Genotyping of the G1138A mutation of the FGFR3 gene in patients with achondroplasia using high-resolution melting analysis

[[abstract]]Objectives: The fibroblast growth factor receptor 3 gene (FGFR3) plays a critical role in cartilage growth-plate differentiation and bony development. It has been shown that 97% of patients with achondroplasia have a G to A transition mutation at position 1138 (c.1138 G>A) of codon 380 of the FGFR3 gene. Design and methods: Exon 8 of the FGFR3 gene was analyzed in 40 patients with achondroplasia, as well as in 50 control individuals for the presence of the c.1138G>A variant using melting curve analysis with a high-resolution melting instrument (HR-1). Results: The high-resolution melting curve analysis successfully genotyped the c.1138G>A mutation in exon 8 of the FGFR3 gene in all 40 patients with achondroplasia without the need of further assays. The technique had a sensitivity and specificity of 100%. Conclusion: High-resolution melting analysis is a simple, rapid, and sensitive one tube assay for genotyping the FGFR3 gene. The technique is a low cost high-throughput FGFR3 screening assay. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved

A Novel Definition of Equivalent Uniform Dose Based on Volume Dose Curve

© 2013 IEEE. With the improvement of mobile device performance, the requirement of equivalent dose description in intensity-modulated radiation therapy is increasing in mobile multimedia for healthcare. The emergence of mobile cloud computing will provide cloud servers and storage for intensity-modulated radiotherapy (IMRT) mobile applications, thus realizing visualized radiotherapy in a real sense. Equivalent uniform dose (EUD) is a biomedical indicator based on the dose measure. In this paper, the dose volume histogram is used to describe the dose distribution of different tissues in target and nontarget regions. The traditional definition of EUD, such as the exponential form and the linear form, has only a few parameters in the model for fast calculation. However, there is no close relationship between this traditional definition and the dose volume histogram. In order to establish the consistency between the EUD and the dose volume histogram, this paper proposes a novel definition of EUD based on the volume dose curve, called VD-EUD. By using a unique organic volume weight curve, it is easy to calculate VD-EUD for different dose distributions. In definition, different weight curves are used to represent the biological effects of different organs. For the target area, we should be more careful about those voxels with a low dose (cold point); thus, the weight curve is monotonically decreasing. While for the nontarget area, the curve is monotonically increasing. Furthermore, we present the curves for parallel, serial, and mixed organs of nontarget areas separately, and we define the weight curve form with only two parameters. Medical doctors can adjust the curve interactively according to different patients and organs. We also propose a fluence map optimization model with the VD-EUD constraint, which means that the proposed EUD constraint will lead to a large feasible solution space. We compare the generalized EUD (gEUD) and the proposed VD-EUD by experiments, which show that the VD-EUD has a closer relationship with the dose volume histogram. If the biological survival probability is equivalent to the VD-EUD, the feasible solution space would be large, and the target areas can be covered. By establishing a personalized organic weight curve, medical doctors can have a unique VD-EUD for each patient. By using the flexible and adjustable EUD definition, we can establish the VD-EUD-based fluence map optimization model, which will lead to a larger solution space than the traditional dose volume constraint-based model. The VD-EUD is a new definition; thus, we need more clinical testing and verification

A gene signature based method for identifying subtypes and subtype-specific drivers in cancer with an application to medulloblastoma

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Investigating cerebral oedema using poroelasticity

Cerebral oedema can be classified as the tangible swelling produced by expansion of the interstitial fluid volume. Hydrocephalus can be succinctly described as the abnormal accumulation of cerebrospinal fluid (CSF) within the brain which ultimately leads to oedema within specific sites of parenchymal tissue. Using hydrocephalus as a test bed, one is able to account for the necessary mechanisms involved in the interaction between oedema formation and cerebral fluid production, transport and drainage. The current state of knowledge about integrative cerebral dynamics and transport phenomena indicates that poroelastic theory may provide a suitable framework to better understand various diseases. In this work, Multiple-Network Poroelastic Theory (MPET) is used to develop a novel spatio-temporal model of fluid regulation and tissue displacement within the various scales of the cerebral environment. The model is applied through two formats, a one-dimensional finite difference – Computational Fluid Dynamics (CFD) coupling framework, as well as a two-dimensional Finite Element Method (FEM) formulation. These are used to investigate the role of endoscopic fourth ventriculostomy in alleviating oedema formation due to fourth ventricle outlet obstruction (1D coupled model) in addition to observing the capability of the FEM template in capturing important characteristics allied to oedema formation, like for instance in the periventricular region (2D model)

Association between amebic liver abscess and Human Immunodeficiency Virus infection in Taiwanese subjects

<p>Abstract</p> <p>Purpose</p> <p>Invasive amebiasis is an emerging parasitic disorder in Taiwan, especially in patients diagnosed with human immunodeficiency virus (HIV) infection. Thirty-three Taiwanese subjects with amebic liver abscess (ALA) were examined and a possible correlation between ALA and HIV infection was investigated.</p> <p>Results</p> <p>Among ALA patients, the proportion of HIV-positive individuals increased during the study period. ALA was the first major clinical presentation in 54% of HIV patients with ALA. Overall, 58% (14/24) of HIV-infected patients had a CD4+ count > 200 cells/μL and 82.1% (23/28) had no concurrent opportunistic infection or other evidence of HIV infection. There was no marked difference in clinical characteristics between HIV-positive and HIV-negative ALA patients except the level of leukocytosis.</p> <p>Conclusion</p> <p>While the clinical characteristics described herein cannot be used to determine whether ALA patients have HIV infection, routine HIV testing is recommended in patients with ALA, even in the absence of HIV symptoms.</p

Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM

<p>Abstract</p> <p>Background</p> <p>Hemophilia A represents the most common and severe inherited hemorrhagic disorder. It is caused by mutations in the F8 gene, which leads to a deficiency or dysfunctional factor VIII protein, an essential cofactor in the factor X activation complex.</p> <p>Methods</p> <p>We used long-distance polymerase chain reaction and denaturing high performance liquid chromatography for mutation scanning of the F8 gene. We designed the competitive multiplex PCR to identify the carrier with exonal deletions. In order to facilitate throughput and minimize the cost of mutation scanning, we also evaluated a new mutation scanning technique, high resolution melting analysis (HRM), as an alternative screening method.</p> <p>Results</p> <p>We presented the results of detailed screening of 122 Taiwanese families with hemophilia A and reported twenty-nine novel mutations. There was one family identified with whole exons deletion, and the carriers were successfully recognized by multiplex PCR. By HRM, the different melting curve patterns were easily identified in 25 out of 28 cases (89%) and 15 out of 15 (100%) carriers. The sensitivity was 93 % (40/43). The overall mutation detection rate of hemophilia A was 100% in this study.</p> <p>Conclusion</p> <p>We proposed a diagnostic strategy for hemophilia A genetic diagnosis. We consider HRM as a powerful screening tool that would provide us with a more cost-effective protocol for hemophilia A mutation identification.</p

Effect of prolonged HAART on oral colonization with Candida and candidiasis

BACKGROUND: Progressive cell-mediated immunodeficiency with decrease of CD4+ lymphocyte count to less than or equal to 200 cells/mm(3 )is a major risk factor for colonization with Candida species and development of candidiasis. Oropharyngeal candidiasis may occur in up to 90% of human immunodeficiency virus (HIV)-infected patients during the course of the disease. This study is to determine the effect of prolonged highly active antiretroviral therapy (HAART) on oropharyngeal colonization with Candida species and oral candidiasis. METHODS: A prospective, longitudinal follow-up study in HIV-infected patients receiving HAART. RESULTS: The mean CD4+ count increased from 232.5 to 316 cells/mm(3 )and the proportion of patients whose CD4+ count less than 200 cells/mm(3 )decreased from 50.0% to 28.9% (p = 0.0003) in patients receiving HAART for at least 2 years. The prevalence of oral candidiasis decreased from 10.6% to 2.1% (p = 0.004). The decrease in Candida colonization was less impressive, falling from 57.8% to 46.5 % (p = 0.06). Of the 142 patients enrolled in at least two surveys, 48 (33.8%) remained colonized with Candida and 42 (29.6%) remained negative. In the remaining 52 patients, 34 switched from culture positive to negative, and an increase in CD4+ lymphocytes was noted in 91.2% of them. Among the 18 patients who switched from culture negative to positive, 61.1% also demonstrated an increase in CD4+ lymphocyte count (p = 0.01). CONCLUSION: These findings indicate that HAART is highly effective in decreasing oral candidiasis in association with a rise in CD4+ lymphocyte counts, but only marginally effective in eliminating Candida from the oropharynx

What drives the evolution of gas kinematics in star-forming galaxies?

One important result from recent large integral field spectrograph (IFS) surveys is that the intrinsic velocity dispersion of galaxies traced by star-forming gas increases with redshift. Massive, rotation-dominated discs are already in place at z ∼ 2, but they are dynamically hotter than spiral galaxies in the local Universe. Although several plausible mechanisms for this elevated velocity dispersion (e.g. star formation feedback, elevated gas supply, or more frequent galaxy interactions) have been proposed, the fundamental driver of the velocity dispersion enhancement at high redshift remains unclear. We investigate the origin of this kinematic evolution using a suite of cosmological simulations from the FIRE (Feedback In Realistic Environments) project. Although IFS surveys generally cover a wider range of stellar masses than in these simulations, the simulated galaxies show trends between intrinsic velocity dispersion (σ intr ), SFR, and z in agreement with observations. In both observations and simulations, galaxies on the star-forming main sequence have median σ intr values that increase from z ∼ 0 to z ∼ 1–1.5, but this increasing trend is less evident at higher redshift. In the FIRE simulations, σ intr can vary significantly on time-scales of 100 Myr. These variations closely mirror the time evolution of the SFR and gas inflow rate (M gas ). By cross-correlating pairs of σ intr, M gas, and SFR, we show that increased gas inflow leads to subsequent enhanced star formation, and enhancements in σ intr tend to temporally coincide with increases in M gas and SFR