ECONOMIC EVALUATION OF WATERSHED MANAGEMENT OPTIONS IN THE IRRIGATED COTTON AREAS OF THE UPPER MURRAY-DARLING BASIN IN NEW SOUTH WALES, AUSTRALIA

The article combines economic and hydrologic modeling on the watershed level and proposes a method for determining optimal spatial location of irrigation enterprises and use of water by source and intensity of irrigation management. This combination of economic/technical investigation results with solution that explicitly accounts for deep-drainage as a source of environmental adversities. Alternative policies to achieve this solution are analyzed.Resource /Energy Economics and Policy,

Using transcriptomics to guide lead optimization in drug discovery projects : lessons learned from the QSTAR project

The pharmaceutical industry is faced with steadily declining R&D efficiency which results in fewer drugs reaching the market despite increased investment. A major cause for this low efficiency is the failure of drug candidates in late-stage development owing to safety issues or previously undiscovered side-effects. We analyzed to what extent gene expression data can help to de-risk drug development in early phases by detecting the biological effects of compounds across disease areas, targets and scaffolds. For eight drug discovery projects within a global pharmaceutical company, gene expression data were informative and able to support go/no-go decisions. Our studies show that gene expression profiling can detect adverse effects of compounds, and is a valuable tool in early-stage drug discovery decision making

Detecting the impact of land cover change on observed rainfall

Analysis of observational data to pinpoint impact of land cover change on local rainfall is difficult due to multiple environmental factors that cannot be strictly controlled. In this study we use a statistical approach to identify the relationship between removal of tree cover and rainfall with data from best available sources for two large areas in Australia. Gridded rainfall data between 1979 and 2015 was used for the areas, while large scale (exogenous) effects were represented by mean rainfall across a much larger area and climatic indicators, such as Southern Oscillation Index and Indian Ocean Dipole. Both generalised additive modelling and step trend tests were used for the analysis. For a region in south central Queensland, the reported change in tree clearing between 2002–2005 did not result in strong statistically significant precipitation changes. On the other hand, results from a bushfire affected region on the border of New South Wales and Victoria suggest significant changes in the rainfall due to changes in tree cover. This indicates the method works better when an abrupt change in the data can be clearly identified. The results from the step trend test also mainly identified a positive relationship between the tree cover and the rainfall at p < 0.1 at the NSW/Victoria region. High rainfall variability and possible regrowth could have impacted the results in the Queensland region

Abnormal vaginal bleeding in women of reproductive age: a descriptive study of initial management in general practice

<p>Abstract</p> <p>Background</p> <p>Abnormal vaginal bleeding (AVB) in women of reproductive age is a common reason for consulting a general practitioner. Nevertheless, how general practitioners (GPs) choose to initially manage AVB is largely unknown, as is the prevalence of underlying pathology of AVB in primary care.</p> <p>Methods</p> <p>To investigate the initial diagnostic procedures and treatment for AVB used in general practice, we performed a descriptive study based on computerised medical records. New consultations for AVB in 2000 and 2001 were selected. Patient characteristics, diagnostic procedures and treatment were analysed.</p> <p>Results</p> <p>In total, 270 new consultations were included. The majority of patients (75%) consulted the GP for AVB only once. GPs performed diagnostic procedures in 54% of all consultations. Overall, additional diagnostic procedures revealed abnormalities in 11% of women. However, the diagnostic procedures implemented by the GPs varied widely per bleeding type and contraceptive use. Anaemia was found in 36% of 45 women tested. Uterine fibroids were found in 41% of 27 women examined by ultrasound. Medication was prescribed in 34% of all consultations. A gynaecological referral was registered in 4% of all contacts.</p> <p>Conclusion</p> <p>Initially, GPs tend to follow a policy of expectant management in women of reproductive age with AVB. However, when additional diagnostic procedures were performed, anaemia and uterine fibroids were found in a considerable number of women.</p

Determining water requirements for Black Box (Eucalyptus largiflorens) floodplain woodlands of high conservation value using drip-irrigation

Black Box (Eucalyptus largiflorens F. Muell.), is a keystone tree species of lowland semi-arid floodplain ecosystems in south-eastern Australia. E. largiflorens woodlands are of high conservation value and threatened by climate change-induced drought and irrigation water diversions due to their location on upper floodplain areas where flood frequency has declined. Water requirements of E. largiflorens have not been well quantified using empirical data. Accordingly, knowledge gaps exist in relation to volumes of environmental water required to maintain and improve ecological condition for disconnected floodplain woodlands. To further assist conservation and water resource management, we tested the use of drip irrigation to provide a variety of water regimes to experimental plots in order to monitor tree responses. Water was provided via irrigation delivery across four regimes representing known volumes of water, referred to as an environmental water provision, applied over a 22-week period for two Austral summers. Benefits to trees were identified by measuring transpiration and plant water status using sap flow sensors and a Scholander pressure chamber, respectively. Results indicate that volumes of 0.3, 0.4, 0.7 and 0.8 ML increased transpiration and improved plant water status in comparison to a control, with delivery recommended to commence early autumn. Greater volumes (1.4 ML), substantially increased transpiration and improved water status, especially when delivered at a rate of similar to 25 mm week(-1) compared to a monthly 'burst' which broadly represented natural, sporadic summer rainfall in the region. For an environmental watering provision of 25 mm week(-1), similar to 178 ha of E. largiflorens woodland can be watered with a 1 GL environmental water allocation. The study methods presented are relevant worldwide and our results further the collective understanding of the benefits environmental water provides to E. largiflorens.The authors gratefully acknowledge funding from the BiodiversityFund of the South Australian Murray-Darling Basin Natural ResourceManagement Board. We thank Riverland West Landcare and RebeccaTurner for their support and assistance; Treasury Wine Estates PtyLtd for provision of environmental water and for establishing andmaintaining the drip irrigation, led by Brendan Turner; Kelly Marsland(MDBA) and Kate Holland (CSIRO Land and Water, Adelaide) foradvice on experimental design; Kate Frahn (SARDI) and JodiePritchard (CSIRO) for field assistance; Martin Nolan and Sultan Umoru(CSIRO Land and Water, Adelaide) for GIS assistanc

Engineering of microheterogeneity-resistant p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens

AbstractBy site-directed mutagenesis, Cys-116 was converted to Ser-116 in p-hydroxybenzoate hydroxylase (EC 1.14.13.2) from Pseudomonas fluorescens. In contrast to wild-type enzyme, the C116S mutant is no longer susceptible to oxidation by hydrogen peroxide and shows no reactivity towards 5,5'-dithiobis(2-nitrobenzoate). Crystals of the C116S mutant are isomorphous with the crystal form of wild-type enzyme. A difference electron density confirms the mutation made

Antigen-driven EGR2 expression is required for exhausted CD8 + T cell stability and maintenance

Chronic stimulation of CD8 T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted cells exist in multiple differentiation states, from stem-like progenitors that are the key mediators of the response to checkpoint blockade, through to terminally exhausted cells. Due to its clinical relevance, there is substantial interest in defining the pathways that control differentiation and maintenance of these subsets. Here, we show that chronic antigen induces the anergy-associated transcription factor EGR2 selectively within progenitor exhausted cells in both chronic LCMV and tumours. EGR2 enables terminal exhaustion and stabilizes the exhausted transcriptional state by both direct EGR2-dependent control of key exhaustion-associated genes, and indirect maintenance of the exhausted epigenetic state. We show that EGR2 is a regulator of exhaustion that epigenetically and transcriptionally maintains the differentiation competency of progenitor exhausted cells. +This work was funded by National Institutes of Health Grant U19-AI100627, the Swiss National Science Foundation and the Novartis Foundation for Medical-Biological Research (S.S.G.), the Australian Cancer Research Foundation (for the Peter Mac Flow Cytometry and Molecular Genomics facilities) and by the National Health and Medical Research Council (NHMRC) through Program Grants 1016953 & 1113904, Ideas Grant APP2001719, Australia Fellowship 585490 (C.C.G.), Senior Principal Research Fellowships (1081858, C.C.G., 1139607, A.K.), and CJ Martin Early Career Fellowship 585518 (I.A.P.)