Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study.

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

Why Do Some Water Utilities Recycle More than Others? A Qualitative Comparative Analysis in New South Wales, Australia

Although the recycling of municipal wastewater can play an important role in water supply security and ecosystem protection, the percentage of wastewater recycled is generally low and strikingly variable. Previous research has employed detailed case studies to examine the factors that contribute to recycling success but usually lacks a comparative perspective across cases. In this study, 25 water utilities in New South Wales, Australia, were compared using fuzzy-set Qualitative Comparative Analysis (fsQCA). This research method applies binary logic and set theory to identify the minimal combinations of conditions that are necessary and/or sufficient for an outcome to occur within the set of cases analyzed. The influence of six factors (rainfall, population density, coastal or inland location, proximity to users; cost recovery and revenue for water supply services) was examined for two outcomes, agricultural use and "heavy" (i.e., commercial/municipal/industrial) use. Each outcome was explained by two different pathways, illustrating that different combinations of conditions are associated with the same outcome. Generally, while economic factors are crucial for heavy use, factors relating to water stress and geographical proximity matter most for agricultural reuse. These results suggest that policies to promote wastewater reuse may be most effective if they target uses that are most feasible for utilities and correspond to the local context. This work also makes a methodological contribution through illustrating the potential utility of fsQCA for understanding the complex drivers of performance in water recycling.