Tumour susceptibility to innate and adaptive immunotherapy changes during tumour maturation

Immunotherapy of tumours using T cells expanded in vitro has met with mixed clinical success suggesting that a greater understanding of tumour/T-cell interaction is required. We used a HPV16E7 oncoprotein-based mouse tumour model to study this further. In this study, we demonstrate that a HPV16E7 tumour passes through at least three stages of immune susceptibility over time. At the earliest time point, infusion of intravenous immune cells fails to control tumour growth although the same cells given subcutaneously at the tumour site are effective. In a second stage, the tumour becomes resistant to subcutaneous infusion of cells but is now susceptible to both adjuvant activated and HPV16E7-specific immune cells transferred intravenously. In the last phase, the tumour is susceptible to intravenous transfer of HPV16E7-specific cells, but not adjuvant-activated immune cells. The requirement for IFN-gamma and perforin also changes with each stage of tumour development. Our data suggest that effective adoptive T-cell therapy of tumour will need to be matched with the stage of tumour development.

An adaptogenic role for omega-3 fatty acids in stress; a randomised placebo controlled double blind intervention study (pilot) [ISRCTN22569553]

Background There is evidence for an adaptive role of the omega -3 fatty acid, docosahexaenoic acid (DHA) during stress. Mechanisms of action may involve regulation of stress mediators, such as the catecholamines and proinflammatory cytokines. Prevention of stress-induced aggression and hostility were demonstrated in a series of clinical trials. This study investigates whether perceived stress is ameliorated by DHA in stressed university staff. Methods Subjects that scored ≥ 17 on the Perceived Stress Scale were randomised into a 6-week pilot intervention study. The diet reactive group was supplemented with 6 g of fish oil containing 1.5 g per day DHA, while the placebo group was supplemented with 6 g a day of olive oil. The groups were compared with each other and a wider cross sectional study population that did not receive either active or placebo intervention. Results There was a significant reduction in perceived stress in both the fish oil and the placebo group from baseline. There was also a significant between-group difference between the fish oil group and the no-treatment controls in the rate of stress reduction (p < 0.05). However, there was not a significant between-group difference between the fish oil and the placebo group, nor the placebo group and the control group. These results are discussed in the context of several methodological limitations. The significant stress reductions in both the fish oil and the placebo group are considered in view of statistical regression, an effect likely to have been exaggerated by the time course of the study, a large placebo effect and the possibility of an active effect from the placebo. Conclusion There were significant differences (p < 0.05) in the fish oil group compared with no-treatment controls. This effect was not demonstrated in the placebo group. As a pilot study, it was not sufficiently powered to find the difference between the fish oil group and the placebo group significant. Further work needs to be undertaken to conclusively demonstrate these data trends. However, the findings from this research support the literature in finding a protective or 'adaptogenic' role for omega-3 fatty acids in stress.

Improving the efficiency of wildlife monitoring by estimating detectability: a case study of foxes (Vulpes vulpes) on the Eyre Peninsula, South Australia

Demonstrating the existence of trends in monitoring data is of increasing practical importance to conservation managers wishing to preserve threatened species or reduce the impact of pest species. However, the ability to do so can be compromised if the species in question has low detectability and the true occupancy level or abundance of the species is thus obscured. Zero-inflated models that explicitly model detectability improve the ability to make sound ecological inference in such situations. In this paper we apply an occupancy model including detectability to data from the initial stages of a fox-monitoring program on the Eyre Peninsula, South Australia. We find that detectability is extremely low (< 18%) and varies according to season and the presence or absence of roadside vegetation. We show that simple methods of using monitoring data to inform management, such as plotting the raw data or performing logistic regression, fail to accurately diagnose either the status of the fox population or its trajectory over time. We use the results of the detectability model to consider how future monitoring could be redesigned to achieve efficiency gains. A wide range of monitoring programs could benefit from similar analyses, as part of an active adaptive approach to improving monitoring and management.

Self-determination theory: A case study of evidence-based coaching

The coach is central to the development of expertise in sport (Bloom, 1985) and is subsequently key to facilitating adaptive forms of motivation to enhance the quality of sport performance (Mallett & Hanrahan, 2004). In designing optimal training environments that are sensitive to the underlying motives of athletes, the coach requires an in-depth understanding of motivation. This paper reports on the application of self-determination theory (SDT; Deci & Ryan, 1985; Ryan & Deci, 2000) to coaching elite athletes. Specifically, the application of SDT to designing an autonomy-supportive motivational climate is outlined, which was used in preparing Australia's two men's relay teams for the 2004 Olympic Games in Athens.

An adaptive and dynamic dimensionality reduction method for high-dimensional indexing

The notorious "dimensionality curse" is a well-known phenomenon for any multi-dimensional indexes attempting to scale up to high dimensions. One well-known approach to overcome degradation in performance with respect to increasing dimensions is to reduce the dimensionality of the original dataset before constructing the index. However, identifying the correlation among the dimensions and effectively reducing them are challenging tasks. In this paper, we present an adaptive Multi-level Mahalanobis-based Dimensionality Reduction (MMDR) technique for high-dimensional indexing. Our MMDR technique has four notable features compared to existing methods. First, it discovers elliptical clusters for more effective dimensionality reduction by using only the low-dimensional subspaces. Second, data points in the different axis systems are indexed using a single B+-tree. Third, our technique is highly scalable in terms of data size and dimension. Finally, it is also dynamic and adaptive to insertions. An extensive performance study was conducted using both real and synthetic datasets, and the results show that our technique not only achieves higher precision, but also enables queries to be processed efficiently. Copyright Springer-Verlag 2005

Adaptive responses of wild mungbean (Vigna radiata ssp sublobata) to photo-thermal environment. I. Phenology

The phenology of 11 diverse accessions of wild mungbean was observed under natural and artificial photoperiod - temperature conditions, in order to examine whether genotypic differences might be attributed to adaptive responses to photo-thermal conditions. There was large variation in phenological response among accessions and across environments, much of which was due to differences in the duration of the pre-flowering phase. Accessions that flowered earlier tended to flower for longer, apart from 2 earlier flowering, inland Australian lines that were also earlier maturing. The patterns of response in time from sowing to flowering over environment were consistent with quantitative short-day photoperiodic adaptation, a conclusion supported by the effects of artificial day-length extension and by 'goodness of fit' of the observed responses to standard models relating rate of development to photoperiod and temperature. The fitted models indicated that rate of development towards flowering was hastened by warmer temperatures, and delayed by longer day lengths, with differential sensitivity between accessions to both factors. The models also suggested that photoperiod was more important for accessions collected closer to the equator, which were generally later flowering as a consequence. Conversely, temperature was relatively more important in lines from higher latitudes. Modelling also suggested that the period from first flowering to maturity was sensitive to photoperiod and temperature. Again, longer days appeared to prolong growth and delay maturity. However, cooler temperatures accelerated rather than slowed maturity, by suppressing further vegetative growth. The variation observed indicated that there is considerable scope for using the wild population to broaden the adaptation of cultivated mungbean. In particular, the unusual response of a late-flowering, photoperiod-insensitive accession warrants further study to establish whether the wild population contains a unique 'long juvenile' trait analogous to that being used for improving phenological adaptation in soybean.

Using "war stories" to train for adaptive performance: Is it better to learn from error or success?

The study examines whether error exposure training can enhance adaptive performance. Fifty-nine experienced fire-fighters undergoing training for incident command participated in the study. War stories were developed based on real events to illustrate successful and unsuccessful incident command decisions. Two training methodologies were compared and evaluated. One group was trained using case studies that depicted incidents containing errors of management with severe consequences in fire-fighting outcomes (error-story training) while a second group was exposed to the same set of case studies except that the case studies depicted the incidents being managed without errors and their consequences (errorless-story training). The results provide some support for the hypothesis that it is better to learn from other people's errors than from their successes. Implications for training are discussed.