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1. Exo1 cooperates with Tel1/ATM in promoting recombination events at DNA replication forks

Author

Galli, M, Frigerio, C, Colombo, C, Casari, E, Longhese, M, Clerici, M, Galli, Michela, Frigerio, Chiara, Colombo, Chiara Vittoria, Casari, Erika, Longhese, Maria Pia, Clerici, Michela, Galli, M, Frigerio, C, Colombo, C, Casari, E, Longhese, M, Clerici, M, Galli, Michela, Frigerio, Chiara, Colombo, Chiara Vittoria, Casari, Erika, Longhese, Maria Pia, and Clerici, Michela

Abstract

Tel1/ataxia telangiectasia mutated (ATM) kinase plays multiple functions in response to DNA damage, promoting checkpoint-mediated cell-cycle arrest and repair of broken DNA. In addition, Saccharomyces cerevisiae Tel1 stabilizes replication forks that arrest upon the treatment with the topoisomerase poison camptothecin (CPT). We discover that inactivation of the Exo1 nuclease exacerbates the sensitivity of Tel1-deficient cells to CPT and other agents that hamper DNA replication. Furthermore, cells lacking both Exo1 and Tel1 activities exhibit sustained checkpoint activation in the presence of CPT, indicating that Tel1 and Exo1 limit the activation of a Mec1-dependent checkpoint. The absence of Tel1 or its kinase activity enhances recombination between inverted DNA repeats induced by replication fork blockage in an Exo1-dependent manner. Thus, we propose that Exo1 processes intermediates arising at stalled forks in tel1 mutants to promote DNA replication recovery and cell survival.

Published
2024

2. Severe Acute Respiratory Syndrome Coronavirus 2 and Medical Evacuation in Lombardy: Lessons Learned from an Unprecedented Pandemic

Author

Stucchi, R, Ripoll-Gallardo, A, Sechi, G, Weinstein, E, Villa, G, Frigerio, C, Federighi, F, Grasselli, G, Zoli, A, Bonora, R, Fumagalli, R, Stucchi R., Ripoll-Gallardo A., Sechi G. M., Weinstein E. S., Villa G. F., Frigerio C., Federighi F., Grasselli G., Zoli A., Bonora R., Fumagalli R., Stucchi, R, Ripoll-Gallardo, A, Sechi, G, Weinstein, E, Villa, G, Frigerio, C, Federighi, F, Grasselli, G, Zoli, A, Bonora, R, Fumagalli, R, Stucchi R., Ripoll-Gallardo A., Sechi G. M., Weinstein E. S., Villa G. F., Frigerio C., Federighi F., Grasselli G., Zoli A., Bonora R., and Fumagalli R.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerging infectious disease pandemic developed in Lombardy (northern Italy) during the last week of February 2020 with a progressive increase of patients presenting with serious clinical findings. Despite the efforts of the Central Italian Government, regional resources were rapidly at capacity. The solution was to plan the medical evacuation (MEDEVAC) of 119 critically ill patients (median age 61 years) to in-patient intensive care units in other Italian regions (77) and Germany (42). Once surviving patients were deemed suitable, the repatriation process concluded the assignment. The aim of this report is to underline the importance of a rapid organization and coordination process between different nodes of an effective national and international network during an emerging infectious disease outbreak and draw lessons learned from similar published reports.

Published
2023

5. The Chromatin Landscape around DNA Double-Strand Breaks in Yeast and Its Influence on DNA Repair Pathway Choice

Author

Frigerio, C, Di Nisio, E, Galli, M, Colombo, C, Negri, R, Clerici, M, Colombo, CV, Frigerio, C, Di Nisio, E, Galli, M, Colombo, C, Negri, R, Clerici, M, and Colombo, CV

Abstract

DNA double-strand breaks (DSBs) are harmful DNA lesions, which elicit catastrophic consequences for genome stability if not properly repaired. DSBs can be repaired by either non-homologous end joining (NHEJ) or homologous recombination (HR). The choice between these two pathways depends on which proteins bind to the DSB ends and how their action is regulated. NHEJ initiates with the binding of the Ku complex to the DNA ends, while HR is initiated by the nucleolytic degradation of the 5′-ended DNA strands, which requires several DNA nucleases/helicases and generates single-stranded DNA overhangs. DSB repair occurs within a precisely organized chromatin environment, where the DNA is wrapped around histone octamers to form the nucleosomes. Nucleosomes impose a barrier to the DNA end processing and repair machinery. Chromatin organization around a DSB is modified to allow proper DSB repair either by the removal of entire nucleosomes, thanks to the action of chromatin remodeling factors, or by post-translational modifications of histones, thus increasing chromatin flexibility and the accessibility of repair enzymes to the DNA. Here, we review histone post-translational modifications occurring around a DSB in the yeast Saccharomyces cerevisiae and their role in DSB repair, with particular attention to DSB repair pathway choice.

Published
2023

6. High-dose-rate brachytherapy as monotherapy for localized prostate cancer using three different doses - 14 years of single-centre experience

Author

Soatti, C, Delishaj, D, D'Amico, R, Frigerio, C, Fumagalli, I, Bonsignore, F, Sangalli, G, Declich, F, Arcangeli, S, Ardizzoia, A, Colombo, A, Soatti C. P., Delishaj D., D'Amico R., Frigerio C., Fumagalli I. C., Bonsignore F., Sangalli G., Declich F., Arcangeli S., Ardizzoia A., Colombo A., Soatti, C, Delishaj, D, D'Amico, R, Frigerio, C, Fumagalli, I, Bonsignore, F, Sangalli, G, Declich, F, Arcangeli, S, Ardizzoia, A, Colombo, A, Soatti C. P., Delishaj D., D'Amico R., Frigerio C., Fumagalli I. C., Bonsignore F., Sangalli G., Declich F., Arcangeli S., Ardizzoia A., and Colombo A.

Abstract

Purpose: To evaluate clinical outcomes in patients with localized prostate cancer (LPC) treated with 3D conformal high-dose-rate (HDR) brachytherapy (BT) as monotherapy. Material and methods: From March 2004 to November 2017, 277 men with LPC underwent 3D conformal HDR-BT as monotherapy, with a temporary implant. The dose prescription was: 38 Gy in 4 fractions (149 patients), 27 Gy in 2 fractions (41 patients), and 19-20 Gy in a single fraction (87 patients). Biochemical progression-free survival (bPFS), progression- free survival (PFS), and cancer-specific survival (CSS) were calculated. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity assessment were performed using Common Terminology Criteria for Adverse Events v5.0. Results: The mean age was 67 (range, 47-81) years. Overall, 145 patients were low-risk, 116 intermediate-risk, and 16 high-risk prostate cancer. After a median follow-up of six years (range, 6-160 months), bPFS, PFS, and CSS were 81%, 96%, and 97%, respectively. Dose prescription, initial prostate specific antigen (iPSA) ≥ 9,5 ng/ml, and high-risk disease resulted in prognostic factors regarding bPFS. Only G2-G3 acute or late GI and GU toxicities were observed. Conclusions: HDR-BT as monotherapy is a valid and safe treatment modality for localized prostate cancer. After a long follow-up, patients receiving 19-20 Gy in a single fraction had a lower biochemical control rate compared to patients receiving 38 Gy in 4 fractions or 27 Gy in 2 fractions. Randomized prospective trials with a longer follow-up are necessary to confirm our results, and define total doses and dose per fraction for HDR-BT in patients with LPC.

Published
2021

7. The regulation of the DNA damage response at telomeres: Focus on kinases

Author

Galli, M, Frigerio, C, Longhese, M, Clerici, M, Galli M., Frigerio C., Longhese M. P., Clerici M., Galli, M, Frigerio, C, Longhese, M, Clerici, M, Galli M., Frigerio C., Longhese M. P., and Clerici M.

Abstract

The natural ends of linear chromosomes resemble those of accidental double-strand breaks (DSBs). DSBs induce a multifaceted cellular response that promotes the repair of lesions and slows down cell cycle progression. This response is not elicited at chromosome ends, which are organized in nucleoprotein structures called telomeres. Besides counteracting DSB response through specialized telomere-binding proteins, telomeres also prevent chromosome shortening. Despite of the different fate of telomeres and DSBs, many proteins involved in the DSB response also localize at telomeres and participate in telomere homeostasis. In particular, the DSB master regulators Tel1/ATM and Mec1/ATR contribute to telomere length maintenance and arrest cell cycle progression when chromosome ends shorten, thus promoting a tumor-suppressive process known as replicative senescence. During senescence, the actions of both these apical kinases and telomere-binding proteins allow checkpoint activation while bulk DNA repair activities at telomeres are still inhibited. Checkpoint-mediated cell cycle arrest also prevents further telomere erosion and deprotection that would favor chromosome rearrangements, which are known to increase cancer-associated genome instability. This review summarizes recent insights into functions and regulation of Tel1/ATM and Mec1/ATR at telomeres both in the presence and in the absence of telomerase, focusing mainly on discoveries in budding yeast.

Published
2021

8. 1446P Weekly hypofractionated palliative radiotherapy in poor performance status and elderly patients unfit for standard radiotherapy: Survival, acute and late toxicity outcomes

Author

Soatti, C.P., primary, Colangelo, F., additional, Mandurino, G., additional, D'Amico, R., additional, Alghisi, A., additional, De Nobili, G., additional, Cocchi, A., additional, Sangalli, G., additional, Frigerio, C., additional, Butti, I., additional, Bonsignore, F., additional, Declich, F., additional, and Delishaj, D., additional

Published
2021
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9. Genetic variability associated withOAS1expression in myeloid cells increases the risk of Alzheimer’s disease and severe COVID-19 outcomes

Author

Juan A. Botía, Thomas M. Piers, Magusali N, Jennifer M. Pocock, Panichnantakul P, Yaman U, Keeley J. Brookes, Maryam Shoai, Graham Ac, Sala Frigerio C, Sevinc Bayram, Mina Ryten, Escott-Price, Kevin Morgan, Regina H. Reynolds, Eftychia Bellou, Dervis A. Salih, John Hardy, Tamar Guetta-Baranes, and Sokolova D

Subjects
Innate immune system, Microglia, Disease, Biology, medicine.disease, medicine.anatomical_structure, Interferon, Immunology, medicine, Tumor necrosis factor alpha, Alzheimer's disease, Gene, medicine.drug, Genetic association
Abstract

Genome-wide association studies of late-onset Alzheimer’s disease (AD) have highlighted the importance of variants associated with genes expressed by the innate immune system in determining risk for AD. Recently, we and others have shown that genes associated with variants that confer risk for AD are significantly enriched in transcriptional networks expressed by amyloid-responsive microglia. This allowed us to predict new risk genes for AD, including the interferon-responsive oligoadenylate synthetase 1 (OAS1). However, the function ofOAS1within microglia and its genetic pathway are not known. Using genotyping from 1,313 individuals with sporadic AD and 1,234 control individuals, we confirm that theOAS1variant, rs1131454, is associated with increased risk for AD and decreasedOAS1expression. Moreover, we note that the same locus was recently associated with critical illness in response to COVID-19, linking variants that are associated with AD and a severe response to COVID-19. By analysing single-cell RNA-sequencing (scRNA-seq) data of isolated microglia fromAPPNL-G-Fknock-in and wild-type C57BL/6J mice, we identify a transcriptional network that is significantly upregulated with age and amyloid deposition, and contains the mouse orthologueOas1a, providing evidence thatOas1aplays an age-dependent function in the innate immune system. We identify a similar interferon-related transcriptional network containingOAS1by analysing scRNA-seq data from human microglia isolated from individuals with AD. Finally, using human iPSC-derived microglial cells (h-iPSC-Mg), we see thatOAS1is required to limit the pro-inflammatory response of microglia. When stimulated with interferon-gamma (IFN-γ), we note that cells with lowerOAS1expression show an exaggerated pro-inflammatory response, with increased expression and secretion of TNF-α. Collectively, our data support a link between genetic risk for AD and susceptibility to critical illness with COVID-19 centred onOAS1and interferon signalling, a finding with potential implications for future treatments of both AD and COVID-19, and the development of biomarkers to track disease progression.

Published
2021
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10. A database of the coseismic effects following the 30 October 2016 Norcia earthquake in Central Italy

Author

Villani, Fabio, Civico, Riccardo, Pucci, Stefano, Pizzimenti, Luca, Nappi, Rosa, De Martini, Paolo Marco, Agosta, F., Alessio, G., Alfonsi, L., Amanti, M., Amoroso, S., Aringoli, D., Auciello, E., Azzaro, R., Baize, S., Bello, S., Benedetti, L., Bertagnini, A., Binda, G., Bisson, M., Blumetti, A.M., Bonadeo, L., Boncio, P., Bornemann, P., Branca, S., Braun, T., Brozzetti, F., Brunori, C.A., Burrato, P., Caciagli, M., Campobasso, C., Carafa, M., Cinti, F.R., Cirillo, D., Comerci, V., Cucci, L., De Ritis, R., Deiana, G., Del Carlo, P., Del Rio, L., Delorme, A., Di Manna, P., Di Naccio, D., Falconi, L., Falcucci, E., Farabollini, P., Faure Walker, J.P., Ferrarini, F., Ferrario, M.F., Ferry, M., Feuillet, N., Fleury, J., Fracassi, U., Frigerio, C., Galluzzo, F., Gambillara, R., Gaudiosi, G., Goodall, H., Gori, S., Gregory, L.C., Guerrieri, L., Hailemikael, S., Hollingsworth, J., Iezzi, F., Invernizzi, C., Jablonská, D., Jacques, E., Jomard, H., Kastelic, V., Klinger, Y., Lavecchia, G., Leclerc, F., Liberi, F., Lisi, A., Livio, F., Lo Sardo, L., Malet, J.P., Mariucci, M.T., Materazzi, M., Maubant, L., Mazzarini, F., McCaffrey, K.J.W., Michetti, A.M., Mildon, Z.K., Montone, P., Moro, M., Nave, R., Odin, M., Pace, B., Paggi, S., Pagliuca, N., Pambianchi, G., Pantosti, D., Patera, A., Pérouse, E., Pezzo, G., Piccardi, L., Pierantoni, P.P., Pignone, M., Pinzi, S., Pistolesi, E., Point, J., Pousse, L., Pozzi, A., Proposito, M., Puglisi, C., Puliti, I., Ricci, T., Ripamonti, L., Rizza, M., Roberts, G.P., Roncoroni, M., Sapia, V., Saroli, M., Sciarra, A., Scotti, O., Skupinski, G., Smedile, A., Soquet, A., Tarabusi, G., Tarquini, S., Terrana, S., Tesson, J., Tondi, E., Valentini, A., Vallone, R., Van der Woerd, J., Vannoli, P., Venuti, A., Vittori, E., Volatili, T., Wedmore, L.N.J., Wilkinson, M., Zambrano, M., Istituto Nazionale di Geofisica e Vulcanologia - Sezione di Roma (INGV), Istituto Nazionale di Geofisica e Vulcanologia, Istituto Nazionale di Geofisica e Vulcanologia - Sezione di Palermo (INGV), Istituto sull’Inquinamento Atmosferico (CNR-IIA), Consiglio Nazionale delle Ricerche (CNR), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Laboratoire Image, Ville, Environnement (LIVE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Littoral, Environnement, Télédétection, Géomatique (LETG - Caen), Littoral, Environnement, Télédétection, Géomatique UMR 6554 (LETG), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-Université de Nantes (UN)-École pratique des hautes études (EPHE)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Scienze Fisiche, Informatiche e Matematiche [Modena], Università degli Studi di Modena e Reggio Emilia (UNIMORE), Géosciences Montpellier, Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Géoazur (GEOAZUR 7329), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de physique du globe de Strasbourg (IPGS), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Istituto Nazionale di Geofisica e Vulcanologia – Sezione di Pisa (INGV), Laboratoire de géologie de l'ENS (LGE), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Institut des Sciences de la Terre (ISTerre), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers (INSU - CNRS)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Joseph Fourier - Grenoble 1 (UJF), Italian National agency for new technologies, Energy and sustainable economic development [Frascati] (ENEA), Departimento di Scienze della Terra [Camerino], Università di Camerino (UNICAM), Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Dynamique globale et déformation active (IPGS) (IPGS-DGDA), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN)-Université de Caen Normandie (UNICAEN), Université de Nantes (UN)-Université de Nantes (UN), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire de géologie de l'ENS (LGENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Università degli Studi di Camerino = University of Camerino (UNICAM), Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Université des Antilles (UA)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Università degli Studi di Camerino (UNICAM), Puglisi, C., Proposito, M., Hailemikael, S., Falconi, L., Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-École pratique des hautes études (EPHE)-Université de Nantes (UN)-Université d'Angers (UA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 2 (UR2), Normandie Université (NU)-Normandie Université (NU), Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Villani, F., Civico, R., Pucci, S., Pizzimenti, L., Nappi, R., De Martini, P. M., Agosta, F., Alessio, G., Alfonsi, L., Amanti, M., Amoroso, S., Aringoli, D., Auciello, E., Azzaro, R., Baize, S., Bello, S., Benedetti, L., Bertagnini, A., Binda, G., Bisson, M., Blumetti, A. M., Bonadeo, L., Boncio, P., Bornemann, P., Branca, S., Braun, T., Brozzetti, F., Brunori, C. A., Burrato, P., Caciagli, M., Campobasso, C., Carafa, M., Cinti, F. R., Cirillo, D., Comerci, V., Cucci, L., De Ritis, R., Deiana, G., Del Carlo, P., Del Rio, L., Delorme, A., Di Manna, P., Di Naccio, D., Falcucci, E., Farabollini, P., Faure Walker, J. P., Ferrarini, F., Ferrario, M. F., Ferry, M., Feuillet, N., Fleury, J., Fracassi, U., Frigerio, C., Galluzzo, F., Gambillara, R., Gaudiosi, G., Goodall, H., Gori, S., Gregory, L. C., Guerrieri, L., Hollingsworth, J., Iezzi, F., Invernizzi, C., Jablonska, D., Jacques, E., Jomard, H., Kastelic, V., Klinger, Y., Lavecchia, G., Leclerc, F., Liberi, F., Lisi, A., Livio, F., Sardo, L., Malet, J. P., Mariucci, M. T., Materazzi, M., Maubant, L., Mazzarini, F., Mccaffrey, K. J. W., Michetti, A. M., Mildon, Z. K., Montone, P., Moro, M., Nave, R., Odin, M., Pace, B., Paggi, S., Pagliuca, N., Pambianchi, G., Pantosti, D., Patera, A., Perouse, E., Pezzo, G., Piccardi, L., Pierantoni, P. P., Pignone, M., Pinzi, S., Pistolesi, E., Point, J., Pousse, L., Pozzi, A., Puliti, I., Ricci, T., Ripamonti, L., Rizza, M., Roberts, G. P., Roncoroni, M., Sapia, V., Saroli, M., Sciarra, A., Scotti, O., Skupinski, G., Smedile, A., Soquet, A., Tarabusi, G., Tarquini, S., Terrana, S., Tesson, J., Tondi, E., Valentini, A., Vallone, R., Van Der Woerd, J., Vannoli, P., Venuti, A., Vittori, E., Volatili, T., Wedmore, L. N. J., Wilkinson, M., and Zambrano, M.

Subjects
Statistics and Probability, data collection, 010504 meteorology & atmospheric sciences, [SDU.STU.GP]Sciences of the Universe [physics]/Earth Sciences/Geophysics [physics.geo-ph], Library and Information Sciences, 010502 geochemistry & geophysics, computer.software_genre, 01 natural sciences, Education, 30 October 2016 Norcia earthquake, Earthquakes, ground deformation process, 0105 earth and related environmental sciences, [SDU.STU.TE]Sciences of the Universe [physics]/Earth Sciences/Tectonics, surface faulting hazard, Central Apennines, Database, Landslide, data acquisition system, Extensional definition, Computer Science Applications, 13. Climate action, Homogeneous, Georeference, ground deformation process, data acquisition system, Central Apennines, 30 October 2016 Norcia earthquake, Statistics, Probability and Uncertainty, computer, Relevant information, Geology, Information Systems
Abstract

We provide a database of the coseismic geological surface effects following the Mw 6.5 Norcia earthquake that hit central Italy on 30 October 2016. This was one of the strongest seismic events to occur in Europe in the past thirty years, causing complex surface ruptures over an area of >400 km2. The database originated from the collaboration of several European teams (Open EMERGEO Working Group; about 130 researchers) coordinated by the Istituto Nazionale di Geofisica e Vulcanologia. The observations were collected by performing detailed field surveys in the epicentral region in order to describe the geometry and kinematics of surface faulting, and subsequently of landslides and other secondary coseismic effects. The resulting database consists of homogeneous georeferenced records identifying 7323 observation points, each of which contains 18 numeric and string fields of relevant information. This database will impact future earthquake studies focused on modelling of the seismic processes in active extensional settings, updating probabilistic estimates of slip distribution, and assessing the hazard of surface faulting.

Published
2018
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11. Surface ruptures following the 30 October 2016 M w 6.5 Norcia earthquake, central Italy

Author

Civico, R., Pucci, S., Villani, F., Pizzimenti, L., De Martini, P. M., Nappi, R., Agosta, F., Alessio, G., Alfonsi, L., Amanti, M., Amoroso, S., Aringoli, D., Auciello, E., Azzaro, R., Baize, S., Bello, S., Benedetti, L., Bertagnini, A., Binda, G., Bisson, M., Blumetti, A. M., Bonadeo, L., Boncio, P., Bornemann, P., Branca, S., Braun, T., Brozzetti, F., Brunori, C. A., Burrato, P., Caciagli, M., Campobasso, C., Carafa, M., Cinti, F. R., Cirillo, D., Comerci, V., Cucci, L., De Ritis, R., Deiana, G., Del Carlo, P., Del Rio, L., Delorme, A., Di Manna, P., Di Naccio, D., Falconi, L., Falcucci, E., Farabollini, P., Faure Walker, J. P., Ferrarini, F., Ferrario, M. F., Ferry, M., Feuillet, N., Fleury, J., Fracassi, U., Frigerio, C., Galluzzo, F., Gambillara, R., Gaudiosi, G., Goodall, H., Gori, S., Gregory, L. C., Guerrieri, L., Hailemikael, S., Iezzi, F., Invernizzi, C., Jablonská, D., Jacques, E., Jomard, H., Kastelic, V., Klinger, Y., Lavecchia, G., Leclerc, F., Liberi, F., Lisi, A., Livio, F., Lo Sardo, L., Malet, J. P., Mariucci, M. T., Materazzi, M., Mazzarini, F., Mccaffrey, K. J. W., Michetti, A. M., Mildon, Z. K., Montone, P., Moro, M., Nave, R., Odin, M., Pace, B., Paggi, S., Pagliuca, N., Pambianchi, G., Pantosti, D., Patera, A., Pérouse, E., Pezzo, G., Piccardi, L., Pierantoni, P. P., Pignone, M., Pinzi, S., Pistolesi, E., Point, J., Pozzi, A., Proposito, M., Puglisi, C., Puliti, I., Ricci, T., Ripamonti, Licia, Rizza, M., Roberts, G. P., Roncoroni, M., Sapia, V., Saroli, M., Sciarra, A., Scotti, O., Skupinski, G., Smedile, A., Tarabusi, G., Tarquini, S., Terrana, S., Tesson, J., Tondi, E., Valentini, A., Vallone, R., Van der Woerd, J., Vannoli, P., Venuti, A., Vittori, E., Volatili, T., Wedmore, L. N. J., Wilkinson, M., Zambrano, M., Istituto Nazionale di Geofisica e Vulcanologia [Bologna] ( INGV ), Géosciences Montpellier, Institut national des sciences de l'Univers ( INSU - CNRS ) -Université de Montpellier ( UM ) -Université des Antilles ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), Istituto Nazionale di Geofisica e Vulcanologia - Sezione di Bologna (INGV), Istituto Nazionale di Geofisica e Vulcanologia, Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Géoazur (GEOAZUR 7329), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Hailemikael, S., Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Université des Antilles (UA)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de physique du globe de Strasbourg (IPGS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut Terre Environnement Strasbourg (ITES), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Agosta, F., Alessio, G., Alfonsi, L., Amanti, M., Amoroso, S., Aringoli, D., Auciello, E., Azzaro, R., Baize, S., Bello, S., Benedetti, L., Bertagnini, A., Binda, G., Bisson, M., Blumetti, A. M., Bonadeo, L., Boncio, P., Bornemann, P., Branca, S., Braun, T., Brozzetti, F., Brunori, C. A., Burrato, P., Caciagli, M., Campobasso, C., Carafa, M., Cinti, F. R., Cirillo, D., Comerci, V., Cucci, L., De Ritis, R., Deiana, G., Del Carlo, P., Del Rio, L., Delorme, A., Di Manna, P., Di Naccio, D., Falconi, L., Falcucci, E., Farabollini, P., Faure Walker, J. P., Ferrarini, F., Ferrario, M. F., Ferry, M., Feuillet1, N., Fleury, J., Fracassi, U., Frigerio, C., Galluzzo, F., Gambillara, R., Gaudiosi, G., Goodall, H., Gori, S., Gregory, L. C., Guerrieri, L., Iezzi, F., Invernizzi, C., Jablonská, D., Jacques, E., Jomard, H., Kastelic, V., Klinger, Y., Lavecchia, G., Leclerc, F., Liberi, F., Lisi, A., Livio, F., Lo Sard8, L., Malet, J. P., Mariucci, M. T., Materazzi5, M., Mazzarini, F., Mccaffrey, K. J. W., Michett, A. M., Mildon, Z. K., Montone, P., Moro, M., Nave, R., Odin, M., Pace, B., Paggi, S., Pagliuca, N., Pambianchi, G., Pantosti, D., Patera, A., Pérouse, E., Pezzo, G., Piccardi, L., Pierantoni, P. P., Pignone, M., Pinzi, S., Pistolesi, E., Point, J., Pozzi, A., Proposito, M., Puglisi, C., Puliti, I., Ricci, T., Ripamonti, L., Rizza, M., Roberts, G. P., Roncoroni, M., Sapia, V., Saroli, M., Sciarra, A., Scotti, O., Skupinski, G., Smedile, A., Tarabusi, G., Tarquini, S., Terrana, S., Tesson, J., Tondi, E., Valentini, A., Vallone, R., Van der Woerd, J., Vannoli, P., Venuti, A., Vittori, E., Volatili, T., Wedmore, L. N. J., Wilkinson, M., Zambrano, M., Institut de Physique du Globe de Paris (IPGP), and Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Surface (mathematics), Surface rupture, 010504 meteorology & atmospheric sciences, [SDU.STU.GP]Sciences of the Universe [physics]/Earth Sciences/Geophysics [physics.geo-ph], Field data, Geography, Planning and Development, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Kinematics, Fault (geology), 010502 geochemistry & geophysics, 01 natural sciences, Surface faulting, geological prompt surveys, lcsh:G3180-9980, Earth and Planetary Sciences (miscellaneous), coseismic ruptures, normal faulting, 2016–2017 seismic sequence, central Italy, Coseismic rupture, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, lcsh:Maps, [SDU.STU.TE]Sciences of the Universe [physics]/Earth Sciences/Tectonics, Geological prompt survey, 2016-2017 seismic sequence, Geological prompt surveys, Normal faulting, Coseismic ruptures, Central Italy, geography, geography.geographical_feature_category, Oblique case, [ SDU.STU ] Sciences of the Universe [physics]/Earth Sciences, es, 13. Climate action, Geology, Seismology
Abstract

We present a 1:25,000 scale map of the coseismic surface ruptures following the 30 October 2016 M-w 6.5 Norcia normal-faulting earthquake, central Italy. Detailed rupture mapping is based on almost 11,000 oblique photographs taken from helicopter flights, that has been verified and integrated with field data (>7000 measurements). Thanks to the common efforts of the Open EMERGEO Working Group (130 people, 25 research institutions and universities from Europe), we were able to document a complex surface faulting pattern with a dominant strike of N135 degrees-160 degrees (SW-dipping) and a subordinate strike of N320 degrees-345 degrees (NE-dipping) along about 28km of the active Mt. Vettore-Mt. Bove fault system. Geometric and kinematic characteristics of the rupture were observed and recorded along closely spaced, parallel or subparallel, overlapping or step-like synthetic and antithetic fault splays of the activated fault systems, comprising a total surface rupture length of approximately 46km when all ruptures were considered.

Published
2018
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12. Rapid reorganization of the Milan metropolitan public safety answering point operations during the initial phase of the COVID-19 outbreak in Italy

Author

Marrazzo, F, Spina, S, Pepe, P, D'Ambrosio, A, Bernasconi, F, Manzoni, P, Graci, C, Frigerio, C, Sacchi, M, Stucchi, R, Teruzzi, M, Baraldi, S, Lovisari, F, Langer, T, Sforza, A, Migliari, M, Sechi, G, Sangalli, F, Fumagalli, R, Marrazzo, Francesco, Spina, Stefano, Pepe, Paul E, D'Ambrosio, Annapaola, Bernasconi, Filippo, Manzoni, Paola, Graci, Carmela, Frigerio, Cristina, Sacchi, Marco, Stucchi, Riccardo, Teruzzi, Mario, Baraldi, Sara, Lovisari, Federica, Langer, Thomas, Sforza, Alessandra, Migliari, Maurizio, Sechi, Giuseppe, Sangalli, Fabio, Fumagalli, Roberto, Marrazzo, F, Spina, S, Pepe, P, D'Ambrosio, A, Bernasconi, F, Manzoni, P, Graci, C, Frigerio, C, Sacchi, M, Stucchi, R, Teruzzi, M, Baraldi, S, Lovisari, F, Langer, T, Sforza, A, Migliari, M, Sechi, G, Sangalli, F, Fumagalli, R, Marrazzo, Francesco, Spina, Stefano, Pepe, Paul E, D'Ambrosio, Annapaola, Bernasconi, Filippo, Manzoni, Paola, Graci, Carmela, Frigerio, Cristina, Sacchi, Marco, Stucchi, Riccardo, Teruzzi, Mario, Baraldi, Sara, Lovisari, Federica, Langer, Thomas, Sforza, Alessandra, Migliari, Maurizio, Sechi, Giuseppe, Sangalli, Fabio, and Fumagalli, Roberto

Abstract

Objective: To quantify how the first public announcement of confirmed coronavirus disease 2019 (COVID-19) in Italy affected a metropolitan region's emergency medical services (EMS) call volume and how rapid introduction of alternative procedures at the public safety answering point (PSAP) managed system resources. Methods: PSAP processes were modified over several days including (1) referral of non-ill callers to public health information call centers; (2) algorithms for detection, isolation, or hospitalization of suspected COVID-19 patients; and (3) specialized medical teams sent to the PSAP for triage and case management, including ambulance dispatches or alternative dispositions. Call volumes, ambulance dispatches, and response intervals for the 2 weeks after announcement were compared to 2017–2019 data and the week before. Results: For 2 weeks following outbreak announcement, the primary-level PSAP (police/fire/EMS) averaged 56% more daily calls compared to prior years and recorded 9281 (106% increase) on Day 4, averaging ∼400/hour. The secondary-level (EMS) PSAP recorded an analogous 63% increase with 3863 calls (∼161/hour; 264% increase) on Day 3. The COVID-19 response team processed the more complex cases (n = 5361), averaging 432 ± 110 daily (∼one-fifth of EMS calls). Although community COVID-19 cases increased exponentially, ambulance response intervals and dispatches (averaging 1120 ± 46 daily) were successfully contained, particularly compared with the week before (1174 ± 40; P = 0.02). Conclusion: With sudden escalating EMS call volumes, rapid reorganization of dispatch operations using tailored algorithms and specially assigned personnel can protect EMS system resources by optimizing patient dispositions, controlling ambulance allocations and mitigating hospital impact. Prudent population-based disaster planning should strongly consider pre-establishing similar highly coordinated medical taskforce contingencies.

Published
2020

13. World Scientific-Now Publishers Series in Business

Author

Frigerio, Chiara, Martinez, M., Iacono, M. P., Rajola, Federico, Jacks, T., Frigerio C. (ORCID:0000-0002-2648-6905), Rajola F. (ORCID:0000-0002-8591-7314), Frigerio, Chiara, Martinez, M., Iacono, M. P., Rajola, Federico, Jacks, T., Frigerio C. (ORCID:0000-0002-2648-6905), and Rajola F. (ORCID:0000-0002-8591-7314)

Abstract

In this chapter, we report the organizational, technological, and individual information technology (IT) issues of Italian IT workers. The participants of our survey are mostly IT professionals, working full time in non-managerial positions. IT strategic planning, IT service management, knowledge management, alignment between IT and business were among the most pressing organizational issues. Top technology concerns include enterprise application integration, business intelligence/analytics, collaborative and workflow tools, and networks/telecommunications. Italian IT employees seem to be satisfied with their work and perceived their workloads to be meaningful. They exhibited low levels of turnover intention and felt quite secure in their jobs.

Published
2020

15. Open Innovation Effectiveness in the Financial Services Sector

Author

Piobbici, Francesco, Rajola, Federico, Frigerio, Chiara, Piobbici F., Rajola F. (ORCID:0000-0002-8591-7314), Frigerio C. (ORCID:0000-0002-2648-6905), Piobbici, Francesco, Rajola, Federico, Frigerio, Chiara, Piobbici F., Rajola F. (ORCID:0000-0002-8591-7314), and Frigerio C. (ORCID:0000-0002-2648-6905)

Abstract

Many factors are changing the financial services industry. At first, we have to consider the macroeconomic scenario characterized by low interest rates, leading to a reduction of the institutions’ profitability and promoting investments aimed to increase the organizations’ efficiency. The regulatory framework is another element to consider, since, after the financial crisis, the authorities introduced new norms, some of them are currently under implementation, like the Market in Financial Instruments Directive II, the Insurance Distribution Directive or the General Data Protection Regulation. The last element we have to consider is the technological one: during the years, many innovations changed the customers’ behaviors, introducing new needs that institutions have to take into account in their strategic plans. Google, Apple, Facebook and Amazon, also called GAFA, have introduced new ways to interact with consumers that are based on instant and easy access to different functionalities.

Published
2019

16. 'Il maestro con la classe più grande del mondo'. La rappresentazione della pedagogia di Alberto Manzi nell'intervista TV Buona maestra (1997) e nella fiction Non è mai troppo tardi (2014)

Author

Polenghi, S., Alfieri, P., Frigerio, C., Debé, A., Felini, D., Aglieri, M., Aglieri, Michele, Michele Aglieri (ORCID:0000-0002-9564-8293), Polenghi, S., Alfieri, P., Frigerio, C., Debé, A., Felini, D., Aglieri, M., Aglieri, Michele, and Michele Aglieri (ORCID:0000-0002-9564-8293)

Abstract

Il contributo ripercorre la figura di Alberto Manzi attraverso due prodotti audiovisivi: l'intervista TV Buona maestra curata nel 1997 dal Dipartimento di Scienze dell'educazione di Bologna e la fiction Non è mai troppo tardi andata in onda sulla RAI nel 2014. L'obiettivo è di valorizzare dei documenti di sicuro interesse, raccogliere la testimonanza di un grande educatore e di estrarere categorie pedagogiche e riflessioni utili allle professioni educative.

Published
2019

17. Towards a map of the Upper Pleistocene loess in the Po Plain Loess Basin

Author

Zerboni, A., Amit, R., Baroni, C., Coltorti, M., Ferrario, M. F., Fioraso, G., Forno, M. G., Frigerio, C., Gianotti, F., Irace, A., DI LIVIO, Fiorenza, Mariani, G. S., Michetti, A. M., Monegato, Giovanni Virgilio, Mozzi, P., Orombelli, G., Perego, Alessia, Porat, N., Rellini, I., Trombino, L., and Cremaschi, M.

Published
2018

18. La valutazione dell'ambiente di apprendimento clinico attraverso il CLEI (Clinical Learning Environment Inventory) in un Ateneo italiano

Author

Colomb, N, Villa, C, Sala, M, Frigerio, C, Giacconi, L, Malvestiti, B, AUSILI, DAVIDE LUIGI, DI MAURO, STEFANIA, Colomb, N, Villa, C, Sala, M, Frigerio, C, Giacconi, L, Malvestiti, B, Ausili, D, and DI MAURO, S

Subjects
clinical learning environment, validation study, cross-sectional survey, MED/45 - SCIENZE INFERMIERISTICHE GENERALI, CLINICHE E PEDIATRICHE
Published
2016

20. LA FILIACION

Author

Frigerio C., César

Published
1974

22. PEN-2 gene mutation in a familial Alzheimer's disease case

Author

SALA FRIGERIO, C, Piscopo, P, Calabrese, E, Crestini, A, MALVEZZI CAMPEGGI, L, CIVITA DI FAVA, R, Fogliarino, S, Albani, D, Marcon, Gabriella, Cherchi, R, Piras, R, Forloni, G, Confaloni, A., SALA FRIGERIO, C, Piscopo, P, Calabrese, E, Crestini, A, MALVEZZI CAMPEGGI, L, CIVITA DI FAVA, R, Fogliarino, S, Albani, D, Marcon, Gabriella, Cherchi, R, Piras, R, Forloni, G, and Confaloni, A.

Published
2005

23. Caractéristiques cliniques et parcours médical des patients atteints de la maladie de Rendu-Osler suivis au CHUV

Author

FRIGERIO, C.

Subjects
Telangiectasia, hereditary hemorrhagic, arteriovenous malformations
Abstract

Objectifs : Les objectifs de ce travail ont consisté à décrire les caractéristiques cliniques et la prise en charge des patients atteints de maladie de Rendu-Osler (MRO) évalués par le réseau multidisciplinaire du CHUV, le parcours médical de ces patients (événements cliniques, informations reçues, examens, traitements) et comparer la prise en charge de patients avant et après la mise en place du réseau multidisciplinaire Rendu-Osler. Méthodes : Les critères d'inclusion ont été un diagnostic de MRO « certain » (3 critères de Curaçao) ou « possible » (2 critères de Curaçao). Le critère d'exclusion était un diagnostic « improbable » de MRO (1 critère de Curaçao). L'identification des patients a été réalisée par une recherche dans les bases de données informatisées du CHUV. Les données ont été recueillies de manière rétrospective par questionnaire. Les variables étudiées ont concerné les différentes manifestations cliniques, les examens et traitements entrepris ainsi que les informations fournies aux patients. Résultats : 56 patients avec MRO ont été identifiés, dont 40/56 (71%) patients ont eu un premier contact avec le CHUV avant 2011 et 16/56 (29%) patients sont entrés au CHUV après 2011. La prévalence des principales manifestations cliniques était : épistaxis 91%, télangiectasies cutanéo-muqueuses 90%, malformations artério-veineuses (MAVs) 70%, dont MAVs pulmonaires 46%, MAVs hépatiques 46%, MAVs digestives 43% et MAVs neurologiques 15%. Un bilan de base complet (formule sanguine, ferritine, échocardiographie, scanner thoracique, échographie ou IRM hépatique) à 2 ans de l'entrée au CHUV a été réalisé chez 10% des patients avant 2011 et 44% des patients après 2011 (p=0.008). L'information aux patients sur les modalités de transmission de la maladie a augmenté de 25% à 75% (p

Published
2014

27. Alteration of the microRNA network during the progression of Alzheimer's disease.

Author

Lau, P., Bossers, K., Janky, R., Salta, E., Sala Frigerio, C., Barbash, S., Rothman, R., Sierksma, A.S.R., Thathiah, A., Greenberg, D., Papadopoulou, A.S., Achsel, T., Ayoubi, T., Soreq, H., Verhaagen, J., Swaab, D.F., Aerts, S., De Strooper, B., Lau, P., Bossers, K., Janky, R., Salta, E., Sala Frigerio, C., Barbash, S., Rothman, R., Sierksma, A.S.R., Thathiah, A., Greenberg, D., Papadopoulou, A.S., Achsel, T., Ayoubi, T., Soreq, H., Verhaagen, J., Swaab, D.F., Aerts, S., and De Strooper, B.

Published
2013

32. Towards a map of the Upper Pleistocene loess of the Po Plain Loess Basin (Northern Italy)

Author

Zerboni, A., Amit, R., Baroni, C., Coltorti, M., Ferrario, M. F., Fioraso, G., Gabriella Forno, M., Frigerio, C., Gianotti, F., Irace, A., Livio, F., GUIDO STEFANO MARIANI, Michetti, A. M., Monegato, G., Mozzi, P., Orombelli, G., Perego, A., Porat, N., Rellini, I., Trombino, L., and Cremaschi, M.

Subjects
Po Plain loess basin, Loess, Mapping, Upper Pleistocene, Archeology (arts and humanities), Geology, Earth-Surface Processes, Paleontology, Loess, Mapping, Po Plain loess basin, Upper Pleistocene

34. The chromatin landscape around DNA double-strand breaks in yeast and its influence on DNA repair pathway choice

Author

MICHELA CLERICI, CHIARA VITTORIA COLOMBO, Chiara Frigerio, ELENA DI NISIO, MICHELA GALLI, Rodolfo Negri, Frigerio, C, Di Nisio, E, Galli, M, Colombo, C, Negri, R, and Clerici, M

Subjects
Organic Chemistry, histone acetylation, BIO/18 - GENETICA, homologous recombination, General Medicine, Saccharomyces cerevisiae, BIO/11 - BIOLOGIA MOLECOLARE, histone ubiquitylation, Catalysis, Computer Science Applications, Inorganic Chemistry, histone phosphorylation, DNA double strand break, histone methylation, Physical and Theoretical Chemistry, Molecular Biology, NHEJ, Spectroscopy
Abstract

DNA double-strand breaks (DSBs) are harmful DNA lesions, which elicit catastrophic consequences for genome stability if not properly repaired. DSBs can be repaired by either non-homologous end joining (NHEJ) or homologous recombination (HR). The choice between these two pathways depends on which proteins bind to the DSB ends and how their action is regulated. NHEJ initiates with the binding of the Ku complex to the DNA ends, while HR is initiated by the nucleolytic degradation of the 5′-ended DNA strands, which requires several DNA nucleases/helicases and generates single-stranded DNA overhangs. DSB repair occurs within a precisely organized chromatin environment, where the DNA is wrapped around histone octamers to form the nucleosomes. Nucleosomes impose a barrier to the DNA end processing and repair machinery. Chromatin organization around a DSB is modified to allow proper DSB repair either by the removal of entire nucleosomes, thanks to the action of chromatin remodeling factors, or by post-translational modifications of histones, thus increasing chromatin flexibility and the accessibility of repair enzymes to the DNA. Here, we review histone post-translational modifications occurring around a DSB in the yeast Saccharomyces cerevisiae and their role in DSB repair, with particular attention to DSB repair pathway choice.

Published
2023

35. Rapid reorganization of the Milan metropolitan public safety answering point operations during the initial phase of the COVID‐19 outbreak in Italy

Author

Annapaola D'Ambrosio, Stefano Spina, Mario Teruzzi, Francesco Marrazzo, Riccardo Stucchi, Paul E. Pepe, Thomas Langer, Giuseppe Maria Sechi, Carmela Graci, Marco Sacchi, Paola Manzoni, Filippo Bernasconi, Cristina Frigerio, Roberto Fumagalli, Maurizio Migliari, Federica Lovisari, Fabio Sangalli, Alessandra Sforza, Sara Baraldi, Marrazzo, F, Spina, S, Pepe, P, D'Ambrosio, A, Bernasconi, F, Manzoni, P, Graci, C, Frigerio, C, Sacchi, M, Stucchi, R, Teruzzi, M, Baraldi, S, Lovisari, F, Langer, T, Sforza, A, Migliari, M, Sechi, G, Sangalli, F, and Fumagalli, R

Subjects
medicine.medical_specialty, Emergency Medical Services, Referral, Population, emergency medical service, COVID-19 pandemic, call centers, Call volume, ambulances, emergency medical dispatch, medicine, Emergency medical services, ambulance, education, Original Research, education.field_of_study, business.industry, Public health, SARS-CoV-2 infection, COVID‐19 pandemic, medicine.disease, Metropolitan area, Triage, SARS‐CoV‐2 infection, disaster planning, Emergency medical dispatch, Medical emergency, business, call center
Abstract

Objective: To quantify how the first public announcement of confirmed coronavirus disease 2019 (COVID-19) in Italy affected a metropolitan region's emergency medical services (EMS) call volume and how rapid introduction of alternative procedures at the public safety answering point (PSAP) managed system resources. Methods: PSAP processes were modified over several days including (1) referral of non-ill callers to public health information call centers; (2) algorithms for detection, isolation, or hospitalization of suspected COVID-19 patients; and (3) specialized medical teams sent to the PSAP for triage and case management, including ambulance dispatches or alternative dispositions. Call volumes, ambulance dispatches, and response intervals for the 2 weeks after announcement were compared to 2017-2019 data and the week before. Results: For 2 weeks following outbreak announcement, the primary-level PSAP (police/fire/EMS) averaged 56% more daily calls compared to prior years and recorded 9281 (106% increase) on Day 4, averaging ∼400/hour. The secondary-level (EMS) PSAP recorded an analogous 63% increase with 3863 calls (∼161/hour; 264% increase) on Day 3. The COVID-19 response team processed the more complex cases (n = 5361), averaging 432 ± 110 daily (∼one-fifth of EMS calls). Although community COVID-19 cases increased exponentially, ambulance response intervals and dispatches (averaging 1120 ± 46 daily) were successfully contained, particularly compared with the week before (1174 ± 40; P = 0.02). Conclusion: With sudden escalating EMS call volumes, rapid reorganization of dispatch operations using tailored algorithms and specially assigned personnel can protect EMS system resources by optimizing patient dispositions, controlling ambulance allocations and mitigating hospital impact. Prudent population-based disaster planning should strongly consider pre-establishing similar highly coordinated medical taskforce contingencies.

Published
2020

36. High-dose-rate brachytherapy as monotherapy for localized prostate cancer using three different doses - 14 years of single-centre experience

Author

Stefano Arcangeli, Carlo Pietro Soatti, G. Sangalli, Durim Delishaj, Francesco Bonsignore, Cristina Frigerio, Romerai D’Amico, F. Declich, Antonio Ardizzoia, Ilaria Costanza Fumagalli, Alessandro Colombo, Soatti, C, Delishaj, D, D'Amico, R, Frigerio, C, Fumagalli, I, Bonsignore, F, Sangalli, G, Declich, F, Arcangeli, S, Ardizzoia, A, and Colombo, A

Subjects
0106 biological sciences, medicine.medical_specialty, medicine.medical_treatment, Brachytherapy, brachytherapy, Urology, 01 natural sciences, Prostate cancer, PSA, medicine, prostate-specific antigen, Radiology, Nuclear Medicine and imaging, Original Paper, business.industry, Genitourinary system, 010401 analytical chemistry, high-dose-rate, Common Terminology Criteria for Adverse Events, medicine.disease, prostate cancer, High-Dose Rate Brachytherapy, 0104 chemical sciences, Prostate-specific antigen, Oncology, Toxicity, Medicine, Implant, business, 010606 plant biology & botany
Abstract

Purpose To evaluate clinical outcomes in patients with localized prostate cancer (LPC) treated with 3D conformal high-dose-rate (HDR) brachytherapy (BT) as monotherapy. Material and methods From March 2004 to November 2017, 277 men with LPC underwent 3D conformal HDR-BT as monotherapy, with a temporary implant. The dose prescription was: 38 Gy in 4 fractions (149 patients), 27 Gy in 2 fractions (41 patients), and 19-20 Gy in a single fraction (87 patients). Biochemical progression-free survival (bPFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity assessment were performed using Common Terminology Criteria for Adverse Events v5.0. Results The mean age was 67 (range, 47-81) years. Overall, 145 patients were low-risk, 116 intermediate-risk, and 16 high-risk prostate cancer. After a median follow-up of six years (range, 6-160 months), bPFS, PFS, and CSS were 81%, 96%, and 97%, respectively. Dose prescription, initial prostate specific antigen (iPSA) ≥ 9,5 ng/ml, and high-risk disease resulted in prognostic factors regarding bPFS. Only G2-G3 acute or late GI and GU toxicities were observed. Conclusions HDR-BT as monotherapy is a valid and safe treatment modality for localized prostate cancer. After a long follow-up, patients receiving 19-20 Gy in a single fraction had a lower biochemical control rate compared to patients receiving 38 Gy in 4 fractions or 27 Gy in 2 fractions. Randomized prospective trials with a longer follow-up are necessary to confirm our results, and define total doses and dose per fraction for HDR-BT in patients with LPC.

Published
2020

37. Surface faulting during the August 24, 2016, Central Italy earthquake (Mw 6.0): preliminary results

Author

Franz A. Livio, A. M. Michetti, E. Vittori, L. Gregory, L. Wedmore, L. Piccardi, E. Tondi, G. Roberts, CENTRAL ITALY EARTHQUAKE W.G., A. M. Blumetti, L. Bonadeo, F. Brunamonte, V. Comerci, P. Dimanna, M. F. Ferrario, J. Faure Walker, C. Frigerio, F. Fumanti, L. Guerrieri, F. Iezzi, G. Leoni, K. McCaffrey, Z. Mildon, R. Phillips, E. Rhodes, R. J. Walters, M. Wilkinson, Livio, F., Michetti, A. M., Vittori, E., Gregory, L., Wedmore, L., Piccardi, L., Tondi, E., Roberts, G., Blumetti, A. M., Bonadeo, L., Brunamonte, F., Comerci, V., Di Manna, P., Ferrario, M. F., Faure Walker, J., Frigerio, C., Fumanti, F., Guerrieri, L., Iezzi, F., Leoni, G., Mccaffrey, K., Mildon, Z., Phillips, R., Rhodes, E., Walters, R. J., and Wilkinson, M.

Subjects
Surface (mathematics), 010504 meteorology & atmospheric sciences, On-fault effects, Field data, active tectonics, lcsh:QC851-999, Fault (geology), 010502 geochemistry & geophysics, Fault scarp, 01 natural sciences, Amatrice earthquake, Displacement (vector), Surface faulting, Interferometric synthetic aperture radar, seismotectonics, 0105 earth and related environmental sciences, geography, Central Italy, geography.geographical_feature_category, Deformation (mechanics), lcsh:QC801-809, earthquake hazard, lcsh:Geophysics. Cosmic physics, es, Geophysics, lcsh:Meteorology. Climatology, Surface expression, Geology, Seismology
Abstract

We present some preliminary results on the mapping of coseismically-induced ground ruptures following the Aug. 24, 2016, Central Italy earthquake (Mw 6.0). The seismogenic source, as highlighted by InSAR and seismological data, ruptured across two adjacent structures: the Vettore and Laga faults. We collected field data on ground breaks along the whole deformed area and two different scenarios of on-fault coseismic displacement arise from these observations. To the north, along the Vettore fault, surface faulting can be mapped quite continuously along a well-defined fault strand while such features are almost absent to the south, along the Laga fault, where flysch-like marly units are present. A major lithological control, affects the surface expression of faulting, resulting in a complex deformation pattern.

Published
2016
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38. Static and rotational intensity modulated techniques for head-neck cancer radiotherapy: a planning comparison

Author

G. Sangalli, Giovanni Mauro Cattaneo, G. Rinaldin, Cristina Frigerio, F. Declich, Sara Broggi, Italo Dell'Oca, Ivana Butti, Lucia Perna, Francesco Bonsignore, Anna Chiara, Nadia Di Muzio, Claudio Fiorino, Broggi, S, Perna, L, Bonsignore, F, Rinaldin, G, Fiorino, C, Chiara, A, Frigerio, C, Butti, I, Sangalli, G, Dell'Oca, I, Di Muzio, N, Cattaneo, Gm, and Declich, F.

Subjects
medicine.medical_treatment, Thyroid Gland, Biophysics, General Physics and Astronomy, Mandible, Head neck cancer, Tomotherapy, Dose homogeneity, Esophagus, Treatment plan, Humans, Parotid Gland, Medicine, Radiology, Nuclear Medicine and imaging, Radiometry, Radiation treatment planning, Radiotherapy, business.industry, Radiotherapy Planning, Computer-Assisted, Brain, Reproducibility of Results, Dose-Response Relationship, Radiation, General Medicine, Intensity (physics), Radiation therapy, Spinal Cord, Head and Neck Neoplasms, Radiotherapy, Intensity-Modulated, Treatment time, Larynx, business, Nuclear medicine, Algorithms
Abstract

Purpose To compare helical Tomotherapy (HT), two volumetric-modulated arc techniques and conventional fixed-field intensity modulated techniques (S-IMRT) for head-neck (HN) cancers. Methods and materials Eighteen HN patients were considered. Four treatment plans were generated for each patient: HT, S-IMRT optimised with Eclipse treatment planning system and two volumetric techniques using Elekta–Oncentra approach (VMAT) and Varian-RapidArc (RA), using two full arcs. All techniques were optimised to simultaneously deliver 66Gy to PTV1 (GTV and enlarged nodes) and 54Gy to PTV2 (subclinical and electively treated nodes). Comparisons were assessed on several dosimetric parameters and, secondarily, on planned MUs and delivery time. Results Concerning PTV coverage, significantly better results were found for HT and RA. HT significantly improved the target coverage both compared to S-IMRT and VMAT. No significant differences were found between S-IMRT and volumetric techniques in terms of dose homogeneity. For OARs, all the techniques were able to satisfy all hard constraints; significantly better results were found for HT, especially in the intermediate dose range (15–30 Gy). S-IMRT reached a significantly better OARs sparing with respect to VMAT and RA. No significant differences were found for body mean dose, excepting higher values of V5–V10 for HT. A reduction of planned MUs and delivery treatment time was found with volumetric techniques. Conclusions The objectives of satisfying target coverage and sparing of critical structures were reached with all techniques. S-IMRT techniques were found more advantageous compared to RA and VMAT for OARs sparing. HT reached the best overall treatment plan quality.

Published
2014

39. Nicastrin gene in familial and sporadic Alzheimer's disease

Author

Alfredo Cantafora, Liana Terreni, Raffaele Maletta, Paola Piscopo, Ida Blotta, Manuela Di Natale, Massimo Franceschi, Maria Caterina Di Perri, Gianluigi Forloni, Annamaria Confaloni, Carlo Sala Frigerio, Alessio Crestini, Lorenzo Malvezzi Campeggi, Gabriella Marcon, Amalia C. Bruni, Confaloni, A, Terreni, L, Piscopo, P, Crestini, A, Campeggi, Lm, Frigerio, C, Blotta, I, Perri, M, DI NATALE, M, Maletta, R, Marcon, Gabriella, Franceschi, M, Bruni, Ac, Forloni, G, and Cantafora, A.

Subjects
Male, Silent mutation, Genotype, Apolipoprotein E4, Population, Mutation, Missense, Nicastrin, Single-nucleotide polymorphism, Biology, Presenilin, Apolipoproteins E, Alzheimer Disease, medicine, Humans, Missense mutation, RNA, Messenger, Age of Onset, education, Polymorphism, Single-Stranded Conformational, Aged, Aged, 80 and over, Genetics, education.field_of_study, Membrane Glycoproteins, Reverse Transcriptase Polymerase Chain Reaction, General Neuroscience, Haplotype, medicine.disease, Case-Control Studies, biology.protein, Tyrosine, Female, Amyloid Precursor Protein Secretases, Asparagine, Alzheimer's disease
Abstract

Nicastrin is a protein recently discovered associated to presenilins and involved in the production of amyloid beta peptide that accumulates in Alzheimer's disease (AD) brain. In this study the nicastrin gene was examined for unknown mutations and polymorphisms in 104 patients with familial AD (52 early-onset and 52 late-onset), 174 sporadic AD and 191 healthy neurological controls of Italian origin. The scanning of the nicastrin gene identified a missense mutation (N417Y) in two patients with sporadic AD, in an early-onset familial AD and in a young control subject. Furthermore, we found two silent mutations and four intronic polymorphisms, three of them co-segregating in a single haplotype. We found some differences in the distribution of genotype alterations in the AD population compared to the controls. However, our data together with other evidence did not support the pathological role of missense mutation N417Y.

Published
2003

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