Estimating the potential impact of entry fees for marine parks on dive tourism in South East Asia

Marine reserves are increasingly being established as a mechanism to protect marine biodiversity and sensitive habitats. As well as providing conservation benefits, marine reserves provide benefits to recreational scuba divers who dive within the reserve, as well as to recreational and commercial fishers outside the reserve through spill-over effects. To ensure benefits are being realised, management of marine reserves requires ongoing monitoring and surveillance. These are not costless, and many marine reserve managers impose an entry fee. In some countries, dive tourism is major income source to coastal industries, and a concern is that high entry fees may dissuade divers. In this paper, the price elasticity of demand for dive tourism in three countries in South East Asia – Indonesia, Thailand and Malaysia – is estimated using a travel-cost model. From the model, the total non-market use value associated with diving in the area is estimated to be in the order of US$4.5 billion a year. The price elasticity of demand in the region is highly inelastic, such that increasing the cost of diving through a management levy would have little impact on total diver numbers.

Australian data do not support current pharmaceutical benefits scheme criteria for use of tumour necrosis factor-α inhibitors in ankylosing spondylitis

On the basis of local data, we write in support of the conclusions of Smith and Ahern that current Pharmaceu- tical Benefits Scheme (PBS) criteria for tumour necrosis factor (TNF)-a inhibitors in ankylosing spondylitis (AS) are not evidence-based. 1 As a prerequisite to the appropriate use of biological therapy in AS, three aspects of the disease need to be defined: (i) diagnosis, (ii) activity and (iii) therapeutic failure (Table 1)....

Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377)

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance ((R)) mutations were assessed before study treatment (baseline) and at virologic failure. Zdv(R), ddI(R), and ddC(R) mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp(R) and 3TC(R) mutations were detected frequently at virologic failure, and Nvp(R) mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional Nvp(R) and 3TC(R) mutations plus Rtv(R) and Nfv(R) mutations. However, Rtv(R) and Nfv(R) mutations were detected at unexpectedly low rates.

Tyrosine kinase inhibitors (nibs)

Traditional chemotherapy involves cytotoxic agents that indiscriminately target all rapidly-dividing cells. This can lead to significant side effects as healthy cells are also targeted.

Legumes or nitrification inhibitors to reduce {N2O} emissions from subtropical cereal cropping systems in Oxisols?

The DAYCENT biogeochemical model was used to investigate how the use of fertilizers coated with nitrification inhibitors and the introduction of legumes in the crop rotation can affect subtropical cereal production and {N2O} emissions. The model was validated using comprehensive multi-seasonal, high-frequency dataset from two field investigations conducted on an Oxisol, which is the most common soil type in subtropical regions. Different N fertilizer rates were tested for each N management strategy and simulated under varying weather conditions. DAYCENT was able to reliably predict soil N dynamics, seasonal {N2O} emissions and crop production, although some discrepancies were observed in the treatments with low or no added N inputs and in the simulation of daily {N2O} fluxes. Simulations highlighted that the high clay content and the relatively low C levels of the Oxisol analyzed in this study limit the chances for significant amounts of N to be lost via deep leaching or denitrification. The application of urea coated with a nitrification inhibitor was the most effective strategy to minimize {N2O} emissions. This strategy however did not increase yields since the nitrification inhibitor did not substantially decrease overall N losses compared to conventional urea. Simulations indicated that replacing part of crop N requirements with N mineralized by legume residues is the most effective strategy to reduce {N2O} emissions and support cereal productivity. The results of this study show that legumes have significant potential to enhance the sustainable and profitable intensification of subtropical cereal cropping systems in Oxisols.

Nitrification (DMPP) and urease (NBPT) inhibitors had no effect on pasture yield, nitrous oxide emissions nor nitrate leaching under irrigation in a hot-dry climate

Modern dairy farming in Australia relies on substantial inputs of fertiliser nitrogen (N) to underpin economic production. However, N lost from dairy systems represents an opportunity cost and can pose a number of environmental risks. Nitrogen cycle inhibitors can be co-applied with N fertilisers to slow the conversion of urea to NH4+ to reduce losses via volatilisation, and slow the conversion of NH4+ to NO3- to minimize leaching of NO3- and gaseous losses via nitrification and denitrification. In a field campaign in a high input ryegrass-kikuyu pasture system we compared the soil N pools, losses and pasture production between a) urea coated with the nitrification inhibitor (3,4-dimethyl pyrazole phosphate - DMPP) b) urea coated with the urease inhibitor (N-(n-butyl) thiophosphoric triamide - NBPT) and c) standard urea. There was no treatment effect (P>0.05) on soil mineral N, pasture yield, N2O flux nor leaching of NO3- cf. standard urea. We hypothesise that at our site, because gaseous losses were highly episodic (rainfall was erratic and displayed no seasonal rainfall nor soil wetting pattern) that there was a lack of coincidence of N application and conditions conducive to gaseous losses, thus the effectiveness of the inhibitor products was minimal and did not result in an increase in pasture yield. There remains a paucity of knowledge on N cycle inhibitors in relation to their effective use in field system to increase N use efficiency. Further research is required to define under what field conditions inhibitor products are effective in order to be able to provide accurate advice to managers of nitrogen in production systems.

Marked increase in proton pump inhibitors use in Australia

Objectives: To examine the trends in the prescribing of subsidised proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs), in the Australian population from 1995 to 2006 to encourage discussion regarding appropriate clinical use. PPIs and H2RAs are the second highest drug cost to the publicly subsidised Pharmaceutical Benefits Scheme (PBS). Design: Government data on numbers of subsidised scripts, quantity and doses for PPIs and H2RAs were analysed by gender and age, dose and indication. Main outcome measure: Drug utilisation as DDD [defined daily dose]/1000 population/day. Results: The use of combined PPIs increased by 1318%. Utilisation increased substantially after the relaxation of the subsidised indications for PPIs in 2001. Omeprazole had the largest market share but was substituted by its S-enantiomer esomeprazole after its introduction in 2002. There was considerable use in the elderly with the peak use being in those aged 80 years and over. The utilisation of H2RAs declined 72% over 12 years. Conclusions: PPI use has increased substantially, not only due to substitution of H2RAs but to expansion in the overall market. Utilisation does not appear to be commensurate with prevalence of gastro-oesophageal reflux disease (GORD) nor with prescribing guidelines for PPIs, with significant financial costs to patients and PBS. This study encourages clinical discussion regarding quality use of these medicines. © 2010 John Wiley & Sons, Ltd.

Improving the selectivity of engineered protease inhibitors: Optimizing the P2 prime residue using a versatile cyclic peptide library

Standard mechanism inhibitors are attractive design templates for engineering reversible serine protease inhibitors. When optimizing interactions between the inhibitor and target protease, many studies focus on the nonprimed segment of the inhibitor's binding loop (encompassing the contact β-strand). However, there are currently few methods for screening residues on the primed segment. Here, we designed a synthetic inhibitor library (based on sunflower trypsin inhibitor-1) for characterizing the P2′ specificity of various serine proteases. Screening the library against 13 different proteases revealed unique P2′ preferences for trypsin, chymotrypsin, matriptase, plasmin, thrombin, four kallikrein-related peptidases, and several clotting factors. Using this information to modify existing engineered inhibitors yielded new variants that showed considerably improved selectivity, reaching up to 7000-fold selectivity over certain off-target proteases. Our study demonstrates the importance of the P2′ residue in standard mechanism inhibition and unveils a new approach for screening P2′ substitutions that will benefit future inhibitor engineering studies.

Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1) provide insights into the role of sequence and conformation in Laskowski mechanism inhibition

Laskowski inhibitors regulate serine proteases by an intriguing mode of action that involves deceiving the protease into synthesizing a peptide bond. Studies exploring naturally occurring Laskowski inhibitors have uncovered several structural features that convey the inhibitor's resistance to hydrolysis and exceptional binding affinity. However, in the context of Laskowski inhibitor engineering, the way that various modifications intended to fine-tune an inhibitor's potency and selectivity impact on its association and dissociation rates remains unclear. This information is important as Laskowski inhibitors are becoming increasingly used as design templates to develop new protease inhibitors for pharmaceutical applications. In this study, we used the cyclic peptide, sunflower trypsin inhibitor-1 (SFTI-1), as a model system to explore how the inhibitor's sequence and structure relate to its binding kinetics and function. Using enzyme assays, MD simulations and NMR spectroscopy to study SFTI variants with diverse sequence and backbone modifications, we show that the geometry of the binding loop mainly influences the inhibitor's potency by modulating the association rate, such that variants lacking a favourable conformation show dramatic losses in activity. Additionally, we show that the inhibitor's sequence (including both the binding loop and its scaffolding) influences its potency and selectivity by modulating both the association and the dissociation rates. These findings provide new insights into protease inhibitor function and design that we apply by engineering novel inhibitors for classical serine proteases, trypsin and chymotrypsin and two kallikrein-related peptidases (KLK5 and KLK14) that are implicated in various cancers and skin diseases.

The association between student characteristics and the development of clinical reasoning in a graduate-entry, PBL medical programme

This study sought to assess the extent to which the entry characteristics of students in a graduate-entry medical programme predict the subsequent development of clinical reasoning ability. Subjects comprised 290 students voluntarily recruited from three successive cohorts of the University of Queensland's MBBS Programme. Clinical reasoning was measured once a year over a period of three years using two methods, a set of 10 Clinical Reasoning Problems (CRPs) and the Diagnostic Thinking Inventory (DTI). Data on gender, age at entry into the programme, nature of primary degree, scores on selection criteria (written examination plus interview) and academic performance in the first two years of the programme were recorded for each student, and their association with clinical reasoning skill analysed using univariate and multivariate analysis. Univariate analysis indicated significant associations between CRP score, gender and primary degree with a significant but small association between DTI and interview score. Stage of progression through the programme was also an important predictor of performance on both indicators. Subsequent multivariate analysis suggested that female gender is a positive predictor of CRP score independently of the nature of a subject's primary degree and stage of progression through the programme, although these latter two variables are interdependent. Positive predictors of clinical reasoning skill are stage of progression through the MBBS programme, female gender and interview score. Although the nature of a student's primary degree is important in the early years of the programme, evidence suggests that by graduation differences between students' clinical reasoning skill due to this factor have been resolved.