Zinc Gluconate in the Treatment of Dysgeusia—a Randomized Clinical Trial

In the treatment of dysgeusia, the use of zinc has been frequently tried, with equivocal results. The aim of the present randomized clinical trial, which involved a sufficiently large sample, was therefore to determine the efficacy of zinc treatment. Fifty patients with idiopathic dysgeusia were carefully selected. Zinc gluconate (140 mg/day; n = 26) or placebo (lactose; n = 24) was randomly assigned to the patients. The patients on zinc improved in terms of gustatory function (p < 0.001) and rated the dysgeusia as being less severe (p < 0.05). Similarly, signs of depression in the zinc group were less severe (Beck Depression Inventory, p < 0.05; mood scale, p < 0.05). With the exception of the salivary calcium level, which was higher in the zinc patients (p < 0.05), no other significant group differences were found. In conclusion, zinc appears to improve general gustatory function and, consequently, general mood scores in dysgeusia patients

Newtonian Cosmology in Lagrangian Formulation: Foundations and Perturbation Theory

The ``Newtonian'' theory of spatially unbounded, self--gravitating, pressureless continua in Lagrangian form is reconsidered. Following a review of the pertinent kinematics, we present alternative formulations of the Lagrangian evolution equations and establish conditions for the equivalence of the Lagrangian and Eulerian representations. We then distinguish open models based on Euclidean space $\R^3$ from closed models based (without loss of generality) on a flat torus \T^3. Using a simple averaging method we show that the spatially averaged variables of an inhomogeneous toroidal model form a spatially homogeneous ``background'' model and that the averages of open models, if they exist at all, in general do not obey the dynamical laws of homogeneous models. We then specialize to those inhomogeneous toroidal models whose (unique) backgrounds have a Hubble flow, and derive Lagrangian evolution equations which govern the (conformally rescaled) displacement of the inhomogeneous flow with respect to its homogeneous background. Finally, we set up an iteration scheme and prove that the resulting equations have unique solutions at any order for given initial data, while for open models there exist infinitely many different solutions for given data.Comment: submitted to G.R.G., TeX 30 pages; AEI preprint 01

The Cosmic No-Hair Theorem and the Nonlinear Stability of Homogeneous Newtonian Cosmological Models

The validity of the cosmic no-hair theorem is investigated in the context of Newtonian cosmology with a perfect fluid matter model and a positive cosmological constant. It is shown that if the initial data for an expanding cosmological model of this type is subjected to a small perturbation then the corresponding solution exists globally in the future and the perturbation decays in a way which can be described precisely. It is emphasized that no linearization of the equations or special symmetry assumptions are needed. The result can also be interpreted as a proof of the nonlinear stability of the homogeneous models. In order to prove the theorem we write the general solution as the sum of a homogeneous background and a perturbation. As a by-product of the analysis it is found that there is an invariant sense in which an inhomogeneous model can be regarded as a perturbation of a unique homogeneous model. A method is given for associating uniquely to each Newtonian cosmological model with compact spatial sections a spatially homogeneous model which incorporates its large-scale dynamics. This procedure appears very natural in the Newton-Cartan theory which we take as the starting point for Newtonian cosmology.Comment: 16 pages, MPA-AR-94-

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

Machine learning and structural analysis of Mycobacterium tuberculosis pan-genome identifies genetic signatures of antibiotic resistance.

Mycobacterium tuberculosis is a serious human pathogen&nbsp;threat exhibiting complex evolution of antimicrobial resistance (AMR). Accordingly, the many publicly available datasets describing its AMR characteristics demand disparate data-type analyses. Here, we develop a reference strain-agnostic computational platform that uses machine learning approaches, complemented by both genetic interaction analysis and 3D structural mutation-mapping, to identify signatures of AMR evolution to 13 antibiotics. This platform is applied to 1595 sequenced strains to yield four key results. First, a pan-genome analysis shows that M. tuberculosis is highly conserved with sequenced variation concentrated in PE/PPE/PGRS genes. Second, the platform corroborates 33 genes known to confer resistance and identifies 24 new genetic signatures of AMR. Third, 97 epistatic interactions across 10 resistance classes are revealed. Fourth, detailed structural analysis of these genes yields mechanistic bases for their selection. The platform can be used to study other human pathogens

Implications of Cosmological Gamma-Ray Absorption II. Modification of gamma-ray spectra

Bearing on the model for the time-dependent metagalactic radiation field developed in the first paper of this series, we compute the gamma-ray attenuation due to pair production in photon-photon scattering. Emphasis is on the effects of varying the star formation rate and the fraction of UV radiation assumed to escape from the star forming regions, the latter being important mainly for high-redshift sources. Conversely, we investigate how the metagalactic radiation field can be measured from the gamma-ray pair creation cutoff as a function of redshift, the Fazio-Stecker relation. For three observed TeV-blazars (Mkn501, Mkn421, H1426+428) we study the effects of gamma-ray attenuation on their spectra in detail.Comment: 10 pages, 6 figures, accepted by A&

Efficacy of Modular Design in Healthcare

Modular design has become an industry leading philosophy for the future of community-based health services. Modular applied as a design principle subdivides a construction system into independently fabricated units, similar in size, shape, and functionality to formulate a structure. The benefits of this approach include time-to-build efficiency, cost-effectiveness, quality and precision, sustainability, continuity, and modification. This process contradicts traditional construction, pre-fabricating spaces off site to be assembled later. Modular architecture is historically correlated with hotel design and is still in its adolescent stage being integrated into hospice. Forward-thinking medical institutes and design firms have begun to experiment with modular design in their projects aiming to provide accessible healthcare in any context, however, discrepancies have surfaced. The complexity of a functional healthcare facility including circulation, adaptability, materiality, and utilities are being overlooked due to monetary hesitation, high demand, and standardized design. Modular healthcare design is still unpopular amongst manufacturers and firms. Through correlational research and simulation software, modular solutions and traditional construction methods can be compared using operational statistics. The purpose of this research is to study the efficacy of the designs proposed by the industry thus far in hopes to refine the process for a safer, enjoyable, more efficient, and replicable solution

Systems biology meets stress ecology: linking molecular and organismal stress responses in Daphnia magna

Background: Ibuprofen and other nonsteroidal anti-inflammatory drugs have been designed to interrupt eicosanoid metabolism in mammals, but little is known of how they affect nontarget organisms. Here we report a systems biology study that simultaneously describes the transcriptomic and phenotypic stress responses of the model crustacean Daphnia magna after exposure to ibuprofen. Results: Our findings reveal intriguing similarities in the mode of action of ibuprofen between vertebrates and invertebrates, and they suggest that ibuprofen has a targeted impact on reproduction at the molecular, organismal, and population level in daphnids. Microarray expression and temporal real-time quantitative PCR profiles of key genes suggest early ibuprofen interruption of crustacean eicosanoid metabolism, which appears to disrupt signal transduction affecting juvenile hormone metabolism and oogenesis. Conclusion: Combining molecular and organismal stress responses provides a guide to possible chronic consequences of environmental stress for population health. This could improve current environmental risk assessment by providing an early indication of the need for higher tier testing. Our study demonstrates the advantages of a systems approach to stress ecology, in which Daphnia will probably play a major role

Anisotropy and inflation in Bianchi I brane worlds

After a more general assumption on the influence of the bulk on the brane, we extend some conclusions by Maartens et al. and Santos et al. on the asymptotic behavior of Bianchi I brane worlds. As a consequence of the nonlocal anisotropic stresses induced by the bulk, in most of our models, the brane does not isotropize and the nonlocal energy does not vanish in the limit in which the mean radius goes to infinity. We have also found the intriguing possibility that the inflation due to the cosmological constant might be prevented by the interaction with the bulk. We show that the problem for the mean radius can be completely solved in our models, which include as particular cases those in the references above.Comment: 10 pages, improved discussion on the likeliness of non-isotropization, completed list of references, matches version to appear in Class. Quantum Gra

Semi-Analytic Stellar Structure in Scalar-Tensor Gravity

Precision tests of gravity can be used to constrain the properties of hypothetical very light scalar fields, but these tests depend crucially on how macroscopic astrophysical objects couple to the new scalar field. We develop quasi-analytic methods for solving the equations of stellar structure using scalar-tensor gravity, with the goal of seeing how stellar properties depend on assumptions made about the scalar coupling at a microscopic level. We illustrate these methods by applying them to Brans-Dicke scalars, and their generalization in which the scalar-matter coupling is a weak function of the scalar field. The four observable parameters that characterize the fields external to a spherically symmetric star (the stellar radius, R, mass, M, scalar `charge', Q, and the scalar's asymptotic value, phi_infty) are subject to two relations because of the matching to the interior solution, generalizing the usual mass-radius, M(R), relation of General Relativity. We identify how these relations depend on the microscopic scalar couplings, agreeing with earlier workers when comparisons are possible. Explicit analytical solutions are obtained for the instructive toy model of constant-density stars, whose properties we compare to more realistic equations of state for neutron star models.Comment: 39 pages, 9 figure