On the extreme hydrologic events determinants by means of Beta-Singh-Maddala reparameterization

In previous studies, beta-k distribution and distribution functions strongly related to that, have played important roles in representing extreme events. Among these distributions, the Beta-Singh-Maddala turned out to be adequate for modelling hydrological extreme events. Starting from this distribution, the aim of the paper is to express the model as a function of indexes of hydrological interest and simultaneously investigate on their dependence with a set of explanatory variables in such a way to explore on possible determinants of extreme hydrologic events. Finally, an application to a real hydrologic dataset is considered in order to show the potentiality of the proposed model in describing data and in understanding effects of covariates on frequently adopted hydrological indicators

NEW THERAPEUTIC OPTIONS FOR THE TREATMENT OF SICKLE CELL DISEASE

Sickle cell disease (SCD; ORPHA232; OMIM # 603903) is a chronic and invalidating disorder distributed worldwide, with high morbidity and mortality.  Given the disease complexity and the multiplicity of pathophysiological targets, development of new therapeutic options is critical, despite the positive effects of hydroxyurea (HU), for many years the only approved drug for SCD. New therapeutic strategies might be divided into (1) pathophysiology-related novel therapies and (2) innovations in curative therapeutic options such as hematopoietic stem cell transplantation and gene therapy. The pathophysiology related novel therapies are: a) Agents which reduce sickling or prevent sickle red cell dehydration; b) Agents targeting SCD vasculopathy and sickle cell-endothelial adhesive events; c) Anti-oxidant agents. This review highlights new therapeutic strategies in SCD and discusses future developments, research implications, and possible innovative clinical trials

Impaired pro‐resolving mechanisms promote abnormal NETosis , fueling autoimmunity in sickle cell disease

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorders with still high mortality and morbidity and limited therapeutic options. SCD is characterized by anemia, chronic hemolysis, and acute vaso-occlusive painful crises. The biocomplexity of SCD goes beyond red cells, involving neutrophils and soluble factors such as cytokines or alternative complement pathway intensively cross-talking with vascular endothelial cells. In addition, in SCD, the overactivation of neutrophils contributes to the production of neutrophil extracellular traps (NETs) (1, 2). This might trigger endothelial vascular injury, promoting acute sickle cell related events and increasing the risk of infections in patients with SC

Development of Algorithm for Clinical Management of Sickle Cell Bone Disease: Evidence for a Role of Vertebral Fractures in Patient Follow-up

Sickle-cell disease (SCD) is a worldwide distributed hemoglobinopathy, characterized by hemolytic anemia associated with vaso-occlusive events. These result in acute and chronic multiorgan damage. Bone is early involved, leading to long-term disability, chronic pain and fractures. Here, we carried out a retrospective study to evaluate sickle bone disease (SBD) in a cohort of adults with SCD. We assessed bone density, metabolism and turnover. We also evaluated the presence of fractures and the correlation between SCD severity and skeletal manifestations. A total of 71 patients with SCD were analyzed. The mean age of population was 39 \ub1 10 years, 56% of which were females. We found osteoporosis in a range between 7% and 18% with a high incidence of vertebral fractures. LDH and AST were predictive for the severity of vertebral fractures, while bone density was not. Noteworthy, we identified -1.4 Standard Deviations T-score as the cutoff for detecting the presence of fractures in patients with SCD. Collectively our data allowed us to develop an algorithm for the management of SBD, which may be useful in daily clinical practice to early intersect and treat SBD

Safety and efficacy of ketorolac continuous infusion for multimodal analgesia of vaso-occlusive crisis in patients with sickle cell disease

Pain is an hallmark of sickle-cell-related acute clinical manifestations as part of acute vaso-occlusive crisis (VOC). In SCD pain has different origins such as vascular or neuropathic pain, which requires multimodal analgesia. This is based on the administration of drugs with different pharmacological mechanisms of action, maximizing analgesia and minimizing their adverse events and the risk of drug-addition in patients experiencing acute-recurrent pain events as in SCD. Ketorolac is a potent non-narcotic analgesic, being relatively safe and effective during pain-management in children and adults. Up to now, there is a lack of safety information on continuous infusion ketorolac as used to control acute pain in patients with SCD, and the benefits/risks ratio needs to be investigated. Here, we report for the first time the safety profile of ketorolac in the special population of patients with SCD. We confirmed that ketorolac in combination with tramadol, an opioid like molecule, is effective in pain control of adult patients with SCD experiencing acute severe VOCs defined by pain visual analog scale. Our study shows that short term (72 h) continuous infusion of ketorolac plus tramadol is not associated with adverse events such as liver or kidney acute disfunction or abnormalities in coagulation parameters during patients' hospitalization and within 30 days after patients discharge. This is extremely important for patients with SCD, who should have access to multimodal therapy to control recurrent acute pain crisis in order to limit central sensitization a fearsome issue of undertreated recurrent acute pain and of chronic pain

The Ionosphere Prediction Service for GNSS Users

Space weather events related to solar activity can affect both ground and space-based infrastructures, potentially resulting in failures or service disruptions across the globe and causing damage to equipment and systems. Global Navigation Satellite Systems (GNSS) represent one of such infrastructures that can suffer from electromagnetic phenomena in the atmosphere, in particular due to the interaction of the RF signals with the ionosphere. The Ionosphere Prediction Service (IPS) is a project funded by European Commission to provide a prototype platform for a monitoring and prediction service of potential ionosphere-related disturbances affecting GNSS user communities. It is designed to help these communities cope with the effects of the ionospheric activity and mitigate the impacts of these effects on the specific GNSS-based application/service. The IPS development has been conceived of two concurrent activities: the design and implementation of the prototype service and the research activity, which represents the scientific backbone of IPS and is at the base of all the models and algorithms used for the computation of the products. The products are the basic IPS output that translate the nowcasting or forecasting information from the whole IPS system down to the final user. They are fine-tuned to match the different needs of the communities (scientific, aviation, high accuracy, etc.) which the service is targeted to and to warn the GNSS users about possible performance degradations in the presence of anomalous solar and atmospheric phenomena. To achieve this overarching aim, four different blocks of products dealing with solar activity, ionospheric activity, GNSS receiver and system performance figures have been developed and integrated into a unique service chain. The service is available to a set of invited users since July 2018 through a web portal and its provision with all the necessary operations will last 6 months. The prototype will be also ported to the Joint Research Centre (JRC). This phase will be useful to further test the platform, and to assess whether and how a dedicated prediction service for International Technical Symposium on Navigation and Timing (ITSNT) 2018 13-16 Nov 2018 ENAC, Toulouse, France Galileo users is to be implemented as part of the service facilities of the Galileo infrastructure.Published2A. Fisica dell'alta atmosfera7SR AMBIENTE – Servizi e ricerca per la societàN/A or not JC

The ionosphere prediction service prototype for GNSS users

The effect of the Earth’s ionosphere represents the single largest contribution to the Global Navigation Satellite System (GNSS) error budget and abnormal ionospheric conditions can impose serious degradation on GNSS system functionality, including integrity, accuracy and availability. With the growing reliance on GNSS for many modern life applications, actionable ionospheric forecasts can contribute to the understanding and mitigation of the impact of the ionosphere on our technology based society. In this context, the Ionosphere Prediction Service (IPS) project was set up to design and develop a prototype platform to translate the forecast of the ionospheric effects into a service customized for specific GNSS user communities. To achieve this overarching aim, four different product groups dealing with solar activity, ionospheric activity, GNSS receiver performance and service performance have been developed and integrated into a service chain, which is made available through a web based platform. This paper provides an overview of the IPS project describing its overall architecture, products and web based platform.PublishedA412A. Fisica dell'alta atmosferaJCR Journa

The Ionosphere Prediction Service

The aim of the Ionosphere Prediction Service (IPS) project is to design and develop a prototype platform to translate the prediction and forecast of the ionosphere effects into a service customized for specific GNSS user communities. The project team is composed by Telespazio (coordinator), Nottingham Scientific Ltd, Telespazio Vega Deutschland, the University of Nottingham, the University of Rome “Tor Vergata” and the Italian Istituto Nazionale di Geofisica e Vulcanologia (INGV). The IPS development is conceived of two concurrent activities: prototype service design and development & research activity that will run along the whole project. Service design and development is conceived into four phases: user requirements collection, architecture specification, implementation and validation of the prototype. A sub-activity analyses also the integration feasibility in the Galileo Service center, located in Madrid. The research activity is the scientific backbone of IPS that will provide the models and algorithms for the forecasting products.PublishedUniversity of Exeter United Kingdom2A. Fisica dell'alta atmosfera7SR AMBIENTE – Servizi e ricerca per la societ

Post-exercise high-sensitivity troponin T levels in patients with suspected unstable angina

Background Previous studies showed that troponin blood levels may increase after exercise. In this study we assessed whether, among patients admitted with suspected unstable angina, the increase in high-sensitive troponin T (hs-TnT) levels after exercise stress test (EST) might help identify those with obstructive coronary artery disease (CAD) and predict symptom recurrence during short term follow-up. Methods Maximal treadmill EST was performed in 69 consecutive patients admitted to the emergency room with a suspicion of unstable angina (acute chest pain but confirmed normal serum levels of cardiac troponins) was measured before and 4 hours after EST. Coronary angiography was performed in 22 patients (32.8%). Results hs-TnT increased after EST compared to baseline in the whole population (from 0.84\ub10.65 to 1.17\ub10.87 ng/dL, p<0.001). The increase was similar in patients with positive (n = 14) and negative (n = 55) EST (p = 0.72), and was also similar in patients with (n = 12) and without (n = 10) obstructive CAD at angiography (p = 0.91). The achievement of a heart rate at peak EST \ufffd85% of that predicted for age was the variable mainly associated with the post- EST hs-TnT increase at multivariable linear regression analysis (p = 0.005). The change after EST of hs-TnT did not predict the recurrence of symptoms or readmission for chest pain at 6-month follow-up. Conclusions Our data show that hs-TnT increased after EST in patients with suspected unstable angina, which seemed largely independent of most clinical and laboratory variables. Thus, hs-TnT assessed after EST does not seem to be helpful to identify patients with obstructive CAD in this kind of patients

Validation of techniques to mitigate copper surface contamination in CUORE

In this article we describe the background challenges for the CUORE experiment posed by surface contamination of inert detector materials such as copper, and present three techniques explored to mitigate these backgrounds. Using data from a dedicated test apparatus constructed to validate and compare these techniques we demonstrate that copper surface contamination levels better than 10E-07 - 10E-08 Bq/cm2 are achieved for 238U and 232Th. If these levels are reproduced in the final CUORE apparatus the projected 90% C.L. upper limit on the number of background counts in the region of interest is 0.02-0.03 counts/keV/kg/y depending on the adopted mitigation technique.Comment: 10 pages, 6 figures, 6 table