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Determining the mechanical properties of tissue such as elasticity and viscosity is fundamental for better understanding and assessment of pathological and physiological processes. Dynamic optical coherence elastography uses shear/surface wave propagation to estimate frequency-dependent wave speed and Young’s modulus. However, for dispersive tissues, the displacement pulse is highly damped and distorted during propagation, diminishing the effectiveness of peak tracking approaches. The majority of methods used to determine mechanical properties assume a rheological model of tissue for the calculation of viscoelastic parameters. Further, plane wave propagation is sometimes assumed which contributes to estimation errors. To overcome these limitations, we invert a general wave propagation model which incorporates (1) the initial force shape of the excitation pulse in the space-time field, (2) wave speed dispersion, (3) wave attenuation caused by the material properties of the sample, (4) wave spreading caused by the outward cylindrical propagation of the wavefronts, and (5) the rheological-independent estimation of the dispersive medium. Experiments were conducted in elastic and viscous tissue-mimicking phantoms by producing a Gaussian push using acoustic radiation force excitation, and measuring the wave propagation using a swept-source frequency domain optical coherence tomography system. Results confirm the effectiveness of the inversion method in estimating viscoelasticity in both the viscous and elastic phantoms when compared to mechanical measurements. Finally, the viscoelastic characterization of collagen hydrogels was conducted. Preliminary results indicate a relationship between collagen concentration and viscoelastic parameters which is important for tissue engineering applications.

Venous access is an essential aspect of hemophilia care. When peripheral venipuncture is not feasible, central venous access devices (CVADs) or the creation of an arteriovenous fistula (AVF) allow the infusion of clotting factor concentrate to treat or prevent bleeding events or eliminate inhibitors. Infection is the primary complication associated with CVADs and the most common reason for their removal. Complications of AVF include occlusion and limb length discrepancies.

Non-invasive techniques to control protein structure and function are needed for tissue engineering applications. This study tested the hypothesis that non-thermal effects of ultrasound can produce changes in collagen microstructure that support directional cell migration. Type I rat tail collagen was polymerized for 15 minutes in the presence of an 8-MHz ultrasound standing wave field over a range of 0 to 30 W/cm2 spatial peak, temporal average intensity. Temperature-matched sham gels were manufactured in a heated water bath without exposure to ultrasound. To test for effects of acoustically-modified collagen on cellular behavior, fibronectin-null mouse embryonic fibroblasts or mouse skin explants were seeded on gel surfaces and cultured up to 7 days prior to imaging with phase or second harmonic generation (SHG) microscopy. Acellular acoustically-modified collagen gels were characterized by regions of radial fiber alignment, increased pore size, and denser fibers, with greater heterogeneity at higher in...

The accuracy and imprecision of three assays used for therapeutic monitoring of tacrolimus were tested using blood-containing weighed-in amounts of the drug, an enzyme-linked immunosorbent assay (ELISA), a microparticle enzyme immunoassay (MEIA I), and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS2) assay. Accuracy was acceptable for the HPLC-MS2 assay at all concentrations tested (10% deviation) and for the ELISA at 1.0 and 4.0 microg/l. Accuracy was not acceptable for the ELISA at 15.0 and 50.0 microg/l or for the MEIA I at all concentrations tested. Imprecision was acceptable for the HPLC-MS2 assay at all concentrations tested (coefficient of variation10%), for the ELISA at 15.0 and 50.0 microg/l, and for the MEIA I at 15.0 and 50.0 microg/l. Imprecision was not acceptable for the ELISA at 1.0 and 4.0 microg/l or for the MEIA I at 1.0 and 4.0 microg/l. This assessment with weighed-in amounts of tacrolimus verified the HPLC-MS2 assay as a reference method. The performance of the two immunoassays with HPLC-MS2 was then compared in the clinical setting using blood from patients with liver (n = 30) and renal (n = 37) transplants. In the liver transplant group (127 samples), the range of tacrolimus concentrations measured by HPLC-MS2, ELISA, and MEIA I was 1.9 to 31.8, 2.1 to 35.0, and less than 0.1 to 36.5 mg/l, respectively. In the renal transplant group (129 samples), the ranges were 1.7 to 26.1, 1.9 to 24.4, and 0.9 to 28.5 microg/l, respectively. Compared with the HPLC-MS2, the ELISA had minimal bias (0.1 to 0.2 microg/l) but unacceptable variability in values (SD13%). The MEIA I had unacceptable bias (1.7-1.8 microg/l) and variability (SD23%). These data indicated that neither the ELISA nor MEIA I is interchangeable with HPLC-MS2. Moreover, in view of the current trend to reduce the therapeutic dose of tacrolimus, quantitative results using the MEIA I would not be obtainable during therapeutic drug monitoring in some patients in whom effective therapeutic concentrations can be less than 5.0 microg/l.

Neural network programs have been developed in an attempt to improve the diagnosis of breast and ovarian cancer using a group of laboratory tests and the age of the patient. The laboratory tests employed in this study include albumin, cholesterol, HDL-cholesterol, triglyceride, apolipoproteins Al and B, NMR linewidth (the Fossel Index) and a tumor marker (i.e., CA 15-3 or CA 125). The breast cancer study involved 104 patients (45 malignant and 59 benign subjects). The ovarian cancer study involved 98 individuals (35 malignant, 36 benign and 27 control subjects). Methods are outlined for identification of the most influential input parameters and optimization of network structure and training. Network characteristics were contrasted with the test results of the appropriate serum tumor marker assay. For the breast cancer study, the best neural network program, using six input parameters, had a sensitivity of only 55.6% and a specificity of 72.9%. The tumor marker CA 15-3 alone gave results of 61.3% and 64.4%, respectively. For the ovarian cancer study, the best neural network program, using six input parameters, had a sensitivity of 80.6% and a specificity of 85.5%. The tumor marker CA 125 alone gave results of 77.8% and 82.3%, respectively. These methods provide an objective approach to neural network optimization and parameter selection applicable to other data bases of clinical and laboratory data.

Hemophilia management requires replacement of the deficient clotting factor. Inhibitor development complicates treatment, and the implementation of and adherence to prophylaxis, considered the standard of care for severe hemophilia, is hampered by the high cost and the need for frequent intravenous infusions. New, less expensive therapies are needed to reduce morbidities, enhance convenience and improve outcomes.We conducted a search of the Medline database from 1990 to 2010 for English language articles pertaining to hemophilia drug therapy. More than 4000 citations were obtained and examined for topic relevance. Additionally, proceedings from the American Society of Hematology, International Society on Thrombosis and Hemostasis, World Federation of Hemophilia, National Hemophilia Foundation and European Association for Haemophilia and Allied Disorders and the ClinicalTrials.gov website were reviewed for relevant publications and information.This article summarizes current research efforts focused on developing less immunogenic and more potent and/or longer-acting clotting factor concentrates that uniquely promote hemostasis, are more affordable and do not require intravenous administration.The availability of orally administered clotting factors will truly transform the lives of hemophilia patients and their families and caregivers.

Laura A. Grygotis1and FelixS. Chew A n 1 1-year-old boy presented with a 3-week history of progressive headache. Physical examination revealed bilateral papilledema. MR imaging of the brain showed a large mass within the right lateral ventricle, filling the atrium, body, and occipital horn, and encroaching on the adjacent brain parenchyma (Fig. lA). No hydrocephalus was found, and the mass enhanced after IV gadolinium injection (Fig. 1B). Cl’ showed that the lesion was hyperdense, lacked calcifications, and enhanced after injection of contrast medium. During surgery, the tumor was found to have an intraventricular portion and an intraparenchymal portion. The intraventricular portion was completely removed. but because of invasiveness and the lack of clear margin between the tumor and normal brain tissue, the resection of the intraparenchymal portion was incomplete. Microscopy showed that the tumor consisted of a disordered arrangement of pleomorphic cuboidal cells. with a recognizable papillary and tubular structure (Fig. 1C) and invasion of neural tissue. The final pathologic diagnosis was choroid plexus carci