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Lenvatinib (LENVA) is an oral antineoplastic drug used for the treatment of hepatocellular carcinoma and thyroid carcinoma. LENVA therapeutic drug monitoring (TDM) should be mandatory for a precision medicine to optimize the drug dosage. To this end, the development of a sensitive and robust quantification method to be applied in the clinical setting is essential. The aim of this work was to develop and validate a sensitive, rapid, and cost-effective LC-MS/MS method for the quantification of LENVA in human plasma. On this premise, sample preparation was based on a protein precipitation and the chromatographic separation was achieved on a Synergi Fusion RP C18 column in 4 min. The method was completely and successfully validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, with good linearity in the range of 0.50–2000 ng/mL (R≥0.9968). Coefficient of variation (CV) for intra- and inter-day precision was ≤11.3% and accuracy ranged from 96.3 to 109.0%, internal standard normalized matrix effect CV% was ≤2.8% and recovery was ≥95.6%. Successful results were obtained for sensitivity (signal to noise (S/N) ratio >21) and selectivity, dilution integrity (CV% ≤ 4.0% and accuracy 99.9–102%), and analyte stability under various handling and storage conditions both in matrix and solvents. This method was applied to quantify LENVA in patient’s plasma samples and covered the concentration range achievable in patients. In conclusion, a sensitive and robust quantification method was developed and validated to be applied in the clinical setting.

Significance Optimal channel networks (OCNs) are a well-studied static model of river network structures. We present exact results showing that every OCN is a natural river tree where a landscape exist such that the flow directions are always directed along its steepest descent. We characterize the family of natural river trees in terms of certain forbidden structures, called “k-path obstacles.” We thus determine conditions for river landscapes to imply a rooted tree as its network of topographic gradients. Our results are significant in particular for applications where OCNs may be used to produce statistically identical replicas of realistic matrices for ecological interactions., We study tree structures termed optimal channel networks (OCNs) that minimize the total gravitational energy loss in the system, an exact property of steady-state landscape configurations that prove dynamically accessible and strikingly similar to natural forms. Here, we show that every OCN is a so-called natural river tree, in the sense that there exists a height function such that the flow directions are always directed along steepest descent. We also study the natural river trees in an arbitrary graph in terms of forbidden substructures, which we call k-path obstacles, and OCNs on a d-dimensional lattice, improving earlier results by determining the minimum energy up to a constant factor for every d≥2. Results extend our capabilities in environmental statistical mechanics.

In questo lavoro è stato studiato il comportamento statico del muro longitudinale destro della chiesa di S. Pietro in Vinculis (nota come S.Pierino) situata a Pisa. Lo studio è stato condotto utilizzando il programma di calcolo agli elementi finiti NOSA, discretizzando la struttura con elementi piani isoparametrici a otto nodi, nell'ipotesi di stato di sforzo piano. La muratura è stata modellata come un materiale elastico non lineare con resistenza a trazione nulla e resistenza a compressione infinita. Si è studiato il muro soggetto al peso proprio e al carico dovuto al peso della copertura. Successivamente è stata condotta un'indagine per valutare l'effetto di cedimenti differenziali delle colonne sul quadro fessurativo e sullo stato di sforzo del muro. Le analisi condotte sono servite a valutare lo stato tensionale e deformativo della struttura nello stato attuale e a individuare le possibili cause che hanno dato origine alle fessure esistenti.

In questa nota vengono affrontati i problemi relativi alle misure di porosità in materiali ceramici in ambito industriale. In modo particolare viene descritta una procedura di misura basata su tecniche non distruttive con l'utilizzo di dispositivi operanti nel range frequenziale delle microonde (banda ISM) e basati sulla misura della frequenza di risonanza di tali dispositivi.