94 research outputs found
Di fascino e fantasia. Fra L. A Muratori (1745) e G. L. Marugi (1788), in "Natura Società Letteratura", Atti del XXII Congresso dell’ADI - Associazione degli Italianisti (Bologna, 13-15 settembre 2018), a cura di A. Campana e F. Giunta, Roma, Adi editore, 2020 Isbn: 9788890790560
No full textBen oltre i confini del ducato estense, Muratori (1672-1750) sin da giovane aderì a forme di modernità improntata alle più importanti accademie e ai circuiti di scambi intellettuali europei. Per oltre sei decenni, la sua viva curiosità si riversò su fenomeni nuovi e vecchi, in rigorosa osservazione scientifica; in particolare nell’opera 'Della forza della fantasia umana' (1745) polemizzò contro magia, stregoneria e altri pregiudizi, bollandoli come fantasie di gente rozza e credulona. Ma sulle forme di ‘immodificabile irrazionalità’ riemergenti per superstizione, incoerenza o incertezza, Nicola Valletta (1750-1814), allievo del Genovesi e docente di diritto all’Università di Napoli, nel 1787 scrisse una Cicalata sul Fascino, volgarmente detto jettatura, fra tono semiserio, in finzione letteraria, e battaglia della ragione dinanzi a motivi oscuri e arcani. Invece per un recupero culturale di tali temi il regnicolo tarantino Marugi (1753-1836) invitava a una riflessione collettiva, oltre l’esoterismo: i suoi 'Capricci sulla jettatura' (1788) appaiono un divertissement non privo di acume antropologico su aspetti della cultura popolare; lo sguardo indagatore dell’autore, medico e riformatore, non si pone tanto come pendant poetico del Muratori, incline al racconto evenemenziale delle pratiche antijettatorie, ma si arricchisce di nuove risonanze, sensibili alle caverne dell’istinto. In Marugj la letterarietà intriga la rappresentazione di fatti e immagini con una freschezza palpabile e in alcuni passaggi antifrastica, al tramonto dei Lumi
Riflessioni sui confini del giudizio di legittimità costituzionale a partire dall’“ordinanza Cappato”
No full textLo scritto si concentra su alcune specifiche questioni che emergono dall’ordinanza della Corte costituzionale n. 217 del 2019. In primo luogo, viene valutata l’idoneità della soluzione proposta dalla Corte a conseguire gli obiettivi indicati nell’ordinanza. In secondo luogo, vengono prese in esame le soluzioni alternative – già consolidatesi nella giurisprudenza costituzionale – che si sarebbero potute scegliere ai medesimi fini. Da ultimo, vengono avanzate proposte de jure condendo che consentirebbero al Giudice costituzionale di modulare gli effetti delle proprie decisioni ed evitare il ricorso a tecniche decisorie – quale quella utilizzata nel c.d. “caso Cappato” – che sembrano travalicare i confini dei “poteri di gestione del processo costituzionale”.The paper focuses on some specific aspects arising from the order of the Constitutional Court No. 217 of 2019. Firstly, the study assesses the suitability of the solution proposed by the Court for achieving the objectives defined in the order. Secondly, the Author considers the alternative solutions – already consolidated in the constitutional case law – which the Constitutional Court could have chosen for reaching the same purposes. Lastly, the paper put forward proposals de jure condendo, in order to allow the Constitutional Judge to modulate the effects of its decisions and to avoid the use of types of decision – such as the one used in the s.c. “Cappato case” – which seem to go beyond the boundaries of “management powers of the constitutional trial”
Declinare il paesaggio di guerra: l’Altipiano di Asiago negli scritti di Carlo Emilio Gadda
No full textAttraverso gli scorci paesaggistici del Giornale di guerra e di prigionia, della Meccanica e del Castello di Udine, si vuole qui ripercorrere l’evoluzione della tecnica descrittiva di Gadda. Analizzando le diverse modalità con cui il paesaggio bellico viene rappresentato, il saggio avanza una proposta interpretativa sulle possibili ragioni delle scelte stilistico-narrative gaddiane, con particolare riferimento alla funzione specifica assunta dal paesaggio di guerra nelle sue diverse declinazioni
A retrospective observational study on cutaneous adverse events induced by immune checkpoint inhibitors
No full textBackground: Cutaneous adverse events (CAEs) related to oncological therapies are a common scenario in daily clinical practice. Methods: This is a retrospective observational study collecting the data regarding CAEs of patients treated with immune checkpoints inhibitors (ICIs) in four different Italian centers. Results: Of 323 patients included, 305 were evaluable for this analysis; 182 patients (59.7%) had metastatic cutaneous melanoma (CM), 99 (32.5%) non-small cell lung cancer (NSCLC) and 24 (7.8%) renal cell carcinoma (RCC). The most frequent CAEs that we found, considering all the 305 patients, were pruriginous maculopapular rash (10.2% of the patients), vitiligo-like areas (7.2% of the patients), psoriasiform rash (6.2% of the patients), asymptomatic maculopapular rash (4.6% of the patients), and lichenoid rash (4.3% of the patients). Vitiligo-like areas occurred more frequently in patients with CM, while a lichenoid rash was more frequently observed in patients with RCC. Treatment interruption was related to drug-induced CAEs in 15.4% of melanoma patients and 0.0% of lung and kidney patients. Patients developing a cutaneous adverse event had better overall response rate and higher progression free survival and overall survival than the patients without CAEs. Conclusions: Our study brings new information on the characteristics of CAEs related to ICIs treatment in three different types of cancers, CM, NSCLC and RCC
Alternative macrophage polarisation associated with resistance to anti-PD1 blockade is possibly supported by the splkcing of FKBP51 immunophilin in melanoma patients
No full textpeer reviewe
Reliability analysis of randomly excited FE modelled structures with interval mass and stiffness via sensitivity analysis
No full textThe present study focuses on reliability analysis of linear discretized structures with uncertain mass and stiffness parameters subjected to stationary Gaussian multi-correlated random excitation. Under the assumption that available information on the uncertain parameters is poor or incomplete, the interval model of uncertainty is adopted. The reliability function for the extreme value stress process is evaluated in the framework of the first-passage theory. Such a function turns out to have an interval nature due to the uncertainty affecting structural parameters. The aim of the analysis is the evaluation of the bounds of the interval reliability function which provide a range of structural performance useful for design purposes. To limit detrimental overestimation caused by the dependency phenomenon, a sensitivity-based procedure is applied. The main advantage of this approach is the capability of providing appropriate combinations of the endpoints of the uncertain parameters which yield accurate estimates of the bounds of the interval reliability function for the extreme value stress process as long as monotonic problems are dealt with. Two case studies are analyzed to demonstrate the accuracy and efficiency of the presented method.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Mechanics and Physics of Structure
Design, fabrication and performance of the 10-in TOM HPD
No full textThe first sealed TOM Hybrid Photon Detector (HPD) with 10-in. diameter has been fabricated and successfully tested at CERN. This HPD has a spherical entrance window and a bialkali photocathode. The fountain focusing optics produces a demagnified image (D = 4) on the round segmented silicon sensor. The signals of the 2048 cells are read out through analog front-end electronics encapsulated in the vacuum envelope. We report on the design, fabrication technique and the experimental results obtained with laboratory test benches. The large TOM HPD is a prototype tube developed for the CLUE cosmic ray experiment. The final tubes, now under development, will be equipped with a solar-blind Rb//2Te photocathode and self triggering front-end electronics
Machine learning based optimization for interval uncertainty propagation
No full textTwo non-intrusive uncertainty propagation approaches are proposed for the performance analysis of engineering systems described by expensive-to-evaluate deterministic computer models with parameters defined as interval variables. These approaches employ a machine learning based optimization strategy, the so-called Bayesian optimization, for evaluating the upper and lower bounds of a generic response variable over the set of possible responses obtained when each interval variable varies independently over its range. The lack of knowledge caused by not evaluating the response function for all the possible combinations of the interval variables is accounted for by developing a probabilistic description of the response variable itself by using a Gaussian Process regression model. An iterative procedure is developed for selecting a small number of simulations to be evaluated for updating this statistical model by using well-established acquisition functions and to assess the response bounds. In both approaches, an initial training dataset is defined. While one approach builds iteratively two distinct training datasets for evaluating separately the upper and lower bounds of the response variable, the other one builds iteratively a single training dataset. Consequently, the two approaches will produce different bound estimates at each iteration. The upper and lower response bounds are expressed as point estimates obtained from the mean function of the posterior distribution. Moreover, a confidence interval on each estimate is provided for effectively communicating to engineers when these estimates are obtained at a combination of the interval variables for which no deterministic simulation has been run. Finally, two metrics are proposed to define conditions for assessing if the predicted bound estimates can be considered satisfactory. The applicability of these two approaches is illustrated with two numerical applications, one focusing on vibration and the other on vibro-acoustics.Mechanics and Physics of Structure
Primary Chemotherapy With Epirubicin And Vinorelbine In Women With Locally Advanced Breast Cancer
No full textBACKGROUND: To assess the activity and toxicity of primary chemotherapy with epirubicin (60 mg/m2 every other week) and vinorelbine (25 mg/m2, weekly) plus granulocyte colony-stimulating factor (G-CSF) for 12 weeks, in patients with locally advanced breast cancer in a multicenter setting.
PATIENTS AND METHODS:
Patients with stage IIIA or IIIB breast cancer, not older than 70, were eligible. A two-stage phase II design was applied. Response was assessed clinically, instrumentally and pathologically.
RESULTS:
Out of 48 enrolled patients, 87.5% received all planned cycles, with a median dose-intensity of 30 mg/m2/week for epirubicin and 23.8 mg/m2/week for vinorelbine. A clinical or instrumental objective response was reached in 42 patients (87.5%, exact 95% CI: 74.7-95.3); significant downstaging was reached in all but one patient; 6 cases had a pathological complete response in the breast, and 2 cases in the lymph nodes too (pathological complete response rate 4.2%, exact 95% CI: 0.5-14.2); a further 2 patients had only microscopic cancer foci at pathological examination of the breast. Radiological tests underestimated the treatment effect on the breast. Toxicity was mild, neutropenia being the most frequent (grade 3-4 in 47% of patients), but never complicated with fever or sepsis. Mild constipation (< or =grade 2) occurred in 35% of patients. Moderate to severe asthenia occurred in 12% of 6 patients. No cardiac toxicity was reported. At 3 years, disease-free survival was 68% and overall survival 81%.
CONCLUSION:
Primary chemotherapy with epirubicin every other week, weekly vinorelbine and G-CSF support is highly active and well tolerated in patients with locally advanced breast cancer
Identification of a highly suppressive Treg subset associated to immunotherapy response
No full textBackground Cancer immunotherapy has shown surprising efficacy in several types of advanced and incurable tumors, particularly, malignant melanoma. There are several immunotherapeutic strategies aimed at enhancing immunological defenses against tumor. Among these, monoclonal antibodies against the so-called “immune checkpoint inhibitors”, that counteract tumor-induced immune-disarming pathways, have shown the best outcomes. Regulatory T lymphocytes or Tregs are a subset of lymphocytes involved in immune-surveillance and maintenance of self-tolerance. Tumor often exploits Tregs to allow tolerance to its own antigens and avoid immune system attack. Tregs are usually increased in melanoma patients. It is noticeable that Tregs is a heterogeneous population with respect to their immunosuppressive capability. Lymphocytes are particularly rich in FKBP51 (FKBP5 gene), an immunophilin better known as the intracellular receptor for FK506 and rapamycin. Melanoma aberrantly expresses this immunophilin, which supports cancer resistance and invasion. Recently, our group has shown that melanoma interaction with immune cells, through PD-L1/PD1, bidirectionally generated the splicing of FKBP5 gene inducing a lower molecular weight form of FKBP51, termed FKBP51s, in both melanoma and lymphocyte. A study performed on PBMC of 64 patients with advanced melanoma (stage III/IV) showed that FKBP51s marks a Treg subset which was correlated, as an independent variable, to anti-CTLA4 (ipilimumab) response. More precisely, a low frequency of Treg FKBP51spos (1.2 and 0.04 and < 0.8%. After a transient increase registered following the first administration, the count decreased to 0.3+0.2% in responder patients. Interestingly, a patient with count = 0.72% developed autoimmune side effects that led to therapy discontinuation. Resolution of side effects was accompanied by an increase in Treg FKBP51s+ value to 9.9%; thenafter, anti-PD1 re-administration produced a successful and objective response. In vitro iTreg generation suggested that FKBP51s was induced in Treg CD25high, Ki67high and p70S6khigh , corresponding to a highly metabolically active profile associated with strong suppressive capability. Conclusion Our data reinforce the hypothesis that melanoma patients that benefit from immune checkpoint targeted therapy are recognizable by an expansion of a Treg subset which plays a central role in de-activation of stimulatory co-signalling pathways, in support of tumor immune evasion. Such a Treg subset is marked by FKBP51s, a splicing protein isoform generated by triggering of surface antigens (PD-L1, PD1) that are abundantly expressed on highly suppressive Tregs
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