A Risk-Based Approach to Automate Preventive Maintenance Tasks Generation by Exploiting Autonomous Robot Inspections in Wind Farms

In this paper, we dealt with some problems of operation and maintenance in wind farms. We focused on the main critical aspects of any maintenance strategy, which must include the identification of the plant elements to inspect as well as the planning of the possible actions aimed at minimizing production losses. At the same time, any maintenance strategy must take into account the possible costs. In fact, those decisions can be made based on risk-based methods. We designed a risk-based maintenance approach to plan inspection tasks to be assigned to service robots in wind power plants. A supervisory control and data acquisition (SCADA) system is employed to collect and manage suitable data (power, wind velocity, and related machine events), and the risk is evaluated on a daily basis over the data collected. The evaluation of the risk is strictly related to the healthiness of the power plant itself. Then, the tasks are created and scheduled based on a certain priority, which is strictly correlated with the evaluated risk. For the analysis of our approach, we used the real data collected on a wind power plant in Greece over 396 days. The power plant is capable to produce an overall power of 7.2 MW, and it is composed of eight wind turbines of 900 KW per each. We observed that, out of 396 days, 50 days presented machine events leading to a related risk evaluation for which our approach will produce 258 inspection tasks. From this analysis, we conclude that the application of the risk-based methodology paired with the exploitation of permanent robots on the field could result in a 225-MWh reduction of the plant's lost production, in other words, an increase of production of 45.6%

Ontological Smart Contracts in OASIS: Ontology for Agents, Systems, and Integration of Services

In this contribution we extend an ontology for modelling agents and their interactions, called Ontology for Agents, Systems, and Integration of Services (in short, OASIS), with conditionals and ontological smart contracts (in short, OSCs). OSCs are ontological representations of smart contracts that allow to establish responsibilities and authorizations among agents and set agreements, whereas conditionals allow one to restrict and limit agent interactions, define activation mechanisms that trigger agent actions, and define constraints and contract terms on OSCs. Conditionals and OSCs, as defined in OASIS, are applied to extend with ontological capabilities digital public ledgers such as the blockchain and smart contracts implemented on it. We will also sketch the architecture of a framework based on the OASIS definition of OSCs that exploits the Ethereum platform and the Interplanetary File System.Comment: This work has been accepted for publication at The 14th International Symposium on Intelligent Distributed Computing, 21--23 September 2020, Scilla, Reggio Calabria, Italy. Proceedings and conference have been postponed to September 2021. Paper accepted on 8 September 202

Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor

Chronic myelogenous leukaemia (CML) is a clonal myeloproliferative disorder. Recent evidence indicates that altered crosstalk between CML and mesenchymal stromal cells may affect leukaemia survival; moreover, vesicles released by both tumour and non-tumour cells into the microenvironment provide a suitable niche for cancer cell growth and survival. We previously demonstrated that leukaemic and stromal cells establish an exosome-mediated bidirectional crosstalk leading to the production of IL8 in stromal cells, thus sustaining the survival of CML cells. Human cell lines used are LAMA84 (CML cells), HS5 (stromal cells) and bone marrow primary stromal cells; gene expression and protein analysis were performed by real-time PCR and Western blot. IL8 and MMP9 secretions were evaluated by ELISA. Exosomes were isolated from CML cells and blood samples of CML patients. Here, we show that LAMA84 and CML patients\u2019 exosomes contain amphiregulin (AREG), thus activating epidermal growth factor receptor (EGFR) signalling in stromal cells. EGFR signalling increases the expression of SNAIL and its targets, MMP9 and IL8. We also demonstrated that pre-treatment of HS5 with LAMA84 exosomes increases the expression of annexin A2 that promotes the adhesion of leukaemic cells to the stromal monolayer, finally supporting the growth and invasiveness of leukaemic cells. Leukaemic and stromal cells establish a bidirectional crosstalk: exosomes promote proliferation and survival of leukaemic cells, both in vitro and in vivo, by inducing IL8 secretion from stromal cells. We propose that this mechanism is activated by a ligand\u2013receptor interaction between AREG, found in CML exosomes, and EGFR in bone marrow stromal cells

Cervical dystonia patients display subclinical gait changes

Gait disorders in cervical dystonia (CD) are reported in patients under DBS or in severe cases complicated with spinal deformities

Extracorporeal shock waves alone or combined with raloxifene promote bone formation and suppress resorption in ovariectomized rats

Osteoporosis is a metabolic skeletal disease characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. We examined the beneficial effect of shock waves (SW) alone or in combination with raloxifene (RAL) on bone loss in ovariectomized rats (OVX). Sixteen weeks after surgery, OVX were treated for five weeks with SW at the antero-lateral side of the right hind leg, one session weekly, at 3 Hz (EFD of 0.33 mJ/mm2), or with RAL (5 mg/kg/die, per os) or with SW+RAL. Sera, femurs, tibiae and vertebrae were sampled for following biochemical and histological analysis. SW, alone or combined with RAL, prevented femur weight reduction and the deterioration of trabecular microarchitecture both in femur and vertebrae. All treatments increased Speed of Sound (SoS) values, improving bone mineral density, altered by OVX. Serum parameters involved in bone remodeling (alkaline phosphatase, receptor activator of nuclear factor kappa-B ligand, osteoprotegerin) and osteoblast proliferation (PTH), altered by ovariectomy, were restored by SW and RAL alone or in combination. In tibiae, SW+RAL significantly reduced cathepsin k and TNF-α levels, indicating the inhibition of osteoclast activity, while all treatments significantly increased runt-related transcription factor 2 and bone morphogenetic-2 expression, suggesting an increase in osteoblastogenic activity. Finally, in bone marrow from tibiae, SW or RAL reduced PPARγ and adiponectin transcription, indicating a shift of mesenchymal cells toward osteoblastogenesis, without showing a synergistic effect. Our data indicate SW therapy, alone and in combination with raloxifene, as an innovative strategy to limit the hypoestrogenic bone loss, restoring the balance between bone formation and resorption

Idiopathic Aqueductal Stenosis: Late Neurocognitive Outcome in ETV Operated Adult Patients

ObjectiveThe aim of the present study is to evaluate a neurocognitive outcome in patients affected by late-onset idiopathic aqueductal stenosis (LIAS) who underwent endoscopic third ventriculostomy (ETV). Materials and MethodsA prospective study was conducted between January 2015 and December 2017 in a series of 10 consecutive adult patients referred to the Neurosurgery Department of IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. All the adult patients admitted with absence of CSF flow through the aqueduct in phase-contrast (PC)-MRI sequences or a turbulence void signal in T2-weighted images in midsagittal thin-slice MR sequences underwent a specific neuroradiological, neurological, and neurocognitive assessment pre- and postoperatively. ResultsAll patients affected by gait and sphincter disturbances improved after ETV. Attentive and executive functions as well as visuo-spatial memory and verbal executive functions improved in several patients. Similarly, the affective and behavioral scales improved in almost 50% of the patients. No major complications have been recorded, and no patients required a second surgery for shunt placement. ConclusionEndoscopic third ventriculostomy represents a safe and effective surgical procedure for the treatment of LIAS. In addition to neurological improvement, we demonstrated also postoperative neurocognitive improvement mainly in attentive and executive functions, visuo-spatial memory, verbal executive functions, and behavioral and affective domains

The Vulvar Immunohistochemical Panel (VIP) Project:Molecular Profiles of Vulvar Squamous Cell Carcinoma

Introduction: The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14-15.87, p = 0.03) and 2.68 (CI 95% = 1.0-7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expressio

Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1-3 D4Z4 reduced alleles: Experience of the FSHD Italian National Registry

OBJECTIVES: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers ( 64 8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1-3 repeats (1-3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1-3 DRA. SETTING: Italy. PARTICIPANTS: 66 index cases and 33 relatives carrying 1-3 DRA. OUTCOMES: The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk. RESULTS: No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1-3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment. CONCLUSIONS: The size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity

il CAI modula l'espressione di Bcr-Abl tramite l'aumento dei Ros in cellule di leucemia mieloide cronica Imatinib-resistenti

La leucemia mieloide cronica (LMC) \ue8 una neoplasia causata da una traslocazione reciproca non bilanciata tra il braccio lungo del cromosoma 9 e quello del cromosoma 22. Tale traslocazione determina la formazione dell\u2019oncogene di fusione bcr-abl codificante per un\u2019oncoproteina con attivit\ue0 tirosin-chinasica costitutiva. Le conoscenze dei meccanismi molecolari alla base della neoplasia, acquisite negli ultimi anni, hanno permesso di sviluppare terapie volte all\u2019inibizione dell\u2019attivit\ue0 chinasica della chimera BCR-ABL. Tra queste, l\u2019imatinib mesilato (IM), inibitore selettivo della protein chinasi, ha rivoluzionato le terapie per la LMC. Sebbene numerosi pazienti in fase cronica, trattati con IM, abbiano raggiunto la remissione completa della neoplasia, in diversi casi si \ue8 avuto ricaduta e/o progressione in fase accelerata o blastica. Da qui la necessit\ue0 di individuare nuovi farmaci che agiscano su bersagli differenti. Il carbossiamidotriazolo (CAI) \ue8 un nuovo farmaco citostatico anticancro in fase II dei clinical trials al NCI. Tale farmaco \ue8 un inibitore dei canali del Ca2+ non voltaggio dipendenti dunque agisce inibendo la proliferazione, la motilit\ue0 e la sopravvivenza di numerose linee tumorali. Il nostro gruppo di ricerca ha dimostrato che dosi sub-tossiche di CAI inibiscono la proliferazione di cellule LMC IM-resistenti (LAMA84R, K562R e KCL22R) ed inducono apoptosi. Tali effetti sono associati alla capacit\ue0 di questo farmaco di determinare un drastico decremento dei livelli generali di fosforilazione in tirosina, inibendo vie di trasduzione del segnale BCR/ABL-dipendenti ed indipendenti, ma anche un drastico decremento dei livelli totali dell\u2019 oncoproteina (Alessandro et al., 2008). Al fine di comprendere in modo pi\uf9 approfondito il meccanismo molecolare d\u2019azione del CAI, abbiamo utilizzato, come modello sperimentale, linee cellulari mieloidi murine (32D) trasfettate con plasmidi codificanti per BCR/ABL-p210 (Full lenght), BCR/ABL-T315I e BCR/ABL-E255K. T315I ed E255K sono mutazioni in Bcr-Abl tra le pi\uf9 rappresentate nella popolazione di pazienti affetti da LMC IM-resistenti. I nostri risultati hanno mostrato che il CAI riduce sia la proliferazione delle tre linee cellulari, in modo dose e tempo dipendente, sia la fosforilazione di Bcr-Abl, ma soprattutto i livelli totali di proteina; il CAI agisce anche sul mutante T315I, su cui persino i farmaci di nuova generazione non hanno mostrato alcuna efficacia. Poich\ue9 il CAI non sembra agire sui livelli di proteina totale tramite una prematura degradazione ubiquitina-proteasoma dipendente n\ue9 sembra regolare in modo significativo il ciclo cellulare, abbiamo ipotizzato che possa agire inducendo un aumento delle specie reattive dell\u2019ossigeno (ROS) all\u2019interno della cellula. A tale scopo abbiamo sottoposto le linee LAMA84R, 32D p210 e 32D T315I a trattamenti con dosi e tempi crescenti di CAI per valutare in tali cellule i livelli di ROS. I risultati ottenuti consentono di concludere che il CAI induce sulle cellule Bcr-Abl+ ed IM-resistenti un aumento della produzione di ROS, in grado di indurre uno stress cellulare. Poich\ue9 il CAI \ue8 gi\ue0 in fase II di sperimentazione clinica, per il trattamento di altre neoplasie, questi risultati forniscono indicazioni rilevanti per un uso razionale di questo farmaco nel trattamento di pazienti affetti da LMC che non rispondono alla monoterapia con IM

The Assessment of the Ethical Organizational Culture: Validation of an Italian Short Version of the Corporate Ethical Virtues Model Based Questionnaire

Background: In the context of the relationship between work and ethics, it is essential to be able to analyse the Ethical Organizational Culture of the work environment through the use of multidimensional tools. The lack of validated tools on the Italian population led us to develop a short Italian version of the Kaptein’s Corporate Ethical Virtues Model. The purpose of this study is to validate this tool to be used in Italy, in public administration notably. Methods: Within an assessment campaign of the working conditions of the operators (all 10422 white collar employees) of an Italian Public Administration for the purposes of welfare and safety of working conditions we performed a validation study. At the time of the survey, an exploratory factor analysis was carried out by selecting the items on the basis of factor loads. We used the Cronbach’s alpha coefficients to evaluate the internal consistency. Confirmatory factor analysis was conducted to assess the goodness-of-fit of the latent structure underlying the ethical culture indicators. Results: In the exploratory factor analysis out of 690 questionnaires, 405 (59%) were filled out; we selected 24 items with a load factor between 0.61 and 0.92. The internal consistency was good (α=0.917). In the confirmatory factor analysis, out of 5497 questionnaires, 3706 (67%) were filled out; the confirmatory factor analysis model showed an excellent adaptation of the model of the eight-dimensional structure of the 24-item questionnaire (RMSEA=0.052 [90%CI 0.050-0.054], CFI=0.96, TLI=0.95). Conclusion: The Italian short version of the Corporate Ethical Virtues Model based Questionnaire demonstrated good psychometric properties. In Italy the adapted questionnaire has evidence of its validity and reliability to be used in further studies and to be able to conduct surveys on ethical climate about companies and to foster actions to improve working conditions in relation to ethics