Coupling X-band dual-polarized mini-radars and hydro-meteorological forecast models: the HYDRORAD project

Abstract. Hydro-meteorological hazards like convective outbreaks leading to torrential rain and floods are among the most critical environmental issues world-wide. In that context weather radar observations have proven to be very useful in providing information on the spatial distribution of rainfall that can support early warning of floods. However, quantitative precipitation estimation by radar is subjected to many limitations and uncertainties. The use of dual-polarization at high frequency (i.e. X-band) has proven particularly useful for mitigating some of the limitation of operational systems, by exploiting the benefit of easiness to transport and deploy and the high spatial and temporal resolution achievable at small antenna sizes. New developments on X-band dual-polarization technology in recent years have received the interest of scientific and operational communities in these systems. New enterprises are focusing on the advancement of cost-efficient mini-radar network technology, based on high-frequency (mainly X-band) and low-power weather radar systems for weather monitoring and hydro-meteorological forecasting. Within the above context, the main objective of the HYDRORAD project was the development of an innovative \\mbox{integrated} decision support tool for weather monitoring and hydro-meteorological applications. The integrated system tool is based on a polarimetric X-band mini-radar network which is the core of the decision support tool, a novel radar products generator and a hydro-meteorological forecast modelling system that ingests mini-radar rainfall products to forecast precipitation and floods. The radar products generator includes algorithms for attenuation correction, hydrometeor classification, a vertical profile reflectivity correction, a new polarimetric rainfall estimators developed for mini-radar observations, and short-term nowcasting of convective cells. The hydro-meteorological modelling system includes the Mesoscale Model 5 (MM5) and the Army Corps of Engineers Hydrologic Engineering Center hydrologic and hydraulic modelling chain. The characteristics of this tool make it ideal to support flood monitoring and forecasting within urban environment and small-scale basins. Preliminary results, carried out during a field campaign in Moldova, showed that the mini-radar based hydro-meteorological forecasting system can constitute a suitable solution for local flood warning and civil flood protection applications

Alkalizing Reactions Streamline Cellular Metabolism in Acidogenic Microorganisms

An understanding of the integrated relationships among the principal cellular functions that govern the bioenergetic reactions of an organism is necessary to determine how cells remain viable and optimise their fitness in the environment. Urease is a complex enzyme that catalyzes the hydrolysis of urea to ammonia and carbonic acid. While the induction of urease activity by several microorganisms has been predominantly considered a stress-response that is initiated to generate a nitrogen source in response to a low environmental pH, here we demonstrate a new role of urease in the optimisation of cellular bioenergetics. We show that urea hydrolysis increases the catabolic efficiency of Streptococcus thermophilus, a lactic acid bacterium that is widely used in the industrial manufacture of dairy products. By modulating the intracellular pH and thereby increasing the activity of β-galactosidase, glycolytic enzymes and lactate dehydrogenase, urease increases the overall change in enthalpy generated by the bioenergetic reactions. A cooperative altruistic behaviour of urease-positive microorganisms on the urease-negative microorganisms within the same environment was also observed. The physiological role of a single enzymatic activity demonstrates a novel and unexpected view of the non-transcriptional regulatory mechanisms that govern the bioenergetics of a bacterial cell, highlighting a new role for cytosol-alkalizing biochemical pathways in acidogenic microorganisms

Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC

The availability of immune checkpoint inhibitors (ICIs) for the management of advanced hepatocellular cancer (HCC) has changed the treatment paradigm. There are emerging questions regarding the efficacy of subsequent anticancer therapies. The primary aim of this retrospective, multicenter study was to examine the types of anticancer treatment received after ICIs and to assess the impact on post-ICI survival. We established an international consortium of 11 tertiary-care referral centers located in the USA (n = 249), Europe (n = 74), and Asia (n = 97), and described patterns of care following ICI therapy. The impact of subsequent therapy on overall survival (OS) was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). A total of 420 patients were treated with ICIs for advanced HCC after one line of systemic therapy (n = 371, 88.8%): 31 (8.8%) had died, 152 (36.2%) received best supportive care (BSC) following ICIs, and 163 patients (38.8%) received subsequent anticancer therapy. Tyrosine kinase inhibitors (TKIs, n = 132, 80.9%), in particular sorafenib (n = 49, 30.0%), were the most common post-ICI therapy followed by external beam radiotherapy (n = 28, 17.2%), further immunotherapy (n = 21, 12.9%), locoregional therapy (n = 23, 14.1%), chemotherapy (n = 9, 5.5%), and surgery (n = 6, 3.6%). Receipt of post-ICI therapy was associated with longer median OS compared with those who had received BSC (12.1 vs. 3.3 months; hazard ratio [HR]: 0.4 (95% CI: 2.7–5.0). No difference in OS was noted in those patients who received TKI before ICIs compared with those who received ICIs followed by TKI. Conclusion: Post-ICI therapy is associated with OS in excess of 12 months, suggesting a role for therapeutic sequencing. OS from TKI therapy was similar to that reported in registration studies, suggesting preserved efficacy following ICIs