Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

International audienceBackgroundNon-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients.MethodsWe used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time’s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination.ResultsFor Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers’ methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82.ConclusionsWe showed that combined analysis of FGFR3 mutation and DNA methylation markers on urine can be a useful strategy in diagnosis, surveillance and for risk stratification of patients with NMIBC. These results provide the basis for a highly accurate noninvasive test for population screening and allowing to decrease the frequency of cystoscopy, an important feature for both patient quality of life improvement and care cost reduction

The phenome analysis of mutant alleles in Leucine-Rich Repeat Receptor-Like Kinase genes in rice reveals new potential targets for stress tolerant cereals

AbstractPlants are constantly exposed to a variety of biotic and abiotic stresses that reduce their fitness and performance. At the molecular level, the perception of extracellular stimuli and the subsequent activation of defense responses require a complex interplay of signaling cascades, in which protein phosphorylation plays a central role. Several studies have shown that some members of the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) family are involved in stress and developmental pathways. We report here a systematic analysis of the role of the members of this gene family by mutant phenotyping in the monocotyledon model plant rice, Oryza sativa. We have then targeted 176 of the ∼320 LRR-RLK genes (55.7%) and genotyped 288 mutant lines. Position of the insertion was confirmed in 128 lines corresponding to 100 LRR-RLK genes (31.6% of the entire family). All mutant lines harboring homozygous insertions have been screened for phenotypes under normal conditions and under various abiotic stresses. Mutant plants have been observed at several stages of growth, from seedlings in Petri dishes to flowering and grain filling under greenhouse conditions. Our results show that 37 of the LRR-RLK rice genes are potential targets for improvement especially in the generation of abiotic stress tolerant cereals

Système de retraite, inégalités de revenus et de patrimoine

Pension system and income and wealth inequalities. When analyzing the choice of a pension system (between a pay as a go system and a capitalized system), one generally focuses on the effects of that choice on savings, on the equilibrium interest rate and wage, hence on the capital stock available in the economy. One also analyzes the effects, depending on the dominant pension system, of the relative yield of the two systems on the discounted income of consumers. We include in the analysis the income distribution between skilled (high wage) and unskilled (low-wage) wage earners and pensioners, concentrating on the possibility that unskilled pensioners get a very low pension level. We use an overlapping generations model, introducing an altruistic behavior which justifies the existence of a bequest between generations and a possible liquidity constraint for unskilled wage earners. The choice of the optimum pension system can differ very much of the one obtained with a single group of wage-earners. The introduction of wealth inequalities through bequests leads to a substantial change in the results, making the concerned consumers indifferent to the design of the pension system and by making production independent from the nature of the pension system. We use an overlapping generations model, introducing an altruistic behavior which justifies the existence of a bequest between generations and a possible liquidity constraint for unskilled wage earners. The choice of the optimum pension system can differ very much of the one obtained with a single group of wage-earners. The introduction of wealth inequalities through bequests leads to a substantial change in the results, making the concerned consumers indifferent to the design of the pension system and by making production independent from the nature of the pension system.Lorsqu'on examine le choix du système de retraite (part de la répartition et de la capitalisation), on se préoccupe en général de l'effet sur l'épargne, le taux d'intérêt et les salaires d'équilibre, donc sur le niveau de capital par tête de l'économie ; aussi du rendement relatif de la répartition et de la capitalisation, et de son effet sur le lien entre le système de retraite et le revenu actualisé des consommateurs. Nous incluons dans l'analyse la répartition des revenus entre les salariés (puis retraités) qualifiés (à revenus élevés) et non qualifiés (à revenus faibles), en nous préoccupant du niveau peut-être très faible des retraites obtenues par les non-qualifiés. Nous utilisons un modèle à générations imbriquées pouvant faire intervenir un comportement altruiste justifiant l'existence d'héritage, ainsi qu'une contrainte de liquidité portant sur les salariés non qualifiés. Le choix du système optimal de retraite peut différer nettement de celui obtenu avec une seule catégorie de salariés. L'introduction d'une inégalité patrimoniale avec l'héritage modifie substantiellement les résultats en rendant les individus concernés insensibles au choix du système de retraite et en rendant le niveau de production indépendant de la nature du système de retraite.Artus Patrick, Legros Florence. Système de retraite, inégalités de revenus et de patrimoine. In: Revue économique, volume 51, n°1, 2000. pp. 27-40

Fonds de pension et équilibre financier

Artus Patrick, Legros Florence. Fonds de pension et équilibre financier. In: Revue d'économie financière, n°23, 1992. Le financement des retraites : La gestion du partage et des risques, sous la direction de Olivier Robert de Massy et Marc-Antoine Kleinpeter. pp. 125-134

Vieillissement de la population, pouvoir électoral, système de retraites et croissance.

"Ageing populations, political behaviour, retirement pension schemes and economic growth" We describe demographic evolutions and the various claims retired people have concerning the organization of the pension system. Then, we use a simple theoretical model to analyze how the pension system differs from the optimal sys­tem if it is designed by a particular social group (the young, the retired...).Vieillissement de la population, pouvoir électoral, système de retraites et croissance Après avoir décrit les évolutions démographiques, et avoir passé en revue les revendications des retraités concernant l'organisation du système de retraite, nous utilisons une modélisation théorique simple pour déterminer dans quelle mesure le système de retraite diffère du système optimal s'il est choisi pour maximiser le bien-être d'un groupe particulier (les « jeunes » actifs, les « vieux » retraités).Artus Patrick, Legros Florence. Vieillissement de la population, pouvoir électoral, système de retraites et croissance. In: Revue économique, volume 48, n°4, 1997. pp. 899-920

Regional currency areas in financial globalization : a survey of current issues

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Épargne des ménages, choix de portefeuille et fiscalité en France

Households' savings, portfolio choices and tax policy in France The determinants of french households' consumption and portfolio composition decisions are examined. A particular attention is given to the assumption of ricardian neutrality, to the analysis of the effects of varions tax mesasures and the way risk is perceived. The implications of the results for fiscal and monetary poh'cies are discussed. The households' savings ratio depends apparently very little on fiscal incentives, on the development of mutual funds or of the short-term consummer credit, or on interest rates. It responds to macroeconomic developments (growth of wealth and disponible income, inflation). The allocation of households wealth between its different components does not itself depend on incentive measures or on fiscality. It varies with the yields on the different assets, the weight given to the capital gains or losses being asset specific.Epargne des ménages choix de portefeuille et fiscalité en France On analyse les déterminants des comportements de consommation et de choix de portefeuille des ménages français. On s'intéresse en particulier aux conséquences des différentes mesures fiscales, à l'hypothèse de neutralité ricardienne et à la prise en compte du risque. Les implications des résultats pour les politiques monétaires et fiscales sont examinées. Le taux d'épargne des ménages dépend apparemment fort peu des incitations fiscales ou réglementaires, du développement des moyens nouveaux de gestion de la trésorerie des particuliers (OPCVM), du développement du crédit à court terme ou de la politique monétaire. Il répond aux développements macro-économiques (croissance de la richesse et des revenus, inflation). Le partage du patrimoine des ménages ne dépend pas non plus des mesures incitatives ou de la fiscalité. Il varie avec les taux de rendement des actifs, le poids accordé aux plus- ou moins-values en capital étant différent d'un actif à l'autre.Artus Patrick, Legros Florence, Bleuze Éric, Nicolaï Jean-Paul. Épargne des ménages, choix de portefeuille et fiscalité en France. In: Revue économique, volume 42, n°4, 1991. pp. 663-700