Etude par analyse enthalpique différentielle d'un verre métallique Fe-Cr-C-P-Si. Influence de la vitesse d'hypertrempe

Les rubans de verre métallique ont été obtenus par hypertrempe du liquide avec différentes vitesses du substrat rotatif donc différentes vitesses d'hypertrempe. L'influence de cette vitesse sur l'état structural des rubans bruts d'élaboration mais également sur la relaxation structurale ultérieure a été précisée en utilisant l'analyse enthalpique différentielle ; outre les informations concernant les effets thermiques associés à la relaxation ou à la cristallisation des différents rubans, cette technique nous a permis de déterminer la température de Curie et de suivre son évolution avec les traitements thermiques. Les résultats obtenus ont été discutés en liaison avec l'évolution des propriétés mécaniques, ce qui a amené à conclure que l'influence de la vitesse d'hypertrempe pouvait s'expliquer par la seule évolution structurale à l'état vitreux. En se basant sur la théorie d'Egami et al. reposant sur la notion de défauts dans les amorphes métalliques, une interprétation, conduisant à la décomposition de la relaxation structurale en deux grands stades, a été avancée

Etude par analyse enthalpique différentielle d'un verre métallique Fe-Cr-C-P-Si. Influence de la vitesse d'hypertrempe

A Fe-Cr-C-P-Si metallic glass was produced by melt-spinning technique with various rates of the rotating strip and consequently different quench rates. The influence of this quench rate on the structural state of the as-quenched ribbons and on the subsequent structural relaxation has been studied by mean of differential scanning calorimetry (DSC). Beyond informations about thermal effects related to structural relaxation and crystallization of the various ribbons, DSC experiments have allowed to determine the Curie temperature and to follow its evolution with heat treatments. A comparison has been done with the evolution of the mechanical properties and it should be assumed that the changes of properties as a function of quench rate are due to structural evolution of the glassy state. Using the theory of Egami et al. based on the concept of « defects » in amorphous metals, an interpretation is given which leads to divide the structural relaxation in two main stages.Les rubans de verre métallique ont été obtenus par hypertrempe du liquide avec différentes vitesses du substrat rotatif donc différentes vitesses d'hypertrempe. L'influence de cette vitesse sur l'état structural des rubans bruts d'élaboration mais également sur la relaxation structurale ultérieure a été précisée en utilisant l'analyse enthalpique différentielle ; outre les informations concernant les effets thermiques associés à la relaxation ou à la cristallisation des différents rubans, cette technique nous a permis de déterminer la température de Curie et de suivre son évolution avec les traitements thermiques. Les résultats obtenus ont été discutés en liaison avec l'évolution des propriétés mécaniques, ce qui a amené à conclure que l'influence de la vitesse d'hypertrempe pouvait s'expliquer par la seule évolution structurale à l'état vitreux. En se basant sur la théorie d'Egami et al. reposant sur la notion de défauts dans les amorphes métalliques, une interprétation, conduisant à la décomposition de la relaxation structurale en deux grands stades, a été avancée

Production and use of reference materials for environmental analyses: conclusions of a workshop

International audienceReference materials (RMs) play a vital role for the verification of the quality control of environmental analysis. The increasing requirements imposed to environmental control laboratories call for greater co-operation among RM producers and end-users to better define future production strategies. It is recognised that the present system is unlikely to be able to cope with the increasing demand for certified and non-certified RMs within the forthcoming years. These issues were discussed in the framework of a workshop funded by the M&T programme of the European Commission, which brought together RM producers, certification experts and end-users. This report summarises the round-table discussions and expert recommendations

Development and validation of a prognostic model in patients with metastatic renal cell carcinoma treated with sunitinib: a European collaboration

Background:Accurate prediction of outcome for metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy is essential. Most of the available models have been developed in patients treated with cytokines, while most of them are fairly complex, including at least five factors. We developed and externally validated a simple model for overall survival (OS) in mRCC. We also studied the recently validated International Database Consortium (IDC) model in our data sets.Methods:The development cohort included 170 mRCC patients treated with sunitinib. The final prognostic model was selected by uni- and multivariate Cox regression analyses. Risk groups were defined by the number of risk factors and by the 25th and 75th percentiles of the model's prognostic index distribution. The model was validated using an independent data set of 266 mRCC patients (validation cohort) treated with the same agent.Results:Eastern Co-operative Oncology Group (ECOG) performance status (PS), time from diagnosis of RCC and number of metastatic sites were included in the final model. Median OS of patients with 1, 2 and 3 risk factors were: 24.7, 12.8 and 5.9 months, respectively, whereas median OS was not reached for patients with 0 risk factors. Concordance (C) index for internal validation was 0.712, whereas C-index for external validation was 0.634, due to differences in survival especially in poor-risk populations between the two cohorts. Predictive performance of the model was improved after recalibration. Application of the mRCC International Database Consortium (IDC) model resulted in a C-index of 0.574 in the development and 0.576 in the validation cohorts (lower than those recently reported for this model). Predictive ability was also improved after recalibration in this analysis. Risk stratification according to IDC model showed more similar outcomes across the development and validation cohorts compared with our model.Conclusion:Our model provides a simple prognostic tool in mRCC patients treated with a targeted agent. It had similar performance with the IDC model, which, however, produced more consistent survival results across the development and validation cohorts. The predictive ability of both models was lower than that suggested by internal validation (our model) or recent published data (IDC model), due to differences between observed and predicted survival among intermediate and poor-risk patients. Our results highlight the importance of external validation and the need for further refinement of existing prognostic models. © 2013 Cancer Research UK. All rights reserved

Development and validation of a prognostic model in patients with metastatic renal cell carcinoma treated with sunitinib: A European collaboration

Background:Accurate prediction of outcome for metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy is essential. Most of the available models have been developed in patients treated with cytokines, while most of them are fairly complex, including at least five factors. We developed and externally validated a simple model for overall survival (OS) in mRCC. We also studied the recently validated International Database Consortium (IDC) model in our data sets.Methods:The development cohort included 170 mRCC patients treated with sunitinib. The final prognostic model was selected by uni- and multivariate Cox regression analyses. Risk groups were defined by the number of risk factors and by the 25th and 75th percentiles of the model's prognostic index distribution. The model was validated using an independent data set of 266 mRCC patients (validation cohort) treated with the same agent.Results:Eastern Co-operative Oncology Group (ECOG) performance status (PS), time from diagnosis of RCC and number of metastatic sites were included in the final model. Median OS of patients with 1, 2 and 3 risk factors were: 24.7, 12.8 and 5.9 months, respectively, whereas median OS was not reached for patients with 0 risk factors. Concordance (C) index for internal validation was 0.712, whereas C-index for external validation was 0.634, due to differences in survival especially in poor-risk populations between the two cohorts. Predictive performance of the model was improved after recalibration. Application of the mRCC International Database Consortium (IDC) model resulted in a C-index of 0.574 in the development and 0.576 in the validation cohorts (lower than those recently reported for this model). Predictive ability was also improved after recalibration in this analysis. Risk stratification according to IDC model showed more similar outcomes across the development and validation cohorts compared with our model.Conclusion:Our model provides a simple prognostic tool in mRCC patients treated with a targeted agent. It had similar performance with the IDC model, which, however, produced more consistent survival results across the development and validation cohorts. The predictive ability of both models was lower than that suggested by internal validation (our model) or recent published data (IDC model), due to differences between observed and predicted survival among intermediate and poor-risk patients. Our results highlight the importance of external validation and the need for further refinement of existing prognostic models. © 2013 Cancer Research UK. All rights reserved

GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism

Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by failure to undergo puberty in the setting of low sex steroids and low gonadotropins. IHH is due to abnormal secretion or action of the master reproductive hormone gonadotropin-releasing hormone (GnRH). Several genes have been found to be mutated in patients with IHH, yet to date no mutations have been identified in the most obvious candidate gene, GNRH1 itself, which encodes the preprohormone that is ultimately processed to produce GnRH. We screened DNA from 310 patients with normosmic IHH (nIHH) and 192 healthy control subjects for sequence changes in GNRH1. In 1 patient with severe congenital nIHH (with micropenis, bilateral cryptorchidism, and absent puberty), a homozygous frameshift mutation that is predicted to disrupt the 3 C-terminal amino acids of the GnRH decapeptide and to produce a premature stop codon was identified. Heterozygous variants not seen in controls were identified in 4 patients with nIHH: 1 nonsynonymous missense mutation in the eighth amino acid of the GnRH decapeptide, 1 nonsense mutation that causes premature termination within the GnRH-associated peptide (GAP), which lies C-terminal to the GnRH decapeptide within the GnRH precursor, and 2 sequence variants that cause nonsynonymous amino-acid substitutions in the signal peptide and in GnRH-associated peptide. Our results establish mutations in GNRH1 as a genetic cause of nIHH

Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma

In a comparison of tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin inhibitor (mTORi) in patients with metastatic clear-cell renal cell carcinoma who received a 1st-line TKI for at least 6 months, the TKI-TKI sequence was favored over the TKI-mTORi. Long-term 2nd-line responders were more likely to have received a second TKI and to have been long-term responders to a 1st-line TKI. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved