| 1. |
- Feugnet, G., et al.
(author)
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Improved laser-induced fluorescence method for bio-attack early warning detection system
- 2008
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE.
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Conference paper (peer-reviewed)abstract
- Laser Induced Fluorescence (LIF) could permit fast early warning systems either for point or standoff detection if a reliable classification of warfare biological agents versus biological or non-biological fluorescing background can be achieved. In order to improve LIF discrimination capability, a new system is described in which the fluorescence pattern is enriched by the use of multiple wavelength delayed excitation while usual spectral fluorescence analysis is extended to time domain to use both aspects as criteria for classification. General considerations and guidelines for the system design are given as well as results showing good discrimination between background and simulants.
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| 2. |
- Vergoossen, Dana L. E., et al.
(author)
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Enrichment of serum IgG4 in MuSK myasthenia gravis patients
- 2022
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In: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 373
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Journal article (peer-reviewed)abstract
- Muscle-specific kinase (MuSK) myasthenia gravis (MG) is a neuromuscular autoimmune disease belonging to a growing group of IgG4 autoimmune diseases (IgG4-AIDs), in which the majority of pathogenic autoantibodies are of the IgG4 subclass. The more prevalent form of MG with acetylcholine receptor (AChR) antibodies is caused by IgG1-3 autoantibodies. A dominant role for IgG4 in autoimmune disease is intriguing due to its antiinflammatory characteristics. It is unclear why MuSK autoantibodies are predominantly IgG4. We hypothesized that MuSK MG patients have a general predisposition to generate IgG4 responses, therefore resulting in high levels of circulating IgG4. To investigate this, we quantified serum Ig isotypes and IgG subclasses using nephelometric and turbidimetric assays in MuSK MG and AChR MG patients not under influence of immunosuppressive treatment. Absolute serum IgG1 was increased in both MuSK and AChR MG patients compared to healthy donors. In addition, only MuSK MG patients on average had significantly increased and enriched serum IgG4. Although more MuSK MG patients had elevated serum IgG4, for most the IgG4 serum levels fell within the normal range. Correlation analyses suggest MuSK-specific antibodies do not solely explain the variation in IgG4 levels. In conclusion, although serum IgG4 levels are slightly increased, the levels do not support ubiquitous IgG4 responses in MuSK MG patients as the underlying cause of dominant IgG4 MuSK antibodies.
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| 3. |
- Ekström, Lars, 1959, et al.
(author)
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Intervertebral disc response to cyclic loading--an animal model.
- 1996
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In: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine. - 0954-4119. ; 210:4, s. 249-58
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Journal article (peer-reviewed)abstract
- The viscoelastic response of a lumbar motion segment loaded in cyclic compression was studied in an in vivo porcine model (N = 7). Using surgical techniques, a miniaturized servohydraulic exciter was attached to the L2-L3 motion segment via pedicle fixation. A dynamic loading scheme was implemented, which consisted of one hour of sinusoidal vibration at 5 Hz, 50 N peak load, followed by one hour of restitution at zero load and one hour of sinusoidal vibration at 5 Hz, 100 N peak load. The force and displacement responses of the motion segment were sampled at 25 Hz. The experimental data were used for evaluating the parameters of two viscoelastic models: a standard linear solid model (three-parameter) and a linear Burger's fluid model (four-parameter). In this study, the creep behaviour under sinusoidal vibration at 5 Hz closely resembled the creep behaviour under static loading observed in previous studies. Expanding the three-parameter solid model into a four-parameter fluid model made it possible to separate out a progressive linear displacement term. This deformation was not fully recovered during restitution and is therefore an indication of a specific effect caused by the cyclic loading. High variability was observed in the parameters determined from the 50 N experimental data, particularly for the elastic modulus E1. However, at the 100 N load level, significant differences between the models were found. Both models accurately predicted the creep response under the first 800 s of 100 N loading, as displayed by mean absolute errors for the calculated deformation data from the experimental data of 1.26 and 0.97 percent for the solid and fluid models respectively. The linear Burger's fluid model, however, yielded superior predictions particularly for the initial elastic response.
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| 4. |
- Haggård, Linnea, et al.
(author)
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beta-glucans reduce LDL cholesterol in patients with myasthenia gravis
- 2013
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In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 67:2, s. 226-227
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Journal article (peer-reviewed)abstract
- We aimed at evaluating whether beta-glucans could improve low-density lipoprotein (LDL) cholesterol levels and/or glycemic control in patients with myasthenia gravis (MG), in whom statins usually have muscle-related side effects. Fifty-nine MG patients participated in the study and received a daily dietary supplement of 3 g of beta-glucans during 8 weeks. Body mass index (BMI) and blood sample analysis of lipid and glucose status were performed before and after 8 weeks intake of beta-glucans. In the 52 patients who completed the study, there was a significant reduction in total cholesterol, LDL, ApoA1 and ApoB (all P<0.003). However, glycemic control and BMI were unaltered. The present study indicates that 8 weeks daily intake of 3 g of beta-glucans significantly reduces total cholesterol, LDL, ApoA1 and ApoB in MG patients. beta-glucans may therefore be of value in improving lipid status in MG patients, without the muscle-related side effects accompanied by statins.
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| 5. |
- Kaigle Holm, Allison, 1964, et al.
(author)
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In vivo dynamic stiffness of the porcine lumbar spine exposed to cyclic loading: influence of load and degeneration.
- 1998
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In: Journal of spinal disorders. - 0895-0385. ; 11:1, s. 65-70
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Journal article (peer-reviewed)abstract
- The dynamic axial stiffness of the L2-3 motion segment subjected to vibratory loading under intact and injured states of the intervertebral disc was studied using an in vivo porcine model. Three groups of animals with the following states of the intervertebral discs were studied: intact disc, acutely injured disc, and degenerated disc. A miniaturized servo-hydraulic exciter was used to sinusoidally vibrate the motion segment from 0.05 to 25 Hz under a compressive load with a peak value of either 100 or 200 N. The dynamic axial stiffness of the intervertebral disc was calculated at 1-Hz intervals over the frequency range. The results showed that the dynamic axial stiffness was frequency dependent. A positive relationship was found between an increase in mean dynamic stiffness and load magnitude. An increase in mean stiffness with successive exposures at the same load magnitude was observed, despite the allowance of a recovery period between loading. The greatest difference was noted between the first and second load sets. No significant change in stiffness was found due to an acute disc injury, whereas a significant increase in mean stiffness was found for the degenerated disc group as compared with the intact group. The form of the frequency response curve, however, remained relatively unaltered regardless of the degenerated state of the disc. With heavier loads, repeated loading, and/or disc degeneration, the stiffness of the intervertebral disc increases. An increase in stiffness can mean a reduction in the amount of allowable motion within the motion segment or a potentially harmful increase in force to obtain the desired motion. This may locally result in greater stresses due to an altered ability of the disc to distribute loads.
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| 6. |
- Laaksonen, Katri, et al.
(author)
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Nanoparticles of TiO2 and VO2 in dielectric media : Conditions for low optical scattering, and comparison between effective medium and four-flux theories
- 2014
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In: Solar Energy Materials and Solar Cells. - : Saunders Elsevier. - 0927-0248 .- 1879-3398. ; 130:SI, s. 132-137
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Journal article (peer-reviewed)abstract
- Spectral transmittance and reflectance in the 300 to 2500 nm solar-optical wavelength range were calculated for nanoparticles of titanium dioxide and vanadium dioxide with radii between 5 and 100 nm embedded in transparent dielectric media. Both of the materials are of large importance in green nanotechnologies: thus TiO2 is a photocatalyst that can be applied as a porous film or a nanoparticle composite on indoor or outdoor surfaces for environmental remediation, and VO2 is a thermochromic material with applications to energy-efficient fenestration. The optical properties, including scattering, of the nanoparticle composites were computed from the Maxwell–Garnett effective-medium theory as well as from a four-flux radiative transfer model. Predictions from these theories approach one another in the limit of small particles and in the absence of optical interference. Effects of light scattering can be modeled only by the four-flux theory, though. We found that nanoparticle radii should be less than ~20 nm in order to avoid pronounced light scattering.
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| 7. |
- Phillips, W D, et al.
(author)
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Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis
- 2015
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In: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 270:SI, s. 29-40
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Journal article (peer-reviewed)abstract
- Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endplate potentials and endplate potentials, and failure of neuromuscular transmission. Similar impairments have been found in mice injected with IgG from MG patients positive for MuSK autoantibody (MuSK-MG). The active and passive models have begun to reveal the mechanisms by which MuSK antibodies disrupt synaptic function at the neuromuscular junction, and should be valuable in developing therapies for MuSK-MG. However, translation into new and improved treatments for patients requires procedures that are not too cumbersome but suitable for examining different aspects of MuSK function and the effects of potential therapies. Study design, conduct and analysis should be carefully considered and transparently reported. Here we review what has been learnt from animal and culture models of MuSK-MG, and offer guidelines for experimental design and conduct of studies, including sample size determination, randomization, outcome parameters and precautions for objective data analysis. These principles may also be relevant to the increasing number of other antibody-mediated diseases that are now recognized.
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| 8. |
- Piehl, F., et al.
(author)
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Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis The RINOMAX Randomized Clinical Trial
- 2022
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In: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157.
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Journal article (peer-reviewed)abstract
- IMPORTANCE Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown. OBJECTIVE To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids. INTERVENTIONS Participants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo. MAIN OUTCOMES AND MEASURES Minimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment. RESULTS Of 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event. CONCLUSIONS AND RELEVANCE A single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment.
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| 9. |
- Rostedt Punga, Anna, et al.
(author)
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Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders
- 2022
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 21:2, s. 176-188
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Research review (peer-reviewed)abstract
- Autoimmune neuromuscular junction disorders are rare. However, myasthenia gravis is being increasingly recognised in people older than 50 years. In the past 5-10 years, epidemiological studies worldwide suggest an incidence of acetylcholine receptor antibody-positive myasthenia gravis of up to 29 cases per 1 million people per year. Muscle-specific tyrosine kinase antibody-positive myasthenia gravis and Lambert-Eaton myasthenic syndrome are about 20 times less common. Several diagnostic methods are available for autoimmune neuromuscular junction disorders, including serological antibody, electrophysiological, imaging, and pharmacological tests. The course of disease can be followed up with internationally accepted clinical scores or patient-reported outcome measures. For prognostic purposes, determining whether the disease is paraneoplastic is of great importance, as myasthenia gravis can be associated with thymoma and Lambert-Eaton myasthenic syndrome with small-cell lung cancer. However, despite well defined diagnostic parameters to classify patients into subgroups, objective biomarkers for use in the clinic or in clinical trials to predict the course of myasthenia gravis and Lambert-Eaton myasthenic syndrome are needed.
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| 10. |
- Sabre, Liis, et al.
(author)
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Circulating microRNA plasma profile in MuSK plus myasthenia gravis
- 2018
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In: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 325, s. 87-91
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Journal article (peer-reviewed)abstract
- Muscle-specific tyrosine kinase antibody positive myasthenia gravis (MuSK+ MG) is an immunological subtype with distinctive pathogenic mechanisms and clinical features. The aim of this study was to analyze the circulating plasma microRNA profile of patients with MuSK + MG. From the discovery cohort miR-210-3p, miR-3243p and miR-328-3p were further analyzed in the validation cohort. We found a distinct plasma profile of miR210-3p and miR-324-3p that were significantly decreased in MuSK+ MG patients compared to healthy controls (4.1 +/- 1.4 vs 5.1 +/- 1.4, p = .006 and 4.7 +/- 1.0 vs 5.4 +/- 1.3, p = .02). These findings reveal a distinct plasma miRNA profile in MuSK+ MG.
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