1,569 research outputs found
Novel autoantibodies and clinical phenotypes in adult and juvenile myositis
Autoantibodies targeting intracellular proteins involved in key processes are detected in patients with idiopathic inflammatory myopathies. These myositisspecific autoantibodies have been increasingly demonstrated to correlate with distinct clinical phenotypes within the myositis spectrum. This review highlights the clinical associations of the myositisspecific autoantibodies, with particular attention to the recently identified and characterized novel myositis autoantibodies: p155/140, p140 (MJ), CADM-140 (MDA5), SAE, and 200/100
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NOx Sensor for Direct Injection Emission Control
The Electricore/Delphi team continues to leverage the electrochemical planar sensor technology that has produced stoichiometric planar and wide range oxygen sensors as the basis for development of a NOx sensor. Zirconia cell technology with an integrated heater will provide the foundation for the sensor structure. Proven materials and packaging technology will help to ensure a cost-effective approach to the manufacture of this sensor. The electronics technique and interface is considered to be an area where new strategies need to be employed to produce higher S/N ratios of the NOx signal with emphasis on signal stability over time for robustness and durability Both continuous mode and pulse mode control techniques are being evaluated. Packaging the electronics requires careful design and circuit partitioning so that only the necessary signal conditioning electronics are coupled directly in the wiring harness, while the remainder is situated within the ECM for durability and costs reasons. This task continues to be on hold due to the limitation that the definition of the interface electronics was unavailable until very late in the project. The sense element is based on the amperometric method utilizing integrated alumina and zirconia ceramics. Precious metal electrodes are used to form the integrated heater, the cell electrodes and leads. Inside the actual sense cell structure, it is first necessary to separate NOx from the remaining oxygen constituents of the exhaust, without reducing the NOx. Once separated, the NOx will be measured using a measurement cell. Development or test coupons have been used to facilitate material selection and refinement, cell, diffusion barrier, and chamber development. The sense element currently requires elaborate interconnections. To facilitate a robust durable connection, mechanical and metallurgical connections are under investigation. Materials and process refinements continue to play an important role in the development of the sensor
The reliability of immunoassays to detect autoantibodies in patients with myositis is dependent on autoantibody specificity
OBJECTIVES: In order to address the reliability of commercial assays to identify myositis-specific and -associated autoantibodies, we aimed to compare the results of two commercial immunoassays with the results obtained by protein immunoprecipitation.METHODS: Autoantibody status was determined using radio-labelled protein immunoprecipitation for patients referred to our laboratory for myositis autoantibody characterization. For each autoantibody of interest, the sera from 25 different patients were analysed by line blot (Euroline Myositis Antigen Profile 4, EuroImmun, LĂŒbeck, Germany) and dot blot (D-Tek BlueDiver, Diagnostic Technology, Belrose, NSW, Australia). Sera from 134 adult healthy controls were analysed.RESULTS: Overall commercial assays performed reasonably well, with high agreement (Cohen's Îș >0.8). Notable exceptions were the detection of rarer anti-synthetases with Îșâ<â0.2 and detection of anti-TIF1Îł, where Îș was 0.70 for the line blot and 0.31 for dot blot. Further analysis suggested that the proportion of patients with anti-TIF1Îł may recognize a conformational epitope, limiting the ability of blotting-based assays that utilize denatured antigen to detect this clinically important autoantibody. A false-positive result occurred in 13.7% of samples analysed by line blot and 12.1% analysed by dot blot.CONCLUSION: The assays analysed do not perform well for all myositis-specific and -associated autoantibodies and overall false positives are relatively common. It is crucial that clinicians are aware of the limitations of the methods used by their local laboratory. Results must be interpreted within the clinical context and immunoprecipitation should still be considered in selected cases, such as apparently autoantibody-negative patients where anti-synthetase syndrome is suspected.</p
Long-term glycaemic control with metforminâ sulphonylureaâpioglitazone triple therapy in PROactive (PROactive 17)
peer reviewedAims We assessed the long-term glycaemic effects and the safety profile of triple therapy with the addition of pioglitazone vs. placebo in patients with Type 2 diabetes treated with combined metforminâsulphonylurea therapy in the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive).
Methods In a post-hoc analysis, we identified patients treated with metformin plus sulphonylurea combination therapy and not receiving insulin at baseline (n = 1314). In those patients, we compared the effects of pioglitazone (force-titrated to 45 mgâ day, n = 654) vs. placebo (n = 660) on glycated haemoglobin (HbA1c) reduction, concomitant changes in medications
and initiation of permanent insulin use (defined as daily insulin use for a period of ⥠90 days or ongoing use at death â final visit).
Results Significantly greater reductions in HbA1c and greater proportions of patients with HbA1c at target were noted with pioglitazone vs, placebo, despite a decrease in the use of other oral glucose-lowering agents. Therewas an approximate twofold increase in progression to permanent insulin use in the placebo group vs. the pioglitazone group: 31.1 vs. 16.1%, respectively,
when added to combination therapy. The overall safety of themetforminâsulphonylureaâpioglitazone triple therapy was good.
Conclusions Intensifying an existing dual oral therapy regimen to a triple oral regimen by adding pioglitazone to the classical metforminâsulphonylurea combination resulted in sustained improvements in glycaemic control and reduced progression to insulin therapy. The advantages and disadvantages of adding pioglitazone instead of adding basal insulin should be assessed
further
Hybridised multigrid preconditioners for a compatible finite element dynamical core
Compatible finite element discretisations for the atmospheric equations of
motion have recently attracted considerable interest. Semi-implicit
timestepping methods require the repeated solution of a large saddle-point
system of linear equations. Preconditioning this system is challenging since
the velocity mass matrix is non-diagonal, leading to a dense Schur complement.
Hybridisable discretisations overcome this issue: weakly enforcing continuity
of the velocity field with Lagrange multipliers leads to a sparse system of
equations, which has a similar structure to the pressure Schur complement in
traditional approaches. We describe how the hybridised sparse system can be
preconditioned with a non-nested two-level preconditioner. To solve the coarse
system, we use the multigrid pressure solver that is employed in the
approximate Schur complement method previously proposed by the some of the
authors. Our approach significantly reduces the number of solver iterations.
The method shows excellent performance and scales to large numbers of cores in
the Met Office next-generation climate- and weather prediction model LFRic.Comment: 24 pages, 13 figures, 5 tables; accepted for publication in Quarterly
Journal of the Royal Meteorological Societ
(1RS,4SR)-3-DichloroÂmethylÂene-1,4-dimethyl-2-oxabicycloÂ[2.2.2]oct-5-ene
X-ray crystallography was used to confirm the structure of the enantio-enriched title compound, C10H12Cl2O, a bicylic enol ether. A bridged boat-like structure is adopted and the dichloroÂmethylÂene C atom is positioned significantly removed from the core bicyclic unit. In the crystal structure, molÂecules pack to form sheets approximately perpendicular to the a and c axes
Computer-controlled apparatus for automated development of continuous flow methods
An automated apparatus to assist in the development of analytical
continuous flow methods is described. The system is capable of
controlling and monitoring a variety of pumps, valves, and
detectors through an IBM PC-AT compatible computer. System
components consist of two types of peristaltic pumps (including a
multiple pump unit), syringe pumps, electrically and pneumatically
actuated valves, and an assortment of spectrophotometric and
electrochemical detectors. Details of the interface circuitry are given
where appropriate. To demonstrate the utility of the system, an
automatically generated response surface is presented for the flow
injection determination of iron(II) by its reaction with
1,10-phenanthroline
Investigation of myositis and scleroderma specific autoantibodies in patients with lung cancer
BACKGROUND: The close temporal association between onset of some connective tissue diseases and cancer suggests a paraneoplastic association. Adult patients with scleroderma with anti-RNA polymerase III autoantibodies and adult patients with dermatomyositis with anti-transcriptional intermediary factor 1 (anti-TIF1) or anti-nuclear matrix protein 2 (anti-NXP2) autoantibodies have a significantly increased risk of developing cancer. Autoantibodies may serve as biomarkers for early detection of cancer and also could be relevant for prediction of responses to immune therapies. We aimed to test whether myositis and scleroderma specific or associated autoantibodies are detectable in individuals with lung cancer.METHODS: Serum from 60 Caucasian patients with lung cancer (30 with small cell lung cancer, 30 with non-small cell lung cancer) was screened for myositis and scleroderma specific and associated autoantibodies by radiolabelled immunoprecipitation.RESULTS: Anti-TIF1, anti-NXP2 or anti-RNA polymerase III autoantibodies were not detected in any of the 60 patients with lung cancer. Anti-glycyl-transfer RNA (tRNA) synthetase (anti-EJ) autoantibodies were detected in one patient with non-small cell lung cancer. No other known myositis or scleroderma autoantibodies were identified.CONCLUSIONS: Myositis and scleroderma specific autoantibodies, including anti-TIF1, anti-NXP2 and anti-RNA polymerase III, are rare in patients with lung cancer without an autoimmune disease. We report here the first case of anti-EJ autoantibodies being detected in a patient with lung cancer without clinical or radiographic evidence of the anti-synthetase syndrome.</p
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