An Outline of the Bayesian Decision Theory

In this paper we give an outline on the Bayesian Decision Theory.Comment: arXiv admin note: text overlap with arXiv:1409.826

Myelosuppression by sunitinib is flt-3 genotype dependent

Personalised Therapeutic

Breakdown of Lindstedt Expansion for Chaotic Maps

In a previous paper of one of us [Europhys. Lett. 59 (2002), 330--336] the validity of Greene's method for determining the critical constant of the standard map (SM) was questioned on the basis of some numerical findings. Here we come back to that analysis and we provide an interpretation of the numerical results by showing that no contradiction is found with respect to Greene's method. We show that the previous results based on the expansion in Lindstedt series do correspond to the transition value but for a different map: the semi-standard map (SSM). Moreover, we study the expansion obtained from the SM and SSM by suppressing the small divisors. The first case turns out to be related to Kepler's equation after a proper transformation of variables. In both cases we give an analytical solution for the radius of convergence, that represents the singularity in the complex plane closest to the origin. Also here, the radius of convergence of the SM's analogue turns out to be lower than the one of the SSM. However, despite the absence of small denominators these two radii are lower than the ones of the true maps for golden mean winding numbers. Finally, the analyticity domain and, in particular, the critical constant for the two maps without small divisors are studied analytically and numerically. The analyticity domain appears to be an perfect circle for the SSM analogue, while it is stretched along the real axis for the SM analogue yielding a critical constant that is larger than its radius of convergence.Comment: 12 pages, 3 figure

Imatinib, sunitinib and pazopanib:From flat-fixed dosing towards a pharmacokinetically guided personalized dose

Tyrosine kinase inhibitors (TKIs) are anti-cancer drugs that target tyrosine kinases, enzymes that are involved in multiple cellular processes. Currently, multiple oral TKIs have been introduced in the treatment of solid tumours, all administered in a fixed dose, although large interpatient pharmacokinetic (PK) variability is described. For imatinib, sunitinib and pazopanib exposure-treatment outcome (efficacy and toxicity) relationships have been established and therapeutic windows have been defined, therefore dose optimization based on the measured blood concentration, called therapeutic drug monitoring (TDM), can be valuable in increasing efficacy and reducing the toxicity of these drugs. In this review, an overview of the current knowledge on TDM guided individualized dosing of imatinib, sunitinib and pazopanib for the treatment of solid tumours is presented. We summarize preclinical and clinical data that have defined thresholds for efficacy and toxicity. Furthermore, PK models and factors that influence the PK of these drugs which partly explain the interpatient PK variability are summarized. Finally, pharmacological interventions that have been performed to optimize plasma concentrations are described. Based on current literature, we advise which methods should be used to optimize exposure to imatinib, sunitinib and pazopanib

Bubbles, clusters and denaturation in genomic DNA: modeling, parametrization, efficient computation

The paper uses mesoscopic, non-linear lattice dynamics based (Peyrard-Bishop-Dauxois, PBD) modeling to describe thermal properties of DNA below and near the denaturation temperature. Computationally efficient notation is introduced for the relevant statistical mechanics. Computed melting profiles of long and short heterogeneous sequences are presented, using a recently introduced reparametrization of the PBD model, and critically discussed. The statistics of extended open bubbles and bound clusters is formulated and results are presented for selected examples.Comment: to appear in a special issue of the Journal of Nonlinear Mathematical Physics (ed. G. Gaeta

Organ-specific responses during brain death:increased aerobic metabolism in the liver and anaerobic metabolism with decreased perfusion in the kidneys

Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted). After 4 hrs, tissue was collected, mitochondria isolated and assessed with high-resolution respirometry. Quantitative proteomics, qPCR, and biochemistry was performed on stored tissue/plasma. Following BD, the liver increased glycolytic gene expression (Pfk-1) with decreased glycogen stores, while the kidneys increased anaerobic- (Ldha) and decreased gluconeogenic-related gene expression (Pck-1). Hepatic oxygen consumption increased, while renal perfusion decreased. ATP levels dropped in both organs while mitochondrial respiration and complex I/ATP synthase activity were unaffected. In conclusion, the liver responds to increased metabolic demands during BD, enhancing aerobic metabolism with functional mitochondria. The kidneys shift towards anaerobic energy production while renal perfusion decreases. Our findings highlight the need for an organ-specific approach to assess and optimise graft quality prior to transplantation, to optimise hepatic metabolic conditions and improve renal perfusion while supporting cellular detoxification