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Backround: We aimed at assessing the prevalence of polypharmacy and potential drug-drug interactions (DDIs) with clinical relevance in elderly patient on Emilia Romagna area. Both outpatients and residents in nursing homes were assessed, with only partially overlapping strategies.Methods: We defined a list of 190 pairs of potentially interacting drugs, based on literature appraisal and availability of therapeutic alternatives. January-June 2018 data on drug use in patients over 65 years-old were collected from nine Local Health Authorities of Emilia Romagna: data on community-dwelling subjects were extracted from archives of reimbursed prescriptions, while drug use in a sample of nursing homes was recorded from clinical charts in one index day within the same semester. The frequency of polypharmacy (at least five or at least 10 concurrent drugs) and of each DDI was calculated.Results: In line with different rates of polypharmacy (80% vs 16%), the risk of exposure to at least one interaction was 53.7% in nursing homes and 26.4% in outpatients. Among DDIs, in nursing homes antidepressants—anxiolytics (11.9%) ranked first, followed by antidepressants—aspirin (7.4%). In outpatients, ACE-inhibitors—non-steroidal anti-inflammatory drugs (NSAIDs) reached 7.2% followed by the calcium channel blockers—α-blockers (2.4%).Discussion: Polypharmacy and risk of DDIs appeared very different in the two settings, due to both technical and clinical reasons. In order to reduce use of benzodiazepines, NSAIDs, antidepressants and relevant DDIs, 1) defining alternative options for pain relief in elderly outpatients, and 2) implementing non-pharmacological management of insomnia and anxiety in nursing homes should be prioritized.

Background Few data are currently available about SB5 in inflammatory bowel diseases (IBD). The aim of this study was to assess the effectiveness and safety of SB5 in a cohort of patients with IBD in stable remission switched from the adalimumab (ADA) originator and in a cohort of patients with IBD naïve to ADA. Methods We prospectively enrolled patients with IBD who started ADA treatment with SB5 (naïve cohort) and those who underwent a nonmedical switch from the ADA originator to SB5 (switching cohort). Clinical remission and safety were assessed at baseline and at 3, 6, and 12 months. In addition, in a small cohort of patients who were switched, we assessed the ADA serum trough levels and antidrug antibodies at baseline, 3, and 6 months. Results In the naïve cohort, the overall remission rate at 12 months was 60.42%, whereas in the switching cohort it was 89.02%. Fifty-three (36.3%) patients experienced an adverse event, and injection site pain was the most common; it was significantly more frequent in the switching cohort (P = 0.001). No differences were found in terms of ADA serum trough levels at baseline, 3, and 6 months after switching. No patient developed antidrug antibodies after the switch. Conclusions We found that SB5 seemed effective and safe in IBD, both in the naïve cohort and in the switching cohort. Further studies are needed to confirm these data in terms of mucosal healing.

This chapter takes at its point of departure SDG 14 (life below water) and the specific target of conservation (SDG 14.5). It shows that interpreting SDG 14.5 within the context and purpose of Agenda 2030 means paying attention to three main sustainability criteria. The first relates to substantive socio-ecological inter-pillar relationality, that is to say an acknowledgement of ontological relationality between pillars, beyond an understanding of sustainability as trade off. The second relates to intra-pillar relationality, that is links between conservation and other environmental sectors and the third to procedural inclusion through participatory decision-making in line with the epistemic pluralisation of sustainability. These three criteria are used to assess the sustainability of current EU marine conservation law. One legislative instrument on marine conservation in EU law is chosen as example, namely the Council Directive 92/43/EEC of 21 May 1992 on the conservation of natural habitats and of wild fauna and flora. The Habitats Directive is the cornerstone of conservation law in the EU and it is among the instruments listed by the European Commission as ways to support the implementation of Agenda 2030 and target 14.5.

To date, four vaccines have been authorised for emergency use and under conditional approval by the European Medicines Agency to prevent COVID-19: Comirnaty, COVID-19 Vaccine Janssen, Spikevax (previously COVID-19 Vaccine Moderna) and Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Although the benefit–risk profile of these vaccines was proven to be largely favourable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, children/adolescents, immunocompromised people and persons with a history of allergy or previous SARS-CoV-2 infection, is still limited. In this narrative review, we critically overview pre- and post-marketing evidence on the potential benefits and risks of marketed COVID-19 vaccines in the above-mentioned special cohorts. In addition, we summarise the recommendations of the scientific societies and regulatory agencies about COVID-19 primary prevention in the same vaccinee categories. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01131-6.

Despite the significant amount of research effort devoted to understanding the structural behavior of grain-silos, each year a large number of silos still fails due to bad design, poor construction, with a frequency much larger than other civil structures. In particular, silos frequently fails during large earthquakes, as occurred during the 1999 Chi-Chi, Taiwan earthquake when almost all the silos located in Taichung Port, 70 km far from the epicenter, collapsed. The EQE report stated that “the seismic design of practice that is used for the design and construction of such facilities clearly requires a major revision”. The fact indicates that actual design procedures have limits and therefore significant advancements in the knowledge of the structural behavior of silo structures are still necessary. The present work presents an analytical formulation for the assessment of the natural periods of grain silos. The predictions of the novel formulation are compared with experimental findings and numerical simulations.

In order to prevent seismic damage on building heritage built before Seismic Standards, constructions require to be assess to verify the structural response in the case of multi-level intensity seismic actions. This problem especially concerns those buildings with a social function as schools, hospitals, etc., or with historical and architectural value as that designed by important builders of the past. This is the case of the bar-restaurant building of “Bellariva” Sport Centre, designed and built in Florence by the World-famous Italian engineer Pier Luigi Nervi in the Sixty years. Its structure is characterized by reinforced concrete frames and hosts the locker rooms of the swimming pool and a bar on the first floor, a restaurant on the second, where a long crack was observed. The presence of a large balcony with heavy perimeter planters near the cracked zone motivated the execution of on-site tests finalized to determine the steel bars connecting the restaurant floor to the balcony. A Ground Penetrating Radar survey was performed in order to determine the internal structure of the floor, dimensions and disposition of steel bars, and to gather information about the connections between perimeter beams and balcony at the level of the restaurant. The experimental campaign allowed to refine a computational Finite Element Model that was utilized for the performance analysis of the structure in the current state. The paper presents the main results of a preliminary seismic analysis carried out on the structure, on the basis of which some retrofit intervention are suggested.

Interferometric radars are widely used for static and dynamic monitoring of large structures such as bridges, culverts, wind turbine towers, chimneys, masonry towers, stay cables, buildings, and monuments. Most of these radars operate in Ku-band (17 GHz). Nevertheless, a higher operative frequency could allow the design of smaller, lighter, and faster equipment. In this paper, a fast MIMO-GBSAR (Multiple-Input Multiple-Output Ground-Based Synthetic Aperture Radar) operating in W-band (77 GHz) has been proposed. The radar can complete a scan in less than 8 s. Furthermore, as its overall dimension is smaller than 230 mm, it can be easily fixed to the head of a camera tripod, which makes its deployment in the field very easy, even by a single operator. The performance of this radar was tested in a controlled environment and in a realistic case study.

Direct lung administration of budesonide in combination with surfactant reduces the incidence of bronchopulmonary dysplasia. Although the therapy is currently undergoing clinical development, the lung distribution of budesonide throughout the premature neonatal lung has not yet been investigated. Here, we applied mass spectrometry imaging (MSI) to investigate the surfactant-assisted distal lung distribution of budesonide. Unlabeled budesonide was either delivered using saline as a vehicle (n = 5) or in combination with a standard dose of the porcine surfactant Poractant alfa (n = 5). These lambs were ventilated for one minute, and then the lungs were extracted for MSI analysis. Another group of lambs (n = 5) received the combination of budesonide and Poractant alfa, followed by two hours of mechanical ventilation. MSI enabled the label-free detection and visualization of both budesonide and the essential constituent of Poractant alfa, the porcine surfactant protein C (SP-C). 2D ion intensity images revealed a non-uniform distribution of budesonide with saline, which appeared clustered in clumps. In contrast, the combination therapy showed a more homogeneous distribution of budesonide throughout the sample, with more budesonide distributed towards the lung periphery. We found similar distribution patterns for the SP-C and budesonide in consecutive lung tissue sections, indicating that budesonide was transported across the lungs associated with the exogenous surfactant. After two hours of mechanical ventilation, the budesonide intensity signal in the 2D ion intensity maps dropped dramatically, suggesting a rapid lung clearance and highlighting the relevance of achieving a uniform surfactant-assisted lung distribution of budesonide early after delivery to maximize the anti-inflammatory and maturational effects throughout the lung.

CHIME, the Copernicus Hyperspectral Imaging Mission for the Environment, is one of the six High Priority Candidate Missions (HPCM) of the evolution in the Copernicus Space Component (CSC) foreseen in the mid-2020s that is proposed for further analysis. In this paper we summarize the results as retrieved by OHB (D) as part of the Phase A/B1. The contract was kicked off in 2018 and concluded in 2020 after finalisation of the Pre-development activities. The proposed instrument is a hyperspectral imager instrument with reflective telescope and grating-based spectrometer. The selected orbit is in the range of 625 ± 30 km, LTDN 10:45 – 11:15 am with a repeat cycle of 20 to 25 days for a single satellite and 10-12.5 days revisit for 2 satellites. The payload of each satellite records at a Spatial Sampling Distance (SSD) of 30m the full spectral range from 400 to 2500nm at a Spectral Sampling interval < 10nm with Low Keystone/Smile. On the front end a high performance TMA with wide-band coated optics collects the light from ground and feeds it to a highly linear almost distortion free spectrometer assembly attaining very good spectral stability. All units are integrated in an optical bench structure that offers excellent AIT access and provides a highly stable LOS. The electro-optical backend contains low-noise cold MCT detectors creating margin in the predicted NEDL performance. The instrument can be calibrated via on-board devices or using reference targets outside the spacecraft. We present the functional decomposition and the physical instrument architecture: the optical design and opto-mechanical layout, the electro-optical imaging chain ant thermal control system.

Background: During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe. Methods: This analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS 1–3), mildly frail (CFS 4–5), or frail (CFS 6–9). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities). Findings: Between March 30 and July 15, 2020, 2434 patients (median age 68 years [IQR 55–77]; 1480 [61%] men, 954 [30%] women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS 6–9 vs CFS 1–3 odds ratio [OR] 2·71 [95% CI 2·04–3·60], p4–5 vs CFS 1–3 OR 1·54 [1·16–2·06], p=0·0030; age ≥65 years: CFS 6–9 vs CFS 1–3 OR 2·90 [2·12–3·97], p4–5 vs CFS 1–3 OR 1·64 [1·20–2·25], p=0·0020). In patients younger than 65 years, an increased hospital mortality risk was only observed in frail patients (CFS 6–9 vs CFS 1–3 OR 2·22 [1·08–4·57], p=0·030; CFS 4–5 vs CFS 1–3 OR 1·08 [0·48–2·39], p=0·86). Frail patients had a higher incidence of admission to intensive care than fit patients (CFS 6–9 vs CFS 1–3 OR 1·54 [1·21–1·97], p=0·0010), whereas mildly frail patients had a lower incidence than fit patients (CFS 4–5 vs CFS 1–3 OR 0·71 [0·55–0·92], p=0·0090). Among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care (CFS 6–9 vs CFS 1–3 OR 2·96 [1·98–4·43], p4–5 vs CFS 1–3 OR 0·93 [0·63–1·38], p=0·72). Among patients aged 65 years and older, frail patients had no significant difference in the incidence of admission to intensive care compared with fit patients (CFS 6–9 vs CFS 1–3 OR 1·27 [0·92–1·75], p=0·14), whereas mildly frail patients had a lower incidence than fit patients (CFS 4–5 vs CFS 1–3 OR 0·66 [0·47–0·93], p=0·018). Interpretation: The results of this study suggest that CFS score is a suitable risk marker for hospital mortality in adult patients with COVID-19. However, treatment decisions based on the CFS in patients younger than 65 years should be made with caution. Funding: LOEY Foundation.

Background and importance Hyperthermic intraperitoneal chemotherapy (HIPEC) associated with cytoreductive surgery (CRS) represents one of the treatments for peritoneal carcinoma of various primitivities. The treatment is effective in terms of disease free interval and survival. From January 2019 to June 2019, 33 HIPEC associated with CRS were performed under the supervision of a team of oncologists, surgeons and pharmacists. Aim and objectives The aim of the work was to describe the management of HIPEC and CRS in an Italian hospital and the response of patients to treatment. Material and methods At the time of surgery, 33 patients had an average peritoneal cancer index of 14.9. Complete cytoreduction was achieved in 29 patients. The drugs used during HIPEC were for: carcinosis with colic primitivity (42.5%): oxaliplatin, fluorouracil, leucovorin in one case; cisplatin, mitomycin in eight cases; mitomycin in three cases; carcinosis with gastric primitivity (21.2%): in six cases cisplatin, mitomycin; in one case cisplatin, paclitaxel; carcinosis with ovarian primitivity (21.2%): in five cases cisplatin, paclitaxel; in two cases cisplatin, doxorubicin; LAMN (9.0%), cisplatin and mitomycin; cholangiocarcinoma (3%), cisplatin, mitomycin; mesothelioma (3%), cisplatin, doxorubicin. The average age of the patients was 55.8 years and 63.6% were women. Results Mean ICU stay was 6.7 days, while the mean total hospital stay was 21.8 days. Inhospital mortality was 12%. The complication rate during hospitalisation (CTCAE ≥2) was 33.3%. Four patients (12%) underwent reoperation. Of the 29 patients discharged from hospital, 8 patients (27.6%) relapsed and, among them, 2 patients (6.9%) died. The mean OS calculated from the Kaplan–Meier curves of the discharged patients was 9.4 months and the mean DFS was 7.4 months. To date, the patients analysed have a survival rate of 81.8% (27 of the 33 patients are alive to date) and a DFS of 71.4% (20 of the 28 patients are currently free from illness). Conclusion and relevance Considering the positive results obtained so far, the study of HIPEC with CRS in peritoneal carcinoma continues, to evaluate its effectiveness. The role of the pharmacist was important in participating in the multidisciplinary team in terms of eligibility of patients for treatment, to prepare oncological therapies and in processing the evaluation data. References and/or acknowledgements Conflict of interest No conflict of interest

One of the key aspects in the process of caring for people with diabetes is Therapeutic Education (TE). TE is a teaching process for training patients so that they can self-manage their care plan. Alongside traditional methods of providing educational content, there are now alternative forms of delivery thanks to the implementation of advanced Information Technologies systems such as conversational agents (CAs). In this context, we present the AIDA project: an ensemble of two different CAs intended to provide a TE tool for people with diabetes. The Artificial Intelligence Diabetes Assistant (AIDA) consists of a text-based chatbot and a speech-based dialog system. Their content has been created and validated by a scientific board. AIDA Chatbot—the text-based agent—provides a broad spectrum of information about diabetes, while AIDA Cookbot—the voice-based agent—presents recipes compliant with a diabetic patient’s diet. We provide a thorough description of the development process for both agents, the technology employed and their usage by the general public. AIDA Chatbot and AIDA Cookbot are freely available and they represent the first example of conversational agents in Italian to support diabetes patients, clinicians and caregivers. Supplementary Information The online version contains supplementary material available at 10.1007/s44163-021-00005-1.

The National Program of I + D + I 2008–2011 and Instituto de Salud Carlos III (ISCIII), the ISCIII Retic REDinREN (RD06/0016/1013, RD12/0021/0023 and RD16/ 0009/0017), the ISCIII (ICI14/00107, PI17/00384 and PI20/00633), Fondo Europeo de Desarrollo Regional (FEDER), Plan Estatal de I + D + I 2013–2016, Plan de Ciencia, Tecnología e Innovación 2013–2017 y 2018–2022 del Principado de Asturias (GRUPIN14-028, IDI-2018-000152) (...), Sanchez-Alvarez, E; Rodriguez-Garcia, M; Locatelli, F; Zoccali, C; Martin-Malo, A; Floege, J; Ketteler, M; London, G; Gorriz, JL; Rutkowski, B; Ferreira, A; Pavlovic, D; Cannata-Andia, JB; Fernandez-Martin, JL

Now let's take a detour and talk about AI, or artificial intelligence, in general and not limited to its application in building a virtual assistant. In fact, to understand most of the components of figure 1 used in today's virtual assistants, it is important to acquire a basic understanding of what AI is and its evolution toward the most recent technology known as deep learning.

Crescent Shaped Braces, CSBs, are steel hysteretic devices which, thanks to their geometrical configuration, are characterized by an enhanced seismic behavior that makes them a promising alternative to conventional diagonal steel braces and other seismic devices such as Buckling Resisting Braces and Scorpions. The present work reports the results of the first experimental campaign devoted to assess the cyclic experimental behavior of CSBs. The main goals of the experimental campaign are: (i) to verify/compare the effectiveness of design formulas for the seismic design of CSB introduced by the authors in a previous research work and the predictions of a simplified non-linear model in terms of force-displacement envelop response; (ii) to assess the experimental non-linear cyclic behavior in terms of ductility capacity, energy dissipation capacity, failures.

Background Non-invasive delivery of nebulized surfactant has been a neonatology long-pursued goal. Nevertheless, the clinical efficacy of nebulized surfactant remains inconclusive, in part, due to the great technical challenges of depositing nebulized drugs in the lungs of preterm infants. The aim of this study was to investigate the feasibility of delivering nebulized surfactant (poractant alfa) in vitro and in vivo with an adapted, neonate-tailored aerosol delivery strategy. Methods Particle size distribution of undiluted poractant alfa aerosols generated by a customized eFlow-Neos nebulizer system was determined by laser diffraction. The theoretical nebulized surfactant lung dose was estimated in vitro in a clinical setting replica including a neonatal continuous positive airway pressure (CPAP) circuit, a cast of the upper airways of a preterm neonate, and a breath simulator programmed with the tidal breathing pattern of an infant with mild respiratory distress syndrome (RDS). A dose-response study with nebulized surfactant covering the 100–600 mg/kg nominal dose-range was conducted in RDS-modelling, lung-lavaged spontaneously-breathing rabbits managed with nasal CPAP. The effects of nebulized poractant alfa on arterial gas exchange and lung mechanics were assessed. Exogenous alveolar disaturated-phosphatidylcholine (DSPC) in the lungs was measured as a proxy of surfactant deposition efficacy. Results Laser diffraction studies demonstrated suitable aerosol characteristics for inhalation (mass median diameter, MMD = 3 μm). The mean surfactant lung dose determined in vitro was 13.7% ± 4.0 of the 200 mg/kg nominal dose. Nebulized surfactant delivered to spontaneously-breathing rabbits during nasal CPAP significantly improved arterial oxygenation compared to animals receiving CPAP only. Particularly, the groups of animals treated with 200 mg/kg and 400 mg/kg of nebulized poractant alfa achieved an equivalent pulmonary response in terms of oxygenation and lung mechanics as the group of animals treated with instilled surfactant (200 mg/kg). Conclusions The customized eFlow-Neos vibrating-membrane nebulizer system efficiently generated respirable aerosols of undiluted poractant alfa. Nebulized surfactant delivered at doses of 200 mg/kg and 400 mg/kg elicited a pulmonary response equivalent to that observed after treatment with an intratracheal surfactant bolus of 200 mg/kg. This bench-characterized nebulized surfactant delivery strategy is now under evaluation in Phase II clinical trial (EUDRACT No.:2016–004547-36). Electronic supplementary material The online version of this article (10.1186/s12931-019-1096-9) contains supplementary material, which is available to authorized users.

There is the urgent need to study the effects of immunomodulating agents as therapy for Covid-19. An observational, cohort, prospective study with 30 days of observation was carried out to assess clinical outcomes in 88 patients hospitalized for Covid-19 pneumonia and treated with canakinumab (300 mg sc). Median time from diagnosis of Covid-19 by viral swab to administration of canakinumab was 7.5 days (range 0–30, IQR 4–11). Median PaO2/FiO2 increased from 160 (range 53–409, IQR 122–210) at baseline to 237 (range 72–533, IQR 158–331) at day 7 after treatment with canakinumab (p 9/L, respectively, p p

In this paper we propose a lossless and lossy onboard compression algorithm for multispectral and hyperspectral images, based on the recent CCSDS-123.0-B-2 standard, which takes advantage of cloud screening in order to perform data volume reduction, by avoiding to transmit pixels that are covered by clouds. In particular, we develop methods addressing two problems: i) how to signal the cloud mask in the compressed file, and ii) how to handle cloudy pixels in order to maximize the amount of compression. Experimental results on a set of LANDSAT 8 ETM+ and AVIRIS images show a significant data volume reduction with respect to the plain use of the CCSDS-123.0-B-2 standard.

Poractant alfa and Calsurf are two natural surfactants widely used in China for the treatment of neonatal respiratory distress syndrome, which are extracted from porcine and calf lungs, respectively. The purpose of this experimental study was to compare their in vitro characteristics and in vivo effects in the improvement of pulmonary function and protection of lung injury. The biophysical properties, ultrastructure, and lipid composition of both surfactant preparations were respectively analysed in vitro by means of Langmuir-Blodgett trough (LBT), atomic force microscopy (AFM), and liquid-chromatography mass-spectrometry (LC-MS). Then, as core pharmacological activity, both head-to-head (100 and 200 mg/kg for both surfactants) and licensed dose comparisons (70 mg/kg Calsurf vs. 200 mg/kg Poractant alfa) between the two surfactants were conducted as prophylaxis in preterm rabbits with primary surfactant deficiency, assessing survival time and rate and dynamic compliance of the respiratory system (Cdyn). Intrapulmonary surfactant pools, morphometric volume density as alveolar expansion (Vv), and lung injury scores were determined post mortem. AFM and LC-MS analysis revealed qualitative differences in the ultrastructure as well as in the lipid composition of both preparations. Calsurf showed a longer plateau region of the LBT isotherm and lower film compressibility. In vivo, both surfactant preparations improved Cdyn at any dose, although maximum benefits in terms of Vv and intrapulmonary surfactant pools were seen with the 200 mg/kg dose in both surfactants. The group of animals treated with 200 mg/kg of Poractant alfa showed a prolonged survival time and rate compared to untreated but ventilated controls, and significantly ameliorated lung injury compared to Calsurf at any dose, including 200 mg/kg. The overall outcomes suggest the pulmonary effects to be dose dependent for both preparations. The group of animals treated with 200 mg/kg of Poractant alfa showed a significant reduction of mortality. Compared to Calsurf, Poractant alfa exerted better effects if licensed doses were compared, which requires further investigation.

Background and importance Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal form of fibrosing interstitial pneumonia with a poor prognosis, characterised by a decline in lung function, reduction in forced vital capacity (FVC), and worsening of dyspnoea and quality of life. Pirfenidone and nintedanib are the only two drugs with antifibrotic effects approved for the treatment of IPF. They both block the receptors of profibrotic growth factors, such as vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF). Because of their critical safety profile, many patients are forced to have dose reductions or treatment interruption to manage side effects such as gastrointestinal disorders (diarrhoea, nausea and vomiting), bleeding (epistaxis and contusions), liver enzyme elevation, rash and photosensitivity. Aim and objectives The aim of this study was to evaluate the safety profile of pirfenidone and nintedanib in the real life setting of the Emilia-Romagna region (RER), Italy. Material and methods We examined all spontaneous adverse drug reaction (ADR) reports for pirfenidone and nintedanib entered into the National Pharmacovigilance Network by RER healthcare professionals and patients from January 2016 to December 2018 and combined these records with consumption data. We compared the ADR/DDDs ratio of the two drugs and characterised the type and rate of ADRs. Results From January 2016 to December 2018, we found 22 ADR reports for pirfenidone and 19 for nintedanib, with an ADR/DDDs ratio of 1.44 and 8.61, respectively. The most frequent ADRs reported were photosensitivity reactions (50%) for pirfenidone and gastrointestinal disorders (53%) for nintedanib; the rate of hepatotoxicity was similar between the two drugs (18% and 16%, respectively). Three records (16%) about nintedanib concerned lack of efficacy. Conclusion and relevance Our results showed that nintedanib had a worse safety profile than pirfenidone, even though the reporting rate is higher in the first years of marketing and pirfenidone has been on the market for longer. The safety profile of the two drugs in a real life setting appeared similar to that found in clinical trials, in terms of both incidence and type of ADRs. References and/or acknowledgements No conflict of interest.

In recent years, interferometric radars have been extensively used as sensors for static and dynamic monitoring of bridges. Generally speaking, a radar can only detect the displacement component along its view direction. As the movement of a real bridge or a large structure can be rather complex, this limitation can be a significant drawback in engineering practice. In order toovercome this limitation, in this article, a multi-monostatic interferometric radar with radio link is proposed. This radar is able to detect a second component of displacement using a transponder. The transponder is connected to the radar through a radio link. The radio link allows the installation of the transponder far away from the radar, and even in the opposite direction. The equipment is based on a MIMO radar, two transceivers for the radio link, and a transponder. The transceivers and the transponder are essentially two antennas and an amplifier system. The equipment is experimentally tested in controlled scenarios and in the case study of Indiano Bridge, Florence, Italy.

In the framework of flow simulations in Discrete Fracture Networks, we consider the problem of identifying possible backbones, namely preferential channels in the network. Backbones can indeed be fruitfully used to analyze clogging or leakage, relevant for example in waste storage problems, or to reduce the computational cost of simulations. With a suitably trained Neural Network at hand, we use the Layer-wise Relevance Propagation as a feature selection method to detect the expected relevance of each fracture in a Discrete Fracture Network and thus identifying the backbone.

After the 2005 M7.6 Kashmir earthquake (Pakistan), field observations reported that several buildings manufactured with local traditional techniques resisted well to that strong seismic event. In this paper the attention is focused on a typical vernacular construction technique commonly named as “Bhatar”, still practiced in the Himalayan regions of India and Pakistan. It is grounded upon the "timber lacing" or "timber reinforcement masonry" concept, i.e. the combination of dry-stacked loose stones with timber beams to increase the wall confinement. Despite its good seismic performances, it has still not been deeply studied from a structural engineering point of view. This paper represents a first attempt to fill this gap. It presents a full analytical study on the structural behaviour of a simple one-storey building unit characterized by a 3.6 m x 3.6 m square plan covered by an heavy wooden roof with 20 cm thick earth coverage, in order to investigate its response under gravity and seismic inertial loadings. Materials properties, static analysis and seismic analysis are discussed. In detail, Shorea Robusta wood and limestone rocks are identified as the most used construction materials for the Bhatar buildings. The Barton's model is applied to characterise the shear strength of the rubble stone layers in the wall. Static analysis reveals that normal stresses at the ground level are around 92 kPa, which can be considered acceptable for common soils. With respect to earthquake, the Bhatar technique can absorb wall cracking and distortion mechanisms, and can dissipate energy through friction between stones. Under the assumption of no vertical ground motion, the acceleration which activates in-plane sliding mechanisms is found to be around 0.5 g, being dependent on the interface friction between adjacent layers. Some preliminary considerations about the out-of-plane seismic behaviour are also provided concerning overturning and bending failure mechanisms. The results are based on assumptions taken by several authors and have not been verified with experimental tests. Nevertheless, some practical suggestions can be derived to improve the seismic shear strength and to ensure friction also in the case of significant vertical component of earthquake ground motions.

Gabion-boxes, made with steel wire mesh and filled with stones of appropriated size, are normally stacked up one into another to form a retaining wall. Given their reduced costs and the easy availability of their constituting materials, gabion-box walls have been extensively used in developing countries (such as Nepal) also to realize simple one-storey residential buildings. In recent years, many of these structures have been subjected to several strong earthquakes and have shown a good seismic behaviour, even if they have never been the object of a proper structural design. In the scientific literature, research studies have been developed on gabion-box walls used as retaining systems, but no investigations have been conducted on the performances of gabion-box walls buildings. In this respect, the general objective of this research work is to give a first insight into the static and seismic behaviour of such gabion-box walls buildings through analytical considerations and numerical models. In detail, with reference to a typical 5 m x 5 m plan model, this paper investigates the in-plane and out-of-plane seismic responses of its constituting walls, by means of simple analytical interpretations and Discrete Element Method (DEM) numerical simulations. Even if this study should be considered as a starting point and even if the fundamental cellular behaviour of the 3-dimensional structure has not been fully taken into account, some criticalities have been disclosed and the order of magnitude of the seismic activation load multipliers has been estimated. The out-of-plane collapse mechanism is characterised by multiplier around 0.15, whilst the in-plane mechanism multiplier depends on the position of the door in the single wall (0.10 – 0.20), but can be easily increased with lintel beams placement. The results are based on the assumptions taken by several authors and have not been verified with experimental tests. Nevertheless, some practical suggestions (basically in terms of spacing and construction details, such as vertical connectors and reinforcing steel knots) can be derived to improve the construction in order to ensure a better seismic behaviour.

Big data and big data analytics’ (BDA) importance for business management is growing at an unmatched pace. Such datasets, and the techniques to analyse them, are indeed able to inundate organizations with huge quantities of precious information. Building on this premise, the purpose of this research is to develop a unitary holistic framework on the strategic impact of big data on large organizations. In order to do so, a cognitive map was developed from a coding analysis of 523 job offers on the European labour market coming from 124 large organizations. The results show the effects of big data and BDA on marketing strategies, strategic business intelligence and, finally, operation and supply chain management.

In this paper a no-contact high-frequency large-bandwidth ground penetrating radar (GPR) scanner specially designed for investigating floors is presented. It operates at 10 GHz central frequency with 4 GHz bandwidth. Its mechanical positioner is able to scan a surface 0.3 m wide and 1.9 m large. The aim of this radar is to gather information about the shallow layers (coat, screed, embedded heating or water pipes) up to 0.5 m depth. The radar has been tested in laboratory and in a real case study: the second floor of the Bellariva sport Centre in Florence (Italy). This floor is under investigation because an evident long crack.

The “Ponte delle Grazie” is a three spans bridge, with a total length of 72 meters, built between 1948 and 1952 in Faenza, Italy. The reinforced concrete main beams of the deck have undergone a strong deterioration over the years. In detail atmospheric agents and chemical aggressions caused a strong deterioration of the concrete, up to the point of making the structure not accessible and at risk of collapse. In fact, the five main beams were heavily damaged, as well as the concrete bearings were strongly compromised. So, an urgent intervention was necessary to save the structure of this historic bridge. A delicate restoration has allowed to remove the deteriorated concrete and to restore the resistant sections with new materials compatible with the old remaining structures. In particular, a specific rehabilitation procedure was studied using fiber-reinforced cement mortar with low elastic modulus, that is shrinkage compensated, in combination with composite materials reinforcements. Without modifying the structural behavior of the bridge, the deteriorated concrete was restored and reinforced, in a sustainable way, in order to make the structure safe and usable again. After the restoration and reinforcement the bridge capacity satisfy a reduced live load useful for urban traffic. After the restoration and reinforcement the bridge capacity satisfy a reduced live load useful for urban traffic. Even if the structure has returned to be suitable for vehicular traffic, it has been necessary to set up a real-time monitoring system, which monitors the live load and the behavior of the bridge. In detail it is used a system of geophones, that are able to detect the displacement of structures by integrating in time their response. They can provide continuous health monitoring of the bridge by transmitting the data to a remote server.

The aim of this paper is to describe the usefulness of multiparametric US in the diagnosis and subsequent follow-up of a case of right-side ischemic colitis and to present a review of the data reported in the literature. Ischemic colitis is frequently diagnosed in the field of gastroenterology. Diagnosis is usually based on the outcome of endoscopy and histological examination, and in case of right-side ischemic colitis also on the results of contrast-enhanced CT. In the described case, multiparametric US indicated the diagnosis including a prognostic judgment, and during follow-up US-monitored patency of the stents positioned under angiographic guidance. One of the available US techniques, CEUS, seems to have a special role in the detection of residual vascularization of the gastrointestinal tract affected by ischemia. However, before introducing this method into daily clinical practice, further studies are required to confirm its diagnostic accuracy.

Background Acute lower limb ischemia (ALLI) poses a major threat to limb survival. For many years, surgical thromboembolectomy was the mainstay of treatment. Recent years have brought an endovascular revolution to the management of ALLI. It seems that the newly designed endovascular thrombectomy devices may shift treatment recommendations toward endovascular options. This protocol study aims to collect evidence supporting the latest hypothesis. Objective The devices under investigation are the Penumbra/Indigo Systems (Penumbra Inc). The objective of this clinical investigation is to evaluate, in a controlled setting, the early safety and effectiveness of the devices and to define the optimal technique for the use of these systems in patients with confirmed peripheral acute occlusions. Methods This study will be an interventional prospective trial of patients with a diagnosis of ALLI treated with Penumbra/Indigo devices. This project is intended to be a national platform where every physician invited to participate could register his or her own data procedure. The primary outcome is the technical success of thromboaspiration with the Indigo System. Assessment of vessel patency will be recorded using the Thrombolysis in Myocardial Infarction (TIMI) score classifications before and after use of the device. Clinical success at follow-up is defined as an improvement of Rutherford classification at 1-month follow-up of one class or more as compared to the preprocedure Rutherford classification. Secondary endpoints include the following: (1) safety rate at discharge, defined as the absence of any serious adverse events; (2) primary patency at 1 month, defined as a target lesion without a hemodynamically significant stenosis or reocclusion on duplex ultrasound (>50%) and without target lesion reintervention within 1 month; and (3) limb salvage at 1 month. Results The study is currently in the recruitment phase and the final patient is expected to be treated by the end of March 2019. A total of 150 patients will be recruited. Analyses will focus on primary and secondary endpoints. Conclusions These new endovascular thrombectomy devices that are specifically designed for peripheral intervention in this difficult set of patients, as those under investigation in the proposed registry, may offer improved clinical outcomes with lower rates of major systemic and local complications. Following completion of this study, it is expected that the value of the Indigo Thrombectomy System in the treatment of ALLI will be better defined. As a result, a shift of treatment recommendations toward endovascular options may be observed in the near future. International Registered Report Identifier (IRRID) DERR1-10.2196/9972

In 2010, after an ordinary snowfall, the long-span steel trusses roof covering a school building located in a small town in North Italy collapsed. The building construction was completed in 2008, while the school was opened to the public just few months before the collapse. Luckily, at the time of the collapse, the building was empty and no people died or were injured. After the collapse, the Court nominated a first Official Technical Consultant in order to investigate on the causes of failure and related responsibilities. Later on, after that the main responsibilities were identified, a second Official Technical Consultant was nominated to further investigate on few specific technical aspects related to the collapse which were not completely clarified during the first investigations. In the present work, the main attention is paid on the structural behavior of the peculiar joint elements used to connect the members and their influence on the collapse, with emphasis on the role played by geometrical imperfections and structural ductility. The lesson learned from the case study could help professional engineers in being aware on the main peculiarities and structural deficiencies of structural systems made by spatial trusses with brittle connections.

Many marine protected areas (MPAs) around the world are ‘paper parks’. A key factor contributing to their ineffectiveness is non-compliance with the rules in place. This paper contributes to the existing academic discussion on ‘paper parks’ by drawing on critical regulation scholarship to develop a theoretical framework to assess and address compliance gaps in MPAs. The theoretical insights are then explored using a case study of the second largest Italian MPA (the ‘Penisola del Sinis-Isola di Mal di Ventre’), employing a multidisciplinary perspective built on both biological and socio-legal expertise. The biological study consists of a review including existing unpublished data on biological resources in the MPA coupled with new analyses on the effects of sea urchin harvesting restrictions. The socio-legal research consists of the analysis of primary qualitative research in the form of semi-structured interviews conducted with key stakeholders at the local and regional level in 2014, followed by two workshops (one with stakeholders and one with the general public) in 2015 to discuss the research findings collectively. The results show that the Sinis MPA is not achieving its conservation goals, primarily because of actors' non-compliance with the rules. The interviews with key stakeholders reveal a number of interlinked social, normative and calculative motivations at the basis of non-compliance. Policy solutions are then offered. This study offers a novel analysis on ‘paper parks’ that may be applicable to other MPAs experiencing similar compliance issues. Copyright © 2016 John Wiley & Sons, Ltd.

Recent research studies have shown that since the last trimester of pregnancy human fetuses are able to listen to and possibly memorize auditory stimuli from the external world, both as music and language are concerned. In particular, they exhibit a specific sensitivity to prosodic features such as melody, intensity, and rhythm that are essential for an infant to learn and develop the native language. This paper presents first results concerning the automated mother language identification of a set of about 7500 cry units coming from French, Arabic and Italian mother-tongue healthy full term newborns. Acoustical parameters and 12 different melodic shapes are computed with the BioVoice software tool and their classification is performed with Random Forest and 4 neuro-fuzzy classifiers. Results show up to 95% differences among the three languages.

Background Adalimumab (ADM) biosimilars have been demonstrated as safe and effective as the ‘originator’ in trials for other autoimmune disorders, but real-life evidence in inflammatory bowel diseases (IBD) is lacking. The aim of the study was to demonstrate maintenance of clinical remission (CR) after switch from ADM ‘originator’ to biosimilar SB5. Methods Data were retrospectively collected from November 2018 to September 2019. All IBD patients in CR after at least 6 months of ‘originator’ and switched to SB5 were included. The primary outcomes were maintenance of CR at 6 months after switch (defined as Partial Mayo Score 0–1 for ulcerative colitis and Harvey–Bradshaw Index ≤4 for Crohn’s disease) and overall comparable safety. A historical cohort of patients treated only with the ‘originator’ was included for comparison, using a Cox regression model with a time-varying covariate. Results In total, 96 patients were included. Baseline characteristics of the cohort are reported in Table 1. Maintenance of CR after 6 months of switch was reported in 89/96 (92.7%) patients. Levels of C-reactive protein (CRP) significantly increased over time from baseline to 6 months (from 2.67 ± 2.61 to 4.98 ± 5.81 mg/dl, p = 0.03), but no difference between the two time points was found when considering a relevant flare only for CRP above the lab cut-off (5 mg/dl). A comparison of CR persistence over time between ‘originator’ cohort and SB5 ‘switching’ cohort did not show any statistical difference (Hazard Ratio 1.07, 95% CI 0.57 – 2.01). With regard to adverse events, SB5 showed an overall safety profile, with only 2/96 (2.1%) patients interrupting the treatment due to anti-TNF-induced psoriasis. In 42/96 (43.8%) of patients, at least one injection site reaction was reported; only in one case a re-switch to ‘originator’ was needed for local intolerance. Conclusion SB5 is safe and effective in maintaining CR after switching from the ‘originator’. Injection site reaction is a frequent but usually manageable side effect. Larger multi-centre cohort and endoscopic assessment are needed to confirm the initial findings.

Background: The gastrointestinal system hosts roughly 1,800 distinct phyla and about 40,000 bacterial classes, which are known as microbiota, and which are able to influence the brain. For instance, microbiota can also influence the immune response through the activation of the immune system or through the release of mediators that are able to cross the brain blood barrier or that can interact with other substances that have free access to the brain, such as tryptophan and kynurenic acid, which is a metabolite of tryptophan and which has been involved in the pathogenesis of schizophrenia. Objectives: This paper reviews the possible relationships between microbiome, schizophrenia and treatment resistance. Given the possibility of a role of immune activation and alterations, we also describe the relationship between schizophrenia and immune inflammatory response. Finally, we report on the studies about the use of probiotic and prebiotics in schizophrenia. Methods: Cochrane library and PubMed were searched from the year 2000 to 2018 for publications about microbiome, immune-mediated pathology, schizophrenia and neurodevelopmental disorders. The following search string was used: (microbiome or immune mediated) AND (schizophrenia OR neurodevelopmental disorder). Associated publications were hand-searched from the list of references of the identified papers. A narrative review was also conducted about the use of probiotics and prebiotics in schizophrenia. Results: There exists a close relationship between the central nervous system and the gastrointestinal tract, which makes it likely that there is a relationship between schizophrenia, including its resistant forms, and microbiota. This paper provides a summary of the most important studies that we identified on the topic. Conclusions: Schizophrenia in particular, remain a challenge for researchers and practitioners and the possibility of a role of the microbiome and of immune-mediated pathology should be better explored, not only in animal models but also in clinical trials of agents that are able to alter gut microbiota and possibly influence the mechanisms of gastrointestinal inflammation. Microbiome targeted treatments have not been well-studied yet in patients with mental illness in general, and with schizophrenia in particular. Nonetheless, the field is well worth of being appropriately investigated.

A small TEM horn antenna for ground penetrating radar (GPR) applications is proposed in this paper. TEM horn antennas are appropriate for GPR applications due to their wide bandwidth, high gain, and good efficiency. The operative band of a GPR antenna is a trade-off between the penetration depth and desirable resolution. At low frequency, radar has more penetration depth but the possible problem is the big size of antenna. So the aim of this study is to design a small size horn antenna with low cut-off frequency. The band is extended to the lower frequency with three major changes with respect to a standard horn: 1) using the TEM double-ridged waveguide with a cylindrically shaped cavity as transition section; 2) putting absorbing material in the back plate of the antenna; 3) using a semi-circle of radius 5 mm set on the top of the flare end section. The proposed antenna has a small size of $(311 \ \mathbf{mm} \times 265 \ \mathbf{mm} \times 385 \ \mathbf{mm})$ , and the simulated results demonstrated good impedance matching from 100 MHz to 2.5 GHz under a return lass $(\mathbf{S}_{11} \leq-10\ \mathbf{dB})$ , and good radiation pattern. The designed TEM horn antenna is modeled in free space and in contact with the ground. The capability of the antenna for detecting buried objects is confirmed with simulation.

In this paper a no-contact ground penetrating radar for investigating painted walls is presented. It operates at 10 GHz central frequency with 4 GHz bandwidth. Its mechanical positioner is able to scan a surface 1.4 m wide and 1.9 m high. This equipment has been specifically designed for investigating the painted walls of the Tutankhamon tomb in the Kings' valley in Egypt. The aim of this radar survey is to gather information about the shallow layers (the plaster and the existence of possible plaster voids affecting the future stability of paintings) up to 0.5 m depth.

PROBA3 is the first high precision formation flying (FF) mission under responsibility of the European Space Agency (ESA). It is a technology mission devoted to in-orbit demonstration of the FF techniques, with two satellites kept at an average inter-satellite distance of 144m. The guiding scientific rationale is to realize a diluted coronagraph with the telescope (ASPIICS) on one satellite and the external occulter on the other satellite to observe the inner Solar corona at high spatial and temporal resolution, down to 1.08R⊙. The two spacecraft will be orbiting in a high eccentricity geocentric trajectory with perigee at 600km and the apogee at 60000Km and with an orbital period of 19hrs. The FF acquisition and operations will last about 6 hrs around the apogee and different metrology systems will be used for realizing and controlling the FF. The alignment active most critical sub-system is the Shadow Positioning Sensors (SPS), a series of Si-PM (Silicon Photomultiplier) disposed around the ASPIICS telescope's entrance aperture and measuring the proper positioning of the penumbra generated by the occulter at the center of the coronagraph’s optical reference frame. The FF alignment measurement accuracies required to the SPS are: 500μm for lateral movements and 50mm for longitudinal movements. This paper gives an overview of the opto-mechanical and electronic design and of the software algorithm for the FF intersatellite positioning. The expected performance of the SPS metrology system are reported.