Investigation of molecular mechanisms of LKB1 function in Dictyostelium development and stress responses and the function of superoxide dismutase C (SodC) in chemotaxis

The serine/threonine kinase LKB1 is a regulator of critical events including development and stress responses in metazoans. The current study was undertaken to determine the function of LKB1 in Dictyostelium . During multicellular development and in response to stress insult, an apparent increase in the DdLKB1 kinase activity was observed. Depletion of DdLKB1 with a knockdown construct led to aberrant development; a severe reduction in prespore cell differentiation and a precocious induction of prestalk cells, which were reminiscent of cells lacking GSK3, a well known cell-fate switch. Furthermore, DdLKB1 depleted cells displayed lower GSK3 activity than wild type cells in response to cAMP stimulation during development and failed to activate AMPK, a well known LKB1 target in mammals, in response to cAMP and stress insults. These results suggest that DdLKB1 positively regulates both GSK3 and AMPK during Dictyostelium development, and DdLKB1 is necessary for AMPK activation during stress response regulation. No apparent GSK3 activation was observed in response to stress insults. Spatial and temporal regulation of phosphatidylinositol-(3,4,5)-triphosphate (PIP3) along the membrane of polarized cells is important for efficient chemotaxis. A REMI screen for PIP3 suppressors in the absence of stimulation led to the identification of SodC as PIP3 regulator. Consistent with their higher PIP3 levels, sodC− cells showed defects in chemotaxis and exhibited higher intra-cellular superoxide levels. Protein localization studies along with observations from GPI specific PI-PLC treatment of wild-type cells suggested that SodC is a GPI anchored outer-membrane protein. SodC showed superoxide dismutase activity in vitro, and motility defects of sodC− cells can be rescued by expressing the intact SodC but not by the mutant SodC, which has point mutations that affect its dismutase function. Treatment of sodC− cells with LY294002, a pharmacological inhibitor of PI3K, partially rescued the polarization and chemoattractant sensing defects but not motility defects. Consistent with increased intracellular superoxide levels, sodC − cells also exhibited higher basal Ras activity, an upstream regulator of PI3K, which can be suppressed by a cell permeable superoxide scavenger, XTT, indicating that SodC is important in regulation of intracellular superoxide levels thereby regulating the Ras activity and PIP3 levels at the membrane.

Investigation of molecular mechanisms of lkb1 function in dictyostelium development and stress responses and the function of superoxide dismutase c (sodc) in chemotaxis

The serine/threonine kinase LKB1 is a regulator of critical events including development and stress responses in metazoans. The current study was undertaken to determine the function of LKB1 in Dictyostelium. During multicellular development and in response to stress insult, an apparent increase in the DdLKB1 kinase activity was observed. Depletion of DdLKB1 with a knockdown construct led to aberrant development; a severe reduction in prespore cell differentiation and a precocious induction of prestalk cells, which were reminiscent of cells lacking GSK3, a well known cell-fate switch. Furthermore, DdLKB1 depleted cells displayed lower GSK3 activity than wild type cells in response to cAMP stimulation during development and failed to activate AMPK, a well known LKB1 target in mammals, in response to cAMP and stress insults. These results suggest that DdLKB1 positively regulates both GSK3 and AMPK during Dictyostelium development, and DdLKB1 is necessary for AMPK activation during stress response regulation. No apparent GSK3 activation was observed in response to stress insults. Spatial and temporal regulation of phosphatidylinositol-(3,4,5)-triphosphate (PIP3) along the membrane of polarized cells is important for efficient chemotaxis. A REMI screen for PIP3 suppressors in the absence of stimulation led to the identification of SodC as PIP3 regulator. Consistent with their higher PIP3 levels, sodC- cells showed defects in chemotaxis and exhibited higher intra-cellular superoxide levels. Protein localization studies along with observations from GPI specific PI-PLC treatment of wild-type cells suggested that SodC is a GPI anchored outer-membrane protein. SodC showed superoxide dismutase activity in vitro, and motility defects of sodC- cells can be rescued by expressing the intact SodC but not by the mutant SodC, which has point mutations that affect its dismutase function. Treatment of sodC- cells with LY294002, a pharmacological inhibitor of PI3K, partially rescued the polarization and chemoattractant sensing defects but not motility defects. Consistent with increased intracellular superoxide levels, sodC- cells also exhibited higher basal Ras activity, an upstream regulator of PI3K, which can be suppressed by a cell permeable superoxide scavenger, XTT, indicating that SodC is important in regulation of intracellular superoxide levels thereby regulating the Ras activity and PIP3 levels at the membrane.

Insegnare matematica nell'era digitale: dall’ardesia al silicio in cinquant’anni

La prima parte dell’elaborato ripercorre la storia dell’introduzione delle tecnologie all’interno delle istituzioni scolastiche, sia dal punto di vista pratico, sia dal punto di vista legislativo, che ha accompagnato questo ingresso tutt’altro che lineare, a partire dagli anni ’80 fino ai giorni nostri grazie alle ultime introduzioni avvenute con la messa in atto del Piano Nazionale Scuola Digitale. Vengono poi descritti alcuni software utilizzati nelle scuole sia in passato che in tempi più recenti per arrivare agli ultimi sviluppi e agli applicativi online per lo studio della matematica. Infine nell’ultimo capitolo è descritta un’unità didattica riguardante lo studio della probabilità, ideata per gli allievi di una scuola secondaria di secondo grado che utilizza la LIM e alcuni software adeguati all’argomento proposto. Quello che emerge, però, è la difficoltà sia nella diffusione delle tecnologie nella scuola, sia nel loro utilizzo da parte dei docenti. Spesso gli insegnanti non hanno un livello adeguato di formazione in ambito tecnologico e quindi non sono in grado di sfruttare pienamente le potenzialità offerte. Il cammino per arrivare ad una completa formazione del personale docente e per la completa digitalizzazione delle scuole è ancora lungo e tortuoso. Tuttavia è importante ricordare che le tecnologie non possono essere la risposta a tutto, bensì un efficace mezzo per attirare l’attenzione e soprattutto stimolare la fantasia di alunni e docenti. Inoltre non si può pensare alcuna tecnologizzazione senza prima aver posto e consolidato le basi di un qualsivoglia argomento da proporre in classe con l’ausilio di software e hardware.

Two devices, each of which measure water velocity; on the right is an acoustic device that is permanently maintained at Gumbo Limbo by PI Rene Price; on the left is a 3D camera with a long fiberoptic lens, deployed for testing purposes by collaborator Evan Variano.

http://digitalcommons.fiu.edu/fce_lter_photos/1303/thumbnail.jpg

Effects of a positive emotion-based adjuvant psychological therapy in colorectal cancer patients: a pilot study

Objective: To examine the effectiveness of an “Enhancing Positive Emotions Procedure” (EPEP) based on positive psychology and cognitive behavioral therapy in relieving distress at the time of adjuvant chemotherapy treatment in colorectal cancer patients (CRC). It is expected that EPEP will increase quality of life and positive affect in CRC patients during chemotherapy treatment intervention and at 1 month follow-up.Method: A group of 24 CRC patients received the EPEP procedure (intervention group), whereas another group of 20 CRC patients did not receive the EPEP (control group). Quality of life (EORTC-QLQC30), and mood (PANAS) were assessed in three moments: prior to enter the study (T1), at the end of the time required to apply the EPEP (T2, 6 weeks after T1), and, at follow-up (T3, one-month after T2). Patient’s assessments of the EPEP (improving in mood states, and significance of the attention received) were assessed with Lickert scales.Results: Insomnia was reduced in the intervention group. Treatment group had better scores on positive affect although there were no significantly differences between groups and over time. There was a trend to better scores at T2 and T3 for the intervention group on global health status, physical, role, and social functioning scales. Patients stated that positive mood was enhanced and that EPEP was an important resource.Conclusions: CRC patients receiving EPEP during chemotherapy believed that this intervention was important. Furthermore, EPEP seems to improve positive affect and quality of life. EPEP has potential benefits, and its implementation to CRC patients should be considered.

Bienestar psicológico, optimismo y resiliencia en mujeres con cáncer de mama

Objective: To evaluate the relationship between Perceived Psychological well-being, Optimism and Resilience in women survivors of breast cancer.Method: The sample was composed of 30 women diagnosed with breast cancer who were undergoing adjuvant treatment in Oncology Units General Hospital of Jerez de la Frontera and the University Hospital Puerta del Mar (Cadiz). The average age was 47.47 years (SD = 6,356) and the average of months from diagnosis of the disease was 9.93 (SD = 8,541). Scale of Psychological Well-being administered Perceived Ryff (1989), the Life Orientation Test Revised (LOT-R) Scheier, Carver and Bridges (1994) and the Scale of Resilience Wagnild and Young (1993) to assess psychological well-being the dispositional optimism and resilience respectivelyResults: Descriptive analyzes show that women diagnosed with breast cancer have levels of psychological well-being, dispositional optimism and higher than the average values provided by Resilience scales. On the other hand, regression analyses revealed that only some of the dimensions of resilience allowed to explain and predict some dimensions of psychological wellbeing, not dispositional optimism.Conclusions: The results seem to confirm the idea that if the capacity of women with breast moderate negative affect generated by the diagnosis itself and the consequences of their cancer treatment works and to promote their adaptation to the new situation we can contribute to increasing psychological well-being.

Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

International audience

Efecto de los dispositivos de emisión de microondas, radiofrecuencia no ablativa y ultrasonido microfocalizado en el tratamiento de la hiperhidrosis primaria revisión sistemática de la literatura

Antecedentes y objetivos: La hiperhidrosis primaria afecta el 2,8% de la población de Estados Unidos. Condición que impacta el desarrollo social de los individuos afectados, ocasionando fobia social. Existen opciones disponibles para el tratamiento de la hiperhidrosis incluyendo medicamentos tópico, sistémico, inyectable y quirúrgico. El objetivo de ésta revisión sistemática de la literatura es determinar la efectividad y seguridad de los dispositivos de emisión de microondas, radiofrecuencia no ablativa y sistema de ultrasonido microfocalizado para el tratamiento de la hiperhidrosis primaria. Materiales y métodos: Se realizó una revisión sistemática de la literatura de artículos obtenidos de bases de datos: Medline, Cochrane, Embase, Ovid y Scielo. Se incluyeron ensayos clínicos aleatorizados controlados, ensayos cuasiexperimentales desde el 2011; donde evaluaran el uso de estos dispositivos en el manejo de hiperhidrosis primaria. Resultados: Se seleccionaron 21 artículos en total. Se encontró que con los tres dispositivos se logra una reducción significativa a puntajes entre 1 y 2 de la escala de Severidad de la Hiperhidrosis; en 3 estudios se encontró mejoría en la calidad de vida; los eventos adversos fueron transitorios, siendo más frecuentes con el dispositivo de emisión de microondas. Conclusión: Primera revisión sistemática de la literatura sobre el efecto de estos tres dispositivos en el manejo de hiperhidrosis. Se espera aportar a la literatura existente una recomendación acerca de la efectividad y seguridad de estos dispositivos para que sea aplicado en los pacientes con diagnóstico de hiperhidrosis primaria.

Tratamiento del rechazo mediado por anticuerpos en pacientes trasplantados renales revisión sistemática

Antecedentes: El trasplante renal es la mejor alternativa terapéutica para la enfermedad renal crónica terminal. Los medicamentos inmunosupresores previenen el rechazo. El rechazo mediado por anticuerpos es frecuente y disminuye la función y duración del injerto. Objetivo: Evaluar sistemáticamente la evidencia disponible relacionada con la eficacia y seguridad del tratamiento para el rechazo mediado por anticuerpos en pacientes trasplantados renales. Metodologia: Revisión sistemática en bases de datos MEDLINE, EMBASE, Scopus y Biblioteca virtual de la salud. Literatura gris google scholar, google academico, www.clinicaltrialsregister.eu, and https://clinicaltrials.gov/. Búsqueda manual referencias artículos pre-seleccionados así como de revisiones previamente publicadas. Se siguieron las recomendacioes guia PRISMA para la identificacion de artículos potenciales, tamizaje y selección teniendo en cuenta los criterios de inclusion. Extracción datos de acuerdo a las variables, revisión calidad de los artículos elegidos utilizando evaluación riesgo de segos de Cochrane. Resultados: Se seleccionaron 9 ensayos clínicos publicados entre 1980 y 2016, incluyeron 222 pacientes (113 brazo de intervención y 109 en el control), seguimiento promedio 16 meses. Intervenciones evaluadas plasmaféresis, inmunoadsorción y rituximab. Hubo una amplia heterogeneidad en la definición de criterios de inclusión, criterios diagnósticos de rechazo y medidas de evaluación de eficacia de las intervenciones. Tres estudios encontraron diferencias estadísticamente significativas entre los grupos de tratamiento. Conclusiones: La evidencia sobre la eficacia de los tratamientos del rechazo mediado por anticuerpos en injertos renales es de baja calidad. Son necesarios ensayos clínicos controlados para poder definir el tratamiento óptimo de estos pacientes.

Caracterización y prevalencia del compromiso ocular en pacientes con enfermedad autoinmune y autoinflamatoria en un centro de referencia reumatológica en Colombia entre los años 2000 a 2015

RESUMEN Objetivo: Estimar la prevalencia de las diferentes enfermedades oftalmológicas que aparecen en el contexto de una enfermedad autoinmune (EAI) en pacientes de un centro de referencia reumatológica en Colombia, según características clínicas y sociodemográficas durante un período de 15 años, comprendido entre los años 2000 a 2015. Métodos: Se realizó un estudio descriptivo, observacional de prevalencia. El tipo de muestreo fue aleatorio estratificado con asignación proporcional en el programa Epidat 3.4. Los datos se analizaron en el programa SPSS v22.0 y se realizó análisis univariado de las variables categóricas, para las variables cuantitativas se realizaron medidas de tendencia central. Resultados: De 1640 historias clínicas revisadas, se encontraron 634 pacientes (38,65%) con compromiso ocular. Si excluimos los pacientes con SS, que por definición presentan ojo seco, 222 pacientes (13,53%) presentaron compromiso oftalmológico. Del total de pacientes, el 83,3% fueron mujeres. La AR fue la enfermedad autoinmune con mayor compromiso oftalmológico con 138 pacientes (62,2%), y en último lugar la sarcoidosis con 1 solo paciente afectado. La QCS fue la manifestación más común en todos los grupos diagnósticos de EAI, con 146 pacientes (63,5%). De 414 pacientes con Síndrome de Sjögren (SS) y QCS 8 presentaron compromiso ocular adicional, siendo la uveítis la segunda patología ocular asociada en pacientes con SS y la primera causa en las espondiloartropatias (71,4 %). Los pacientes con catarata (4,1%) presentaron la mayor prevalencia de uso de corticoide (88.8%). De 222 pacientes, 28 (12,6%) presentaron uveítis. Del total de pacientes, 16 (7,2%) presentaron maculopatía por antimalaráricos y 6 (18,75%) de los pacientes con LES. Los ANAS se presentaron en el 100% los pacientes con trastorno vascular de la retina. Los pacientes con epiescleritis presentaron la mayor proporción de positivización de anticuerpos anti-DNA. La EAI que más presentó epiescleritis fue LES con 4 pacientes (12,5%) El 22% de paciente con anticuerpos anti-RNP presentaron escleritis y 32,1% de los pacientes con uveítis presentaron HLA-B27 positivo. Las manifestaciones oftalmológicas precedieron a las sistémicas entre un 11,1% y un 33,3% de los pacientes. Conclusión: Las enfermedades oculares se presentan con frecuencia en los pacientes colombianos con EAI (38.65%), siendo la AR la enfermedad con mayor compromiso ocular (62,2%) y la QCS la enfermedad ocular con mayor prevalencia en todas las EAI (63,5%). La uveítis se presentó en 28 pacientes (12,6%). Las manifestaciones oftalmológicas pueden preceder a las sistémicas. El examen oftalmológico debe ser incluido en los pacientes con EAI, por ser la enfermedad ocular una comorbilidad frecuente. Adicionalmente, los efectos oftalmológicos de las medicaciones sistémicas utilizadas en EAI deben ser estrechamente monitorizados, durante el curso del tratamiento.

Rendimento de grãos e eficiência do uso de água no cultivo de milho geneticamente modificado no município de Teresina - PI, Brasil, em condições climáticas contrastantes.

2015

Azacitidine and Lenalidomide Combination Therapy in Myelodysplastic Syndromes: Topography and Translational Relevance of Nuclear Phospholipase C β - dependent Signalling

Nuclear inositide signalling pathways, and particularly those regulated by PI-PLCβ1, are associated with cell proliferation and differentiation. Myelodysplastic syndromes (MDS) are a heterogeneous spectrum of chronic myeloid hemopathies with associated symptomatic cytopenias and substantial potential for evolution to acute myeloid leukemia (AML). MDS patients are currently treated with two main approaches, epigenetic (Azacitidine) and immunomodulatory (Lenalidomide: above all in cell clones bearing a deletion of the long arm of the chromosome 5 [del(5q)]). As Azacitidine and Lenalidomide alone can show adverse effects or patients can be refractory, an experimental current approach is the combination of the two drugs. Clinically, this combination therapy is promising, while its molecular effect has to be clarified. Stemming from these data, in this study the effect of an Azacitidine-Lenalidomide combination therapy was studied, in both MDS patients and hematopoietic cell lines. The specific aims of this study were to evaluate the effect of Azacitidine and Lenalidomide MDS therapy on: cell cycle regulation, hematopoietic differentiation, gene mutation and miR expression. Lenalidomide alone, via PI-PLCβ1/PKC pathway, was able to induce a selective G0/G1 arrest of the cell cycle in del(5q) cells, slowing down their rate proliferation and favouring erythropoiesis activation. In addition, although the mutation profile at baseline was not entirely capable of predicting the clinical effect of Azacitidine and Lenalidomide therapy, the presence of specific point mutations affecting three inositide genes (PI3KCD, AKT3, PLCG2) was correlated to and anticipated a negative clinical outcome. Moreover, the differential miR expression was detectable even from the 4th cycle of therapy in responder patients, as compared to non-responders. In MDS, this is the first evidence that the molecular mutation profiling of inositide genes or a specific mini-cluster of differentially expressed miRs, targeting inositide signaling molecules, can be associated with the clinical response, thus possibly predicting the effect of the therapy.

The impact of phosphoinositide metabolic enzymes in glioblastoma: a tale of phosphoinositide-specific phospholipase C PLCβ1 and 5-phosphatase SKIP

Background: Glioblastoma multiforme (GBM) is one of the deadliest and most aggressive form of primary brain tumor. Unfortunately, current GBM treatment therapies are not effective in treating GBM patients. They usually experience very poor prognosis with a median survival of approximately 12 months. Only 3-5% survive up to 3 years or more. A large-scale gene profile study revealed that several genes involved in essential cellular processes are altered in GBM, thus, explaining why existing therapies are not effective. The survival of GBM patients depends on understanding the molecular and key signaling events associated with these altered physiological processes in GBM. Phosphoinositides (PI) form just a tiny fraction of the total lipid content in humans, however they are implicated in almost all essential biological processes, such as acting as second messengers in spatio-temporal regulation of cell signaling, cytoskeletal reorganization, cell adhesion, migration, apoptosis, vesicular trafficking, differentiation, cell cycle and post-translational modifications. Interestingly, these essential processes are altered in GBM. More importantly, incoming reports have associated PI metabolism, which is mediated by several PI phosphatases such as SKIP, lipases such as PLCβ1, and other kinases, to regulate GBM associated cellular processes. Even as PLCβ1 and SKIP are involved in regulating aberrant cellular processes in several other cancers, very few studies, of which majority are in-silico-based, have focused on the impact of PLCβ1 and SKIP in GBM. Hence, it is important to employ clinical, in vitro, and in vivo GBM models to define the actual impact of PLCβ1 and SKIP in GBM. AIM: Since studies of PLCβ1 and SKIP in GBM are limited, this study aimed at determining the pathological impact of PI metabolic enzymes, PLCB1 and SKIP, in GBM patient samples, GBM cell line models, and xenograft models for SKIP. Results: For the first time, this study confirmed through qPCR that PLCβ1 gene expression is lower in human GBM patient samples. Moreover, PLCβ1 gene expression inversely correlates with pathological grades of glioma; it decreases as glioma grades increases or worsens. Silencing PLCβ1 in U87MG GBM cells produces a dual impact in GBM by participating in both pro-tumoral and anti-tumoral roles. PLCβ1 knockdown cells were observed to have more migratory abilities, increased cell to extracellular matrix (ECM) adhesion, transition from epithelial phenotype to mesenchymal phenotype through the upregulation of EMT transcription factors Twist1 and Slug, and mesenchymal marker, vimentin. On the other hand, p-Akt and p-mTOR protein expression were downregulated in PLCβ1 knockdown cells. Thus, the oncogenic pathway PI3K/Akt/mTOR pathway is inhibited during PLCβ1 knockdown. Consistently, cell viability in PLCβ1 knockdown cells were significantly decreased compared to controls. As for SKIP, this study demonstrated that about 48% of SKIP colocalizes with nuclear PtdIns(4,5)P2 to nuclear speckles and that SKIP knockdown alters nuclear PtdIns(4,5)P2 in a cell-type dependent manner. In addition, SKIP silencing increased tumor volume and weight in xenografts than controls by reducing apoptosis and increasing viability. All in all, these data confirm that PLCβ1 and SKIP are involved in GBM pathology and a complete understanding of their roles in GBM may be beneficial.

Manutenzione su condizione e analisi dei ricambi per macchine automatiche nell’ottica industria 4.0. Il caso SACMI S.C.

In questo elaborato di tesi si affronta uno studio inerente alla Manutenzione su Condizione (CBM), applicata ad una macchina automatica adibita alla produzione di capsule in plastica, in collaborazione con il gruppo SACMI S.C. di Imola. Nel Capitolo 1 viene fornita una introduzione sul tema della manutenzione e sulla sua evoluzione dalla prima rivoluzione industriale ad oggi. Nel Capitolo 2 vengono descritti i principi teorici della manutenzione predittiva e se ne analizza lo stato dell’arte. Nel Capitolo 3 viene fornita una introduzione sull’azienda SACMI S.C. e in seguito vengono descritte nel dettaglio le macchine sulle quali si sono concentrate le successive analisi. Nel Capitolo 4 viene approfondito l’estrusore, uno dei componenti principali delle macchine analizzate. Nel Capitolo 5 viene presentato un esempio di valutazione dell’efficienza di alcune macchine collegate in serie attraverso il calcolo di un indicatore chiamato Overall Equipment Effectiveness (OEE). Il Capitolo 6 rappresenta il cuore della tesi e contiene tutte le analisi di CBM effettuate durante il periodo di tirocinio. Vengono analizzati i principali gruppi funzionali della macchina a partire da quelli più critici per tempi o costi di manutenzione. Le analisi sono state condotte ricercando all’interno di tutto il parco macchine quelle che presentavano delle condizioni di funzionamento sospette. Nel Capitolo 7 vengono presentate alcune analisi relative ai tempi di fermo macchina dovuti alle manutenzioni preventive e ai costi dei ricambi previsti dal manuale di manutenzione. Queste analisi vengono poi declinate su un caso reale nel quale si calcola il costo dei ricambi negli ultimi cinque anni distinguendo tra costi dovuti ad azioni preventive o correttive. Nel Capitolo 8 vengono presentate le conclusioni, mentre nel Capitolo 9 sono presentati gli sviluppi futuri di questo lavoro.

Analisi della performance sismica di un edificio esistente in C.A. mediante metodo SLaMA e valutazione delle perdite economiche attese

A metà del secolo scorso in Italia un elevato numero di edifici in cemento armato con struttura a telaio è stata realizzata, in accordo con la Normativa dell’epoca, per resistere unicamente alle azioni verticali presentando un’elevata vulnerabilità nei riguardi delle azioni sismiche. I cambiamenti apportati dalle più recenti Normative volgono l’attenzione alla problematica della vulnerabilità sismica degli edifici esistenti, rendendo l’analisi del comportamento di questi ultimi un tema di grande rilevanza ed attualità. In questo contesto, viene selezionato un edificio esistente per il quale viene valutata la capacità sismica mediante una metodologia analitica denominata SLaMA, e vengono stimate le perdite economiche sismiche utilizzando la metodologia del Sisma Bonus Italiano. L’utilizzo di metodologie di calcolo semplificate rappresenta al giorno d’oggi una robusta alternativa da utilizzare in fase di valutazione progettuale preliminare. Le operazioni eseguite per l’edificio esistente vengono poi ripetute anche per due differenti opzioni di rinforzo strutturale proposte per lo stesso. I risultati ottenuti in termini di capacità sono stati posti a confronto con quelli ricavati dalla modellazione ad elementi finiti su software di calcolo per validare il metodo semplificato, mentre i risultati derivati dal calcolo delle perdite economiche sono stati confrontati con quelli ricavati mediante una metodologia più raffinata di analisi per verificare la corrispondenza e l’accuratezza del parametro di perdita calcolato (PAM). Infine, vengono esposti i risultati ottenuti per gli edifici analizzati proponendo dei confronti fra gli stessi, in modo da individuare la scelta progettuale più conveniente sia in merito alla performance sismica dell’edificio che alla riduzione della perdita economica attesa.