A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer

Purpose: To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer. Methods: Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib. QT/QTc interval on the electrocardiograph (ECG) was measured in triplicate with a Holter 12-lead ECG at baseline and after 1 cycle of sorafenib. Heart rate (HR) and blood pressure (BP) were obtained in duplicate at baseline and after 1 and 4 cycles of sorafenib. Plasma pharmacokinetic data were obtained for sorafenib and its 3 main metabolites after 1 and 4 cycles of sorafenib. Results: LVEF (SD) mean change from baseline was -0.8 ($\pm$8.6) LVEF(%) after 2 cycles (n=31) and -1.2 $\pm$7.8) LVEF(%) after 4 cycles of sorafenib (n=24). The QT/QTc mean changes from baseline observed at maximum sorafenib concentrations ($t_{max}$) after 1 cycle (n=31) were small (QTcB: 4.2 ms; QTcF: 9.0 ms). Mean changes observed after 1 cycle in BP (n=31) and HR (n=30) at maximum sorafenib concentrations ($t_{max}$) were moderate (up to 11.7 mm Hg and -6.6 bpm, respectively). No correlation was found between the AUC and ($C_{max}$) of sorafenib and its main metabolites and any cardiovascular parameters. Conclusions: The effects of sorafenib on changes in QT/QTc interval on the ECG, LVEF, BP, and HR were modest and unlikely to be of clinical significance in the setting of advanced cancer treatment

A Model for the Assessment of Wheel–Rail Contact in the Presence of Solid Contaminants

An analytical model for the assessment of a contact in the presence of a solid contaminant is presented, mainly aimed at studying the damage to railway wheels and rails operating in third-bodycontaminated environments. The model, developed under 2D plane strain idealization, includes multiple evenly spaced rigid cylindrical contaminant bodies entrapped between two elastic cylinders. It allows a very fast calculation of the pressure distribution on the surfaces in contact and it can be used for evaluating the stress field in the subsurface region, at both the small scale of the contact between the main body and the contaminant body and the full scale of the contact between the two main bodies. The model was validated by comparison with finite element (FE) analyses, showing its accuracy. Some examples of application showed the model’s ability to predict the limit of the influence of the solid contaminant bodies and the depth where cyclic plasticity phenomena occur in wheel–rail contacts

Production of crude earth bricks in Chad - Cameroon

La deforestazione è una delle minacce più drammatiche per l’equilibrio ambientale e la sicurezza alimentare in molte regioni del mondo, particolarmente nell’Africa sub – sahariana. Essa è accelerata dalle attività umane, fra le quali la cottura di mattoni in terra, che richiede grandi quantità di legna per le elevate temperature richieste. Al fine di ridurre la deforestazione, sono state studiate, da diversi punti di vista, le potenzialità della terra cruda come materiale da costruzione, prendendo come caso di studio la valle del Logone, zona di frontiera fra Ciad e Camerun. Dopo un’indagine sul posto, finalizzata a rilevare lo stato dell’arte delle tecnologie di produzione di mattoni, è stata avviata l’installazione di un impianto pilota, basato in particolare su una nuova pressa progettata per questo scopo. Il progetto è stato finanziato dall’Unione Europea nell’ambito del programma ACP “Scienza e tecnologia”

Early botulinum toxin type a injection for post-stroke spasticity: A longitudinal cohort study

Early management of spasticity may improve stroke outcome. Botulinum toxin type A (BoNT-A) is recommended treatment for post-stroke spasticity (PSS). However, it is usually administered in the chronic phase of stroke. Our aim was to determine whether the length of time between stroke onset and initial BoNT-A injection has an effect on outcomes after PSS treatment. This multicenter, longitudinal, cohort study included stroke patients (time since onset 90 days, the MAS were higher at 4 and 12 weeks than at 24 weeks compared to those injected ≤90 days since stroke. Our findings suggest that BoNT-A treatment for PSS should be initiated within 3 months after stroke onset in order to obtain a greater reduction in muscle tone at 1 and 3 months afterwards