Gaucher Disease and Myelofibrosis: A Combined Disease or a Misdiagnosis?

Background: Gaucher disease (GD) and primary myelofibrosis (PMF) share similar clinical and laboratory features, such as cytopenia, hepatosplenomegaly, and marrow fibrosis, often resulting in a misdiagnosis. Case Report: We report here the case of a young woman with hepatosplenomegaly, leukopenia, and thrombocytopenia. Based on bone marrow (BM) findings and on liver biopsy showing extramedullary hematopoiesis, an initial diagnosis of PMF was formulated. The patient refused stem cell transplantation from an HLA-identical sibling. Low-dose melphalan was given, without any improvement. Two years later, a BM evaluation showed Gaucher cells. Low glucocerebrosidase and high chitotriosidase levels were indicative for GD. Molecular analysis revealed N370S/complex I mutations. Enzyme replacement therapy with imiglucerase was commenced, resulting in clinical and hematological improvements. Due to an unexpected and persistent organomegaly, PMF combined with GD were suspected. JAK2V617F, JAK2 exon 12, MPL, calreticulin, and exon 9 mutations were negative, and BM examination showed no marrow fibrosis. PMF was excluded. Twenty years after starting treatment, the peripheral cell count and liver size were normal, whereas splenomegaly persisted. Conclusion: In order to avoid a misdiagnosis, a diagnostic algorithm for patients with hepatosplenomegaly combined with cytopenia is suggested

Effective Transport Template for Particle Separation in Microfluidic Bumper Arrays

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Microfluidic bumper arrays are increasingly being used for the size-based sorting of particle suspensions. The separation mechanism is based on the interaction between a spatially periodic array of obstacles and the suspended particles as they are driven through the obstacle lattice either by volume forces or by the Stokesian drag of the surrounding fluid. By this mechanism, a focused stream of suspended particles of different sizes entering the lattice splits into different currents, each entraining assigned ranges of particle dimensions, and each characterized by a specific angle with respect to the main device axis. In this work, we build up on recent results stemming from macrotransport process theory to derive a closed-form solution for the steady-state distribution of advecting-diffusing particles in the presence of anisotropic dispersion, which typically characterizes large-scale behavior of particle motion through the periodic lattice. Attention is focused on separation resolution, that ultimately controls the feasibility of the separation in specific applications

Dispersion phenomena in microchannels: Transition from Taylor-Aris to convection-dominated regime

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.This article addresses the qualitative and quantitative properties of solute transport and dispersion in microchannel of finite-length. As the Peclet number increases a transition from the Taylor-Aris to a new regime referred as convection dominated dispersion occurs, which is controlled by the velocity profile near the stagnation points at the solid walls. The properties characterizing dispersion dominated regime can be used for analytical purposes as a chromatographic-based velocimetry and for determining the eventual occurrence of slip at the solid walls of microchannels

Long-term bone outcomes in Italian patients with Gaucher disease type 1 or type 3 treated with imiglucerase: A sub-study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry

Background: Gaucher disease (GD) is a lysosomal storage disorder. We evaluated the “real-world” effectiveness of first-line imiglucerase on long-term bone outcomes in Italian patients in the International Collaborative Gaucher Group (ICGG) Gaucher Registry. Methods: Patients treated with imiglucerase for ≥2 years and with bone assessments at baseline and during follow-up were selected. Data on bone pain, bone crises, marrow infiltration, avascular necrosis, infarction, lytic lesions, Erlenmeyer flask deformity, bone fractures, mineral density, and imiglucerase dosage were evaluated. Results: Data on bone manifestations were available for 73 of 229 patients (31.9 %). Bone crises frequency decreased significantly from baseline to the most recent follow-up (p < 0.001), with some improvement observed in bone pain prevalence. Bone pain and bone crises prevalence decreased significantly from baseline at 2 to <4 and 4 to <6 years (all p < 0.05). A low median (25th, 75th percentile) baseline imiglucerase dosage was identified in patients reporting bone pain or bone crises (15.0 [13.7, 30.0] and 22.8 [17.5, 36.0] U/kg once every 2 weeks, respectively). Conclusion: Our study suggests that the management of GD in Italy, with regards to imiglucerase dosage, is suboptimal and confirms the need for clinicians to monitor and correctly treat bone disease according to best practice guidelines

Time fractional Schrodinger equation

The Schrodinger equation is considered with the first order time derivative changed to a Caputo fractional derivative, the time fractional Schrodinger equation. The resulting Hamiltonian is found to be non-Hermitian and non-local in time. The resulting wave functions are thus not invariant under time reversal. The time fractional Schrodinger equation is solved for a free particle and for a potential well. Probability and the resulting energy levels are found to increase over time to a limiting value depending on the order of the time derivative. New identities for the Mittag-Leffler function are also found and presented in an appendix.Comment: 23 page

Fractional differentiability of nowhere differentiable functions and dimensions

Weierstrass's everywhere continuous but nowhere differentiable function is shown to be locally continuously fractionally differentiable everywhere for all orders below the `critical order' 2-s and not so for orders between 2-s and 1, where s, 1<s<2 is the box dimension of the graph of the function. This observation is consolidated in the general result showing a direct connection between local fractional differentiability and the box dimension/ local Holder exponent. Levy index for one dimensional Levy flights is shown to be the critical order of its characteristic function. Local fractional derivatives of multifractal signals (non-random functions) are shown to provide the local Holder exponent. It is argued that Local fractional derivatives provide a powerful tool to analyze pointwise behavior of irregular signals.Comment: minor changes, 19 pages, Late

Precision Measurements of Stretching and Compression in Fluid Mixing

The mixing of an impurity into a flowing fluid is an important process in many areas of science, including geophysical processes, chemical reactors, and microfluidic devices. In some cases, for example periodic flows, the concepts of nonlinear dynamics provide a deep theoretical basis for understanding mixing. Unfortunately, the building blocks of this theory, i.e. the fixed points and invariant manifolds of the associated Poincare map, have remained inaccessible to direct experimental study, thus limiting the insight that could be obtained. Using precision measurements of tracer particle trajectories in a two-dimensional fluid flow producing chaotic mixing, we directly measure the time-dependent stretching and compression fields. These quantities, previously available only numerically, attain local maxima along lines coinciding with the stable and unstable manifolds, thus revealing the dynamical structures that control mixing. Contours or level sets of a passive impurity field are found to be aligned parallel to the lines of large compression (unstable manifolds) at each instant. This connection appears to persist as the onset of turbulence is approached.Comment: 5 pages, 5 figure