C4R Project Increases Rail Capacity without Laying Down New Tracks

AbstractRail freight transport is today characterized by inefficiencies in the use of the existing infrastructure while the growing demand is activated by giant containers vessels handling thousands of units in the ports. Lack of industrialization prevents gaining from economies of scale while bottlenecks penalize the optimization of the network use. The rail freight transport market share remains low whereas for environmental reasons immediate progress is required. Capacity4Rail intends to analyze the key factors enabling rail freight market share to increase on the most promising segments.The innovations planned by Capacity4Rail are concentrated on three macro-areas from the concept to simulations and tests: wagon structure design, wagon equipment technology and train maneuverability.For the wagon structure, the project focuses on the new design giving direct efficiency: better payload, less deadweight, extended usable length, maintenance cost reduction. With a reduced weight due to the use of new materials the design evolution allows to make the best use of the gauge profile.For the wagon equipment technology a continuous electric line carrying a bus of information all along the train and bringing energy to the wagon allows placing various sensors increasing safety and reliability. With this new wagon connectivity, predictive maintenance is developed but also accurate real time information are available for the customers enhancing the planning efficiency of the next supply chain evolution. The wagons are equipped with an electric command of the pneumatic brakes for an instant and simultaneous braking and releasing. The brakes of all wagons reduces drastically the longitudinal forces in the couplings enabling progressive lengthening of the train reducing operational costs and network capacity consumption per ton transported.For the train, this new braking system improves its maneuverability, giving access to better paths aiming to reduce the wear of the wheels created by the new brake composite shoes imposed for noise reduction.All these potential progress are researched and checked in terms of affordability taking into account not only the global added value created but an equitable reward of all the stakeholders having invested for such innovations. Proposed roadmaps incorporate viable business models for a progressive implementation on the basis of simulations. A virtuous circle is initiated improving the use of assets, reducing noise, informing customers more efficiently, reducing maintenance and operational costs in an affordable way

Rail freight research: How market trends and customers' needs drive technology innovation

The article presents an investigation of current market trends and customers’ requirements, which have driven research aimed at developing a novel wagon concept that integrates innovative solutions relating to the identified major challenges for the freight vehicles of the future. These challenges are: i. Freight condition monitoring; ii. Lightweight wagon design; and iii. Predictive maintenance. This research was initiated by the INNOWAG project, which is funded by the Shift2Rail Joint Undertaking under the EU’s Horizon 2020 research and innovation programme. The major challenges in rail freight competitiveness relate to the increasing complexity and sophistication of supply chains, increasing transport capacity and logistic capability, as well as improving RAMS and lowering LCC. Therefore, the goal is to develop intelligent cargo monitoring and predictive maintenance solutions integrated on a novel concept of lightweight wagon

The Discipline of Pediatric Urology: Prerogatives and Necessities

To the Editor, The aim of this “position paper” is to describe the discipline of Pediatric Urology with its clinical and cultural competencies, represent the reasons for legitimizing its existence, and reinforce its importance in the “scenario” of the National Italian Healthcare System. The requisites and the educational requirements were defined by both the Italian Ministry of Health with the State-Regions Conference, and the European Union [...

Breast conserving treatment for ductal carcinoma in situ in the elderly: Can radiation therapy be avoided? Our experience

AbstractIntroduction: Ductal Carcinoma In Situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 15–20% of all new breast cancers. If appropriately managed, DCIS has a small chance of impacting on patient life expectancy. Despite the possibility of a further recurrence or of a development in an invasive form, we are unable to select treatment of choice especially in the elderly. In particularly we risk an overtreatment of women at low risk of progression to invasive breast cancer. The aim of this study was to retrospectively evaluate the outcome of elderly patients affected by DCIS not undergoing Radiation Therapy (RT) after Breast Conserving Surgery (BCS). Material and methods: We reviewed our prospectively-maintained database from 1998 to 2013, selecting all women over 65 years old diagnosed with DCIS who did not receive RT for personal choice. We considered two groups, according to the risk of local recurrence (Low Risk (Group 1) vs. High Risk (Group 2)). Results: We identified 44 cases of DCIS treated with surgery alone or with surgery followed by adjuvant tamoxifen. 24 patients presented low risk of local recurrence (Group 1) and 20 had characteristics associated to high risk of local recurrence (Group 2). At a median follow-up of 66.3 months, no local recurrences have been described in group 1. No patients presented distant metastases, while 4 patients died for other causes. At a median follow-up of 72 months we observed 5 local recurrences in the second group (p < 0.05). Conclusion: Our results suggest that radiation therapy can be safely avoided in a selected group of elderly patients affected by DCIS

In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants

BACKGROUND: Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. METHODS: a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. RESULTS: DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal responders with no treatment changes. CONCLUSIONS: DS enables a larger window of detection of emerging BCR-ABL1 KD mutations predicting for an impending relapse. A 'Warning' response may represent a rational trigger, besides 'Failure', for DS-based mutation screening in CML patients undergoing second-line TKI therapy

Scenarios of Electromobility. Cross ferilisation and Dissemination of Best Practices and Researches within EU Policies Webinar proceedings

La pubblicazione riporta gli esiti del webinar incentrato sull'user center design dei veicoli elettrici, delle loro infrastrutture di ricarica e sulle sperimentazioni dei veicoli elettrici leggeri nei sistemi di trasporto urbano di Torino e Venaria Reale (IT), Villach (Austria) e Calvià (Spagna). La pubblicazione e il seminario sono parte del progetto STEVE, finanziato dal programma europeo Horizon2020, e incentrato sulla sperimentazione di modelli di mobilità elettrica leggera nelle aree urbane. Il progetto ha coinvolto città, piccole e medie imprese e università di sette paesi europei. Urban Lab ha collaborato con la Città di Torino a delineare le raccomandazioni rivolte ai decision makers in materia di pianificazione della mobilità urbana, emerse dai risultati dei tre anni di progetto

Health-related quality of life in patients with chronic myeloid leukemia receiving first-line therapy with nilotinib

BACKGROUND: Although a wealth of efficacy and safety data is available for many tyrosine kinase inhibitors used in chronic myeloid leukemia (CML), there is a dearth of information on their impact on patients' health-related quality of life (HRQOL). The primary objective of this study was to evaluate HRQOL and fatigue outcomes in patients with CML receiving first-line therapy with nilotinib. METHODS: This was a multicenter, prospective study enrolling 130 patients with chronic-phase CML. HRQOL and fatigue were evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and its validated Fatigue module at the baseline and then at 3, 6, 12, 18, and 24 months. The primary prespecified HRQOL endpoints defined in the study protocol for longitudinal analysis were the Physical Functioning, Social Functioning, Role Functioning, and Fatigue scales. The remaining scales were investigated on an exploratory basis. RESULTS: The rate of baseline compliance with the HRQOL assessment was 95.4% (124 of 130), and the rate of overall compliance with HRQOL forms was 91%. Among the 4 prespecified primary HRQOL endpoints, statistically significant improvements over time were found for Physical Functioning (P =.013), Role Functioning (P =.004), and Fatigue (P <.001). Clinically meaningful improvements were found already 3 months after the treatment start. The baseline patient self-reported fatigue severity was an independent predictive factor for the achievement of a major molecular response with an odds ratio of 0.960 (95% confidence interval, 0.934-0.988; P =.005). CONCLUSIONS: For most patients, HRQOL improvements with nilotinib occur during the early phase of therapy and are maintained over time. Also, a more systematic HRQOL evaluation during the diagnostic workup of CML may help to predict clinical outcomes. Cancer 2018;124:2228-37. © 2018 American Cancer Society

Prognostic Factors for Overall Survival In Chronic Myeloid Leukemia Patients: A Multicentric Cohort Study by the Italian CML GIMEMA Network

An observational prospective study was conducted by the CML Italian network to analyze the role of baseline patient characteristics and first line treatments on overall survival and CML-related mortality in 1206 newly diagnosed CML patients, 608 treated with imatinib (IMA) and 598 with 2nd generation tyrosine kinase inhibitors (2GTKI). IMA-treated patients were much older (median age 69 years, IQR 58-77) than the 2GTKI group (52, IQR 41-63) and had more comorbidities. Estimated 4-year overall survival of the entire cohort was 89% (95%CI 85.9-91.4). Overall, 73 patients (6.1%) died: 17 (2.8%) in the 2GTKI vs 56 (9.2%) in the IMA cohort (adjusted HR=0.50; 95% CI=0.26-0.94), but no differences were detected for CML-related mortality (10 (1.7%) vs 11 (1.8%) in the 2GTKIs vs IMA cohort (sHR=1.61; 0.52-4.96). The ELTS score was associated to CML mortality (high risk vs low, HR=9.67; 95%CI 2.94-31.74; p&lt;0.001), while age (per year, HR=1.03; 95%CI 1.00-1.06; p=0.064), CCI (4-5 vs 2, HR=5.22; 95%CI 2.56-10.65; p&lt;0.001), ELTS score (high risk vs low, HR=3.11; 95%CI 1.52-6.35, p=0.002) and 2GTKI vs IMA (HR=0.26; 95%CI 0.10-0.65, p=0.004) were associated to an increased risk of non-related CML mortality. The ELTS score showed a better discriminant ability than the Sokal score in all comparisons

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 6410% at 3 months, 641% at 6 months, 640.1% at 12 months, 640.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 &gt;10% at 3 and 6 months, &gt;1% at 12 months, and &gt;0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR