Safe discontinuation of nilotinib in a patient with chronic myeloid leukemia: a case report

Case presentation. We report the case of a 64-year-old Caucasian man diagnosed with chronic-phase chronic myeloid leukemia in April 2005. After 4 years of treatment with imatinib, he became intolerant to the drug and was switched to nilotinib. Two years later, he decided to stop nilotinib. Undetectable molecular response persisted for 30 months after discontinuation of the drug. Introduction. Although there is a considerable amount of data in the literature on safe discontinuation of first-generation tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia, little is known about discontinuation of second-generation tyrosine kinase inhibitor therapy. Most previous studies have been focused on dasatinib, and the few cases of nilotinib withdrawal that have been reported had a median follow-up of 12 months. To the best of our knowledge, the present report is the first to describe nilotinib withdrawal with 30 months of follow-up. Conclusion: Our present case suggests that nilotinib withdrawal is safe for patients with chronic myeloid leukemia who achieve a stable undetectable molecular response. Our patient was homozygous for killer immunoglobulin-like receptor haplotype A, previously reported to be a promising immunogenetic marker for undetectable molecular response. We recommend additional studies to investigate patient immunogenetic profiles and their potential role in complete response to therap

Strategic maritime container transport design in oligopolistic markets

AbstractThis paper considers the maritime container assignment problem in a market setting with two competing firms. Given a series of known, exogenous demands for service between pairs of ports, each company is free to design a liner service network serving a subset of the ports and demand, subject to the size of their fleets and the potential for profit. The model is designed as a three-stage complete information game: in the first stage, the firms simultaneously invest in their fleet; in the second stage, they individually design their networks and solve the route assignment problem with respect to the transport demand they expect to serve, given the fleet determined in the first stage; in the final stage, the firms compete in terms of freight rates on each origin-destination movement. The game is solved by backward induction. Numerical solutions are provided to characterize the equilibria of the game

Viscous corrections to anisotropic flow and transverse momentum spectra from transport theory

Viscous hydrodynamics is commonly used to model the evolution of the matter created in an ultra-relativistic heavy-ion collision. It provides a good description of transverse momentum spectra and anisotropic flow. These observables, however, cannot be consistently derived using viscous hydrodynamics alone, because they depend on the microscopic interactions at freeze-out. We derive the ideal hydrodynamic limit and the first-order viscous correction to anisotropic flow ($v_2$, $v_3$ and $v_4$) and momentum spectrum using a transport calculation. The linear response coefficient to the initial anisotropy, $v_n(p_T)/\varepsilon_n$, depends little on $n$ in the ideal hydrodynamic limit. The viscous correction to the spectrum depends not only on the differential cross section, but also on the initial momentum distribution. This dependence is not captured by standard second-order viscous hydrodynamics. The viscous correction to anisotropic flow increases with $p_T$, but this increase is slower than usually assumed in viscous hydrodynamic calculations. In particular, it is too slow to explain the observed maximum of $v_n$ at $p_T\sim 3$ GeV/c.Comment: minor revisio

Space-charge effects in high-energy photoemission

Pump-and-probe photoelectron spectroscopy (PES) with femtosecond pulsed sources opens new perspectives in the investigation of the ultrafast dynamics of physical and chemical processes at the surfaces and interfaces of solids. Nevertheless, for very intense photon pulses a large number of photoelectrons are simultaneously emitted and their mutual Coulomb repulsion is sufficiently strong to significantly modify their trajectory and kinetic energy. This phenomenon, referred as space-charge effect, determines a broadening and shift in energy for the typical PES structures and a dramatic loss of energy resolution. In this article we examine the effects of space charge in PES with a particular focus on time-resolved hard X-ray (~10 keV) experiments. The trajectory of the electrons photoemitted from pure Cu in a hard X-ray PES experiment has been reproduced through $N$-body simulations and the broadening of the photoemission core-level peaks has been monitored as a function of various parameters (photons per pulse, linear dimension of the photon spot, photon energy). The energy broadening results directly proportional to the number $N$ of electrons emitted per pulse (mainly represented by secondary electrons) and inversely proportional to the linear dimension $a$ of the photon spot on the sample surface, in agreement with the literature data about ultraviolet and soft X-ray experiments. The evolution in time of the energy broadening during the flight of the photoelectrons is also studied. Despite its detrimental consequences on the energy spectra, we found that space charge has negligible effects on the momentum distribution of photoelectrons and a momentum broadening is not expected to affect angle-resolved experiments. Strategy to reduce the energy broadening and the feasibility of hard X-ray PES experiments at the new free-electron laser facilities are discussed.Comment: 15 pages, 2 tables, 8 figure

VULNERABILITY ASSESSMENT FOR PRELIMINARY FLOOD RISK MAPPING AND MANAGEMENT IN COASTAL AREAS

Planning and management of coastal environment, both terrestrial and marine, is affected by several actions in environment resource conservation and improvement paying specific attention to risk forecasting and preventing. In such context the EU flood Directive 2007/60/EC, which requires Member States the assessment and management of flood risk, and the EU water framework Directive (2000/60/EC) are the key factors in the integrated river basin management to assure an efficient and rational use of resources. Afterwards, coastal risk assessment and mapping is a propaedeutic phase to plan and manage coastal areas. In this work risk analysis refers to the results obtained by the combined application of coastal flooding and erosion risks in the activities carried out to prepare Regional Coast Management Plan for the Ionian coast of Basilicata Region located in the south of Italy. In order to define the driving forces acting on the shore, high resolution lidar data, bathymetric information and wave climate statistics acquired by meteorological analyses on wind field data referred to different acquisition times are used. The systemic vulnerability estimation is achieved by composing both hazard factors combined in the Criticality Coastal Index depending on of the assessment of Coastal Flood Index and Coastal Erosion Index based on morphologic and socio-economic variables

Quantitative contraction rates for Sinkhorn algorithm: beyond bounded costs and compact marginals

We show non-asymptotic geometric convergence of Sinkhorn iterates to the Schr\"odinger potentials, solutions of the quadratic Entropic Optimal Transport problem on $\mathbb{R}^d$. Our results hold under mild assumptions on the marginal inputs: in particular, we only assume that they admit an asymptotically positive log-concavity profile, covering as special cases log-concave distributions and bounded smooth perturbations of quadratic potentials. More precisely, we provide exponential $\mathrm{L}^1$ and pointwise convergence of the iterates (resp. their gradient and Hessian) to Schr\"odinger potentials (resp. their gradient and Hessian) for large enough values of the regularization parameter. As a corollary, we establish exponential convergence of Sinkhorn plans and bridges w.r.t. a symmetric relative entropy. Up to the authors' knowledge, these are the first results which establish geometric convergence of Sinkhorn algorithm in a general setting without assuming bounded cost functions or compactly supported marginals. Our results are proven following a probabilistic approach that rests on integrated semiconvexity estimates for Sinkhorn iterates that are of independent interest.Comment: 51 page

CpGmotifs : a tool to discover DNA motifs associated to CpG methylation events

BackgroundThe investigation of molecular alterations associated with the conservation and variation of DNA methylation in eukaryotes is gaining interest in the biomedical research community. Among the different determinants of methylation stability, the DNA composition of the CpG surrounding regions has been shown to have a crucial role in the maintenance and establishment of methylation statuses. This aspect has been previously characterized in a quantitative manner by inspecting the nucleotidic composition in the region. Research in this field still lacks a qualitative perspective, linked to the identification of certain sequences (or DNA motifs) related to particular DNA methylation phenomena.ResultsHere we present a novel computational strategy based on short DNA motif discovery in order to characterize sequence patterns related to aberrant CpG methylation events. We provide our framework as a user-friendly, shiny-based application, CpGmotifs, to easily retrieve and characterize DNA patterns related to CpG methylation in the human genome. Our tool supports the functional interpretation of deregulated methylation events by predicting transcription factors binding sites (TFBS) encompassing the identified motifs.ConclusionsCpGmotifs is an open source software. Its source code is available on GitHub https://github.com/Greco-Lab/CpGmotifs and a ready-to-use docker image is provided on DockerHub at https://hub.docker.com/r/grecolab/cpgmotifs.Peer reviewe