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Background Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM): <400 cal and < 20% fat or 10 g per meal. Methods A single arm study of pazopanib with a LFM in 16 adult patients with metastatic RCC with a clear cell component, RECIST 1.1 measurable disease, ECOG PS ≤ 2, and ≤ 3 prior therapies. Pazopanib at 400 mg daily given with LFM for 12 weeks. Incremental dose increases up to 800 mg, or irreversible decreases to 200 mg, allowed every 2 weeks. Primary study endpoint was safety; adverse events (AE) measured per CTCAE version 4.0. Secondary endpoints of RECIST 1.1 response with assessment as 12 weeks; pharmacokinetic (PK) analysis at nine time points, and CYP3A4 polymorphism evaluation. Results Pazopanib with a LFM was well tolerated; 13 of 16 subjects completed all 12 weeks. Three patients withdrew due to adverse events (AEs), with five occurrences of grade 3 AEs. Conclusions Pazopanib with a LFM has acceptable safety and comparable efficacy to fasting administration. Total median pazopanib dose per subject for the study duration was 63.5% of maximum possible conventional dose. A larger study is warranted. Clinical Trial Registration Number: NCT02729194.
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Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma de Células Renales/terapia , Dieta con Restricción de Grasas/métodos , Neoplasias Renales/terapia , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Anciano , Carcinoma de Células Renales/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Indazoles , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
The photoelectron spectrum of CeO(-) exhibits what appears to be a single predominant electronic transition over an energy range in which numerous close-lying electronic states of CeO neutral are well known. The photoelectron spectrum of Ce(OH)2 (-), a molecule in which the Ce atom shares the same formal oxidation state as the Ce atom in CeO(-), also exhibits what appears to be a single transition. From the spectra, the adiabatic electron affinities of CeO and Ce(OH)2 are determined to be 0.936 ± 0.007 eV and 0.69 ± 0.03 eV, respectively. From the electron affinity of CeO, the CeO(-) bond dissociation energy was determined to be 7.7 eV, 0.5 eV lower than the neutral bond dissociation energy. The ground state orbital occupancies of both CeO(-) and Ce(OH)2 (-) are calculated to have 4f 6s(2) Ce(+) superconfigurations, with open-shell states having 4f5d6s superconfiguration predicted to be over 1 eV higher in energy. Low-intensity transitions observed at higher electron binding energies in the spectrum of CeO(-) are tentatively assigned to the (1)Σ(+) (Ω = 0) state of CeO with the Ce+26s2 superconfiguration.
RESUMEN
Reactions between small cerium oxide cluster anions and deuterated water were monitored as a function of both water concentration and temperature in order to determine the temperature dependence of the rate constants. Sequential oxidation reactions of the Ce(x)O(y)â» (x = 2, 3) suboxide cluster anions were found to exhibit anti-Arrhenius behavior, with activation energies ranging from 0 to -18 kJ mol⻹. Direct oxidation of species up to y = x was observed, after which, -OD abstraction and D2O addition reactions were observed. However, the stoichiometric Ce2O4â» and Ce3O6â» cluster anions also emerge in reactions between D2O and the respective precursors, Ce2O3Dâ» and Ce3O5D2â». Ce2O4â» and Ce3O6â» product intensities diminish relative to deuteroxide complex intensities with increasing temperature. The kinetics of these reactions are compared to the kinetics of the previously studied Mo(x)O(y)â» and W(x)O(y)â» reactions with water, and the possible implications for the reaction mechanisms are discussed.
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Distance-of-flight mass spectrometry (DOFMS) is a velocity-based mass-separation technique in which ions are separated in space along the plane of a spatially selective detector. In the present work, a solid-state charge-detection array, the focal-plane camera (FPC), was incorporated into the DOFMS platform. Use of the FPC with our DOFMS instrument resulted in improvements in analytical performance, usability, and versatility over a previous generation instrument that employed a microchannel-plate/phosphor DOF detector. Notably, FPC detection provided resolution improvements of at least a factor of 2, with typical DOF linewidths of 300 µm (R((fwhm)) = 1000). The merits of solid-state detection for DOFMS are evaluated, and methods to extend the DOFMS mass range are considered.
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Espectrometría de Masas/instrumentación , Espectrometría de Masas/métodos , Cobre/análisis , Plomo/análisis , Estaño/análisis , Zinc/análisisRESUMEN
A 512-channel Faraday-strip array detector has been developed and fitted to a Mattauch-Herzog geometry mass spectrograph for the simultaneous acquisition of multiple mass-to-charge values. Several advantages are realized by using simultaneous detection methods, including higher duty cycles, removal of correlated noise, and multianalyte transient analyses independent of spectral skew. The new 512-channel version offers narrower, more closely spaced pixels, providing improved spectral peak sampling and resolution. In addition, the electronics in the amplification stage of the new detector array incorporate a sample-and-hold feature that enables truly simultaneous interrogation of all 512 channels. While sensitivity and linear dynamic range remain impressive for this Faraday-based detector system, limits of detection and isotope ratio data have suffered slightly from leaky p-n junctions produced during the manufacture of the semiconductor-based amplification and readout stages. This paper describes the new 512-channel detector array, the current dominant noise sources, and the figures of merit for the device as pertaining to inductively coupled plasma ionization.