Developing Economic Arrangements for Water Resources Management – The Potential of Stakeholder-oriented Water Valuation

As water is increasingly recognized as a scarce resource, the use of economic arrangements for water resources management seems increasingly promising. Experiences show that economic arrangements can contribute to a more efficient use of water resources but only if specific conditions are met, related to a well-functioning institutional framework and regulations that ensure that the use of economic arrangements is balanced with broader societal objectives. One of the remaining questions is how to replicate the existing cases where economic arrangements are successfully used in water resources management in other areas where the conditions seem promising. Therefore, this paper reviews three cases in the USA, Ecuador and Australia where economic arrangements have been successfully applied, focusing on the processes that have characterized their evolution. Based on these cases, it is concluded that stakeholder-oriented valuation can offer useful support for the development of economic arrangements for water resources management and an approach for such stakeholder-oriented water valuation is briefly outlined and illustrated

Decompressing Stoma as Bridge to Elective Surgery is an Effective Strategy for Left-sided Obstructive Colon Cancer:A National, Propensity-score Matched Study

OBJECTIVE: The purpose of this population-based study was to compare decompressing stoma (DS) as bridge to surgery (BTS) with emergency resection (ER) for left-sided obstructive colon cancer (LSOCC) using propensity-score matching. SUMMARY BACKGROUND DATA: Recently, an increased use of DS as BTS for LSOCC has been observed in the Netherlands. Unfortunately, good quality comparative analyses with ER are scarce. METHODS: Patients diagnosed with nonlocally advanced LSOCC between 2009 and 2016 in 75 Dutch hospitals, who underwent DS or ER in the curative setting, were propensity-score matched in a 1:2 ratio. The primary outcome measure was 90-day mortality, and main secondary outcomes were 3-year overall survival and permanent stoma rate. RESULTS: Of 2048 eligible patients, 236 patients who underwent DS were matched with 472 patients undergoing ER. After DS, more laparoscopic resections were performed (56.8% vs 9.2%, P < 0.001) and more primary anastomoses were constructed (88.5% vs 40.7%, P < 0.001). DS resulted in significantly lower 90-day mortality compared to ER (1.7% vs 7.2%, P = 0.006), and this effect could be mainly attributed to the subgroup of patients over 70 years (3.5% vs 13.7%, P = 0.027). Patients treated with DS as BTS had better 3-year overall survival (79.4% vs 73.3%, hazard ratio 0.36, 95% confidence interval 0.20-0.65) and fewer permanent stomas (23.4% vs 42.4%, P < 0.001). CONCLUSIONS: In this nationwide propensity-score matched study, DS as a BTS for LSOCC was associated with lower 90-day mortality and better 3-year overall survival compared to ER, especially in patients over 70 years of age

Rapid Generation of MicroRNA Sponges for MicroRNA Inhibition

MicroRNA (miRNA) sponges are transcripts with repeated miRNA antisense sequences that can sequester miRNAs from endogenous targets. MiRNA sponges are valuable tools for miRNA loss-of-function studies both in vitro and in vivo. We developed a fast and flexible method to generate miRNA sponges and tested their efficiency in various assays. Using a single directional ligation reaction we generated sponges with 10 or more miRNA binding sites. Luciferase and AGO2-immuno precipitation (IP) assays confirmed effective binding of the miRNAs to the sponges. Using a GFP competition assay we showed that miR-19 sponges with central mismatches in the miRNA binding sites are efficient miRNA inhibitors while sponges with perfect antisense binding sites are not. Quantification of miRNA sponge levels suggests that this is at least in part due to degradation of the perfect antisense sponge transcripts. Finally, we provide evidence that combined inhibition of miRNAs of the miR-17∼92 cluster results in a more effective growth inhibition as compared to inhibition of individual miRNAs. In conclusion, we describe and validate a method to rapidly generate miRNA sponges for miRNA loss-of-function studies

Intensive Case Finding and Isoniazid Preventative Therapy in HIV Infected Individuals in Africa: Economic Model and Value of Information Analysis

Background: Tuberculosis (TB) accounts of much of the morbidity and mortality associated with HIV. We evaluate the costeffectiveness of different strategies to actively screen for TB disease in HIV positive individuals, where isoniazid preventative therapy (IPT) is given to those screening negative, and use value of information analysis (VOI) to identify future research priorities. Methodology / Principal Findings: We built an individual sampling model to investigate the costs (2010 US Dollars) and consequences of screening for TB, and providing TB treatment or IPT in adults testing HIV positive in Sub-Saharan Africa. A systematic review and meta-analysis was conducted to assess performance of the nine different TB screening strategies evaluated. Probabilistic sensitivity analysis was conducted to incorporate decision uncertainty, and expected value of perfect information for the entire model and for groups of parameters was calculated. Screening all HIV infected individuals with sputum microscopy was the least costly strategy, with other strategies not cost-effective at WHO recommended thresholds. Screening those with TB symptoms with sputum microscopy and CXR would be cost-effective at a threshold ICER of $7,800 per quality-adjusted life year (QALY), but associated with significant uncertainty. VOI analysis suggests further information would be of value. Conclusions / Significance: Resource-constrained countries in sub-Saharan Africa wishing to scale up TB preventativ