Development of dependable controllers in the context of machines design

Proceedings of ICMD 2013In the domain of machines' design, one of the most important issues to solve is related with the controller's design, mainly, guaranteeing that the machine will behave as expected. In order to achieve a dependable controller, some steps can be considered, such as the formalization of its specification - before being translated to the program that will be inserted in the controller device - and the respective analysis and verification. Nowadays, some formal analysis techniques, such as formal verification, are used to achieve this purpose. The dependability of a controller, however, is impacted by its execution context. This paper proposes an approach for the formal verification of the specification of mechatronic system's controllers, which considers, on the formal verification tasks, the behavior of the plant and the behavior of the Human Machine Interface of the Mechatronic system. Some conclusions are extrapolated for other systems of the same kind

Intronless WNT10B-short variant underlies new recurrent allele-specific rearrangement in acute myeloid leukaemia.

Defects in the control of Wnt signaling have emerged as a recurrent mechanism involved in cancer pathogenesis and acute myeloid leukaemia (AML), including the hematopoietic regeneration-associated WNT10B in AC133bright leukaemia cells, although the existence of a specific mechanism remains unproven. We have obtained evidences for a recurrent rearrangement, which involved the WNT10B locus (WNT10BR) within intron 1 (IVS1) and flanked at the 5' by non-human sequences whose origin remains to be elucidated; it also expressed a transcript variant (WNT10BIVS1) which was mainly detected in a cohort of patients with intermediate/unfavorable risk AML. We also identified in two separate cases, affected by AML and breast cancer respectively, a genomic transposable short form of human WNT10B (ht-WNT10B). The intronless ht-WNT10B resembles a long non-coding RNA (lncRNA), which suggests its involvement in a non-random microhomology-mediated recombination generating the rearranged WNT10BR. Furthermore, our studies supports an autocrine activation primed by the formation of WNT10B-FZD4/5 complexes in the breast cancer MCF7 cells that express the WNT10BIVS1. Chemical interference of WNT-ligands production by the porcupine inhibitor IWP-2 achieved a dose-dependent suppression of the WNT10B-FZD4/5 interactions. These results present the first evidence for a recurrent rearrangement promoted by a mobile ht-WNT10B oncogene, as a relevant mechanism for Wnt involvement in human cancer

Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study

To assess the prognosis of peripheral T-cell lymphoma unspecified, we retrospectively analyzed 385 cases fulfilling the criteria defined by the World Health Organization classification. Factors associated with a worse overall survival (OS) in a univariate analysis were age older than 60 years (P=.0002), equal to or more than 2 extranodal sites (P=.0002), lactic dehydrogenase (LDH) value at normal levels or above (P<.0001), performance status (PS) equal to or more than 2 (Pless than or equal to.0001), stage III or higher (P=.0001), and bone marrow involvement (P=.0001). Multivariate analysis showed that age (relative risk, 1.732; 95% CI, 1.300-2.309; P<.0001), PS (relative risk, 1.719; 95% CI, 1.269-2.327, P<.0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564; P<.0001), and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023; P=.026) were factors independently predictive for survival. Using these 4 variables we constructed a new prognostic model that singled out 4 groups at different risk: group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%, respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and 38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and 18.0%, respectively; group 4,3 or 4 factors, with a 5-year and 10-year OS of 18.3 and 12.6%, respectively (Pless than or equal to.0001; log-rank, 66.79)

High incidence of late effects found in Hodgkin's lymphoma survivors, following recall for breast cancer screening

Assessment of late effects in a cohort of female Hodgkin's lymphoma patients treated with mantle radiotherapy, identified from the DoH breast cancer screening recall showed high mortality and frequent undiagnosed abnormalities in tissues affected by radiotherapy. With increasing age, this patient group may suffer premature cardiac and respiratory morbidity

Chemotherapy followed by low dose radiotherapy in childhood Hodgkin's disease: retrospective analysis of results and prognostic factors

PURPOSE: To report the treatment results and prognostic factors of childhood patients with Hodgkin's disease treated with chemotherapy (CT) followed by low dose radiotherapy (RT). PATIENTS AND METHODS: This retrospective series analyzed 166 patients under 18 years old, treated from January 1985 to December 2003. Median age was 10 years (range 2–18). The male to female ratio was 2,3 : 1. Lymphonode enlargement was the most frequent clinical manifestation (68%), and the time of symptom duration was less than 6 months in 55% of the patients. In histological analysis Nodular Sclerosis was the most prevalent type (48%) followed by Mixed Celularity (34.6%). The staging group according Ann Arbor classification was: I (11.7%), II (36.4%), III (32.1%) and IV (19.8%). The standard treatment consisted of chemotherapy multiple drug combination according the period of treatment protocols vigent: ABVD in 39% (n-65) of the cases, by VEEP in 13 %(n-22), MOPP in 13 %(n-22), OPPA-13 %(n-22) and ABVD/OPPA in 22 %(n-33). Radiotherapy was device to all areas of initial presentation of disease. Dose less or equal than 21 Gy was used in 90.2% of patients with most part of them (90%) by involved field (IFRT) or mantle field. RESULTS: The OS and EFS in 10 years were 89% and 87%. Survival according to clinical stage as 94.7%, 91.3%, 82.3% and 71% for stages I to IV(p = 0,005). The OS was in 91.3% of patients who received RT and in 72.6% of patients who did not (p = 0,003). Multivariate analysis showed presence of B symptoms, no radiotherapy and advanced clinical stage to be associated with a worse prognosis. CONCLUSION: This data demonstrating the importance of RT consolidation with low dose and reduced volume, in all clinical stage of childhood HD, producing satisfactory ten years OS and EFS. As the disease is highly curable, any data of long term follow-up should be presented in order to better direct therapy, and to identify groups of patients who would not benefit from radiation treatment

Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now?

Updated international guidelines published in 2006 have broadened the scope for the use of granulocyte colony-stimulating factor (G-CSF) in supporting delivery of myelosuppressive chemotherapy. G-CSF prophylaxis is now recommended when the overall risk of febrile neutropenia (FN) due to regimen and individual patient factors is ≥20%, for supporting dose-dense and dose-intense chemotherapy and to help maintain dose density where dose reductions have been shown to compromise outcomes. Indeed, there is now a large body of evidence for the efficacy of G-CSFs in supporting dose-dense chemotherapy. Predictive tools that can help target those patients who are most at risk of FN are now becoming available. Recent analyses have shown that, by reducing the risk of FN and chemotherapy dose delays and reductions, G-CSF prophylaxis can potentially enhance survival benefits in patients receiving chemotherapy in curative settings. Accumulating data from ‘real-world’ clinical practice settings indicate that patients often receive abbreviated courses of daily G-CSF and consequently obtain a reduced level of FN protection. A single dose of PEGylated G-CSF (pegfilgrastim) may provide a more effective, as well as a more convenient, alternative to daily G-CSF. Prospective studies are needed to validate the importance of delivering the full dose intensity of standard chemotherapy regimens, with G-CSF support where appropriate, across a range of settings. These studies should also incorporate prospective evaluation of risk stratification for neutropenia and its complications

Corrigendum: Intronless WNT10B-short variant underlies new recurrent allele-specific rearrangement in acute myeloid leukaemia (Scientific Reports (2017) 6 (37201) DOI: 10.1038/srep37201)

This Article contains typographical errors in the Methods section under subheading 'WNT10B/WNT10BIVS1 Gene expression analysis'. "The WNT10B (P4-P2 primers) amplification was performed with following thermal conditions: 94 \ub0C for 1 min, 33 cycles at 94\ub0 for 30 s, 58 \ub0C for 30 s, 72 \ub0C for 30 s and 72 \ub0C for 5 min. The amplification of WNT10BIVS1 (P3-P2 primers) was performed as follows: 94 \ub0C for 1 min, 33 cycles at 94\ub0 for 30 s, 61 \ub0C for 30 s, 72 \ub0C for 30 s and 72 \ub0C for 5 min". should read: "The WNT10B (P4-P1 primers) amplification was performed with following thermal conditions: 94 \ub0C for 1 min, 33 cycles at 94\ub0 for 30 s, 58 \ub0C for 30 s, 72 \ub0C for 30 s and 72 \ub0C for 5 min. The amplification of WNT10BIVS1 (P3-P1 primers) was performed as follows: 94 \ub0C for 1 min, 33 cycles at 94\ub0 for 30 s, 61 \ub0C for 30 s, 72 \ub0C for 30 s and 72 \ub0C for 5 min". In the same section, under subheading 'WNT10B/WNT10BIVS1 Absolute quantification', "We performed the experiment on Bio-Rad's QX100 ddPCR system and the reaction mixtures in a final 20 \u3bc l volume consisted of 10 \u3bc l of 2 7 One-Step RT-ddPCR Supermix (Bio-Rad, CA, USA), 1 mM Manganese Acetate solution (Bio-Rad, CA, USA), 0.5 \u3bc M of primers (WNT10B: P4-P2, WNT10BIVS1 P3-P2), 0.25 \u3bc M WNT10B-dd1 and WNT10BIVS1-dd2 probes". should read: "We performed the experiment on Bio-Rad's QX100 ddPCR system and the reaction mixtures in a final 20 \u3bc l volume consisted of 10 \u3bc l of 2 7 One-Step RT-ddPCR Supermix (Bio-Rad, CA, USA), 1 mM Manganese Acetate solution (Bio-Rad, CA, USA), 0.5 \u3bc M of primers (WNT10B: P4-P1, WNT10BIVS1-P3-P1), 0.25 \u3bc M WNT10B-dd1 and WNT10BIVS1-dd2 probes"

Il manoscritto Saibante-Hamilton 390 : edizione critica

L\u2019illustre codice Saibante-Hamilton 390 della Staatsbibliothek zu Berlin, che qui si pubblica in edizione critica, ha destato l\u2019interesse di alcuni tra i pi\uf9 grandi filologi romanzi dell\u2019Otto e Novecento. Realizzato verosimilmente a Treviso negli anni Ottanta del Duecento, il manufatto conserva un florile-gio di testi latini e volgari di straordinaria importanza: \ue8 \uabil primo manoscritto italiano a presentarsi in forma di raccolta coerente, e i testi volgari in esso contenuti (spesso degli unica) rappresentano il pi\uf9 antico corpus di opere di carattere didattico-moraleggiante dell\u2019Italia settentrionale. Le numerose miniature del codice intrecciano un fitto dialogo con i testi e hanno funzione non solo decorativa, ma an-che, e ancor pi\uf9, di complemento esegetico\ubb (dall\u2019Avvertenza, p. V). Il volume raccoglie, la prima volta, l\u2019edizione critica integrale di questo monumentum delle Origini ita-liane, accompagnato da uno studio multiprospettico che ripercorre la storia antica e moderna del codi-ce, facendo emergere le particolarit\ue0 del suo assetto materiale, ma anche i numerosi \u2013 e talvolta negletti \u2013 pregi letterari, artistici, storico-culturali che hanno dato vita alla sua peculiare fisionomia. L\u2019edizione complessiva del codice, che permette di osservare l\u2019oggetto nella sua materialit\ue0 e nella sua realt\ue0 testimoniale consente, da un lato, la piena intelligenza dei testi che lo compongono, osservati nel-la stratificazione testuale e linguistica che li caratterizza; dall\u2019altro, offre l\u2019opportunit\ue0 d\u2019indagare ap-pieno il rapporto tra testo e immagine che fa del manoscritto un caso pressoch\ue9 unico nel panorama della produzione manoscritta dei primi secoli della letteratura italiana. Le note introduttive e i commenti puntuali a ciascuna delle opere, insieme al formario analitico comple-to (volgare e latino) corredano l\u2019edizione del pi\uf9 aggiornato e sistematico impianto esegetico dedicato ai testi conservati dal manoscritto. L\u2019edizione, i saggi, i commenti, le note linguistiche e il formario, insieme agli studi codicologici e sto-rico-artistici, nonch\ue9 all\u2019indagine puntuale dei paratesti e dell\u2019impianto illustrativo indicano altres\uec un nuovo ed efficace paradigma nello studio dei grandi manoscritti letterari medievali.The renowned Saibante-Hamilton 390 manuscript, held in the Staatsbibliothek of Berlin and here presented for the first time in a critical edition, has sparked the interest of the greatest philologists of the nineteenth and twentieth centuries. Presumably produced in Treviso in the early 1280s, it preserves a florilegium of Latin and vernacular texts of extraordinary importance: it is \u201cthe first Italian manuscript organized as a coherent collection, and the vernacular texts contained in it represent the most ancient corpus of didactic-moralizing works of northern Italy. The copious illuminations of the codex are in a constant dialogue with the texts and play not only a decorative role, but also an important interpretive one\u201d(from the Avvertenza, p. V). This volume presents, for the first time, the integral critical edition of a monument of the Italian Origins, accompanied by a multi-disciplinary study that traces the ancient and modern history of the codex, bringing out its specificities, but also its literary, artistic and historical-cultural qualities. The complete edition, which affords access to the object in its materiality, also allows, on the one hand, the full comprehension of the texts that compose it, examined in their peculiar textual and linguistic stratification; on the other, it gives the opportunity to investigate the relationship between the texts and illuminations that complement them. Such an apparent and explicit relationship makes the manuscript a unique artifact in the history of book production of the first centuries of Italian (and European) literature. The introductory notes and the commentaries to each text, together with the analytical form list (in the vernacular and in Latin) of all the texts offer an updated and organized exegetical system; the codicological and art historical analysis, the investigation on the para-texts and the illustrative system, which are integrated in the exegetical section, propose a new and effective paradigm for the study of the great literary manuscripts of the Middle Ages

Primary mediastinal B-cell lymphoma with sclerosis: an aggressive tumor with distinctive clinical and pathologic features.

PURPOSE: To evaluate the clinical features of presentation, the morphologic and immunohistochemical pattern, the modality of spread, and the response to current treatments of patients with primary mediastinal B-cell lymphoma, a recently documented subtype of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty consecutive patients (14 males, 16 females; median age, 26 years) with primary mediastinal B-cell lymphoma with sclerosis were studied. RESULTS: The clinical aspects were largely homogeneous: 93% presented with chest symptoms of a rapidly enlarging mass of the anterior mediastinum; the tumor was bulky in 73%, and superior vena cava syndrome (SVCS) was present in 57%. Also, patients without SVCS symptoms showed subclinical venacaval compression at computed tomographic (CT) scan, for a total incidence of caval obstruction of 80%. Intrathoracic extension to adjacent organs was seen in 47% of patients. Despite its invasive behavior, only four patients showed extrathoracic spread at diagnosis. In 23 cases, the tumor presented with morphologic features that resembled follicular center-cell lymphomas. In seven, the neoplastic population was composed mainly of centrocyte-like cells with abundant clear cytoplasm not referable to any known B-cell lymphoma subtype. All cases showed huge sclerosis. Of 29 patients assessable for response, 16 (55%) achieved a complete response (CR): five of 14 (36%) treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 11 of 15 (73%) treated with methotrexate plus leucovarin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) or etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) (P = .047). We could identify no clinical, biologic, or histopathologic features significantly correlated with response. After chemotherapy, 14 of 16 remitters received consolidation radiotherapy to the mediastinum. At 3 years, the actuarial survival rate is 38% for all cases and 72% for remitters. None of the 13 patients who did not achieve CR responded to salvage treatments. CONCLUSION: This study shows that primary mediastinal B-cell lymphoma with sclerosis is a distinctive subtype of NHL with unique clinicopathologic aspects and aggressive behavior. Prompt recognition and aggressive treatment may provide long survival in a good proportion of cases. However, a subset of patients is extremely refractory to first