Fuzzy modelling of acid mine drainage environments using geochemical, ecological and mineralogical indicators

Fuzzy logic was applied to model acid mine drainage (AMD) and to obtain a classification index of the environmental impact in a contaminated riverine system. The data set used to develop this fuzzy model (a fuzzy classifier) concerns an abandoned mine in Northern Portugal— Valdarcas mining site. Here, distinctive drainage environments (spatial patterns) can be observed based on the AMD formed in the sulphide-rich waste-dumps. Such environments were established, as the effluent flows through the mining area, using several kinds of indicators. These are physical–chemical, ecological and mineralogical parameters, being expressed in a quantitative or qualitative basis. The fuzzy classifier proposed in this paper is a min– max fuzzy inference system, representing the spatial behaviour of those indicators, using the AMD environments as patterns. As they represent different levels (classes) of contamination, the fuzzy classifier can be used as a tool, allowing a more reasonable approach, compared with classical models, to characterize the environmental impact caused by AMD. In a general way it can be applied to other sites where sulphide-rich waste-dumps are promoting the pollution of superficial water through the generation of AMD

Intrathoracic solitary fibrous tumor - an international multicenter study on clinical outcome and novel circulating biomarkers

Intrathoracic solitary fibrous tumor (SFT) is a rare disease. Radical resection is the standard of care. However, estimating prognosis and planning follow-up and treatment strategies remains challenging. Data were retrospectively collected by five international centers to explore outcome and biomarkers for predicting event-free-survival (EFS). 125 histological proven SFT patients (74 female; 59.2%; 104 benign; 83.2%) were analyzed. The one-, three-, five- and ten-year EFS after curative-intent surgery was 98%, 90%, 77% and 67%, respectively. Patients age (>/=59 vs. 10 cm vs. 5 vs. < 5 HR 3.91, CI 1.40-10.89, p = 0.009) were prognostic after univariate analyses. After multivariate analyses tumor-dignity and fibrinogen remained as independent prognosticators. Besides validating the role of age, tumor-dignity, tumor-size, stage and resection margins, we identified for the first time inflammatory markers as prognosticators in SFT

NF-κB, stem cells and breast cancer: the links get stronger

Self-renewing breast cancer stem cells are key actors in perpetuating tumour existence and in treatment resistance and relapse. The molecular pathways required for their maintenance are starting to be elucidated. Among them is the transcription factor NF-κB, which is known to play critical roles in cell survival, inflammation and immunity. Recent studies indicate that mammary epithelial NF-κB regulates the self-renewal of breast cancer stem cells in a model of Her2-dependent tumourigenesis. We will describe here the NF-κB-activating pathways that are involved in this process and in which progenitor cells this transcription factor is actually activated

Relation of Improvement in Estimated Glomerular Filtration Rate With Atorvastatin to Reductions in Hospitalizations for Heart Failure (from the Treating to New Targets [TNT] Study)

Impaired kidney function often accompanies heart failure (HF) and is associated with a worse prognosis. This post hoc analysis of the Treating to New Targets (TNT) trial examined whether the observed decrease in HF hospitalizations with high- compared to low-dose atorvastatin could be related to improvements in kidney function. Of 10,001 TNT participants, 9,376 had estimated glomerular filtration rate (eGFR) measurements at baseline and 1 year and were included in this analysis. The association of change in year-1 eGFR and subsequent HF hospitalization was examined using Cox regression models. In total 218 participants developed subsequent HF hospitalization. Little change in eGFR occurred over 1 year in the atorvastatin 10-mg group, whereas eGFR improved in the 80-mg group by 1.48 ml/min/1.73 m(2) (95% confidence interval 1.29 to 1.67, p <0.0001). Subsequent HF was preceded by a decrease in eGFR over 1 year compared to modest improvement in those without subsequent HF (−0.09 ± 7.89 vs 0.81 ± 6.90 ml/min/1.73 m(2), p = 0.0015). After adjusting for baseline eGFR, each 5-ml/min/1.73 m(2) increase in eGFR at 1 year was associated with a lower risk of subsequent HF hospitalization (hazard ratio 0.85, 95% confidence interval 0.77 to 0.94, p = 0.002). This relation was independent of treatment effect or change in low-density lipoprotein cholesterol level at 1 year. In conclusion, treatment with high- compared to low-dose atorvastatin was associated with improvement in eGFR at 1 year, which was related to a decrease in subsequent HF hospitalization. This suggests that improvement in kidney function may be related to the beneficial effect of high-dose atorvastatin on HF hospitalization

Changing atmospheric CO2 concentration was the primary driver of early Cenozoic climate

The Early Eocene Climate Optimum (EECO, which occurred about 51 to 53 million years ago)1, was the warmest interval of the past 65 million years, with mean annual surface air temperature over ten degrees Celsius warmer than during the pre-industrial period2–4. Subsequent global cooling in the middle and late Eocene epoch, especially at high latitudes, eventually led to continental ice sheet development in Antarctica in the early Oligocene epoch (about 33.6 million years ago). However, existing estimates place atmospheric carbon dioxide (CO2) levels during the Eocene at 500–3,000 parts per million5–7, and in the absence of tighter constraints carbon–climate interactions over this interval remain uncertain. Here we use recent analytical and methodological developments8–11 to generate a new high-fidelity record of CO2 concentrations using the boron isotope (δ11Β) composition of well preserved planktonic foraminifera from the Tanzania Drilling Project, revising previous estimates6. Although species-level uncertainties make absolute values difficult to constrain, CO2 concentrations during the EECO were around 1,400 parts per million. The relative decline in CO2 concentration through the Eocene is more robustly constrained at about fifty per cent, with a further decline into the Oligocene12. Provided the latitudinal dependency of sea surface temperature change for a given climate forcing in the Eocene was similar to that of the late Quaternary period13, this CO2 decline was sufficient to drive the well documented high- and low-latitude cooling that occurred through the Eocene14. Once the change in global temperature between the pre-industrial period and the Eocene caused by the action of all known slow feedbacks (apart from those associated with the carbon cycle) is removed2–4, both the EECO and the late Eocene exhibit an equilibrium climate sensitivity relative to the pre-industrial period of 2.1 to 4.6 degrees Celsius per CO2 doubling (66 per cent confidence), which is similar to the canonical range (1.5 to 4.5 degrees Celsius15), indicating that a large fraction of the warmth of the early Eocene greenhouse was driven by increased CO2 concentrations, and that climate sensitivity was relatively constant throughout this period

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types