long-run results are also estimated by using the dynamic ordinary least squares and the fully modified ordinary least squares. The empirical results indicate the existence of a cointegration relationship among the variables. The long-run foreign income, own-price, and cross-price elasticities are found to be 0.7 to 0.8, −1.3 to −1.5, and 2.1 to 2.2, respectively.

Do maternally derived antibodies and early immune experience shape the adult immune response?

1. Immunological imprinting by maternally derived antibodies has been proposed to have both positive and negative consequences for offspring immunity in early and adult life. However, few studies of maternal effects on immunity have followed individuals past the juvenile stages.

2. Using laboratory Japanese quail, we developed a novel method of directly manipulating yolk antibodies of neonates, and then followed individuals through a series of immune challenges until they were of reproductive age.

3. Our method of directly injecting purified antibodies into the yolk sac of newly hatched chicks successfully elevated the plasma titres of specific anti-KLH IgY in neonates. This allows us to test whether differences in neonatal anti-KLH IgY affect immunity at the juvenile and adult stages of life.

4. We found little evidence for an effect of maternal antibodies on juvenile stage immune response, in contrast to results from previous studies. Adult immune response depended largely on the magnitude of the juvenile immune response regardless of the identity of the antigen in the juvenile immune challenge, and did not depend on neonatal IgY titres. Our results are consistent with a priming effect of early immune experience on adult stage immune responsiveness, but we found no evidence of carryover effects of yolk-derived antibodies on adult immunity.

5. This study employs new methodology for investigation of maternal antibodies and presents results suggesting that further studies of maternal effects on immunity will require careful consideration of the numerous ways maternally derived yolk components can impact the different types of immune response.

Ecological and life-history factors influencing the evolution of maternal antibody allocation : a phylogenetic comparison

Maternally derived yolk antibodies provide neonates with immune protection in early life at negligible cost to mothers. However, developmental effects on the neonate's future immunity are potentially costly and thus could limit yolk antibody deposition. The benefits to neonatal immunity must be balanced against costs, which may depend on neonate vulnerability to pathogens, developmental trajectories and the immunological strategies best suited to a species' pace of life. We measured yolk antibodies and life-history features of 23 species of small Neotropical birds and assessed the evidence for each of several hypotheses for life history and ecological effects on the evolution of yolk antibody levels. Developmental period and yolk antibodies are negatively related, which possibly reflect the importance of humoral immune priming through antigen exposure, and selection to avoid autoimmunity, in species with a slower pace of life. There is also a strong relationship between body size and yolk antibody concentration, suggesting that larger species are architecturally equipped to produce and transfer higher concentrations of antibodies. These results suggest that developmental effects of maternally derived antibodies, such as imprinting effects on B-cell diversity or autoimmune effects, are important and deserve more consideration in future research.

Systemic activation of dendritic cells by toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity

The mechanisms responsible for the immunosuppression associated with sepsis or some chronic blood infections remain poorly understood. Here we show that infection with a malaria parasite (Plasmodium berghei) or simple systemic exposure to bacterial or viral Toll-like receptor ligands inhibited cross-priming. Reduced cross-priming was a consequence of downregulation of cross-presentation by activated dendritic cells due to systemic activation that did not otherwise globally inhibit T cell proliferation. Although activated dendritic cells retained their capacity to present viral antigens via the endogenous major histocompatibility complex class I processing pathway, antiviral responses were greatly impaired in mice exposed to Toll-like receptor ligands. This is consistent with a key function for cross-presentation in antiviral immunity and helps explain the immunosuppressive effects of systemic infection. Moreover, inhibition of cross-presentation was overcome by injection of dendritic cells bearing antigen, which provides a new strategy for generating immunity during immunosuppressive blood infections.

Firm survival through a crisis : the influence of market orientation, marketing innovation and business strategy

As an outcome of the economic crisis, the global manufacturing sector is collapsing. Focusing on Chinese manufacturing small and medium enterprises (SMEs), this study investigates whether marketing innovation, defined as improvements in the marketing mix, can assist in withstanding the challenges of operating under the current economic conditions. A conceptual model linking market orientation, marketing innovation, competitive advantage and firm survival is tested using structural equation modelling. Three key findings are derived. First, the examined Chinese manufacturing SMEs had a greater perceived likelihood of survival had they developed and sustained a competitive advantage. Second, marketing innovation assisted in developing and sustaining competitive advantages based on differentiation and cost leadership strategies. Third, marketing innovation capabilities improved when the examined manufacturing SMEs were competitor oriented and had good inter-functional capabilities.

Inter-relationships between innovation and market orientation in SMEs

Purpose – This study aims to explore the nature of the interactions between two strategies, innovation and market orientation. By examining the components of these constructs the paper seeks to identify key components of market orientation that are antecedent factors of the innovation performance of the firm.

Design/methodology/approach – Correlation analysis was undertaken on data from a survey of 73 manufacturing firms in the Greater Western Sydney economic development zone in Australia. The data were supplemented by information obtained from the firm's annual reports.

Findings – Innovation was found to be positively correlated to market orientation (customer orientation, competitor orientation and inter-functional co-ordination) and both of these constructs were found to be positively correlated to firm performance and the degree of change in the firm's competitive environment.

Research limitations/implications – Possible limitations are: the low survey response rate; the nature of the sampled population; and the spread of industries involved, which could limit the generalisability of the results. The next steps will be to conduct deeper analysis into the factors that make up the subscales of the two constructs and to determine how market orientation or its associated activities interact with the innovation process.

Practical implications – In order to maximize a firm's financial performance, organizations should increase both their market orientation and their innovation activities as these factors operate synergistically.

Originality/value – This study is arguably the first to establish the finding that the degree of change in the competitive environment and the level of market orientation are linked, and the identification of the components of market orientation that are linked to firm innovation. These findings suggest that firm innovation and firm market orientation are strategic reactions to changes in the firm's competitive environment.

Performance score variation between days at Australian national and Olympic women's artistic gymnastics competition

We determined the inter-day variability in elite-standard women's artistic gymnastics competition scores. National (50 gymnasts for up to three days) and Olympic (24 gymnasts for up to five days) competition scores published in the public domain (‘Giant poster pull-out’, 2010; Gymnastics Australia, 2008) were evaluated using three statistical measures. Analyses of the inter-day differences in the mean scores as a percentage (MDiff%), coefficient of variation percentages for the mean score across both days (CV%), and Pearson correlation coefficients for the inter-day score (r) were interpreted using thresholds from trivial to large. National-class gymnasts' two-day performance variation was trivial for vault, small for floor and beam, and moderate for bars. When senior gymnasts competed for a third day the performance variation increased to moderate for vault. Across five days of Olympic competition there were trivial (e.g. CV%: vault = 0.8) to small (e.g. CV%: bars = 2.0) variations in performances between days on all apparatus. Olympians' performance score consistency is superior to senior, national-class competitors. The performance score consistency required for gymnasts who aspire to participate at the Olympics as a top-24 competitor is better than 3%.