Monoclonal antibodies in type 2 asthma : a systematic review and network meta-analysis

Since novel treatments to target eosinophilic inflammation in Type 2 asthma are emerging, we aimed to evaluate and meta-analyze the efficacy of monoclonal antibodies to reduce exacerbation rate. PubMed and Web of Science were searched for phase II and phase III randomized clinical trials with monoclonal antibodies targeting key mediators of type 2-associated asthma. Thirty trials were selected involving biologics that target the IL-5 pathway, IL-13, the common IL-4 and IL-13 receptor, IL-9, IL-2 and TSLP. As no head-to-head trials were retrieved from literature, we performed an arm-based network meta-analysis to compare effects on exacerbation rate between the different treatments. Mepolizumab, reslizumab and benralizumab significantly reduced the risk of exacerbations compared to placebo (by 47-52%, 50-60%, and 28-51% respectively). Reslizumab and benralizumab also improved lung function. Dupilumab and tezepelumab improved lung function in frequent exacerbators. Lebrikizumab had no significant effect on the number of exacerbations, symptom control or health-related quality of life. Tralokinumab improved lung function compared to placebo. Network meta-analysis of all treatment and placebo arms, showed no superiority of one biologic over the others. Large reductions in exacerbation rates were observed compared to placebo, though only benralizumab was sufficiently powered (n = 2051) to demonstrate significantly decreased exacerbation rates in the subgroup analysis of IL-5 acting agents compared to placebo. Monoclonal antibodies such as mepolizumab, reslizumab and benralizumab have proven their benefit to reduce exacerbation rates in severe persistent eosinophilic asthma in the published trials. However, no statistically significant superiority was observed of one biologic over the other in the network meta-analysis. More studies with direct head to head comparisons and better defined endotypes are required

Remediation strategies and management of oil spill hazard along the Emilia-Romagna coast (Italy)

In the Adriatic Sea, large vessel traffic is dense, and accordingly there is a great deal of operational pollution along with the constant threat of accidents and incidents. The Emilia-Romagna region does not have any planning documents for managing the oil spill risk. The aim of the thesis is to propose strategies for a management plan (not currently available) and intervention strategies of coastal protection from oil spill events utilizing models (simulations) of potential scenarios which could happen near the Emiglia-Romagna coast, and how it should be the proper reaction due to this possible accidents, in a way to build preparedness and improve the efficiency regarding to the response, raising the level of safety and marine security security towards those events that can impact not only environmental units, but also other society development pillars as economy and health.I would like to thank my professors from the Univesity of Algarve, specially to Óscar Ferreira, José Paulo Monteiro and Alice Newton, for believing in my capabilities and giving me proper background to follow this master sharing with excellence their knowledge. Fourthly the WACOMA consortium, for believing in a sustainable,diverse and multicultural future uniting all the different parts of the world for a main cause; A proper use and management of our coasts and body of waters

Wave forecasting dependent from bottom roughness: The case of the Marano and Grado Lagoon

Several forecasting curves have been developed in order to provide a useful estimation of the wind wave field generated on shallow depths. In particular, these equations can be successfully applied in confined and sheltered basins, such as lakes, or even lagoons and semi \u2013 enclosed estuarine in coastal environments. The important role of the bottom friction dissipation in the generation process has been deeply recognized, leading to a reformulation of the available curves in terms of the equivalent bed roughness. In the present study, the recent new set of equations is considered and applied to a coastal lagoon. The results in terms of significant wave height and peak period are compared to those derived from a complete numerical model and other previous curves. The performed application corroborates and further validate the forecasting equations

An Integrated Approach to Study the Morphodynamics of the Lignano Tidal Inlet

The morphological evolution of a tidal inlet is the combined result of tides and wind waves, which interact in a non\u2010linear manner and over very different time\u2010scales. Likewise, the presence of maritime structures built in the vicinity of the tidal inlet, for coastal or port defense or to stabilize the inlet itself, can greatly affect this dynamic equilibrium, changing erosional and depositional patterns of the adjacent shoreline. In this study, the narrowing phenomenon of the Lignano tidal inlet subsequent to the construction of the related port, is examined through an integrated approach in order to propose and verify a possible form of evolution. This approach is the result of the combination of three methods\u2014the historical reconstruction of the shifting of the coastline, an empirical scheme which describes the qualitative morphology of a mixed\u2010energy tidal inlet, and a process\u2010based morphodynamic modeling\u2014which adopt a bi\u2010dimensional depth averaged (2DH) approach. The application of numerical modeling has required the definition of a reduced input set of data representing an average year, in particular for wind and tidal conditions, including the meteorological component. The magnitude and the directions of the simulated dominant sediment transport are coherent with real processes both from a qualitative and a quantitative point of view

Simulation of pollutants spreading from a sewage outfall in the Rijeka Bay

Results from a 3D numerical simulation of wind-induced currents and pollution spreading from a sewage outfall are described.The goal was to predict seawater sanitary quality in the Rijeka Bay, Adriatic Sea. A sea motion model was coupled with a modelof transport and chemical reactions of fecal coliforms (FC), fecal streptococci (FS) and dissolved oxygen. The selected simulationperiod of 36 hours following wastewater discharge was found to be sufficient for a significant extinction of bacteria. The simulationwas carried out for eight wind directions and two intensities (moderate and high). Mesh convergence was obtained. Twomesh sizes were coupled: coarse, for the whole Bay, and fine, for the northern part of the Bay, close to the sewage discharge ofthe Rijeka city.For all considered wind directions, the pollution plume with a concentration higher than 100 FC and 100 FS per 100 ml of seawateris conveyed mostly parallel to the coast in either north-west or south-east directions. The plume does not rise to the surfacebut stays at the depth of 10 to 20 meters. This is a consequence of the hydrodynamics of the Rijeka Bay: the bora wind carriesthe surface water layer out of the Bay through the Middle and Great Gates, while cold water enters the Bay from the layer belowthe thermocline. During the southern wind (jugo), the situation is reversed: warmer surface water enters the Bay through eitherthe Middle Gate or the Great Gate, while cold seawater exits through the bottom layer, accumulating warmer seawater in the Bay.The conclusion is that the Rijeka city sewage discharge Delta is well-designed, and the microorganism concentration is wellwithin the suggested regulatory range. The discharge site is far enough from the coast, where local streamlines are mostly parallelto the coast, hence the elevated pollution concentration does not come close to swimming and recreational areas. Even if thedischarge increases by 50%, which is unlikely in the near future, the pollution at beaches will stay within regulatory boundaries

A validated energy model of a solar dish-Stirling system considering the cleanliness of mirrors

Solar systems based on the coupling of parabolic concentrating collectors and thermal engines (i.e. dish-Stirling systems) are among the most efficient generators of solar power currently available. This study focuses on the modelling of functioning data from a 32 kWe dish-Stirling solar plant installed at a facility test site on the University of Palermo campus, in Southern Italy. The proposed model, based on real monitored data, the energy balance of the collector and the partial load efficiency of the Stirling engine, can be used easily to simulate the annual energy production of such systems, making use of the solar radiation database, with the aim of encouraging a greater commercialisation of this technology. Introducing further simplifying assumptions based on our experimental data, the model can be linearised providing a new analytical expression of the parameters that characterise the widely used Stine empirical model. The model was calibrated against data corresponding to the collector with clean mirrors and used to predict the net electric production of the dish-Stirling accurately. A numerical method for assessing the daily level of mirror soiling without the use of direct reflectivity measures was also defined. The proposed methodology was used to evaluate the history of mirror soiling for the observation period, which shows a strong correlation with the recorded sequence of rains and dust depositions. The results of this study emphasise how desert dust transport events, frequent occurrences in parts of the Mediterranean, can have a dramatic impact on the electric power generation of dish-Stirling plants

Benralizumab improves patient reported outcomes and functional parameters in difficult-to-treat patients with severe asthma: Data from a real-life cohort

In the last decade, an increasing number of randomized controlled trials (RCTs) on biologic therapy in patients with severe asthma have included patient-reported outcomes (PROs) as secondary efficacy measures. The majority of these RCTs showed a benefit in symptoms and quality of life. However, the magnitude of this benefit remains uncertain, because it rarely exceeded the minimal important difference (MID), owing to a significant improvement in the control group (placebo effect). Real-life studies on biologic therapies assessing PRO are scarce. They may support and integrate RCT results through their different experimental design. This real-life retrospective study provides data on 15 patients with difficult-to-treat severe eosinophilic asthma treated with benralizumab up to 6 months. Asthma quality of life questionnaire (AQLQ) and asthma control test (ACT) were assessed and administered at each visit to minimize the Hawthorne effect. Changes in general accepted efficacy measures, such as forced expiratory volume in 1 s (FEV1), peak expiratory flux (PEF), exacerbation rate and blood eosinophils, from baseline were also assessed. AQLQ and ACT improved from 3.9 ± 0.4 to 5.2 ± 0.4 and from15.6 ± 5.7 to 18.1 ± 5.6, respectively. FEV1 increased of about 250 ml (+14%). PEF increased from 288 ± 107 to 333 ± 133 l/min. The number of exacerbations requiring OCS courses decreased from 2.8 ± 2.2 to 0.5 ± 0.8. Eosinophil counts dropped to 25.6 ± 15 cells/microliter. In conclusion, most patients reported improvements in AQLQ and ACT greater than MID, suggesting that these outcome represent a sensitive tool in real-life effectiveness studies. Our approach reduced the limitations of transition questions and the Hawthorne effect, increasing findings reliability

Real-Life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma.

Background: The humanized monoclonal antibody benralizumab targets the α subunit of the interleukin-5 (IL-5) receptor and the FcγRIIIa receptor expressed by natural killer cells. Through this dual mechanism of action, benralizumab neutralizes the pro-eosinophil functions of IL-5 and promotes eosinophil apoptosis. Objectives and methods: The present real-life study aimed to evaluate, in 22 allergic patients with severe eosinophilic asthma, the effects of benralizumab on asthma exacerbations and lung hyperinflation. Results: In this regard here we show that, after 24 weeks of add-on treatment, benralizumab completely depleted peripheral blood eosinophils (from 810 to 0 cells/μL; p < 0.0001), and significantly decreased both asthma exacerbation number (from 4 to 0; p < 0.0001) and residual volume (from 2720 to 2300 mL; p < 0.01). Moreover, at the same time point (24 weeks) benralizumab also increased pre-bronchodilator FEV1 (from 1295 to 1985 mL; p < 0.0001), FVC (from 2390 to 2974 mL; p < 0.0001), FEF25−75 (from 0.6 to 1.42 L/sec; p < 0.0001), IC (from 1940 to 2460 mL; not significant), and ACT score (from 14.73 to 22.95; p < 0.0001), as well as reduced prednisone intake (from 25 to 0 mg; p < 0.0001). Conclusion: In conclusion, our results suggest that via its anti-eosinophil actions benralizumab improved airflow limitation, lung hyperinflation, and respiratory symptoms, as well as lowered asthma exacerbation rate and abrogated OCS consumption in most patients

Ephemeral rollover points and clinothem evolution in the modern Po Delta based on repeated bathymetric surveys

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