Pandemia e contratto. Alcune proposte per il contenimento dell?incertezza.

Il diritto dei contratti ambisce sempre a preservare continuità e certezza dei rapporti. La pandemia è però un?emergenza senza precedenti (per lo meno contemporanei) e chiede all?interprete uno sforzo supplementare perché la soglia di continuità e certezza resti alta, tanto per i rapporti instaurati nel corso della crisi, quanto per quelli già in atto ma destinati a perdurare. Le risposte devono fondere le regole in vigore per i tempi ordinari con quelle imposte dall?emergenza, senza incrinare ma anzi rinsaldando il valore del contratto come ordinamento dei privati

cae update of cae models on actual manufactured shapes

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P495: UNLOCKING THE POTENTIAL OF SYNTHETIC PATIENTS FOR ACCELERATING CLINICAL TRIALS: RESULTS OF THE FIRST GIMEMA EXPERIENCE

Background: Artificial intelligence is contributing to improve different medicine areas including clinical trial design. One field that holds a great potential is represented by the use of digital data as an alternative to real ones. The generation of a virtual cohort of patients might be advantageous since an artificial group of patients resembles the real dataset in all the key features but it does not include any identifiable real-patient data, tackling - by a privacy standpoint – the “burden” of collecting data subjects’ consent as well as the shortcomings of common anonymization techniques. Aims: To test the feasibility of this approach and evaluate its potential in clinical trial design, we built an in-silico cohort based on the large dataset of patients enrolled in the GIMEMA AML1310 study (Venditti et al. 2019), which entailed a “3 + 7”-like induction and a risk-adapted, MRD-directed post-remission transplant allocation. Methods: To create the synthetic cohort of patients, a machine learning generative model was constructed from the real individual-level data of the AML1310 study, capturing its patterns and statistical properties. AML1310 enrolled 500 patients (median age 49 years old) in 55 GIMEMA Institutions. All patients were NCCN2009 risk classified and analyzed by morphology, cytogenetics, molecular biology and multiparametric flow cytometry. The subset of 445 patients with ELN2017 risk classification available was used. To this purpose, the R package “synthpop” was used considering a parametric method: for binary data the logistic regression, for a factor with > 2 levels the polytomous logistic regression, for an ordered factor with > 2 levels the ordered polytomous logistic regression. For time to event variables the classification and regression trees method was used. Next, we verified the adherence of the virtual cohort to the original one in terms of age, gender, PS, WBC count, FLT3 and NPM1 mutations, risk category, CR achievement, MRD, transplant rate. Virtual and real cohorts were also compared in terms of survival outcomes. Results: By using the real-patient dataset from the AML1310 trial, a virtual cohort of 850 patients, named synthAML1310, was generated. By comparing the two cohorts, we observed that the clinico-biological characteristics and response evaluations (CR and MRD rates) did not differ significantly. Moreover, as depicted in Figure 1, the curves of OS and DFS were superimposable. Indeed, at 2 years, OS was 57% (52.5%-61.9%) in the original and 59.1% (55.9%-62.6%) in the synthAML1310 cohort. DFS was 55.1% (49.8%-60.9%) in the original and 55.1% (51.3%-59.2%) in the synthetic cohort. Summary/Conclusion: These results demonstrate the success of this approach in producing a virtual dataset that perfectly mimics the original and that, from a “privacy by design” perspective, minimizes the risk of re-identification of patients. Mirroring an AML population treated with a conventional chemotherapeutic approach, synthAML1310 is suitable to represent the control group when testing novel innovative treatments, most likely in an in-silico randomized trial, but also in other settings like propensity score matching analyses in observational studies. Shifting to an in-silico trial would overcome the challenges of randomized trials and it would be beneficial also for patients. since, they would receive only the experimental treatment without being exposed to the “less active“ therapy, thus limiting treatment failures and toxicity. Also, enrolment and the attainment of final results would be faster

A vision for a lightweight railway wheelset of the future

Rail vehicle lightweighting using fibre reinforced polymer composite materials is essential for the future of rail. This is recognised as a means of reducing carbon dioxide production through lower energy consumption, as well as reducing the impact on track degradation, thus delivering improved rail capacity and performance. This paper presents an overview of the work conducted within work package three of the NEXTGEAR project focused on the ‘wheelset of the future’. Three concepts for a hybrid metallic-composite railway axle are proposed and their strengths and weaknesses are assessed. A finite element analysis on the selected concept was conducted, including a solution for the bonded joints of the metallic collars which provide the interface to the wheels and bearings. An axle mass reduction of over 63% was shown. An overview is also provided regarding the analysis of manufacturability of the axle, non-destructive methods for axle inspection/structural health monitoring and effects of impacts from ballast stones. Finally, a preliminary evaluation of the benefits arising from the reduction of the unsprung masses is provided, based on multibody simulations of vehicle dynamics

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Objective To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the frst pandemic wave, Lombardia. Methods Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions We detected an increased incidence of GBS in COVID-19 patients which can refect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures