Deconstructing antiobesity compound action : requirement of serotonin 5-HT2B receptors for dexfenfluramine anorectic effects

The now-banned anorectic molecule, dexfenfluramine, promotes serotonin release through a serotonin transporter-dependent mechanism, and it has been widely prescribed for the treatment of obesity. Previous studies have identified that 5-HT(2B) receptors have important roles in dexfenfluramine side effects, that is, pulmonary hypertension, plasma serotonin level regulation, and valvulopathy. We thus investigated a putative contribution of 5-HT(2B) receptors in dexfenfluramine-dependent feeding behavior in mice. Interestingly, the hypophagic response to dexfenfluramine (3-10 mg/kg) observed in wild-type mice (1-4 h) was eliminated in mice lacking 5-HT(2B) receptors (5-HT(2B)(-/-)). These findings were further validated by the lack of hypophagic response to dexfenfluramine in wild-type mice treated with RS127445, a highly selective and potent antagonist (pKi=8.22 ± 0.24). Using microdialysis, we observed that in 5-HT(2B)(-/-) awake mice, the dexfenfluramine-induced hypothalamic peak of serotonin release (1 h) was strongly reduced (fourfold) compared with wild type. Moreover, using hypothalamic synaptosomes, we established the serotonergic neuron autonomous properties of this effect: a strong serotonin release was observed upon dexfenfluramine stimulation of synaptosome preparation from wild type but not from mice lacking active 5-HT(2B) receptors. These findings strongly suggest that activation of presynaptic 5-HT(2B) receptors is a limiting step in the serotonin transporter dependent-releasing effect of dexfenfluramine, whereas other serotonin receptors act downstream with respect to feeding behavior.

Service quality and performance measurement : evidence from the Indian Water Sector

The conventional measures of benchmarking focus mainly on the water produced or water delivered, and ignore the service quality, and as a result the 'low-cost and low-quality' utilities are rated as efficient units. Benchmarking must credit utilities for improvements in service delivery. This study measures the performance of 20 urban water utilities using data from an Asian Development Bank survey of Indian water utilities in 2005. It applies data envelopment analysis to measure the performance of utilities. The results reveal that incorporation of a quality dimension into the analysis significantly increases the average performance of utilities. The difference between conventional quantity-based measures and quality-adjusted estimates implies that there are significant opportunity costs of maintaining the quality of services in water delivery.

New country market feasibility analyses

Opportunity screening is also known as feasibility testing, which is the process of assessing whether a particular business opportunity is within the capacity of either an entrepreneur or an intrapreneur, and also whether it can create sustainable revenues. As the funnel diagram shows, the number of opportunities diminishes as we move to the right through the diagram. This is because not every idea identified in the opportunity identification stage as potentially interesting, and then framed into a business opportunity in the opportunity development stage, will satisfy the formal and informal screening criteria. The informal screening process occurs in all stages of the development process. For example, not every idea that has been identified will be converted into a business opportunity; similarly, not every business opportunity progresses to a feasibility test. Subsequently, only the best business opportunities are screened, and only the very best of those screened then progress to the business plan step.

Nucleopolyhedrovirus introduction in Australia

Nucleopolyhedrovirus (NPV) has become an integral part of integrated pest management (IPM) in many Australian agricultural and horticultural crops. This is the culmination of years of work conducted by researchers at the Queensland Department of Primary Industries and Fisheries (QDPI&F) and Ag Biotech Australia Pty Ltd. In the early 1970’s researchers at QDPI&F identified and isolated a virus in Helicoverpa armigera populations in the field. This NPV was extensively studied and shown to be highly specific to Helicoverpa and Heliothis species. Further work showed that when used appropriately the virus could be used effectively to manage these insects in crops such as sorghum, cotton, chickpea and sweet corn. A similar virus was first commercially produced in the USA in the 1970’s. This product, Elcar®, was introduced into Australia in the late 1970’s by Shell Chemicals with limited success. A major factor contributing to the poor adoption of Elcar was the concurrent enormous success of the synthetic pyrethroids. The importance of integrated pest management was probably also not widely accepted at that time. Gradual development of insect resistance to synthetic pyrethroids and other synthetic insecticides in Australia and the increased awareness of the importance of IPM meant that researchers once again turned their attentions to environmentally friendly pest management tools such NPV and beneficial insects. In the 1990’s a company called Rhone-Poulenc registered an NPV for use in Australian sorghum, chickpea and cotton. This product, Gemstar®, was imported from the USA. In 2000 Ag Biotech Australia established an in-vivo production facility in Australia to produce commercial volumes of a product similar to the imported product. This product was branded, ViVUS®, and was first registered and sold commercially in Australia in 2003. The initial production of ViVUS used a virus identical to the American product but replicating it in an Australian Helicoverpa species, H. armigera. Subsequent research collaboration between QDPI&F and Ag Biotech reinvigorated interest in the local virus strain. This was purified and the production system adapted to produce it on a commercial scale. This new version of ViVUS, which was branded ViVUS Gold®, was first registered and sold commercially in 2004. Widespread insect resistance to insecticides and a greater understanding of integrated pest management is leading to increased adoption of technologies such NPV in Australian agriculture.

Representation of facial expression categories in continuous arousal-valence space: Feature and correlation

Representation of facial expressions using continuous dimensions has shown to be inherently more expressive and psychologically meaningful than using categorized emotions, and thus has gained increasing attention over recent years. Many sub-problems have arisen in this new field that remain only partially understood. A comparison of the regression performance of different texture and geometric features and investigation of the correlations between continuous dimensional axes and basic categorized emotions are two of these. This paper presents empirical studies addressing these problems, and it reports results from an evaluation of different methods for detecting spontaneous facial expressions within the arousal-valence dimensional space (AV). The evaluation compares the performance of texture features (SIFT, Gabor, LBP) against geometric features (FAP-based distances), and the fusion of the two. It also compares the prediction of arousal and valence, obtained using the best fusion method, to the corresponding ground truths. Spatial distribution, shift, similarity, and correlation are considered for the six basic categorized emotions (i.e. anger, disgust, fear, happiness, sadness, surprise). Using the NVIE database, results show that the fusion of LBP and FAP features performs the best. The results from the NVIE and FEEDTUM databases reveal novel findings about the correlations of arousal and valence dimensions to each of six basic emotion categories.

Can skin cancer prevention and early detection be improved via mobile phone text messaging? a randomised, attention-control trial.

Objective. To test the impact of a theory-based, SMS (text message)-delivered behavioural intervention (Healthy Text) targeting sun protection or skin self-examination behaviours compared to attention-control. Method. Overall, 546 participants aged 18–42 years were randomised using a computer-generated number list to the skin self-examination (N = 176), sun protection (N = 187), or attention-control (N = 183) text messages group. Each group received 21 text messages about their assigned topic over 12 months (12 weekly messages for three months, then monthly messages for the next nine months). Data was collected via telephone survey at baseline, three-, and 12-months across Queensland from January 2012 to August 2013. Results. One year after baseline, the sun protection (mean change 0.12; P = 0.030) and skin self-examination groups (mean change 0.12; P = 0.035) had significantly greater improvement in their sun protection habits (SPH) index compared to the attention-control group (reference mean change 0.02). The increase in the proportion of participants who reported any skin self-examination from baseline to 12 months was significantly greater in the skin self-examination intervention group (103/163; 63%; P < 0.001) than the sun protection (83/173; 48%), or attention-control (65/165; 36%) groups. There was no significant effect of the intervention for participants who self-reported whole-body skin self-examination, sun tanning behaviour, or sunburn behaviours. Conclusion. The Healthy Text intervention was effective in inducing significant improvements in sun protection and any type of skin self-examination behaviours.

Performance characterisation of a stormwater treatment bioretention basin

Treatment performance of bioretention basins closely depends on hydrologic and hydraulic factors such as rainfall characteristics and inflow and outflow discharges. An in-depth understanding of the influence of these factors on water quality treatment performance can provide important guidance for effective bioretention basin design. In this paper, hydraulic and hydrologic factors impacting pollutant removal by a bioretention basin were assessed under field conditions. Outcomes of the study confirmed that the antecedent dry period plays an important role in influencing treatment performance. A relatively long antecedent dry period reduces nitrite and ammonium concentrations while increasing the nitrate concentration, which confirms that nitrification occurs within the bioretention basin. Additionally, pollutant leaching influences bioretention basin treatment performance, reducing the nutrients removal efficiency, which was lower for high rainfall events. These outcomes will contribute to a greater understanding of the treatment performance of bioretention basins, assisting in the design, operation and maintenance of these systems.

Design, construction and evaluation of systems to predict risk in obstetrics

We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy. We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy.

Mississippi Delta subsidence primarily caused by compaction of Holocene strata

Coastal subsidence causes sea-level rise, shoreline erosion and wetland loss, which poses a threat to coastal populations. This is especially evident in the Mississippi Delta in the southern United States, which was devastated by Hurricane Katrina in 2005. The loss of protective wetlands is considered a critical factor in the extensive flood damage. The causes of subsidence in coastal Louisiana, attributed to factors as diverse as shallow compaction and deep crustal processes, remain controversial. Current estimates of subsidence rates vary by several orders of magnitude. Here, we use a series of radiocarbon-dated sediment cores from the Mississippi Delta to analyse late Holocene deposits and assess compaction rates. We find that millennial-scale compaction rates primarily associated with peat can reach 5mm per year, values that exceed recent model predictions. Locally and on timescales of decades to centuries, rates are likely to be 10 mm or more per year. We conclude that compaction of Holocene strata contributes significantly to the exceptionally high rates of relative sea-level rise and coastal wetland loss in the Mississippi Delta, and is likely to cause subsidence in other organic-rich and often densely populated coastal plains.

Veracity of the archive : a research approach to the collection and verification of urban morphological records using qualitative data analysis software

Critical to the research of urban morphologists is the availability of historical records that document the urban transformation of the study area. However, thus far little work has been done towards an empirical approach to the validation of archival data in this field. Outlined in this paper, therefore, is a new methodology for validating the accuracy of archival records and mapping data, accrued through the process of urban morphological research, so as to establish a reliable platform from which analysis can proceed. The paper particularly addresses the problems of inaccuracies in existing curated historical information, as well as errors in archival research by student assistants, which together give rise to unacceptable levels of uncertainty in the documentation. The paper discusses the problems relating to the reliability of historical information, demonstrates the importance of data verification in urban morphological research, and proposes a rigorous method for objective testing of collected archival data through the use of qualitative data analysis software.

Thriller

Shifts in genre definitions and classifications over time are very much a part of a living art form such as cinema. Films that today we might identify as bearing some of the hallmarks of the thriller, but which were not understood as such at the time of release, have been made in Australia since the earliest days of narrative cinema. The Story of the Kelly Gang (Charles Tait, 1906) contains some of the thriller’s stock elements: crime, conspiracy, suspense, a chase, heroes and villains. The fact that these elements are not exclusive to the thriller underscores the point that genres change, evolve, and often overlap. While contemporary reportage attests that The Story of the Kelly Gang thrilled audiences, it was not named as a ‘thriller’ at the time. Even so, a genealogy of the thriller can be traced through Australian film history, despite quiescent periods.

Making stories matter: Using participatory new media storytelling and evaluation to serve marginalised and regional communities

In this chapter, we draw on our experiences facilitating community storytelling workshops in regional Queensland in partnership with the Queensland branch of Oral History Association of Australia (OHAA Qld) in order to develop a best practice model for promoting creative approaches to recording oral narratives using digital tools, informed by creative writing practice and embedded evaluation (Klaebe 2012 & 2013). These experiences offer an insight into how creative approaches to training can facilitate the sharing and preservation of stories in regional communities.