An improved instrumental variable method for industrial robot model identification

Abstract Industrial robots are electro-mechanical systems with double integrator behaviour, necessitating operation and model identification under closed-loop control conditions. The Inverse Dynamic Identification Model (IDIM) is a mechanical model based on Newton’s laws that has the advantage of being linear with respect to the parameters. Existing Instrumental Variable (IDIM-IV) estimation provides a robust solution to this estimation problem and the paper introduces an improved IDIM-PIV method that takes account of the additive noise characteristics by adding prefilters that provide lower variance estimates of the IDIM parameters. Inspired by the prefiltering approach used in optimal Refined Instrumental Variable (RIV) estimation, the IDIM-PIV method identifies the nonlinear physical model of the robot, as well as the noise model resulting from the feedback control system. It also has the advantage of providing a systematic prefiltering process, in contrast to that required for the previous IDIM-IV method. The issue of an unknown controller is also considered and resolved using existing parametric identification. The evaluation of the new estimation algorithms on a six degrees-of-freedom rigid robot shows that they improve statistical efficiency, with the controller either known or identified as an intrinsic part of the IDIM-PIV algorithm

Iron: a target for the management of Kaposi's sarcoma?

BACKGROUND: Kaposi's sarcoma (KS) is a mesenchymal tumour associated with human herpesvirus-8 infection. However, the incidence of human herpesvirus-8 infection is far higher than the prevalence of KS, suggesting that viral infection per se is not sufficient for the development of malignancy and that one or more additional cofactors are required. DISCUSSION: Epidemiological data suggest that iron may be one of the cofactors involved in the pathogenesis of KS. Iron is a well-known carcinogen and may favour KS growth through several pathways. Based on the apoptotic and antiproliferative effect of iron chelation on KS cells, it is suggested that iron withdrawal strategies could be developed for the management of KS. Studies using potent iron chelators in suitable KS animal models are critical to evaluate whether iron deprivation may be a useful anti-KS strategy. SUMMARY: It is suggested that iron may be one of non-viral co-factors involved of KS pathogenesis and that iron withdrawal strategies might interfere with tumour growth in patients with KS

Matrix-assisted UV laser desorption of biopolymers: influence of the interactions in the target

The influence of the nature of the matrix and of the macroscopic structure of the target on the MALD spectra of proteins has been systematically studied for matrices such as 2,5-dihydroxybenzoic acid, 3,5-dimethoxy-4-hydroxycinnamic acid, 3-hydroxy-4-methoxycinnamic acid and α-cyano-4-hydroxycinnamic acid. Only 3,5-dimethoxy-4-hydroxycinnamic has been found to give homogeneous targets and reproducible spectra. The neutral contribution to the protein molecular and cluster peaks, which depends on the the laser fluence and on the mass of the protein, also strongly depends on the nature of the matrix

P8.02Overexpression of PD-1 and PD-L1 in renal cell carcinoma is associated with poor prognosis in metastatic patients treated with sunitinib.

International audienceAnti vascular growth epithelial factor (VEGF) therapies are currently used in first line of metastatic clear cell renal cell carcinoma (ccRCC), but some patients are inherently resistant to these treatments. Immunotherapy based on disruption of immune checkpoints, such as Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1), has been showed promising results. PD-1 and PD-L1 are mainly expressed by T-Cells and tumor cells respectively. Interaction between PD-1 and PD-L1 down-regulates antitumor activity and could be involved in resistance to anti-VEGF therapies. This study assessed PD-1 and PD-L1 expressions in primary ccRCC of metastatic patients with sunitinib first-line treatment and its correlation with clinical outcomes. Formalin-fixed paraffin samples were obtained from primary ccRCC before any systemic treatment. Prognostic pathological criteria and clinical data were collected with a median follow up of 27 months after introduction of sunitinib. PD-1 and PD-L1 expressions were evaluated by immunohistochemistry on the most inflammatory and the highest Fuhrman nuclear grade areas respectively, considering tumor heterogeneity. Kaplan Meier survival curves were compared by log rank test. PD-1 and PD-L1 were considered overexpressed when at least a moderate to marked density of positive immune cells and at least 30% of tumor cells were positive with moderate to strong membranous staining intensity, respectively. Overexpression of both PD-1 and PD-L1 was observed in a subgroup of 17/47 primary ccRCC (36%). Patients in this subgroup compared to others had a worse progression free survival (p = 0.001) with medians of 9 months and 14 months respectively. Even if statistical significance was not reached, there was also a trend toward a worse median overall survival (18 months versus 32). This is the first study to assess the PD-1 and PD-L1 expressions in primary ccRCC of metastatic patients with sunitinib first-line treatment. The subgroup with both PD-1 and PD-L1 overexpression should be individualized as having a peculiar immune phenotype. These patients experienced poor prognosis when treated by sunitinib and may be good candidates from anti-PD-1 or anti-PD-L1 immunotherapies

Le carcinome rénal à cellules claires (CRCC) sans altération du gène de Von Hippel-Lindau (VHL) : une entité anatomo-clinique à part ?

National audienceObjectifs Le CRCC est caractérisé par une inactivation du gène suppresseur de tumeur VHL dans plus de 70 % des cas. La voie VHL/HIF est une voie principale d’oncogenèse aboutissant lorsque VHL est inactivé à une surexpression de gènes cibles pro-angiogéniques. L’objectif est de corréler le statut complet de VHL 1/aux critères anatomopathologiques, 2/à l’expression intra-tumorale de VEGF et 3/au suivi clinique des patients. Méthodes 98 CRCC opérés entre 2002 et 2005 ont été inclus rétrospectivement avec un suivi moyen de 10,5 ans. Dix critères histopronostiques et l’expression en immunohistochimie de VEGFA ont été étudiés. À partir des prélèvements congelés, la recherche de délétion de VHL par analyse de copies du gène (MLPA), de mutation de VHL par séquençage, d’une méthylation de son promoteur par MS-MLPA a été menée. Résultats Les CRCC présentaient une délétion, une mutation et/ou une méthylation du promoteur dans respectivement 72,4 %, 69,4 % et 14,2 % des cas, méthylation et mutation étant mutuellement exclusives. 33,6 % des CRCC avaient 0 ou 1 altération de VHL contre 66,3 % avec 2 anomalies. Ces CRCC étaient associés à un grade de Furhman 4 (p = 0,039), aux métastases synchrones (p = 0,043) et à une surexpression de VEGFA \textgreater 50 % (p = 0,003). De plus, les CRCC sans aucune anomalie de VHL (11,2 % de cas) étaient associés à une composante sarcomatoïde \textgreater 20 % (p \textless 0,001) et aux métastases ganglionnaires (p = 0,019), avec une survie spécifique de 33 mois comparés aux CRCC avec 1 ou 2 altérations de VHL (107 mois, p = 0,016). Conclusion Il s’agit de la première étude menée avec un suivi de 10 ans corrélant dans le CRCC le statut complet de VHL avec des critères anatomopathologiques et de suivi clinique. Nous montrons que les CRCC sans aucune altération de VHL sont des tumeurs hautement agressives, qu’il convient d’isole

Metastatic Clear-cell Renal Cell Carcinoma With a Long-term Response to Sunitinib A Distinct Phenotype Independently Associated With Low PD-L1 Expression

International audienceBACKGROUND: Long-term responders (LTRs) are defined by at least 18 months of response to sunitinib in metastatic clear-cell renal cell carcinoma (ccRCC). Well-described by clinical studies, the phenotype of these tumors has never been explored.PATIENTS AND METHODS: In a retrospective and multicenter study, 90 ccRCCs of patients with metastatic disease were analyzed. Immunohistochemistry (carbonic anhydrase IX, vascular endothelial growth factor, c-MET, programmed death-ligand 1 [PD-L1], and PD-1) and VHL status were performed. Progression-free survival and overall survival were calculated from sunitinib introduction and from progression. LTRs and their corresponding tumors were compared with others using univariate and multivariate analysis.RESULTS: Twenty-eight patients were LTRs. They had a median progression-free survival of 28 months versus 4 months for other patients (P < .001). Similarly, LTRs had a median overall survival of 49 months versus 14 months (P < .001), even from progression (median, 21 vs. 7 months; P = .029). They were associated with a favorable or intermediate risk (International Metastatic Renal Cell Carcinoma Database Consortium model) (P = .007) and less liver metastasis (P = .036). They experienced more frequent complete or partial responses at the first radiologic evaluation (P = .035). The corresponding ccRCCs were associated with less nucleolar International Society for Urological Pathology grade 4 (P = .037) and hilar fat infiltration (P = .006). They were also associated with low PD-L1 expression (P = .02). Only the International Metastatic Renal Cell Carcinoma Database Consortium model and PD-L1 expression remained significant after multivariate analysis (P = .014 and P = .029, respectively).CONCLUSION: Primary tumor characteristics of LTRs were studied for the first time and demonstrated a different phenotype. Interestingly, they were characterized by low expression of PD-L1, suggesting a potentially lower impact of targeted immunotherapy in these patients