Insulin-like Growth Factor-1 Receptor (IGF-1R) expression on Circulating Tumor Cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial

Purpose To evaluate the prognostic value of IGF-1R expression on circulating tumor cells (CTCs) in a prospective randomized clinical trial comparing chemotherapy plus metformin with chemotherapy alone in metastatic breast cancer (MBC) patients. Methods CTCs were collected at baseline and at the end of chemotherapy. An automated sample preparation and analysis system (CellSearch) were customized for detecting IGF-1R expression. The prognostic role of CTC count and IGF-1R was assessed for PFS and OS by univariate and multivariate analyses. Results Seventy-two out of 126 randomized patients were evaluated: 57% had >= 1 IGF-1R positive CTC and 37.5% >= 4 IGF-1R negative cells; 42% had CTC count >= 5/7.5 ml. At univariate analysis, the number of IGF-1R negative CTCs was strongly associated with risk of progression and death: HR 1.93 (P = 0.013) and 3.65 (P = 0.001), respectively; no association was detected between number of IGF-1R positive CTCs and PFS or OS (P = 0.322 and P = 0.840). The prognostic role of CTC count was confirmed: HR 1.69, P = 0.042 for PFS and HR 2.80 for OS, P = 0.002. By multivariate analysis, the prognostic role of the number of IGF-1R negative CTCs was maintained, while no residual prognostic role of CTC count or number of IGF-1R positive cells was found. Conclusion Loss of IGF-1R in CTCs is associated with a significantly worse outcome in MBC patients. This finding supports further evaluation for the role of IGF-1R on CTCs to improve patient stratification and to implement new targeted strategies. Clinical trial registration: Clinicaltrials.gov (NCT01885013); European Clinical Trials Database (EudraCT No.2009-014,662-26)

Single tube liquid biopsy for advanced non-small cell lung cancer

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM(high) circulating tumor cells (CTC), EpCAM(low) CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM(high) CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM(low) CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had >= 2 EpCAM(high) CTC, 15% had >= 2 EpCAM(low) CTC, 27% had >= 18 tdEV and 19% had ctDNA with >= 10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAM(high) CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM(low) CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy

Real-time networked control of an industrial robot manipulator via discrete-time second order sliding modes

This article presents the networked control of a robotic anthropomorphic manipulator based on a second-order sliding mode technique, where the control objective is to track a desired trajectory for the manipulator. The adopted control scheme allows an easy and effective distribution of the control algorithm over two networked machines. While the predictability of real-time tasks execution is achieved by the Soft Hard Real-Time Kernel (S.Ha.R.K.) real-time operating system, the communication is established via a standard Ethernet network. The performances of the control system are evaluated under different experimental system configurations using, to perform the experiments, a COMAU SMART3-S2 industrial robot, and the results are analysed to put into evidence the robustness of the proposed approach against possible network delays, packet losses and unmodelled effects

Second Order Sliding Mode Real-Time Networked Control of a Robotic Manipulator

Abstrac

Environment modelling for the robust motion planning and control of planar rigid robot manipulators

Trajectory planning and tracking are crucial tasks in any application using robot manipulators. These tasks become particularly difficult when obstacles are present in the manipulatorpsilas workspace. In this paper it is assumed that the obstacles can be approximated in a conservative way with discs. The goal is to represent the obstacles in the robot configuration space, in order to allow an efficient and accurate trajectory planning and tracking. Moreover, the paper provides the methods for checking the collision between the n-joint manipulator and the obstacles. Trajectory planning depends on tracking accuracy. In this paper an adequate tracking accuracy is guaranteed assuming the use of a suitably designed robust controller

Qualità della vita base della qualità del lavoro

Il presente lavoro si è proposto di analizzare la formazione del benessere nella sua multidimensionalità fondandosi teoricamente su un approccio macro riproduttivo esteso. L’approccio scelto consente di evidenziare la rilevanza nella misurazione dei livelli di benessere di componenti non monetarie e analizza i livelli di benessere sia a livello individuale che a livello familiare. Un risultato collaterale dell’analisi è stato la costruzione, attraverso l’approccio combinato micro-macro, ispirato al metodo del propensity score matching, di un data set che contiene indicatori attinenti alle diverse dimensioni ritenute rilevanti per l’analisi del modello teorico di riferimento ottenuto integrando i microdati della Banca d’Italia sui ‘Bilanci delle famiglie Italiane’ del 2000 (IBFI) con un vettore di informazioni presenti nell’indagine ISTAT ‘Famiglie, soggetti sociali e condizioni dell’infanzia’ del 1998. La formazione del benessere e la sua misurazione ha richiesto, per mantenere la complessità richiesta dall’oggetto di analisi, l’uso di tecniche fuzzy e la costruzione di un sistema fuzzy esperto all’interno del quale sono confluiti gli assi delle condizioni di vita con riferimento sia alla dimensione individuale che alle dimensioni riguardanti il nucleo familiare. L’implementazione del sistema al data set integrato ha consentito di rilevare le differenze di genere nella formazione del benessere e di mostrare le diseguaglianze che l’attenzione alla sola dimensione familiare o alle sole componenti monetarie non consentiva di cogliere

Obstacle Modelling Oriented to Safe Motion Planning and Control for Planar Rigid Robot Manipulators

Trajectory planning and tracking are crucial tasks in any application using robot manipulators. These tasks become particularly challenging when obstacles are present in the manipulator workspace. In this paper a n-joint planar robot manipulator is considered and it is assumed that obstacles located in its workspace can be approximated in a conservative way with circles. The goal is to represent the obstacles in the robot configuration space. The representation allows to obtain an efficient and accurate trajectory planning and tracking. A simple but effective path planning strategy is proposed in the paper. Since path planning depends on tracking accuracy, in this paper an adequate tracking accuracy is guaranteed by means of a suitably designed Second Order Sliding Mode Controller (SOSMC). The proposed approach guarantees a collision-free motion of the manipulator in its workspace in spite of the presence of obstacles, as confirmed by experimental results