We study the impact of fake news on votes for populist parties in the Italian elections of 2018. Our empirical strategy exploits the historical variation in Italian-speaking and German-speaking voters in the Italian region of Trentino Alto-Adige/Südtirol as an exogenous source of assignment to fake news exposure. Using municipal data, we compare the effect of exposure to fake news on the vote for populist parties in the 2013 and 2018 elections. To do so, we introduce a novel indicator of populism using text mining on the Facebook posts of Italian parties before the elections. Our findings support the view that exposure to fake news favours populist parties regardless of prior support for populist parties, but also that fake news alone cannot explain most of the growth in populism.
Lung tumor-infiltrating neutrophils are known to support growth and dissemination of cancer cells and to suppress T cell responses. However, the precise impact of tissue neutrophils on programming and differentiation of anticancer CD8 T cells in vivo remains poorly understood. Here, we identified cancer cell-autonomous secretion of CXCL5 as sufficient to drive infiltration of mature, protumorigenic neutrophils in a mouse model of non-small cell lung cancer (NSCLC). Consistently, CXCL5 transcripts correlate with neutrophil density and poor prognosis in a large human lung adenocarcinoma compendium. CXCL5 genetic deletion, unlike antibody-mediated depletion, completely and selectively prevented neutrophils accumulation in lung tissues. Depletion of tumor-infiltrating neutrophils promoted expansion of tumor-specific CD8 T cells, differentiation into effector cells and acquisition of cytolytic functions. Transfer of effector CD8 T cells into neutrophil-rich tumors, inhibited IFN-ϒ production, indicating active suppression of effector functions. Importantly, blocking neutrophils infiltration in the lung, overcame resistance to checkpoint blockade. Hence, this study demonstrates that neutrophils curb acquisition of cytolytic functions in lung tumor tissues and suggests targeting of CXCL5 as a strategy to restore anti-tumoral T cell functions.
Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2–12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063–7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.
The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a “should be considered” recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.
Background Monoclonal antibodies acting on the calcitonin gene-related peptide (CGRP) or its receptor have changed migraine preventive treatment. Those treatments have led to reconsidering the outcomes of migraine prevention. Available data mostly considered benefits in terms of relative efficacy (percent or absolute decrease in monthly migraine days [MMDs] or headache days compared with baseline). However, not enough attention has been paid to residual MMDs and/or migraine-related disability in treated patients. In the present study, we aimed at comparing the relative and absolute efficacy of erenumab. Methods ESTEEMen was a collaborative project among 16 European headache centers which already performed real-life data collections on patients treated with erenumab for at least 12 weeks. For the present study, we performed a subgroup analysis on patients with complete data on MMDs at baseline and at weeks 9-12 of treatment. Starting from efficacy thresholds proposed by previous literature, we classified patients into 0-29%, 30-49%, 50-74%, and ≥75% responders according to MMD decrease from baseline to weeks 9-12 of treatment. For each response category, we reported the median MMDs and Headache Impact test-6 (HIT-6) scores at baseline and at weeks 9-12. We categorized the number of residual MMDs at weeks 9-12 as follows: 0-3, 4-7, 8-14, ≥15. We classified HIT-6 score into four categories: ≤49, 50-55, 56-59, and ≥60. To keep in line with the original scope of the ESTEEMen study, calculations were performed in men and women. Results Out of 1215 patients, at weeks 9-12, 381 (31.4%) had a 0-29% response, 186 (15.3%) a 30-49% response, 396 (32.6%) a 50-74% response, and 252 (20.7%) a ≥75% response; 246 patients (20.2%) had 0-3 residual MMDs, 443 (36.5%) had 4-7 MMDs, 299 (24.6%) had 8-14 MMDs, and 227 (18.7%) had ≥15 MMDs. Among patients with 50-74% response, 246 (62.1%) had 4-7 and 94 (23.7%) 8-14 residual MMDs, while among patients with ≥75% response 187 (74.2%) had 0-3 and 65 (25.8%) had 4-7 residual MMDs. Conclusions The present study shows that even patients with good relative response to erenumab may have a clinically non-negligible residual migraine burden. Relative measures of efficacy cannot be enough to thoroughly consider the efficacy of migraine prevention.
Background: Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔPes) and nasal (ΔPnos) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. Methods: From January 1, 2021, to September 1, 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of non-invasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 h after starting NRS. Correlation between ΔPes and ΔPnos served as primary outcome. The effect of ΔPnos measurements on respiratory rate and ΔPes was also assessed. Results: ΔPes and ΔPnos were strongly correlated at admission (R2 = 0.88, p < 0.001) and 24 h apart (R2 = 0.94, p < 0.001). The nasal plug insertion and the mouth closure required for ΔPnos measurement did not result in significant change of respiratory rate and ΔPes. The correlation between measures at 24 h remained significant even after splitting the study population according to the type of NRS (high-flow nasal cannulas [R2 = 0.79, p < 0.001] or non-invasive ventilation [R2 = 0.95, p < 0.001]). Conclusions: In a cohort of patients with ARF, nasal pressure swings did not alter respiratory mechanics in the short term and were highly correlated with esophageal pressure swings during spontaneous tidal breathing. ΔPnos might warrant further investigation as a measure of inspiratory effort in patients with ARF. Trial registration: NCT03826797 . Registered October 2016.
Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, $$\delta$$ δ -aminolaevulinic acid and porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations.
The ratio between arterial blood partial pressure of oxygen and fraction of inspired oxygen (PaO 2 /FiO 2 ) was largely used for grading and managing the respiratory failure in non-mechanically ventilated COVID-19. In these patients, the assessment of the true FiO 2 in the inspired mixture may be difficult with consequent inaccuracies in PaO 2 /FiO 2 assessment. In 30 severe COVID-19 patients, we observed that PaO 2 /FiO 2 values measured immediately before and after the transition from high-flow nasal cannula (HFNC) to one commercially available Venturi mask O 2 therapy were similar (bias mean value 0, standard deviation 23 mmHg). In COVID-19 patients recovering from respiratory failure, PaO 2 /FiO 2 is not different whether measured with a commercially available Venturi mask or HFNC.
The European Commission defined the new concept of Industry 5.0 meaning a more human-centric, resilient, and sustainable approach for the design of industrial systems and operations. A deep understanding of the work environment and organization is important to start analysing the working conditions and the resulting User eXperience (UX) of the operators. Also, the knowledge about users’ needs and ergonomics is fundamental to optimize the workers’ wellbeing, working conditions, and industrial results. In this context, the paper presents a strategy to effectively assess the UX of workers to promote human-centric vision of manufacturing sites, enhancing the overall sustainability of the modern factories. A set of non-invasive wearable devices is used to monitor human activities and collect physiological parameters, as well as questionnaires to gather subjective self-assessment. This set-up was applied to virtual reality (VR) simulation, replicating heavy duty work sequence tasks that took place in an oil and gas pipes manufacturing site. This approach allowed the identification of possible stressful conditions for the operator, from physical and mental perspectives, which may compromise the performance. This research was funded by the European Community's HORIZON 2020 programme under grant agreement No. 958303 (PENELOPE).
Background The agricultural and construction sectors demand enormous amounts of natural resources and generate environmental impacts that negatively affect ecosystems. One of the main problems is the generation and inadequate management of waste. For this reason, under the approaches of the new sustainable and circular models, waste valorization has been prioritised as a strategy for advancing towards the sustainability of production systems. This research aims to carry out a general analysis of Agricultural Waste Biomass (AWB) in the production of bio-based products for the construction sector. Bibliometric techniques were applied for the general analysis of the scientific production obtained from Scopus. A systematic review identified the main research approaches. In addition, European projects were reviewed to assess the practical application. This study is novel and provides relevant contributions to new trends in the valorisation of AWB in the building sector and the sustainability benefits. For policymakers, it is a source of information on the contribution of new policies to scientific advances and the aspects that need to be strengthened to improve sustainable and circular practices in both sectors. Results The results show that 74% of the research has been published within the last 5 years. Regarding the main types of AWBs, rice husk ash and sugar cane bagasse ash are the most commonly used in manufacturing a wide variety of bio-based building products. Cement, concrete and bricks are the main bio-based products obtained from AWB. However, a new approach to utilisation was identified in road construction. Conclusions The findings indicate that the AWB is an important resource with great potential for the construction sector. Similarly, that policies on sustainable and circular development have driven scientific progress on new alternatives for the valorisation of AWB to improve sustainability in the construction sector. Although the practical application has also been driven through European projects, development at this level is still low. Therefore, it is necessary to strengthen partnerships between these two sectors and improve government strategies on sustainability and circularity to overcome existing constraints.
Self-organized TiO2 nanotube (TNT) layers formed by an anodization process have emerged for the conception of innovative systems in the conversion and storage of energy. Herein, the latest progress in power sources with a remarkable electrochemical performance involving these versatile nanomaterials is reported. Besides the key role of their physico-chemical properties, the significance of interfaces established with other materials to achieve the fabrication of batteries, supercapacitors and fuel cells showing high electrochemical performance is also highlighted. Particularly, recent approaches based on the chemical modifications of the TNTs by doping, solid-state reactions, atomic layer deposition, electrodeposition of metallic nanoparticles and copolymers are presented. In addition, the strong potential offered by TNT layers for future research works is discussed. This progress report seeks to demonstrate the strong input of anodic TNT layers for developing the next generation of autonomous devices while stimulating more research efforts dedicated to modern technological applications.
Narcolepsy is a rare disabling neurological disease, affecting children and adults. The most recent development of measurement tools for narcolepsy were developed for adults; only a few tools are available for children without comparison on their validity. This research aims at comparing the validity of existing measurement tools in paediatric narcolepsy. From an ongoing randomized controlled trial, we extracted the data blind to the treatment of the 93 first terminating patients on which we compared the Paediatric Daytime Sleepiness Scale (PDSS), the Ullanlina Narcolepsy scale (UNS), the Child and Adolescent Sleepiness Questionnaire (CASS), the maintenance of wakefulness test (MWT), and the cataplexy episodes count (CEC). The comparison was carried out on reliability, internal consistency, sensitivity to change, minimum important difference, construct validity and concurrent validity. We provide evidence that the Ullanlina UNS score, currently used for screening purposes, constitutes a reliable and sensitive overall symptom measurement tool. Its subscore (UNS-CTP) based on the first four items permits a sensitive measurement of cataplexy, whereas the UNS-EDS subscore was found inferior to the PDSS scale. Compared with the objective measurement of symptoms (MWT, CEC), these scales better correlated with the clinical global impression of change in time, they are characterized by higher sensitivity, and they are much easier to use.
The aim of this work is to prove a Harnack inequality and the Hölder continuity for weak solutions to the Kolmogorov equation Lu=f with measurable coefficients, integrable lower order terms and nonzero source term. We introduce a functional space W, suitable for the study of weak solutions to Lu=f, that allows us to prove a weak Poincaré inequality. Our analysis is based on a weak Harnack inequality, a weak Poincaré inequality combined with a L2−L∞ estimate and a classical covering argument (Ink-Spots Theorem).
In this paper, the vibration correlation technique (VCT) has been used as a nondestructive method for predicting the buckling load of grid-stiffened composite conical shells. This technique is capable of predicting the buckling load of structures without reaching failure point through modal testing. The grid-stiffened composite conical shell has been fabricated using the filament winding process. To perform the experiment, the fundamental natural frequency of the specimen is measured under stepped axial compression loading. The procedure is followed up without actually reaching the instability point when the structure collapses and is no longer usable. A finite element model has been built using ABAQUS software considering the effect of geometric imperfection in order to determine the correlation between natural frequency and applied compressive load. A comparison of the experimental and numerical approaches indicated that the difference between numerical buckling loads and those obtained via the VCT is negligible. Moreover, the VCT has provided a reliable estimate of the buckling load, especially when the maximum applied load is greater than 67% of the experimental buckling load.
The plants Artemisia roxburghiana Besser and Elsholtzia fruticosa Rehder were evaluated as innovative crops for the production of essential oils with valuable biological activity. For both species, Clevenger distillation resulted in high essential oil contents of 1.08 and 1.79 mL·100 g⁻¹ dry weight for A. roxburghiana and E. fruticosa, respectively. According to the results of GC/FID and GC/MS analyses, the composition of essential oil of A. roxburghiana was characterized by cis-thujone (23.05%), 1,8-cineole (21.56%), and camphor (13.82%), while E. fruticosa oil was rich in 1,8-cineole (50.06%) and γ-terpinene (14.11%). The bioactivity of the oils of the two species was evaluated in vitro against both pathogenic Gram-positive and Gram-negative bacterial strains by disc diffusion assay and determination of the minimal inhibitory concentration. They were also tested as natural insecticides by carrying out mortality and fecundity analyses against the aphid Mizus persicae. E. fruticosa oil showed higher antibacterial activity compared to A. roxburghiana, particularly against Staphylococcus aureus (MIC 2.0 and 62.5 mg·mL⁻¹) and Escherichia coli (MIC 7.8 and 62.5 mg·mL⁻¹). Both plant species revealed high aphicidal activity against the polyphagous pest M. Persicae according to the nymph mortality and fecundity reduction, and their efficacy was comparable to that of azadyrachtin. This study shows the prospects of the two investigated species as possible innovative crops for the production of essential oils to be employed in agro-industry.
A single performance indicator, the solar transmittance factor (STF), has been proposed in previous works, together with the derived solar transmittance index (STI). It is aimed at evaluating the summer performance of the roofing system and allowing the selection of the most effective mix of surface and mass properties. It is easily calculated from low-level indicators such as U-value, module of periodic thermal transmittance, and solar reflectance. In the present work, the correlation between STF and the cooling energy demand, integrated over a reference period, was studied, as well as the peak of ceiling temperature increase with respect to the indoor temperature, relevant for thermal comfort. In particular, the thermal behavior of different roof types with variable insulation was calculated numerically by TRNSYS 17 for a wide set of locations and environmental conditions. Unlike other commonly used indicators, to which the analysis has been extended, a strong correlation with STF was found for both cooling energy demand and ceiling temperature rise.
Security token offerings (STOs), based on blockchain technology, are attracting increasing attention as an innovative alternative means of venture financing. Information about specific STOs is generally provided in white papers. This study analyses the content of white papers using a unique sample of 188 STOs from 2017 to 2021 to identify which topic is related to campaign success. We leverage latent Dirichlet allocation (LDA) topic modelling to identify the topics and themes in white papers. Nine topics are identified through LDA: company description, distributed ledger technology components, energy and green issues, financial and legal issues, artificial intelligence, and tech applications in different industries—specifically, healthcare, manufacturing and construction, education, and financial services. We find that energy and green issues represent one of the most prominent topics among all types of projects and that their disclosure is positively related to the probability of campaign success and the amount of funding raised. Another prominent topic that affects campaign outcomes is technology in the healthcare industry, reflecting wider investment trends in this sector. Our results may help entrepreneurs to improve their campaign disclosures and present new issues for policymakers regarding investments in digital tokens.
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