Selective sparing of bladder and rectum sub-regions in radiotherapy of prostate cancer combining knowledge-based automatic planning and multicriteria optimization

Background and Purpose: The association between dose to selected bladder and rectum symptom-related sub- regions (SRS) and late toxicity after prostate cancer radiotherapy has been evidenced by voxel-wise analyses. The aim of the current study was to explore the feasibility of combining knowledge-based (KB) and multi-criteria optimization (MCO) to spare SRSs without compromising planning target volume (PTV) dose delivery, including pelvic-node irradiation. Materials and Methods: Forty-five previously treated patients (74.2 Gy/28fr) were selected and SRSs (in the bladder, associated with late dysuria/hematuria/retention; in the rectum, associated with bleeding) were generated using deformable registration. A KB model was used to obtain clinically suitable plans (KB-plan). KB- plans were further optimized using MCO, aiming to reduce dose to the SRSs while safeguarding target dose coverage, homogeneity and avoiding worsening dose volume histograms of the whole bladder, rectum and other organs at risk. The resulting MCO-generated plans were examined to identify the best-compromise plan (KB + MCO-plan). Results: The mean SRS dose decreased in almost all patients for each SRS. D1% also decreased in the large majority, less frequently for dysuria/bleeding SRS. Mean differences were statistically significant (p < 0.05) and ranged between 1.3 and 2.2 Gy with maximum reduction of mean dose up to 3&#8211;5 Gy for the four SRSs. The better sparing of SRSs was obtained without compromising PTVs coverage. Conclusions: Selectively sparing SRSs without compromising PTV coverage is feasible and has the potential to reduce toxicities in prostate cancer radiotherapy. Further investigation to better quantify the expected risk reduction of late toxicities is warranted.This work has been supported by Fondazione Regionale per la Ricerca Biomedica, project nr. 110 - JTC PerPlanRT ERA PerMed, GA 779282.Publicad

Il curricolo verticale nella scuola del primo ciclo. Analisi, percorsi, strumenti

Un Istituto comprensivo è composto da tre ordini di scuola (dell'infanzia, primaria e secondaria di primo grado) con caratteristiche molto diverse, talvolta difficili da raccordare. Ciò nonostante, il curricolo d’Istituto (o verticale) va costruito insieme, con l'apporto di tutti gli insegnanti. Su quali basi? Il gruppo Università-Scuola del Laboratorio RED (Ricerca Educativa e Didattica) dell’Università Ca’ Foscari di Venezia, ha studiato e sperimentato, nelle pratiche formative, modelli aperti di progettazione del curricolo verticale per competenze, come proposto dalle Indicazioni nazionali, centrato sui nodi concettuali formativi, ovvero sui processi che sovrintendono agli apprendimenti nelle interconnessioni tra i multiformi potenziali formativi degli allievi e la ricchezza dei processi di conoscenza nei diversi ambiti disciplinari. Questo volume testimonia le analisi e i percorsi di ricerca-forma-azione nelle scuole, con gli insegnanti sperimentatori in classe

Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST

: Gastrointestinal stromal tumors (GISTs) are rare, mesenchymal tumors of the gastrointestinal tract, characterized by either KIT or PDGFRA mutation in about 85% of cases. KIT/PDGFRA wild type gastrointestinal stromal tumors (wtGIST) account for the remaining 15% of GIST and represent an unmet medical need: their prevalence and potential medical vulnerabilities are not completely defined, and effective therapeutic strategies are still lacking. In this study we set a patient-derived preclinical model of wtGIST to investigate their phenotypic features, along with their susceptibility to cellular immunotherapy with cytokine-induced killer lymphocytes (CIK) and interferons (IFN). We generated 11 wtGIST primary cell lines (wtGISTc). The main CIK ligands (MIC A/B; ULBPs), along with PD-L1/2, were expressed by wtGISTc and the expression of HLA-I molecules was preserved. Patient-derived CIK were capable of intense killing in vitro against wtGISTc resistant to both imatinib and sunitinib. We found that CIK produce a high level of granzyme B, IFNα and IFNγ. CIK-conditioned supernatant was responsible for part of the observed tumoricidal effect, along with positive bystander modulatory activities enhancing the expression of PD-L1/2 and HLA-I molecules. IFNα, but not In, had direct antitumor effects on 50% (4/8) of TKI-resistant wtGISTc, positively correlated with the tumor expression of IFN receptors. wtGIST cells that survived IFNα were still sensitive to CIK immunotherapy. Our data support the exploration of CIK immunotherapy in clinical studies for TKI-resistant wtGIST, proposing reevaluation for IFNα within this challenging setting

Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome

About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlinico “P. Giaccone” of Palermo, were genetically tested for germline BRCA1/2 variants through Next-Generation Sequencing analysis. The mutational screening showed that 639 (73.1%) out of 874 patients were BRCA-w.t., whereas 67 (7.7%) were carriers of germline BRCA1/2 VUSs, and 168 (19.2%) harbored germline BRCA1/2 pathogenic/likely pathogenic variants. Our analysis revealed the presence of 59 different VUSs detected in 67 patients, 46 of which were affected by BC and 21 by OC. Twenty-one (35.6%) out of 59 variants were located on BRCA1 gene, whereas 38 (64.4%) on BRCA2. We detected six alterations in BRCA1 and two in BRCA2 with unclear interpretation of clinical significance. Familial anamnesis of a patient harboring the BRCA1-c.3367G&gt;T suggests for this variant a potential of pathogenicity, therefore it should be carefully investigated. Understanding clinical significance of germline BRCA1/2 VUS could improve, in future, the identification of potentially high-risk variants useful for clinical management of BC or OC patients and family members

Reduced humoral response to two doses of COVID-19 vaccine in patients with inflammatory bowel disease: Data from ESCAPE-IBD, an IG-IBD study

Background Patients on immunosuppressive drugs have been excluded from COVID-19 vaccines trials, creating concerns regarding their efficacy. Aims To explore the humoral response to COVID-19 vaccines in patients with inflammatory bowel disease (IBD) Methods Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE-IBD) is a prospective, multicentre study promoted by the Italian Group for the study of Inflammatory Bowel Disease. We present data on serological response eight weeks after the second dose of COVID-19 vaccination in IBD patients and healthy controls (HCs). Results 1076 patients with IBD and 1126 HCs were analyzed. Seropositivity for anti-SARS-CoV-2 IgG was reported for most IBD patients, even if with a lesser rate compared with HCs (92.1% vs. 97.9%; p&lt;0.001). HCs had higher antibody concentrations (median OD 8.72 [IQR 5.2-14-2]) compared to the whole cohort of IBD patients (median OD 1.54 [IQR 0.8-3.6]; p&lt;0.001) and the subgroup of IBD patients (n=280) without any treatment or on aminosalicylates only (median OD 1.72 [IQR 1.0–4.1]; p&lt;0.001). Conclusions Although most IBD patients showed seropositivity after COVID-19 vaccines, the magnitude of the humoral response was significantly lower than in HCs. Differently from other studies, these findings seem to be mostly unrelated to the use of immune-modifying treatments (ClinicalTrials.govID:NCT04769258)

Innovative bracing system for CFS-LWG structures: planning of a research project

Due to their numerous advantages, Lightweight Steel (LWS) systems made of Cold Formed Steel (CFS) profiles have widely spread for low- and medium- rise residential buildings in seismic areas. A new research project has been started at University of Naples “Federico II” in cooperation with Lamieredil S.p.A. Company. The main goal of the project is the development of an innovative lateral force resisting system (LFRS), consisting of a CFS stud wall equipped with an anti-seismic device. The anti-seismic device mainly consists of a pre-tensioned Ultra High Strength (UHS) steel brace, working as pre-tensioned elastic spring, which may dissipate seismic energy by its yielding. The lateral performances of this LFRS will be evaluated through an experimental campaign carried out at Lab of the Department of Structures for Engineering and Architecture, University of Naples “Federico II”. The experimental activity will mainly include monotonic and cyclic tests on fullscale walls and shake-table tests on a representative mock-up. The paper summarizes the research project in detail, the experimental program and the design of the innovative system and prototype

Seismic design rules for lightweight steel shear walls with steel sheet sheathing in the 2nd-generation Eurocodes

The current structural European codes for seismic design EN1998-1 do not provide design criteria for cold formed steel (CFS) shear walls with steel sheet sheathing, limiting their use as a lateral force resisting system (LFRS) in lightweight steel (LWS) buildings. To overcome this lack of guidelines, a specific study has been carried out at the University of Naples “Federico II”. The main goals of the study are the validation/calibration of the Effective strip method (ESM) by Yanagi & Yu [26] and the definition of seismic design parameters according to the European format. The main results show that ESM gives a reliable prediction if the shear resistance of screw connections is evaluated based on equations from AISI S100 [1]. A safety factor for resistance equal to 1.25 can be used for the evaluation of the design wall resistance according to Limit state design (LSD) and an overstrength (expected resistance) factor equal to 1.4 can be adopted for the design of non-ductile components according to capacity desig

Seismic performance evaluation of CFS strap-braced buildings through experimental tests

Lightweight steel (LWS) buildings, made of cold-formed steel (CFS) systems, have many advantages and are often employed in seismic areas as low- and medium rise buildings. However, in Europe the codification does not provide specific rules for seismic design of those structures. In light of this, the University of Naples “Federico II” has recently completed a research project in cooperation with Lamieredil S.p.A. Italian Company, aimed to investigate the seismic behaviour of non-dissipative strap-braced structures. The partnership between academia and industry also led to development of a patented system. This paper discusses the selection and design process of the case study buildings and the overall experimental activity, going from small-scale tests of components, to static tests of full-scale walls, up to shake-table tests of two reduced scale mock-ups, which differ only for the adopted floor typology. The influence of floor typology on the seismic response of CFS strap-braced structures is also provided. Tests results confirmed that, although no specific seismic rules were employed, strap-braced structures had a good seismic response achieving high inter-storey drifts without showing severe damages

In-plane seismic behavior of lightweight steel drywall façades through quasi-static reversed cyclic tests

A lightweight steel (LWS) drywall façade is one of the most widely used architectural non-structural components in a building. This paper presents the results of in-plane quasi-static reserved cyclic tests carried out on 14 different full-scale façades made with LWS framing. The main goal of the study is to investigate the effect of various construction details on the seismic response of the selected facades. The investigated parameters include single or double frame walls, type of sheathing panels, presence of finishing, variation in surrounding constructional elements, absence of track members, type of connection to the surrounding constructional elements, and presence of protrusion. The effect of the construction parameters on the lateral response of the façades was examined in terms of strength, stiffness, force-displacement force–displacement hysteretic response, and damage mechanisms. Therefore, the damage phenomena observed during the tests are reported, associating them with the three damage limit states based on the level of damage. For the definition of seismic vulnerability, the fragility curves for different façade typologies are also presented. Finally, based on the fragility data, the evaluation of seismic performance according to IDR limits for non-structural components given by Eurocode 8 is also performed