An EIA method on single donor solubilized HLA antigens for the identification of anti-HLA antibodies

Primary biliary cirrhosis (PBC) is an immunologically mediated disease in which activated T lymphocytes attack and destroy epithelial cells in the small intralobular bile ducts of genetically susceptible patients. This article reviews the results of treatment of PBC with immunomodulatory agents. Results with drugs such as glucocorticoids, azathioprine, and chlorambucil have been disappointing because of either limited efficacy (azathioprine), toxicity (chlorambucil), or both (glucocorticoids). Colchicine improved tests of liver function in three prospective studies and was associated with improved survival for up to 4 years. However, survival benefits were lost at 8 years. Colchicine appears to slow the rate of progression of PBC but not to stop it. Preliminary results suggest that colchicine may have synergistic effects if used together with ursodeoxycholic acid, particularly in patients who are only partially responsive to ursodeoxycholic acid. Results with cyclosporine have been disappointing because of limited efficacy and predictable toxicity. The modest improvement in tests of liver function and survival are counterbalanced by the development of hypertension in some and worsening renal function in most. There is little beneficial effect on symptoms or histology. Results with methotrexate are promising. There are improvements in symptoms and tests of liver function that are equal to those seen with ursodeoxycholic acid and significant improvement in liver histology. Some patients, particularly those with striking inflammation and granulomas in portal triads, appear to have achieved sustained remission while on methotrexate. The effects of methotrexate are additive to those of ursodeoxycholic acid in patients whose blood tests have responded only partially to ursodeoxycholic acid. The most effective treatment of PBC will most likely use a combination of drugs such as ursodeoxycholic acid, colchicine, and methotrexate.     

Relationship between seizure frequency and costs and quality of life of outpatients with partial epilepsy in France, Germany, and the United Kingdom

PURPOSE: The relationship between seizure frequency and both health care costs and quality of life (QOL) was investigated in a retrospective, cross-sectional, multicenter study in France, Germany, and the United Kingdom. METHODS: Three hundred outpatients with stable partial epilepsy were approximately evenly distributed among five seizure-frequency groups, ranging from seizure-free in the last 3 months (group 1) to daily seizures (group 5). Economic data, obtained through patient interviews and record abstraction, comprised direct medical costs, direct nonmedical costs, and indirect costs for the preceding 3 months. Total societal costs in the three countries were pooled and converted to United States dollar equivalents. QOL was assessed through a self-administered questionnaire, the Functional Status Questionnaire (FSQ). RESULTS: Mean total costs increased from $780 in group 1 to $2,171 in group 5 (p = 0.0001), with significant increases in each cost category as seizure frequency increased. Greater seizure frequency also significantly (p = 0.0270) correlated with lower employment rates, which ranged from 57% in group 1 to 30% in group 5. QOL declined as seizure frequency increased. Particularly affected were basic and intermediate activities of daily living (ADL), mental health, social activity, and feeling about health. CONCLUSIONS: The study results show that higher seizure frequencies are associated with higher direct and indirect costs and with reduced QOL for patients with epilepsy.     

Validation of the three-dimensional acquisition mode in positron emission tomography for the quantitation of [18F]fluoro-DOPA uptake in the human striata

Three-dimensional (3D) positron emission tomography (PET) is attractive for [18F]fluoro-DOPA studies, since the sensitivity improvement is maximal for radioactive sources located in central planes, which is usually the case for the human striata. However, the image quantitation in that mode must be assessed because of the nearly threefold increase in scattered coincidences. We report the results of [18F]fluoro-DOPA studies performed on six normal volunteers. Each one was scanned in the 3D and two-dimensional (2D) modes on the same tomograph. The quantitation in the 3D and 2D modes was compared for a Patlak graphical analysis with the occipital counts as the input function (Ki) and a striatooccipital ratio analysis. We find that, in 3D PET, a scatter correction is required to preserve the same quantitation as in 2D PET. When the 3D data sets are corrected for scatter, the quantitation of the [18F]fluoro-DOPA uptake, using the Patlak analysis, is similar in the 2D and 3D acquisition modes. Conversely, analysis of the striatooccipital ratio leads to higher values in 3D PET because of a better in-plane resolution. Finally, using the 3D mode, the dose injected to the subjects can be reduced by a factor greater than 1.5 without any loss in accuracy compared to the 2D mode.     

Quantized based image watermarking in an independent domain

This paper presents a performance study for two well known quantized based watermarking schemes Scalar Costa Scheme (SCS), and Trellis Coded Quantization scheme (TCQ) in an independent domain. For our study, the independent domain is obtained by the combination of the cited schemes with Independent Component Analysis (ICA). The Independent Component Analysis is used while inserting and extracting the message. Thus a performance compromise improvement of the original SCS and TCQ schemes in terms of robustness, capacity, and security is shown. Then the obtained schemes performances are compared to the Spread Transform (ST) based scheme well known for its proven good robustness properties. Our results show that, using watermarking with side information in independent domain permits to improve the global SCS and TCQ schemes performances. For example, in the case of SCS, by studying the Bit Error Rate (BER) in function of the watermark to noise ratio (WNR), the robustness has been improved by 20 dB (1 decade) when WNR is equal to 0 dB. Moreover, the capacity study shows for the same WNR=0 dB, the amount of information to be transmitted without error for a given noise level of the proposed SCS combined with ICA scheme (SCS-ICA) is much higher than that of the existing schemes. Finally, the study of the probability density functions (PDF) of the original and marked signals has shown that the Cachin-security level of the TCQ in an independent domain scheme (TCQ-ICA) is the best one compared to the other known schemes.     

Effect of Thermomechanical Fatigue on Precipitation Microstructure in Two Precipitation-Hardened Cast Aluminum Alloys

Thermal loading induces modifications of the precipitation microstructure of Al–Si–Cu–Mg alloys. This study focuses on the effect of deformation on precipitation microstructure during thermomechanical loadings. Several specimens were thermomechanically cycled while others were exposed to the same thermal cycles without any mechanical loading. The nature and morphological characteristics of the precipitation microstructure of the thermomechanically cycled specimens are compared to those of the thermally aged ones, using transmission electron microscopy (TEM), in order to assess the effect of deformation on the precipitation microstructure and especially on the kinetics of precipitate growth. The absence of any significant effect of superimposed straining during thermal cycling is discussed. Implications for the prevision of yield strength degradation during service operation are briefly presented.

     

Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.     

Preparation of ultra‐low‐density microcellular materials

Microcellular polymeric materials can be obtained by the polymerization of a high‐internal‐phase emulsion. These materials are good candidates as targets toward inertial confinement fusion. This application requires severe specifications, including a very low density and a small cell size. In this study, we examined the influence of parameters such as emulsification conditions, surfactant nature, and the presence of a porogen on the obtainment of those requirements. It was possible to obtain microcellular polymeric foams with apparent densities as low as 0.0126 g/cm³. However, it was difficult to obtain very low material density and still maintain a small average pore size. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 2053–2063, 2005