Towards coordinated site monitoring and common strategies for mitigation of Radio Frequency Interference at the Italian radio telescopes

We present a project to implement a national common strategy for the mitigation of the steadily deteriorating Radio Frequency Interference (RFI) situation at the Italian radio telescopes. The project involves the Medicina, Noto, and Sardinia dish antennas and comprised the definition of a coordinated plan for site monitoring as well as the implementation of state-of-the-art hardware and software tools for RFI mitigation. Coordinated monitoring of frequency bands up to 40 GHz has been performed by means of continuous observations and dedicated measurement campaigns with fixed stations and mobile laboratories. Measurements were executed on the frequency bands allocated to the radio astronomy and space research service for shared or exclusive use and on the wider ones employed by the current and under-development receivers at the telescopes. Results of the monitoring campaigns provide a reference scenario useful to evaluate the evolution of the interference situation at the telescopes sites and a case series to test and improve the hardware and software tools we conceived to counteract radio frequency interference. We developed a multi-purpose digital backend for high spectral and time resolution observations over large bandwidths. Observational results demonstrate that the spectrometer robustness and sensitivity enable the efficient detection and analysis of interfering signals in radio astronomical data. A prototype off-line software tool for interference detection and flagging has been also implemented. This package is capable to handle the huge amount of data delivered by the most modern instrumentation on board of the Italian radio telecsopes, like dense focal plane arrays, and its modularity easen the integration of new algorithms and the re-usability in different contexts or telescopes.Comment: 39 pages, 10 Figures and 7 Tables. INAF Technical Report n. 149 (2022). http://hdl.handle.net/20.500.12386/3208

A synthetic peptide that prevents cAMP regulation in mammalian hyperpolarization-activated cyclic nucleotide-gated (HCN) channels

Binding of TRIP8b to the cyclic nucleotide binding domain (CNBD) of mammalian hyperpolarization-activated cyclic nucleotide-gated (HCN) channels prevents their regulation by cAMP. Since TRIP8b is expressed exclusively in the brain, we envisage that it can be used for orthogonal control of HCN channels beyond the central nervous system. To this end, we have identified by rational design a 40-aa long peptide (TRIP8bnano) that recapitulates affinity and gating effects of TRIP8b in HCN isoforms (hHCN1, mHCN2, rbHCN4) and in the cardiac current If in rabbit and mouse sinoatrial node cardiomyocytes. Guided by an NMR-derived structural model that identifies the key molecular interactions between TRIP8bnano and the HCN CNBD, we further designed a cell-penetrating peptide (TAT-TRIP8bnano) which successfully prevented β-adrenergic activation of mouse If leaving the stimulation of the L-type calcium current (ICaL) unaffected. TRIP8bnano represents a novel approach to selectively control HCN activation, which yields the promise of a more targeted pharmacology compared to pore blockers

Foscolo critico

Il volume, primo della collana open access dei "Quaderni di Gargnano", ospita i contributi presentati al XV Convegno internazionale di Letteratura italiana "Gennaro Barbarisi", tenutosi a Gargnano del Garda dal 24 al 26 settembre 2012. Il "Quaderno", dedicato al Foscolo critico, accoglie contributi di Giovanni Biancardi, Arnaldo Bruni, Andrea Campana, Massimo Castellozzi, Gustavo Costa, Alfredo Cottignoli, Christian Del Vento, Sandro Gentili, Franco Longoni, Ilaria Mangiavacchi, Donatella Martinelli, Giuseppe Natale, Enzo Neppi, Matteo Palumbo, Elena Parrini Cantini, Chiara Piola Caselli. \uc8 aperto da una Prefazione di Claudia Berra, Paolo Borsa e Giulia Ravera.This volume on "Foscolo critico" is the first volume of the "Quaderni di Gargnano", an open access book series which publishes the Proceedings of the "Gennaro Barbarisi" International Conferences on Italian Literature, held in Gargnano del Garda. It contains contributions by Giovanni Biancardi, Arnaldo Bruni, Andrea Campana, Massimo Castellozzi, Gustavo Costa, Alfredo Cottignoli, Christian Del Vento, Sandro Gentili, Franco Longoni, Ilaria Mangiavacchi, Donatella Martinelli, Giuseppe Natale, Enzo Neppi, Matteo Palumbo, Elena Parrini Cantini, Chiara Piola Caselli, preceded by a Preface by the Editor: Claudia Berra, Paolo Borsa, Giulia Ravera

Safety of extended interval dosing immune checkpoint inhibitors:a multicenter cohort study

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.</p

The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/ 27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). Methods and objectives: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. Conclusion: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project

SARS-CoV-2 omicron (B.1.1.529)-related COVID-19 sequelae in vaccinated and unvaccinated patients with cancer: results from the OnCovid registry

Background COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. Methods OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. Findings At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [ 50 center dot 7%] of 1902 patients with sex data were female and 938 [49 center dot 3%] were male). Overall, 317 (16 center dot 6%; 95% CI 14 center dot 8-18 center dot 5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the prevaccination phase (191 [19 center dot 1%; 95% CI 16 center dot 4-22 center dot 0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16 center dot 8%; 13 center dot 8- 20 center dot 3] of 653 patients, p=0 center dot 24), but significantly lower in the omicron phase (16 [6 center dot 2%; 3 center dot 5-10 center dot 2] of 256 patients, p<0 center dot 0001). In the alpha- delta phase, 84 (18 center dot 3%; 95% CI 14 center dot 6-22 center dot 7) of 458 unvaccinated patients and three (9 center dot 4%; 1 center dot 9- 27 center dot 3) of 32 unvaccinated patients in the omicron phase had sequelae. Patients who received a booster and those who received two vaccine doses had a significantly lower prevalence of overall COVID-19 sequelae than unvaccinated or partially vaccinated patients (ten [7 center dot 4%; 95% CI 3 center dot 5-13 center dot 5] of 136 boosted patients, 18 [9 center dot 8%; 5 center dot 8-15 center dot 5] of 183 patients who had two vaccine doses vs 277 [ 18 center dot 5%; 16 center dot 5-20 center dot 9] of 1489 unvaccinated patients, p=0 center dot 0001), respiratory sequelae (six [4 center dot 4%; 1 center dot 6-9 center dot 6], 11 [6 center dot 0%; 3 center dot 0-10 center dot 7] vs 148 [9 center dot 9%; 8 center dot 4- 11 center dot 6], p= 0 center dot 030), and prolonged fatigue (three [2 center dot 2%; 0 center dot 1-6 center dot 4], ten [5 center dot 4%; 2 center dot 6-10 center dot 0] vs 115 [7 center dot 7%; 6 center dot 3-9 center dot 3], p=0 center dot 037)

Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study

Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts. Conclusions: Among metastatic NSCLC patients with PD-L1 expression ≥50% receiving first-line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first-line chemotherapy

Processi di riorganizzazione nella filiera cerealicola. Le strategie delle imprese sementiere di piccola-media dimensione

Il settore sementiero cerealicolo sta assistendo negli ultimi tempi ad una serie di cambiamenti di pari passo con il quadro di evoluzione in atto nei sistemi agroalimentari, che coinvolge la domanda da parte dei consumatori, le strategie di marketing delle imprese dell’agroindustria, le sollecitazioni che vengono da alcune criticità più generali. Oltre al particolare dinamismo che caratterizza tutto il sistema agroalimentare, il mondo delle sementi risente di un nuovo interesse per il “seme”, che si manifesta anche al di fuori degli operatori del sistema. Come si comportano le ditte sementiere cerealicole medio-piccole di fronte ai cambiamenti in atto? Il presente lavoro di tesi si propone di approfondire l’evoluzione delle strategie messe in atto da imprese sementiere di piccola-media dimensione in relazione alle dinamiche del contesto in cui operano. L’obiettivo è cercare di comprendere se ed in quale modo venga percepito il cambiamento e se e quali scelte specifiche vengano messe in atto. La tesi è così articolata. Apre con un primo capitolo dedicato alla descrizione del contesto di riferimento, in cui vengono evidenziate le sollecitazioni a cui il sistema agroalimentare è sottoposto: la necessità di affrontare la transizione ecologica, la spinta che a tale riguardo viene dalle politiche europee in materia di agricoltura e più in generale di sviluppo, le opportunità che vengono dalla transizione, in termini di maggiori opportunità di sviluppo economico (rientrano in questo ambito i percorsi di rilocalizzazione dei sistemi agroalimentari). Nel secondo capitolo si passa a una descrizione del settore cerealicolo italiano. Dopo alcuni dati recenti sull’evoluzione del settore si focalizza sul comparto sementiero cerealicolo, sugli orientamenti del miglioramento genetico nella produzione di sementi, sulle specificità della produzione di sementi per l’agricoltura biologica e sulle dinamiche introdotte dal venir meno del sistema delle deroghe. Nel terzo capitolo viene sviluppata l’indagine condotta direttamente sulle strategie delle piccole ditte sementiere. Si apre con la descrizione delle scelte metodologiche e analitiche. L’indagine è stata svolta attraverso interviste qualitative dirette a tre aziende operanti nel centro Italia, due toscane e una marchigiana. Sono state inoltre utilizzate altre tre interviste a persone esperte del comparto sementiero e delle dinamiche che interessano in modo specifico il settore cerealicolo. Sui materiali informativi raccolti, l’analisi delle scelte delle imprese è stata condotta attraverso il metodo della SWOT analysis, al fine di capire il grado di consapevolezza delle opportunità e minacce esterne e dei punti di forza e debolezza interni. Nel quarto capitolo vengono discussi i risultati attraverso un’analisi trasversale, finalizzata ad evidenziare i comportamenti e le scelte delle imprese rispetto ai punti illustrati nella prima parte del lavoro. L’analisi dei risultati ha messo in evidenza come il quadro di riferimento sia molto variegato e non si possa parlare di "specificità strategica” delle piccole ditte sementiere locali. Le tre ditte sementiere prese in considerazione sono tutte consapevoli della transizione ecologica verso cui sta andando l’agricoltura e ognuna reagisce a suo modo. I cambiamenti in atto sono percepiti sia come un’opportunità che come una minaccia: chi è già dentro la transizione ecologica si trova in una posizione di vantaggio rispetto ai concorrenti; questi ultimi però si stanno già organizzando per rispondere al nuovo mercato. Le diverse strategie presenti nella gestione delle sementi rispecchiano la diversità delle filiere di cui le imprese sementiere sono parte. Si possono distinguere: medie realtà che si stanno riorganizzando per entrare nel biologico attraverso forme organizzative (come le O.P.) che consentano di gestire meglio le relazioni di filiera; realtà consortili che si creano l’esclusiva per vecchie varietà di sementi ricercate sul mercato; piccole realtà che, da sempre nel biologico, hanno intrapreso una strada di ulteriore specializzazione, diventando ditte sementiere per consolidare le nicchie in cui sono inserite; piccole ditte sementiere che sono fuori da determinati circuiti e che non si sentono in grado di entrare da sole nel biologico, continuando a rimanere legate alla clientela tradizionale. Le prospettive non sono ancora ben definite ma certamente la fine delle deroghe sulle sementi biologiche di cereali porterà un forte cambiamento. Forse le piccole ditte sementiere saranno più agili nel diversificare la produzione, o forse quelle più grandi, avvantaggiate da economie di scala e di rete, entreranno nel comparto biologico con piede pesante, portando a una diminuzione di costi di produzione e prezzi al dettaglio ma anche al rischio di perdita di specificità e qualità. Quello che sta succedendo nel sistema sementiero sembra rispecchiare quello che si sta profilando nell’intero sistema agroalimentare: stiamo andando verso un sistema agroalimentare più diversificato rispetto al modello dominante, rivelatosi in gran parte non sostenibile dal punto di vista ambientale e sociale, così come spesso non solido né equo dal punto di vista economico. La diversificazione del sistema sementiero può svolgere in tale processo un ruolo fondamentale, e divenire particolarmente significativa per le imprese di piccole-medie dimensioni