Implementation of a Bayesian design in a dose-escalation study of an experimental agent in healthy volunteers

Bayesian decision procedures have recently been developed for dose escalation in phase I clinical trials concerning pharmacokinetic responses observed in healthy volunteers. This article describes how that general methodology was extended and evaluated for implementation in a specific phase I trial of a novel compound. At the time of writing, the study is ongoing, and it will be some time before the sponsor will wish to put the results into the public domain. This article is an account of how the study was designed in a way that should prove to be safe, accurate, and efficient whatever the true nature of the compound. The study involves the observation of two pharmacokinetic endpoints relating to the plasma concentration of the compound itself and of a metabolite as well as a safety endpoint relating to the occurrence of adverse events. Construction of the design and its evaluation via simulation are presented.

An energy budget agent-based model of earthworm populations and its application to study the effects of pesticides

Earthworms are important organisms in soil communities and so are used as model organisms in environmental risk assessments of chemicals. However current risk assessments of soil invertebrates are based on short-term laboratory studies, of limited ecological relevance, supplemented if necessary by site-specific field trials, which sometimes are challenging to apply across the whole agricultural landscape. Here, we investigate whether population responses to environmental stressors and pesticide exposure can be accurately predicted by combining energy budget and agent-based models (ABMs), based on knowledge of how individuals respond to their local circumstances. A simple energy budget model was implemented within each earthworm Eisenia fetida in the ABM, based on a priori parameter estimates. From broadly accepted physiological principles, simple algorithms specify how energy acquisition and expenditure drive life cycle processes. Each individual allocates energy between maintenance, growth and/or reproduction under varying conditions of food density, soil temperature and soil moisture. When simulating published experiments, good model fits were obtained to experimental data on individual growth, reproduction and starvation. Using the energy budget model as a platform we developed methods to identify which of the physiological parameters in the energy budget model (rates of ingestion, maintenance, growth or reproduction) are primarily affected by pesticide applications, producing four hypotheses about how toxicity acts. We tested these hypotheses by comparing model outputs with published toxicity data on the effects of copper oxychloride and chlorpyrifos on E. fetida. Both growth and reproduction were directly affected in experiments in which sufficient food was provided, whilst maintenance was targeted under food limitation. Although we only incorporate toxic effects at the individual level we show how ABMs can readily extrapolate to larger scales by providing good model fits to field population data. The ability of the presented model to fit the available field and laboratory data for E. fetida demonstrates the promise of the agent-based approach in ecology, by showing how biological knowledge can be used to make ecological inferences. Further work is required to extend the approach to populations of more ecologically relevant species studied at the field scale. Such a model could help extrapolate from laboratory to field conditions and from one set of field conditions to another or from species to species.

Mercury: An agent of poverty in Ghana's small-scale gold-mining sector?

There is consensus worldwide that the artisanal and small-scale mining (ASM) sector is comprised of individuals who are trapped in a vicious cycle of poverty, lacking the necessary financial and technological means to improve their standards of living. Minimal work, however, has been undertaken to identify the very factors behind miners' plight, which inevitably vary from country to country. This paper uses a case study of Ghana to argue that an increased dependence upon mercury for amalgamation In artisanal gold-mining communities is one such-albeit overlooked-"agent of poverty". There is mounting empirical evidence which suggests that dealings with the monoponistic middlemen who supply mercury, purchases of costly medicines to remedy ailments caused by mercury poisoning, and a lack of appropriate safeguards and alternatives to amalgamation, are preventing gold miners from improving their practices and livelihoods. The solution to the problem lies in breaking this cycle of dependency, which can be achieved by providing miners with robust support services, mercury-free technologies and education. (c) 2006 Elsevier Ltd. All rights reserved.

In vitro determination of prebiotic properties of oligosaccharides derived from an orange juice manufacturing by-product stream

Fermentation properties of oligosaccharides derived from orange peel pectin were assessed in mixed fecal bacterial culture. The orange peel oligosaccharide fraction contained glucose in addition to rhamnogalacturonan and xylogalacturonan pectic oligosaccharides. Twenty-four-hour, temperature- and pH-controlled, stirred anaerobic fecal batch cultures were used to determine the effects that oligosaccharides derived from orange products had on the composition of the fecal microbiota. The effects were measured through fluorescent in situ hybridization to determine changes in bacterial populations, fermentation end products were analyzed by high-performance liquid chromatography to assess short-chain fatty acid concentrations, and subsequently, a prebiotic index (PI) was determined. Pectic oligosaccharides (POS) were able to increase the bifidobacterial and Eubacterium rectale numbers, albeit resulting in a lower prebiotic index than that from fructo-oligosaccharide metabolism. Orange albedo maintained the growth of most bacterial populations and gave a PI similar to that of soluble starch. Fermentation of POS resulted in an increase in the Eubacterium rectale numbers and concomitantly increased butyrate production. In conclusion, this study has shown that POS can have a beneficial effect on the fecal microflora; however, a classical prebiotic effect was not found. An increase in the Eubacterium rectale population was found, and butyrate levels increased, which is of potential benefit to the host.

Evaluating a realistic agent in an advice-giving task

The aim of this study was to empirically evaluate an embodied conversational agent called GRETA in an effort to answer two main questions: (1) What are the benefits (and costs) of presenting information via an animated agent, with certain characteristics, in a 'persuasion' task, compared to other forms of display? (2) How important is it that emotional expressions are added in a way that is consistent with the content of the message, in animated agents? To address these questions, a positively framed healthy eating message was created which was variously presented via GRETA, a matched human actor, GRETA's voice only (no face) or as text only. Furthermore, versions of GRETA were created which displayed additional emotional facial expressions in a way that was either consistent or inconsistent with the content of the message. Overall, it was found that although GRETA received significantly higher ratings for helpfulness and likability, presenting the message via GRETA led to the poorest memory performance among users. Importantly, however, when GRETA's additional emotional expressions were consistent with the content of the verbal message, the negative effect on memory performance disappeared. Overall, the findings point to the importance of achieving consistency in animated agents. (c) 2005 Elsevier Ltd. All rights reserved.

Over the counter medicines and the need for immediate action: a further evaluation of European Commission recommended wordings for communicating risk

A study examined people's interpretation of European Commission (EC) recommended verbal descriptors for risk of medicine side effects, and actions to take if they do occur. Members of the general public were presented with a fictitious (but realistic) scenario about suffering from a stiff neck, visiting the local pharmacy and purchasing an over the counter (OTC) medicine (Ibruprofen). The medicine came with an information leaflet which included information about the medicine's side effects, their risk of occurrence, and recommended actions to take if adverse effects are experienced. Probability of occurrence was presented numerically (6%) or verbally, using the recommended EC descriptor (common). Results showed that, in line with findings of our earlier work with prescribed medicines, participants significantly overestimated side effect risk. Furthermore, the differences in interpretation were reflected in their judgements of satisfaction, side effect severity, risk to health, and intention to take the medicine. Finally, we observed no significant difference between people's interpretation of the recommended action descriptors ('immediately' and 'as soon as possible'). (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Effects of a novel galactooligosaccharide on the faecal microbiota of healthy and inflammatory bowel disease cats during a randomized, double-blind, cross-over feeding study

Inflammatory bowel disease (IBD) is a common gastrointestinal disorder of cats with no known aetiological agent. Previous work has suggested that the faecal microbiota of IBD cats is significantly different from that of healthy cats, including significantly lower bifidobacteria, bacteroides and total counts in IBD cats and significantly lower levels of sulfate-reducing bacteria in healthy cats. Prebiotics, including galactooligosaccharides (GOS), have been shown to elicit a bifidogenic effect in humans and other animals. The purpose of the current study was to examine the impact of a novel GOS supplementation on the faecal microbiota of healthy and IBD cats during a randomized, double-blind, cross-over feeding study. Eight oligonucleotide probes targeting specific bacterial populations and DAPI stain (total bacteria) were used to monitor the feline faecal microbiota. Overall, inter-animal variation was high; while a trend of increased bifidobacterial levels was seen with GOS supplementation it was not statistically significant in either healthy or IBD cats. No significant differences were observed in the faecal microbiota of IBD cats and healthy cats fed the same diet. Members of the family Coriobacteriaceae (Atopobium cluster) were found to be the most abundant bacteria in the feline microbiota.

Extending higher educational opportunities through e-learning: a case study from Sri Lanka

The Knowledge Economy favours high skilled and adaptable workers, typically those with a degree. Information and Communication Technologies (ICTs) have the potential to extend educational opportunities through e-Learning. In Sri Lanka efforts have been made to employ ICTs in this way. The case study of Orange Valley University (pseudonymous) is presented, exploring the impact of ICT-based distance education on access to higher education. This ethnographic research employed questionnaires, qualitative interviews and documentary analysis. Online learning was found to appeal to a specific segment of the population. Flexibility and prestige were found to be important influences on programme selection. The majority possessed resources and skills for e-Learning; access and quality issues were considered.

Towards an improved understanding of farmers' behaviour: the integrative agent-centred (IAC) framework

An effective approach to research on farmers' behaviour is based on: i) an explicit and well-motivated behavioural theory; ii) an integrative approach; and iii) understanding feedback processes and dynamics. While current approaches may effectively tackle some of them, they often fail to combine them together. The paper presents the integrative agent-centred (IAC) framework, which aims at filling this gap. It functions in accordance with these three pillars and provides a conceptual structure to understand farmers' behaviour in agricultural systems. The IAC framework is agent-centred and supports the understanding of farmers' behavior consistently with the perspective of agricultural systems as complex social-ecological systems. It combines different behavioural drivers, bridges between micro and macro levels, and depicts a potentially varied model of human agency. The use of the framework in practice is illustrated through two studies on pesticide use among smallholders in Colombia. The examples show how the framework can be implemented to derive policy implications to foster a transition towards more sustainable agricultural practices. The paper finally suggests that the framework can support different research designs for the study of agents' behaviour in agricultural and social-ecological systems.

Provider diversity in the English NHS: a study of recent developments in four local health economies

Objectives: The overall objective of the research was to assess the impact of provider diversity on quality and innovation in the English NHS. The aims were to map the extent of diverse provider activity, identify the differences in performance between Third Sector Organisations (TSOs), for-profit private enterprises, and incumbent organisations within the NHS, and the factors that affect the entry and growth of new private and TSOs. Methods: Case studies of four Local Health Economies (LHEs). Data included: semi-structured interviews with 48 managerial and clinical staff from NHS organizations and providers from the private and Third Sector; some documentary evidence; a focus group with service users; and routine data from the Care Quality Commission and Companies House. Data collection was mainly between November 2008 and November 2009. Results: Involvement of diverse providers in the NHS is limited. Commissioners’ local strategies influence degrees of diversity. Barriers to the entry for TSOs include lack of economies of scale in the bidding process. Private providers have greater concern to improve patient pathways and patient experience, whereas TSOs deliver quality improvements by using a more holistic approach and a greater degree of community involvement. Entry of new providers drives NHS Trusts to respond by making improvements. Information sharing diminishes as competition intensifies. Conclusions: There is scope to increase the participation of diverse providers in the NHS, but care must be taken not to damage public accountability, overall productivity, equity and NHS providers (especially acute hospitals, which are likely to remain in the NHS) in the process.

The use of public participation and economic appraisal for public involvement in large-scale hydropower projects: Case study of the Nam Theun 2 Hydropower Project

Gaining public acceptance is one of the main issues with large-scale low-carbon projects such as hydropower development. It has been recommended by the World Commission on Dams that to gain public acceptance, publicinvolvement is necessary in the decision-making process (WCD, 2000). As financially-significant actors in the planning and implementation of large-scale hydropowerprojects in developing country contexts, the paper examines the ways in which publicinvolvement may be influenced by international financial institutions. Using the casestudy of the NamTheun2HydropowerProject in Laos, the paper analyses how publicinvolvement facilitated by the Asian Development Bank had a bearing on procedural and distributional justice. The paper analyses the extent of publicparticipation and the assessment of full social and environmental costs of the project in the Cost-Benefit Analysis conducted during the projectappraisal stage. It is argued that while efforts were made to involve the public, there were several factors that influenced procedural and distributional justice: the late contribution of the Asian Development Bank in the projectappraisal stage; and the issue of non-market values and discount rate to calculate the full social and environmental costs.

The gender gap in real estate sales: negotiation skill or agent selection?

This study examines differences in net selling price for residential real estate across male and female agents. A sample of 2,020 home sales transactions from Fulton County, Georgia are analyzed in a two-stage least squares, geospatial autoregressive corrected, semi-log hedonic model to test for gender and gender selection effects. Although agent gender seems to play a role in naïve models, its role becomes inconclusive as variables controlling for possible price and time on market expectations of the buyers and sellers are introduced to the models. Clear differences in real estate sales prices, time on market, and agent incomes across genders are unlikely due to differences in negotiation performance between genders or the mix of genders in a two-agent negotiation. The evidence suggests an interesting alternative to agent performance: that buyers and sellers with different reservation price and time on market expectations, such as those selling foreclosure homes, tend to select agents along gender lines.

In vivo characterization of Lactobacillus johnsonii FI9785 for use as a defined competitive exclusion agent against bacterial pathogens in poultry

Aims: To test the efficacy of Lactobacillus johnsonii FI9785 in reducing the colonization and shedding of Salmonella enterica serotype Enteritidis, Escherichia coli O78:K80 and Clostridium perfringens in poultry. Methods and Results: Specific pathogen-free chicks (1 day old) were dosed with a single oral inoculum of 1 x 10(9) CFU. Lactobacillus johnsonii FI9785 and 24 h later were challenged in separate experiments with S. Enteritidis (S1400, nal(r)) and E. coli O78:K80 (EC34195, nal(r)). There were no significant effects against S. Enteritidis whereas colonization of the small intestine by E. coli O78:K80 was reduced significantly. Both S. Enteritidis and E. coli colonized the caeca and colon to levels equivalent to control birds and there was no reduction in shedding as assessed by a semi-quantitative cloacal swabbing technique. Specific pathogen-free chicks (20 day old) were dosed with a single oral inoculum of 1 x 10(9) CFU L. johnsonii FI9785 and 24 h later were challenged with C. perfringens. A single oral dose of L. johnsonii FI9785 was sufficient to suppress all aspects of colonization and persistence of C. perfringens. Conclusions: Lactobacillus johnsonii FI9785 may be given to poultry for use as a competitive exclusion agent to control C. perfringens. Significance and Impact of the Study: Lactobacillus johnsonii FI9785 may be a valuable tool to control the endemic disease of necrotic enteritis, thereby reducing economic losses associated with reduced use of antimicrobials in the poultry industry.

A multi-agent system for pervasive healthcare

Wireless technology based pervasive healthcare has been proposed in many applications such as disease management and accident prevention for cost saving and promoting citizen’s wellbeing. However, the emphasis so far is on the artefacts with limited attentions to guiding the development of an effective and efficient solution for pervasive healthcare. Therefore, this paper aims to propose a framework of multi-agent systems design for pervasive healthcare by adopting the concept of pervasive informatics and using the methods of organisational semiotics. The proposed multi-agent system for pervasive healthcare utilises sensory information to support healthcare professionals for providing appropriate care. The key contributions contain theoretical aspect and practical aspect. In theory, this paper articulates the information interactions between the pervasive healthcare environment and stakeholders by using the methods of organisational semiotics; in practice, the proposed framework improves the healthcare quality by providing appropriate medical attentions when and as needed. In this paper, both systems and functional architecture of the multi-agent system are elaborated with the use of wireless technologies such as RFID and wireless sensor networks. The future study will focus on the implementation of the proposed framework.

Information communication technologies and distance education in Sri Lanka: a case study of two universities

Sri Lanka's participation rates in higher education are low and have risen only slightly in the last few decades; the number of places for higher education in the state university system only caters for around 3% of the university entrant age cohort. The literature reveals that the highly competitive global knowledge economy increasingly favours workers with high levels of education who are also lifelong learners. This lack of access to higher education for a sizable proportion of the labour force is identified as a severe impediment to Sri Lanka‟s competitiveness in the global knowledge economy. The literature also suggests that Information and Communication Technologies are increasingly relied upon in many contexts in order to deliver flexible learning, to cater especially for the needs of lifelong learners in today‟s higher educational landscape. The government of Sri Lanka invested heavily in ICTs for distance education during the period 2003-2009 in a bid to increase access to higher education; but there has been little research into the impact of this. To address this lack, this study investigated the impact of ICTs on distance education in Sri Lanka with respect to increasing access to higher education. In order to achieve this aim, the research focused on Sri Lanka‟s effort from three perspectives: policy perspective, implementation perspective and user perspective. A multiple case study research using an ethnographic approach was conducted to observe Orange Valley University‟s and Yellow Fields University‟s (pseudonymous) implementation of distance education programmes using questionnaires, qualitative interviewing and document analysis. In total, data for the analysis was collected from 129 questionnaires, 33 individual interviews and 2 group interviews. The research revealed that ICTs have indeed increased opportunities for higher education; but mainly for people of affluent families from the Western Province. Issues identified were categorized under the themes: quality assurance, location, language, digital literacies and access to resources. Recommendations were offered to tackle the identified issues in accordance with the study findings. The study also revealed the strong presence of a multifaceted digital divide in the country. In conclusion, this research has shown that iii although ICT-enabled distance education has the potential to increase access to higher education the present implementation of the system in Sri Lanka has been less than successful.