89 research outputs found

    Sustainable Forest Management Preferences of Interest Groups in Three Regions with Different Levels of Industrial Forestry: An Exploratory Attribute-Based Choice Experiment

    Get PDF
    The challenge of sustainable forest management is to integrate diverse and sometimes conflicting management objectives. In order to achieve this goal, we need a better understanding of the aspects influencing the preferences of diverse groups and how these groups make trade-offs between different attributes of SFM. We compare the SFM preferences of interest groups in regions with different forest use histories based on the reasoning that the condition of the forest reflects the forest use history of the area. The condition of the forest also shapes an individual’s forest values and attitudes. These held values and attitudes are thought to influence SFM preferences. We tested whether the SFM preferences vary amongst the different interest groups within and across regions. We collected data from 252 persons using a choice experiment approach, where participants chose multiple times among different options described by a combination of attributes that are assigned different levels. The novelty of our approach was the use of choice experiments in the assessment of regional preference differences. Given the complexity of interregional comparison and the small sample size, this was an exploratory study based on a purposive rather than random sample. Nevertheless, our results suggest that the aggregation of preferences of all individuals within a region does not reveal all information necessary for forest management planning since opposing viewpoints could cancel each other out and lead to an interpretation that does not reflect possibly polarised views. Although based on a small\ud sample size, the preferences of interest groups within a region are generally statistically significantly different from each other; however preferences of interest groups across regions are also significantly different. This illustrates the potential importance of assessing heterogeneity by region and by group

    The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.

    Get PDF
    The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we describe the identification of three series of chemically distinct S6K1 inhibitors. In addition, we report a novel PKA-S6K1 chimeric protein with five mutations in or near its ATP-binding site, which was used to determine the binding mode of two of the three inhibitor series, and provided a robust system to aid the optimisation of the oxadiazole-substituted benzimidazole inhibitor series. We show that the resulting oxadiazole-substituted aza-benzimidazole is a potent and ligand efficient S6 kinase inhibitor, which blocks the phosphorylation of RPS6 at Ser235/236 in TSC negative HCV29 human bladder cancer cells by inhibiting S6 kinase activity and thus provides a useful tool compound to investigate the function of S6 kinases

    Rare disruptive variants in the DISC1 Interactome and Regulome : association with cognitive ability and schizophrenia

    Get PDF
    Schizophrenia (SCZ), bipolar disorder (BD) and recurrent major depressive disorder (rMDD) are common psychiatric illnesses. All have been associated with lower cognitive ability, and show evidence of genetic overlap and substantial evidence of pleiotropy with cognitive function and neuroticism. Disrupted in schizophrenia 1 (DISC1) protein directly interacts with a large set of proteins (DISC1 Interactome) that are involved in brain development and signaling. Modulation of DISC1 expression alters the expression of a circumscribed set of genes (DISC1 Regulome) that are also implicated in brain biology and disorder. Here we report targeted sequencing of 59 DISC1 Interactome genes and 154 Regulome genes in 654 psychiatric patients and 889 cognitively-phenotyped control subjects, on whom we previously reported evidence for trait association from complete sequencing of the DISC1 locus. Burden analyses of rare and singleton variants predicted to be damaging were performed for psychiatric disorders, cognitive variables and personality traits. The DISC1 Interactome and Regulome showed differential association across the phenotypes tested. After family-wise error correction across all traits (FWERacross), an increased burden of singleton disruptive variants in the Regulome was associated with SCZ (FWERacross P=0.0339). The burden of singleton disruptive variants in the DISC1 Interactome was associated with low cognitive ability at age 11 (FWERacross P=0.0043). These results identify altered regulation of schizophrenia candidate genes by DISC1 and its core Interactome as an alternate pathway for schizophrenia risk, consistent with the emerging effects of rare copy number variants associated with intellectual disability.Peer reviewe

    Unexpected removal of the most neutral cationic pharmaceutical in river waters

    Get PDF
    Contamination of surface waters by pharmaceuticals is now widespread. There are few data on their environmental behaviour, particularly for those which are cationic at typical surface water pH. As the external surfaces of bacterio-plankton cells are hydrophilic with a net negative charge, it was anticipated that bacterio-plankton in surface-waters would preferentially remove the most extensively-ionised cation at a given pH. To test this hypothesis, the persistence of four, widely-used, cationic pharmaceuticals, chloroquine, quinine, fluphenazine and levamisole, was assessed in batch microcosms, comprising water and bacterio-plankton, to which pharmaceuticals were added and incubated for 21 days. Results show that levamisole concentrations decreased by 19 % in microcosms containing bacterio-plankton, and by 13 % in a parallel microcosm containing tripeptide as a priming agent. In contrast to levamisole, concentrations of quinine, chloroquine and fluphenazine were unchanged over 21 days in microcosms containing bacterio-plankton. At the river-water pH, levamisole is 28 % cationic, while quinine is 91–98 % cationic, chloroquine 99 % cationic and fluphenazine 72–86 % cationic. Thus, the most neutral compound, levamisole, showed greatest removal, contradicting the expected bacterio-plankton preference for ionised molecules. However, levamisole was the most hydrophilic molecule, based on its octanol–water solubility coefficient (K ow). Overall, the pattern of pharmaceutical behaviour within the incubations did not reflect the relative hydrophilicity of the pharmaceuticals predicted by the octanol–water distribution coefficient, D ow, suggesting that improved predictive power, with respect to modelling bioaccumulation, may be needed to develop robust environmental risk assessments for cationic pharmaceuticals

    Effects of the number of alternatives in public good discrete choice experiments

    Full text link
    Choice experiments (CEs) are commonly used to estimate monetary values for characteristics of public goods, but there are unresolved design issues. The number of alternatives is one of them. Increasing the number of alternatives increases the potential information learned from a sample of a limited size, which may assist subjects in selecting a preferred alternative (referred as matching) or may make choices more difficult (referred as complexity). A convergent-validity study is conducted to compare CE designs with status quo (SQ) plus one, two or three alternatives. To enhance convergent-validity insights, we use the SQ plus one treatment, which is a theoretically supported treatment, as a counterfactual treatment. We fail to find convergent validity between the one-alternative treatment and the two- and three-alternative treatments. Yet there is little difference in welfare estimates between the two- and three-alternative treatments. We find a net matching effect in the one-alternative treatment as the number of attribute-level changes increases, which reduces the likelihood of choosing the SQ alternative. We find net complexity effects in the two- and three-alternative treatments, which increases the likelihood of subjects choosing the SQ alternative as the number of choice questions increases. Our results support the use of SQ plus one-alternative design, suggest caution when using a SQ plus two- and three-alternative designs

    Valuing non-market economic impacts from natural hazards

    No full text
    Prioritising investments to minimise or mitigate natural hazards such as wildfires and storms is of increasing importance to hazard managers. Prioritisation of this type can be strengthened by considering benefit and cost impacts. To evaluate benefits and costs, managers require an understanding of both the tangible economic benefits and costs of mitigation decisions, and the often intangible values associated with environmental, social and health-related outcomes. We review the state of non-market valuation studies that provide monetary equivalent estimates for the intangible benefits and costs that can be affected by natural hazard events or their mitigation. We discuss whether managers can usefully call upon these available estimates, with a view to using the benefit transfer approach to include non-market values in economic decision frameworks. Additional context-specific non-market valuation studies are required to provide a more accurate selection of value estimates for natural hazard decision making. Decision making would benefit from considering these values explicitly in prioritising natural hazard investments. © 2019, The Author(s)
    • 

    corecore