A Loosely-Coupled Collaborative Integrated Environmental Modelling Framework

Integration of environmental models requires full support of the modelling community. When a large number of models are integrated, it requires consistency within scale, datasets, and model to model interactions to minimize the uncertainty among the models. The integrated environmental modelling (IEM) framework is a necessary approach to integrate multiple environmental models for a particular study. When modellers cannot afford considerable amount of time to get involved with full and tightly-integrated IEM or an IEM has very short time frame to complete, then a loosely-coupled collaborative IEM environment can provide the benefits of the integrated approach while minimizing the effort of each individual modeller. However, such a framework will require setting rules that all participants must adhere to. These rules address the issues of model inputs and model to model interaction. The framework should also provide value-added functionality to make the IEM framework more transparent and applicable

The Land and Water Integration Decision Support System

Integration of data and component models describing habitat-based land use, non-point source pollutants transport, and water and soil quality forms the decision support development processes to assist policy makers in examining management options for dealing with the impacts of land use on water for agricultural issues in Canada. The land and water integration decision support system emphasizes on scale consistency, scenario gaming and testing, pollutant source tracing and optimal solutions. Examples of a watershed-based decision support system on water quality impact were presented as part of an assessment for the evaluation of best management practice options for future agricultural intensification scenario

Novel actions of next-generation taxanes benefit advanced stages of prostate cancer.

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro and in xenograft tumors for cabazitaxel response. RESULTS: The data herein show that (i) cabazitaxel exerts stronger cytostatic and cytotoxic response compared with docetaxel, especially in CRPC; (ii) cabazitaxel induces aberrant mitosis, leading to pyknotic and multinucleated cells; (iii) taxanes do not act through the androgen receptor (AR); (iv) gene-expression profiling reveals distinct molecular actions for cabazitaxel; and (v) tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to cabazitaxel. CONCLUSIONS: Cabazitaxel not only induces improved cytostatic and cytotoxic effects, but also affects distinct molecular pathways, compared with docetaxel, which could underlie its efficacy after docetaxel treatment has failed in patients with CRPC. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization to taxanes, which could benefit up to 50% of CRPC cases