Conditional independence relations among biological markers may improve clinical decision as in the case of triple negative breast cancers

The associations existing among different biomarkers are important in clinical settings because they contribute to the characterisation of specific pathways related to the natural history of the disease, genetic and environmental determinants. Despite the availability of binary/linear (or at least monotonic) correlation indices, the full exploitation of molecular information depends on the knowledge of direct/indirect conditional independence (and eventually causal) relationships among biomarkers, and with target variables in the population of interest. In other words, that depends on inferences which are performed on the joint multivariate distribution of markers and target variables. Graphical models, such as Bayesian Networks, are well suited to this purpose. Therefore, we reconsidered a previously published case study on classical biomarkers in breast cancer, namely estrogen receptor (ER), progesterone receptor (PR), a proliferative index (Ki67/MIB-1) and to protein HER2/neu (NEU) and p53, to infer conditional independence relations existing in the joint distribution by inferring (learning) the structure of graphs entailing those relations of independence. We also examined the conditional distribution of a special molecular phenotype, called triple-negative, in which ER, PR and NEU were absent. We confirmed that ER is a key marker and we found that it was able to define subpopulations of patients characterized by different conditional independence relations among biomarkers. We also found a preliminary evidence that, given a triple-negative profile, the distribution of p53 protein is mostly supported in 'zero' and 'high' states providing useful information in selecting patients that could benefit from an adjuvant anthracyclines/alkylating agent-based chemotherapy

Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver

<p>Abstract</p> <p>Background</p> <p>The NO - cGMP system plays a key role in the regulation of sinusoidal tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the dilatory action of cGMP. We, therefore, investigated the effects of PDE-5 inhibitors on hepatic and systemic hemodynamics in rats.</p> <p>Methods</p> <p>Hemodynamic parameters were monitored for 60 min. after intravenous injection of sildenafil and vardenafil [1, 10 and 100 μg/kg (sil1, sil10, sil100, var1, var10, var100)] in anesthetized rats.</p> <p>Results</p> <p>Cardiac output and heart rate remained constant. After a short dip, mean arterial blood pressure again increased. Systemic vascular resistance transiently decreased slightly. Changes in hepatic hemodynamic parameters started after few minutes and continued for at least 60 min. Portal (var10 -31%, sil10 -34%) and hepatic arterial resistance (var10 -30%, sil10 -32%) decreased significantly (p < 0.05). At the same time portal venous (var10 +29%, sil10 +24%), hepatic arterial (var10 +34%, sil10 +48%), and hepatic parenchymal blood flow (var10 +15%, sil10 +15%) increased significantly (p < 0.05). The fractional liver blood flow (total liver flow/cardiac output) increased significantly (var10 26%, sil10 23%). Portal pressure remained constant or tended to decrease. 10 μg/kg was the most effective dose for both PDE-5 inhibitors.</p> <p>Conclusion</p> <p>Low doses of phosphodiesterase-5 inhibitors have distinct effects on hepatic hemodynamic parameters. Their therapeutic use in portal hypertension should therefore be evaluated.</p

Temporal Variations of Near-surface Seismic Data at the Ploemeur (France) Hydrogeological Observatory

International audienceNear-surface seismic methods are mainly used to determine the geometrical characteristics of hydrosystems (and to provide elements that are interesting for hydrogeologists such as separating aquifer layers, setting up systems boundaries, highlighting fractures etc.). Recent methodological advances suggest the high potential of seismic methods to investigate the mechanical properties of the Critical Zone (CZ), by exploiting the full wealth of seismic records. Indeed, the behavior of Shear (S) and Pressure (P) waves in the presence of water is partially decoupled, so that the ratio of their propagation velocities VP/VS is strongly linked to water saturation. We propose here a time-lapse application of this approach. Two seismic acquisitions were carried out under distinct hydrogeological conditions along the same line at the Ploemeur hydrogeological observatory (South Brittany, France). Vertical component seismic data were recorded to extract: (i) P-wave first arrival times and (ii) Rayleigh-wave phase velocities. The significant variations with time and space, of both datasets, indicate marked changes in mechanical properties of the CZ that have to be compared to soil moisture variations in the unsaturated zone and groundwater level variations

Estimating picking errors in near-surface seismic data to enable their time-lapse interpretation on hydrosystems

International audienceTime‐lapse applications of seismic methods have been recently suggested at the near‐surface scale to track hydrological properties variations due to climate, water level changes or permafrost thaw for instance. But when it comes to traveltime tomography or surface‐wave dispersion inversion, a careful estimation of the data variability associated to the picking process must be considered prior to any time‐lapse interpretation. In this study, we propose to estimate picking errors that are due to the inherent subjectivity of human operators using statistical analysis based on picking repeatability. Two seismic datasets were collected along the same profile under distinct hydrological conditions, across a granite‐micaschist contact at the Ploemeur hydrological observatory (France). Both datasets were recorded using identical equipment and acquisition parameters. A thorough statistical analysis is conducted to estimate picking uncertainties, at the 99 % confidence level, for both Pressure (P) wave first arrival time and surface‐wave phase velocity. With the suggested workflow, we are able to identify 33 % of the P‐wave traveltimes and 16 % of the surface‐wave dispersion data that can be considered significant enough for time‐lapse interpretations. In this selected portion of the data, point‐by‐point differences are highlighting important variations linked to different hydrogeological properties of the subsurface. These variations show strong contrasts with a non‐monotonous behaviour along the line, offering new insights to better constrain the dynamics of this hydrosystem

Life cycle assessment of three water systems in Copenhagen-a management tool of the future.

Environmental life-cycle assessment (LCA) was applied to evaluate three different water systems of the water sector in Copenhagen, Denmark, including technologies within water supply, facilities recycling water and treatment of sewer overflow. In these three water systems LCA was used to evaluate the environmental impacts of each of the processes involved. The overall conclusion was that LCA is suitable as a decision support tool in the water sector as it provides a holistic evaluation platform of the considered alternatives categorized in environmental impact categories. The use of LCA in the water sector of this region has limitation since it not yet considers impact categories assessing freshwater scarcity and ecological sustainability.</jats:p