Hidden Consequence of Active Local Lorentz Invariance

In this paper we investigate a hidden consequence of the hypothesis that Lagrangians and field equations must be invariant under active local Lorentz transformations. We show that this hypothesis implies in an equivalence between spacetime structures with several curvature and torsion possibilities.Comment: Some misprints appearing in the published version have been correcte

A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations

Tiotropium Respimat efficacy and safety in asthma:Relationship to age

Background: Data are limited on the differential response to long-acting bronchodilators in older versus younger adults with asthma. Objective: To determine whether the response to tiotropium Respimat differed in older versus younger patients with asthma. Methods: Post hoc analyses of 4 randomized, double-blind, placebo-controlled studies in adults with asthma were carried out. Two studies compared tiotropium Respimat 5 μg once daily with placebo, both added to high-dose inhaled corticosteroid (ICS) plus long-acting β2-agonist (ie, severe asthma). The other 2 evaluated tiotropium Respimat 2.5 or 5 μg once daily, salmeterol 50 μg twice daily, or placebo, all added to medium-dose ICS (moderate asthma). Data were analyzed in 2 pools: (1) severe and (2) moderate asthma. Efficacy end points: trough and peak FEV1; trough forced vital capacity; Asthma Control Questionnaire total score and responder percentage, all at week 24. One set of analyses was performed with age as a continuous covariate; the second was conducted in categories less than 40, 40 to 60, and more than 60 years, with treatment-by-age subgroup interaction P values obtained. Safety was analyzed in age categories. Results: Across the age categories, treatment-by-age subgroup interaction P values for trough FEV1 were.13 and.77 for patients with severe and moderate asthma, respectively, not indicating significant impact of age on overall treatment effect, with this observation replicated in the 2 continuum analyses. The other end points (including safety) were also not impacted by age. Conclusions: Once-daily tiotropium Respimat add-on to ICS or ICS/long-acting β2-agonist therapy was effective and well tolerated in patients with asthma independent of age

The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis.

A previous study showed that, in carriers of the apolipoprotein E (APOE) genotype ε3/ε3 or ε3/ε4, the presence of a very long (VL) polyT repeat allele in "translocase of outer mitochondrial membrane 40" (TOMM40) was less frequent in patients with sporadic inclusion body myositis (sIBM) compared with controls and associated with a later age of sIBM symptom onset, suggesting a protective effect of this haplotype. To further investigate the influence of these genetic factors in sIBM, we analyzed a large sIBM cohort of 158 cases as part of an International sIBM Genetics Study. No significant association was found between APOE or TOMM40 genotypes and the risk of developing sIBM. We found that the presence of at least 1 VL polyT repeat allele in TOMM40 was significantly associated with about 4 years later onset of sIBM symptoms. The age of onset was delayed by 5 years when the patients were also carriers of the APOE genotype ε3/ε3. In addition, males were likely to have a later age of onset than females. Therefore, the TOMM40 VL polyT repeat, although not influencing disease susceptibility, has a disease-modifying effect on sIBM, which can be enhanced by the APOE genotype ε3/ε3

A Completely Covariant Approach to Transformation Optics

We show that the Plebanski based approach to transformation optics overlooks some subtleties in the electrodynamics of moving dielectrics that restricts its applicability to a certain class of transformations. An alternative, completely covariant, approach is developed that is more generally applicable and provides a clearer picture of transformation optics.Comment: 10 pages. This version: Additional references added, corrected a small error in Eq. (28) (Eq. (29) in present version), some revision of the text, appendix content moved to the main body of the text, figure removed. Corresponds more closely to published version. Prepared for a special issue on transformation optics published by Journal of Optic