Can a fully integrated approach enclose the drainage system design and the flood risk analysis?

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Added value of a regional coupled model: the case study for marine heatwaves in the Caribbean

There is an urgent need to improve capacity to predict marine heatwaves given their substantial negative impacts on marine ecosystems. Here we present the added value of a regional climate simulation, performed with the regional Coupled-Ocean–Atmosphere-Wave-Sediment Transport model COAWST, centered over the Caribbean – one of the first of its kind on a climatological scale. We show its added value with regards to temporal distribution of marine heatwaves, compared with state-of-the-art global models. In this region, global models tend to simulate too few heatwaves that last too long compared to the observation-based dataset of CoralTemp. The regional climate model agrees more favourably with the CoralTemp dataset, particularly in winter. While examining potential mechanisms behind the differences we find that the more realistic representation of marine heatwaves in the regional model arises from the sea surface temperatures ability to increase/decrease more quickly in the regional model than in the global model. The reason for this is two fold. Firstly, the regional model has a shallower mixed layer than the global model which results in a lower heat capacity that allows its sea surface temperatures to warm and cool more quickly. The second reason is found during days when marine heatwaves are increasing in intensity. During these days, reduced wind speeds leads to less latent heat release and a faster warming surface, more so in the regional model than in the global models.publishedVersio

Experimental study of uni and bi-directional exchange flows in a large scale rotating trapezoidal channel

International audienceA large-scale experimental study has been conducted at the Coriolis Rotating Platform to investigate the dynamics of uni- and bi-directional exchange flows along a channel with a trapezoidal cross section under the influence of background rotation. High-resolution two-dimensional particle image velocimetry and micro-conductivity probes were used to obtain detailed velocity fields and density profiles of the exchange flow generated across the channel under different parametric conditions. Experimental measurements give new insight into the stratified-flow dynamics dependence on the magnitude of Burger number, defined as the ratio of the Rossby radius to the channel width, such that values lower than 0.5 characterize unsteady exchange flows. The measurements highlight the role that both ambient rotation and net-barotropic forcing have on the geostrophic adjustment of the dense outflowing layer and on the corresponding counter-flowing water layer fluxes. The coupled effect of these two parametric conditions largely affects the transverse velocity distribution and, for the largest net-barotropic flow in the upper fresh water layer, leads to the partial blockage of the lower saline outflow. Moreover, an increase in the mixing layer thickness, associated with larger rotation rates, and due the interface dynamics, is observed, with shear-driven interfacial instabilities analyzed to highlight the influence of both ambient rotation and net-barotropic forcin

Concomitant mutations G12D and G13D on the exon 2 of the KRAS gene. Two cases of women with colon adenocarcinoma

Colorectal cancer (CRC) is rapidly increasing representing the second most frequent cause of cancer-related deaths. From a clinical-molecular standpoint the therapeutically management of CRC focuses on main alterations found in the RAS family protein, where single mutations of KRAS are considered both the hallmark and the target of this tumor. Double and concomitant alterations of KRAS are still far to be interpreted as molecular characteristics which could potentially address different and more personalized treatments for patients. Here, we firstly describe the case of two patients at different stages (pT2N0M0 and pT4cN1cM1) but similarly showing a double concurrent mutations G12D and G13D in the exon 2 of the KRAS gene, normally mutually exclusive. We also evaluated genetic testing of dihydropyrimidine dehydrogenase (DPYD) and microsatellite instability (MSI) by real-time PCR and additional molecular mutations by next generation sequencing (NGS) which resulted coherently to the progression of the disease. Accordingly, we reinterpreted and discuss the clinical history of both cases treated as single mutations of KRAS but similarly progressing towards a metastatic asset. We concluded that double mutations of KRAS cannot be interpreted as univocal genomic alterations and that they could severely impact the clinical outcome in CRC, requiring a tighter monitoring of patients throughout the time.Abstract: Colorectal cancer (CRC) is rapidly increasing representing the second most frequent cause of cancer-related deaths. From a clinical-molecular standpoint the therapeutically management of CRC focuses on main alterations found in the RAS family protein, where single mutations of KRAS are considered both the hallmark and the target of this tumor. Double and concomitant alterations of KRAS are still far to be interpreted as molecular characteristics which could potentially address different and more personalized treatments for patients. Here, we firstly describe the case of two patients at different stages (pT2N0M0 and pT4cN1cM1) but similarly showing a double concurrent mutations G12D and G13D in the exon 2 of the KRAS gene, normally mutually exclusive. We also evaluated genetic testing of dihydropyrimidine dehydrogenase (DPYD) and microsatellite instability (MSI) by real-time PCR and additional molecular mutations by next generation sequencing (NGS) which resulted coherently to the progression of the disease. Accordingly, we reinterpreted and discuss the clinical history of both cases treated as single mutations of KRAS but similarly progressing towards a metastatic asset. We concluded that double mutations of KRAS cannot be interpreted as univocal genomic alterations and that they could severely impact the clinical outcome in CRC, requiring a tighter monitoring of patients throughout the time

BIM for infrastructure: an efficient process to achieve 4D and 5D digital dimensions

Introduction of the Building Information Modeling (BIM) approach in Civil Engineering practices allows a design optimization through both an improved control of all the components of a project and an increased efficiency in the collaboration between all professionals involved. In Italy, major attention is being paid by scientists and professionals on this subject area, especially after the implementation of the national law DM 560/2017. This document will gradually rule the integration of BIM-based procedures for contractors in major public tenders. The present paper aims to propose a methodology for implementing an optimization dynamic model of time (4D) and costs (5D) across different project phases. To achieve this aim, the process relies on several authoring tools and 4D/5D modeling software, capable to incorporate a variety of project data in a unique and shared environment. The most effective methodology to maximize the interoperability between various codes will be presented. In this regard, a dynamic model involving an optimizationoriented approach for both the quantity surveying and the definition of the design management timeline is introduced. It is important to emphasize that these aspects are two of the major issues for the evaluation criteria in a civil engineering project. Also, this bidirectional process allows for a more accurate estimation of project costs as well as to achieve an optimized timeline of construction activities. Finally, it worth reminding that in case of constrained changes during the design phase, a dynamic model permits to effectively reiterate the process with a significant reduction of the overall computational time

The dynamics of bi-directional exchange flows

The global demand for low carbon electricity requires a variety of energy generation approaches, the choice of which is dependent on multiple criteria. Tidal flows have long been identified as a reliable source of energy, with a high degree of predictability. To this end a novel turbine has been developed that could be well suited to energy generation in both tidal flows, or water courses. In this study a Smoothed Particle Hydrodynamics (SPH) model, namely DualSPHysics, is used to predict the behavior of this novel turbine design. Which will be used to guide the design process. The SPH method was chosen as the design of the turbine uses several connected parts, that requires free movement and interactions to properly represent the prototype and was found to be capable of expressing this behavior

Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer

High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10–15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum–maximum: 4–36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan–Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38–6.18], p 5 0.005), and time to progression (log-rank p < 0.001; HR 7.17 [1.89–27.21], p 5 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment

Evaluation of Endometrial Urocortin Secretion for Prediction of Pregnancy after Intrauterine Insemination

Abstract Background: Urocortin is a neuropeptide produced by the human endometrium and has biological effects putatively important for promoting blastocyst implantation. We measured urocortin concentrations in samples of endometrial wash fluid collected from women with unexplained infertility who underwent intrauterine insemination (IUI). Methods: Patients 28–42 years of age (n = 71) were consecutively enrolled after a complete clinical evaluation. Endometrial wash fluid was retrieved before IUI, at the time of ultrasound evaluation of endometrial thickness. Urocortin concentrations were assayed with a specific ELISA. Results: After IUI, 28 patients (39%) became pregnant. Urocortin concentrations were significantly higher in women who became pregnant than in those who did not (0.38 μg/L vs 0.13 μg/L, P <0.0001). At a cutoff of 0.321 μg/L, urocortin results were positive in 61% [95% confidence interval (CI), 41%–78%] of women who had successful implantation and negative in 98% (95% CI, 88%–99.6%) of those who did not. The pregnancy rate for women with urocortin concentrations >0.32 μg/L was 94%, which differed significantly (P <0.05) from the overall pregnancy rate of 39% in the study population. Conclusions: Urocortin is measurable in endometrial wash fluid, and its concentrations before IUI are higher in women who subsequently achieve pregnancy. These data suggest that the probability of having a successful pregnancy-producing IUI may be better estimated by measuring urocortin in endometrial wash fluid

The dynamics of bi-directional exchange flows::implication for morphodynamic change within estuaries and sea straits

Environmental and geophysical flows, including dense bottom gravity currents in the ocean and buoyancy-driven exchange flows in marginal seas, are strongly controlled by topographic features. These are known to exert significant influence on both internal mixing and secondary circulations generated by these flows. In such cases, uni-directional or bi-directional exchange flows develop when horizontal density differences and/or pressure gradients are present between adjacent water bodies connected by a submerged channel. The flow dynamics of the dense lower layer depend primarily on the volumetric flux and channel cross-sectional shape, while the stratified interfacial flow mixing characteristics, leading to fluid entrainment/detrainment, are also dependent on the buoyancy flux and motion within the upper (lower density) water mass. For submerged channels that are relatively wide compared to the internal Rossby radius of deformation, Earth rotation effects introduce geostrophic adjustment of these internal fluid motions, which can suppress turbulent mixing generated at the interface and result in the development of Ekman layers that induce secondary, cross-channel circulations, even within straight channels. Moreover, recent studies of dense, gravity currents generated in rotating and non-rotating systems, respectively, indicated that the V-shaped channel topography had a strong influence on both flow distribution and associated interfacial mixing characteristics along the channel. However, such topographic controls on the interfacial mixing and secondary circulations generated by bi-directional exchange flows are not yet fully understood and remain to be investigated thoroughly in the laboratory. Also the effect of mobile bed for bi-directional exchange flows generated in deformable channels along with the physical interactions between the lower dense water flow and the erodible bed sediments will have a strong influence in (re-)shaping the overall channel bed topography (i.e. bed morphodynamics). Consequently, the resulting temporal changes in cross-sectional channel bathymetry (i.e. through erosion and deposition processes) would also be expected to have associated feedbacks on transverse asymmetries in the bi-directional exchange flow structure, as well as on the internal flow stability