Assessment of Immature Platelet Fraction in the Diagnosis of Wiskott-Aldrich Syndrome.

Children with Wiskott-Aldrich syndrome (WAS) are often first diagnosed with immune thrombocytopenia (ITP), potentially leading to both inappropriate treatment and the delay of life-saving definitive therapy. WAS is traditionally differentiated from ITP based on the small size of WAS platelets. In practice, microthrombocytopenia is often not present or not appreciated in children with WAS. To develop an alternative method of differentiating WAS from ITP, we retrospectively reviewed all complete blood counts and measurements of immature platelet fraction (IPF) in 18 subjects with WAS and 38 subjects with a diagnosis of ITP treated at our hospital. Examination of peripheral blood smears revealed a wide range of platelet sizes in subjects with WAS. Mean platelet volume (MPV) was not reported in 26% of subjects, and subjects in whom MPV was not reported had lower platelet counts than did subjects in whom MPV was reported. Subjects with WAS had a lower IPF than would be expected for their level of thrombocytopenia, and the IPF in subjects with WAS was significantly lower than in subjects with a diagnosis of ITP. Using logistic regression, we developed and validated a rule based on platelet count and IPF that was more sensitive for the diagnosis of WAS than was the MPV, and was applicable regardless of the level of platelets or the availability of the MPV. Our observations demonstrate that MPV is often not available in severely thrombocytopenic subjects, which may hinder the diagnosis of WAS. In addition, subjects with WAS have a low IPF, which is consistent with the notion that a platelet production defect contributes to the thrombocytopenia of WAS. Knowledge of this detail of WAS pathophysiology allows to differentiate WAS from ITP with increased sensitivity, thereby allowing a physician to spare children with WAS from inappropriate treatment, and make definitive therapy available in a timely manner

Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response

Cancer is a disease driven by random DNA mutations and the interaction of many complex phenomena. To improve the understanding and ultimately find more effective treatments, researchers leverage computer simulations mimicking the tumor growth in silico. The challenge here is to account for the many phenomena influencing the disease progression and treatment protocols. This work introduces a computational model to simulate vascular tumor growth and the response to drug treatments in 3D. It consists of two agent-based models for the tumor cells and the vasculature. Moreover, partial differential equations govern the diffusive dynamics of the nutrients, the vascular endothelial growth factor, and two cancer drugs. The model focuses explicitly on breast cancer cells over-expressing HER2 receptors and a treatment combining standard chemotherapy (Doxorubicin) and monoclonal antibodies with anti-angiogenic properties (Trastuzumab). However, large parts of the model generalize to other scenarios. We show that the model qualitatively captures the effects of the combination therapy by comparing our simulation results with previously published pre-clinical data. Furthermore, we demonstrate the scalability of the model and the associated C++ code by simulating a vascular tumor occupying a volume of 400mm3 using a total of 92.5 million agents

Gyroscopic motion of superfluid trapped atomic condensates

The gyroscopic motion of a trapped Bose gas containing a vortex is studied. We model the system as a classical top, as a superposition of coherent hydrodynamic states, by solution of the Bogoliubov equations, and by integration of the time-dependent Gross-Pitaevskii equation. The frequency spectrum of Bogoliubov excitations, including quantum frequency shifts, is calculated and the quantal precession frequency is found to be consistent with experimental results, though a small discrepancy exists. The superfluid precession is found to be well described by the classical and hydrodynamic models. However the frequency shifts and helical oscillations associated with vortex bending and twisting require a quantal treatment. In gyroscopic precession, the vortex excitation modes $m=\pm 1$ are the dominant features giving a vortex kink or bend, while the $m=+2$ is found to be the dominant Kelvin wave associated with vortex twisting.Comment: 18 pages, 7 figures, 1 tabl

Simulation of actively controlled spacecraft with flexible appendages

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76688/1/AIAA-25388-716.pd

Radical functionalization of unsaturated amino acids: synthesis of side-chain-fluorinated, azido-substituted, and hydroxylated amino acids

A range of enantiomerically pure protected side-chain-fluorinated amino acids has been prepared (13 examples) by treatment of protected amino acids containing unsaturated side chains with a combination of Fe(III)/NaBH4 and Selectfluor. The modification of the conditions by replacement of Selectfluor with NaN3 allowed the preparation of side-chain azido-substituted amino acids (five examples), which upon catalytic hydrogenation gave the corresponding amines, isolated as lactams (four examples). Radical hydration of the unsaturated side chains leading to side-chain-hydroxylated protected amino acids has also been demonstrated

Theory and methodology for estimation and control of errors due to modeling, approximation, and uncertainty

The reliability of computer predictions of physical events depends on several factors: the mathematical model of the event, the numerical approximation of the model, and the random nature of data characterizing the model. This paper addresses the mathematical theories, algorithms, and results aimed at estimating and controlling modeling error, numerical approximation error, and error due to randomness in material coefficients and loads. A posteriori error estimates are derived and applications to problems in solid mechanics are presented. (C) 2004 Elsevier B.V. All rights reserved

A parametric finite element solution of the generalised Bloch-Torrey equation for arbitrary domains

Nuclear magnetic resonance (NMR) has proven of enormous value in the investigation of porous media. Its use allows to study pore size distributions, tortuosity, and permeability as a function of the relaxation time, diffusivity, and flow. This information plays an important role in plenty of applications, ranging from oil industry to medical diagnosis. A complete NMR analysis involves the solution of the Bloch-Torrey (BT) equation. However, solving this equation analytically becomes intractable for all but the simplest geometries. We present an efficient numerical framework for solving the complete BT equation in arbitrarily complex domains. In addition to the standard BT equation, the generalised BT formulation takes into account the flow and relaxation terms, allowing a better representation of the phenomena under scope. The presented framework is flexible enough to deal parametrically with any order of convergence in the spatial domain. The major advantage of such approach is to allow both faster computations and sensitivity analyses over realistic geometries. Moreover, we developed a second-order implicit scheme for the temporal discretisation with similar computational demands as the existing explicit methods. This represents a huge step forward for obtaining reliable results with few iterations. Comparisons with analytical solutions and real data show the flexibility and accuracy of the proposed methodology

A shelf-life study of silica- and carbon-based mesoporous materials

Mesoporous silica- and carbon-based materials, including bioactive glasses, have proven potential as components of medical devices and as drug carriers. From an application perspective, knowledge about the shelf-life stability of these materials under various conditions is vital. Here, mesoporous bioactive glasses (MBGs) synthesized by aerosol-assisted spray-drying and by a batch sol–gel method, mesoporous silicas of SBA-15 type, and mesoporous carbons CMK-1 and CMK-3 have been stored under varying conditions, e.g. at different temperature and relative humidity (RH), and in different storage vessels. The results show that the silica-based materials stored in Eppendorfs are sensitive to humidity. Spray dried MBGs decompose within 1 month at a RH >5%, whilst sol–gel MBGs are more stable up to a RH >60%. Changing the storage vessel to sealed glass flasks increases the MBGs lifetime significantly, with no degradation during 2 months of storage at a RH = 75%. SBA-15 stored in Eppendorfs are more stable compared to MBGs, and addition of F- ions added during the synthesis affects the material degradation rate. Mesoporous carbons are stable under all conditions for all time points. This systematic study clearly demonstrates the importance of storage conditions for mesoporous materials which is crucial knowledge for commercialization of these materials