Practical management of sunitinib toxicities in the treatment of pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (pNETs) are infrequent malignancies which manifest in both functional (hormone-secreting) and more commonly non-functional (non-secreting) forms. The oral multitargeted tyrosine kinase inhibitor sunitinib and mammalian target of rapamycin (mTOR) inhibitor everolimus are approved as targeted therapies for patients with well-differentiated, non-resectable disease and evidence of disease progression. The recent approval of sunitinib for the management of advanced pNET is based on a continuous daily dosing (CDD) schedule that differs from the intermittent 4weeks on/2weeks off (4/2) schedule approved for sunitinib in advanced renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST). Therefore, although clinicians may be familiar with therapy management approaches for sunitinib in advanced RCC and GIST, there is less available experience for the management of patients with a CDD schedule. Here, we discuss the similarities and differences in the treatment of pNET with sunitinib compared with advanced RCC and GIST. In particular, we focus on the occurrence and management of sunitinib-related toxicity in patients with pNET by drawing on experience in these other malignancies. We aim to provide a relevant and useful guide for clinicians treating patients with pNET covering the management of events such as fatigue, mucositis, hand-foot syndrome, and hypertension.

Londres, réception de M. et Mme Poincaré au Guildhall [hôtel de ville de Londres, le 11 novembre 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 56905

Immunocytochemical and pharmacological characterization of metabotropic glutamate receptors of the vestibular end organs in the frog.

Using immunocytochemistry and multiunit recording of afferent activity of the whole vestibular nerve, we investigated the role of metabotropic glutamate receptors (mGluR) in the afferent neurotransmission in the frog semicircular canals (SCC). Group I (mGluR1alpha) and group II (mGluR2/3) mGluR immunoreactivities were distributed to the vestibular ganglion neurons, and this can be attributed to a postsynaptic locus of metabotropic regulation of rapid excitatory transmission. The effects of group I/II mGluR agonist (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD) and antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) on resting and chemically induced afferent activity were studied. ACPD (10-100 microM) enhanced the resting discharge frequency. MCPG (5-100 microM) led to a concentration-dependent decrease of both resting activity and ACPD-induced responses. If the discharge frequency had previously been restored by L-glutamate (L-Glu) in high-Mg2+ solution, ACPD elicited a transient increase in the firing rate in the afferent nerve suggesting that ACPD acts on postsynaptic receptors. The L-Glu agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA), were tested during application of ACPD. AMPA- and NMDA-induced responses were higher in the presence than absence of ACPD, implicating mGluR in the modulation of ionotropic glutamate receptors. These results indicate that activation of mGluR potentiates AMPA and NMDA responses through a postsynaptic interaction. We conclude that ACPD may exert modulating postsynaptic effects on vestibular afferents and that this process is activity-dependent.

M. Poincaré à l'université de Glasgow : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 56950

28-1-20, voyage présidentiel à Nieuport : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57784

Análisis empírico de la discriminación salarial por género y etnia en el Ecuador en el año 2008

La población femenina y la indígena del Ecuador han presentado continuamente desigualdades de ingresos respecto a la población masculina y a la no indígena, respectivamente. El presente trabajo reporta que una parte de las diferencias salariales a favor de los hombres y de la población no indígena es resultado de la discriminación salarial por razones de género y etnia. Este resultado se ha obtenido estimando ecuaciones mincerianas de ingresos corrigiendo el problema de se sgo de selección muestral y utilizando la metodología de descomposición de las brechas salariales de Oaxaca (1973) y Newmak (1988) también corregidas por el problema de sesgo de selección muestral.

26 rue Marbeau, hôtel [particulier] de M. Poincaré : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57636

28-12-19 [voyage présidentiel pour la remise de la] Légion d'honneur à [la ville de] Bapaume [la foule écoutant le discours présidentiel parmi les ruines] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57376

18/2/20, réception des 4 présidents à l'Hôtel de ville [MM. Loubet, Deschanel, Poincaré, Fallières] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58100

28-1-20, voyage présidentiel à Nieuport : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57786

Pancreatic stone protein as a novel marker for neonatal sepsis.

PURPOSE: Early-onset sepsis (EOS) is one of the main causes for the admission of newborns to the neonatal intensive care unit. However, traditional infection markers are poor diagnostic markers of EOS. Pancreatic stone protein (PSP) is a promising sepsis marker in adults. The aim of this study was to investigate whether determining PSP improves the diagnosis of EOS in comparison with other infection markers. METHODS: This was a prospective multicentre study involving 137 infants with a gestational age of >34 weeks who were admitted with suspected EOS. PSP, procalcitonin (PCT), soluble human triggering receptor expressed on myeloid cells-1 (sTREM-1), macrophage migration inhibitory factor (MIF) and C-reactive protein (CRP) were measured at admission. Receiver-operating characteristic (ROC) curve analysis was performed. RESULTS: The level of PSP in infected infants was significantly higher than that in uninfected ones (median 11.3 vs. 7.5 ng/ml, respectively; p = 0.001). The ROC area under the curve was 0.69 [95 % confidence interval (CI) 0.59-0.80; p < 0.001] for PSP, 0.77 (95 % CI 0.66-0.87; p < 0.001) for PCT, 0.66 (95 % CI 0.55-0.77; p = 0.006) for CRP, 0.62 (0.51-0.73; p = 0.055) for sTREM-1 and 0.54 (0.41-0.67; p = 0.54) for MIF. PSP independently of PCT predicted EOS (p < 0.001), and the use of both markers concomitantly significantly increased the ability to diagnose EOS. A bioscore combining PSP (>9 ng/ml) and PCT (>2 ng/ml) was the best predictor of EOS (0.83; 95 % CI 0.74-0.93; p < 0.001) and resulted in a negative predictive value of 100 % and a positive predictive value of 71 %. CONCLUSIONS: In this prospective study, the diagnostic performance of PSP and PCT was superior to that of traditional markers and a combination bioscore improved the diagnosis of sepsis. Our findings suggest that PSP is a valuable biomarker in combination with PCT in EOS.

28-1-20, voyage présidentiel à Furnes, enfants chantant la Brabançonne : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57778

[28-1-20, voyage présidentiel à Furnes] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57779

15/2/20, Thionville, M. Poincaré et la grande-duchesse Charlotte [de Luxembourg, le jour de la remise de la croix d'honneur à la ville] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58021