A regional Bayesian POT model for flood frequency analysis

Flood frequency analysis is usually based on the fitting of an extreme value distribution to the local streamflow series. However, when the local data series is short, frequency analysis results become unreliable. Regional frequency analysis is a convenient way to reduce the estimation uncertainty. In this work, we propose a regional Bayesian model for short record length sites. This model is less restrictive than the index flood model while preserving the formalism of "homogeneous regions". The performance of the proposed model is assessed on a set of gauging stations in France. The accuracy of quantile estimates as a function of the degree of homogeneity of the pooling group is also analysed. The results indicate that the regional Bayesian model outperforms the index flood model and local estimators. Furthermore, it seems that working with relatively large and homogeneous regions may lead to more accurate results than working with smaller and highly homogeneous regions

Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. METHODS: To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. RESULTS: NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. CONCLUSION: In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo

Reporting and Methods in Clinical Prediction Research: A Systematic Review

Walter Bouwmeester and colleagues investigated the reporting and methods of prediction studies in 2008, in six high-impact general medical journals, and found that the majority of prediction studies do not follow current methodological recommendations

Overview of the River Basin Management Plans Developed in Greece Under the Context of the Water Framework Directive 2000/60/EC Focusing on the Economic Analysis

The most important piece of legislation towards integrated water management in Europe is the Water Framework Directive 2000/60/EC (WFD) based on the river basin. During its implementation each Member State (MS) should prepare a River Basin Management Plan (RBMP) accompanied with the Programme of Measures (PoMs) aiming at achieving good quality for all water bodies. The paper aims at presenting a summary of the progress regarding the RBMPs developed by each EU27 MS and special focus is given in Greece. The paper attempts a comparative analysis of the 12 Greek RBMPs highlighting the problems occurred and the drawbacks identified. Special focus is given in the economic analysis assessment where different methodologies are used to estimate the full water cost. Finally suggestions are given that can be taken into consideration during the second WFD implementation cycle in Greece

Modeling Human TBX5 Haploinsufficiency Predicts Regulatory Networks for Congenital Heart Disease.

Haploinsufficiency of transcriptional regulators causes human congenital heart disease (CHD); however, the underlying CHD gene regulatory network (GRN) imbalances are unknown. Here, we define transcriptional consequences of reduced dosage of the CHD transcription factor, TBX5, in individual cells during cardiomyocyte differentiation from human induced pluripotent stem cells (iPSCs). We discovered highly sensitive dysregulation of TBX5-dependent pathways-including lineage decisions and genes associated with heart development, cardiomyocyte function, and CHD genetics-in discrete subpopulations of cardiomyocytes. Spatial transcriptomic mapping revealed chamber-restricted expression for many TBX5-sensitive transcripts. GRN analysis indicated that cardiac network stability, including vulnerable CHD-linked nodes, is sensitive to TBX5 dosage. A GRN-predicted genetic interaction between Tbx5 and Mef2c, manifesting as ventricular septation defects, was validated in mice. These results demonstrate exquisite and diverse sensitivity to TBX5 dosage in heterogeneous subsets of iPSC-derived cardiomyocytes and predicts candidate GRNs for human CHDs, with implications for quantitative transcriptional regulation in disease