Inclusion body myositis: therapeutic approaches.

The idiopathic inflammatory myopathies are a heterogeneous group of diseases that include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and other less common myopathies. These are clinically and histopathologically distinct diseases with many shared clinical features. IBM, the most commonly acquired inflammatory muscle disease occurs in individuals aged over 50 years, and is characterized by slowly progressive muscle weakness and atrophy affecting proximal and distal muscle groups, often asymmetrically. Unlike DM and PM, IBM is typically refractory to immunotherapy. Although corticosteroids have not been tested in randomized controlled trials, the general consensus is that they are not efficacious. There is some suggestion that intravenous immunoglobulin slows disease progression, but its long-term effectiveness is unclear. The evidence for other immunosuppressive therapies has been derived mainly from case reports and open studies and the results are discouraging. Only a few clinical trials have been conducted on IBM, making it difficult to provide clear recommendations for treatment. Moreover, IBM is a slowly progressive disease so assessment of treatment efficacy is problematic due to the longer-duration trials needed to determine treatment effects. Newer therapies may be promising, but further investigation to document efficacy would be expensive given the aforementioned need for longer trials. In this review, various treatments that have been employed in IBM will be discussed even though none of the interventions has sufficient evidence to support its routine use

Exact determination of the volume of an inclusion in a body having constant shear modulus

We derive an exact formula for the volume fraction of an inclusion in a body when the inclusion and the body are linearly elastic materials with the same shear modulus. Our formula depends on an appropriate measurement of the displacement and traction around the boundary of the body. In particular, the boundary conditions around the boundary of the body must be such that they mimic the body being placed in an infinite medium with an appropriate displacement applied at infinity

Treatment for inclusion body myositis

Background Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment. Objectives To assess the effects of treatment for IBM. Search methods On 7 October 2014 we search ed the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials. Selection criteria We considered randomised or quasi-randomised trials, including cross-over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews. Data collection and analysis We used standard Cochrane methodological procedures. Main results The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta-1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) -0.06, 95% CI -0.15 to 0.03) between IFN beta-1a and placebo (moderate-quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate-quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low-quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re-analysis. Other comparisons were also reported in single trials. An open trial of anti-T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events. Authors\u27 conclusions Trials of interferon beta-1a and MTX provided moderate-quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures

Bound State Calculations of the Three-Dimensional Yakubovsky Equations with the inclusion of Three-Body Forces

The four-body Yakubovsky equations in a Three-Dimensional approach with the inclusion of the three-body forces is proposed. The four-body bound state with two- and three-body interactions is formulated in Three-Dimensional approach for identical particles as function of vector Jacobi momenta, specifically the magnitudes of the momenta and the angles between them. The modified three dimensional Yakubovsky integral equations is successfully solved with the scalar two-meson exchange three-body force where the Malfliet-Tjon-type two-body force is implemented. The three-body force effects on the energy eigenvalue and the four-body wave function, as well as accuracy of our numerical calculations are presented.The four-body Yakubovsky equations in a Three-Dimensional approach with the inclusion of the three-body forces is proposed. The four-body bound state with two- and three-body interactions is formulated in Three-Dimensional approach for identical particles as function of vector Jacobi momenta, specifically the magnitudes of the momenta and the angles between them. The modified three dimensional Yakubovsky integral equations is successfully solved with the scalar two-meson exchange three-body force where the Malfliet-Tjon-type two-body force is implemented. The three-body force effects on the energy eigenvalue and the four-body wave function, as well as accuracy of our numerical calculations are presented.Comment: 23 pages, 2 eps figures, 5 tables. Major changes; version to appear in European Physical Journal

Effect of Urea and Distillers Inclusion in Dry- Rolled Corn Based Diets on Heifer Performance and Carcass Characteristics

Crossbred heifers (n=96, BW = 810 ± 20) were utilized to evaluate the effects of increasing wet distillers grains plus solubles and urea inclusion in a dry rolled corn based finishing diet on performance and carcass characteristics. Heifers were individually fed using a calan gate system with a 2 × 2 factorial arrangement of treatments. Factors included distillers inclusion at either 10 or 20% of diet DM and urea inclusion at either 0.2 or 1.4% of diet DM. Th ere was no difference for final body weight, average daily gain, and feed conversion on a live or carcass adjusted basis for either urea or distillers inclusion in the diet. Dry matter intake was reduced with increased urea inclusion; however, distillers inclusion did not influence intake. Added distillers and urea in the diet had minimal impact on performance suggesting supplemental urea in a dry rolled corn based finishing diets is of minimal benefit when feeding at least 10% distillers grains

Three-body force effect on neutrino emissivities of neutron stars within the framework of the Brueckner-Hartree-Fock approach

The three-body force (TBF) effect on the neutrino emissivity in neutron star matter and the total neutrino emissivity of neutron stars have been investigated within the framework of the Brueckner-Hartree-Fock approach by adopting the AV18 two-body interaction plus a microscopic TBF. The neutrino emissivity from the direct Urca process turns out to be much larger than that from the modified Urca process. Inclusion of the TBF reduces strongly the density thresholds of the direct Urca processes involving electrons and muons. The TBF effect on the total neutrino emissivity of neutron stars is shown to be negligibly weak for neutron stars with small masses. For neutron stars with large masses, the TBF effect becomes visible and inclusion of the TBF may enhance the total neutrino emissivity by about 50% for neutron stars with a given mass of $M=1.6M_{\odot}$.Comment: 7 pages, 3 figure

Potential Harmonics Expansion Method for Trapped Interacting Bosons : Inclusion of Two-Body Correlation

We study a system of $A$ identical interacting bosons trapped by an external field by solving ab initio the many-body Schroedinger equation. A complete solution by using, for example, the traditional hyperspherical harmonics (HH) basis develops serious problems due to the large degeneracy of HH basis, symmetrization of the wave function, calculation of the matrix elements, etc. for large $A$. Instead of the HH basis, here we use the "potential harmonics" (PH) basis, which is a subset of HH basis. We assume that the contribution to the orbital and grand orbital [in $3(A-1)$-dimensional space of the reduced motion] quantum numbers comes only from the interacting pair. This implies inclusion of two-body correlations only and disregard of all higher-body correlations. Such an assumption is ideally suited for the Bose-Einstein condensate (BEC), which is extremely dilute. Unlike the $(3A-4)$ hyperspherical variables in HH basis, the PH basis involves only three {\it{active}} variables. It drastically reduces the number of coupled equations and calculation of the potential matrix becomes tremendously simplified, as it involves integrals over only three variables for any $A$. One can easily incorporate realistic atom-atom interactions in a straight forward manner. We study the ground and excited state properties of the condensate for both attractive and repulsive interactions for various particle number.Comment: 36 pages, 7 included figures, plain late