Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

BACKGROUND: Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. METHODS: Subchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m(3 )for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m(3 )for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m(3 )and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. RESULTS: Animals exposed to manganese sulfate at ≥0.3 mg Mn/m(3 )for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m(3 )for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. CONCLUSION: High-dose subchronic manganese sulfate inhalation is associated with increased lung manganese concentrations and small airway inflammatory changes in the absence of observable clinical signs. Subchronic exposure to manganese sulfate at exposure concentrations (≤0.3 mg Mn/m(3)) similar to the current 8-hr occupational threshold limit value established for inhaled manganese was not associated with pulmonary pathology

Covariant description of inelastic electron--deuteron scattering:predictions of the relativistic impulse approximation

Using the covariant spectator theory and the transversity formalism, the unpolarized, coincidence cross section for deuteron electrodisintegration, $d(e,e'p)n$, is studied. The relativistic kinematics are reviewed, and simple theoretical formulae for the relativistic impulse approximation (RIA) are derived and discussed. Numerical predictions for the scattering in the high $Q^2$ region obtained from the RIA and five other approximations are presented and compared. We conclude that measurements of the unpolarized coincidence cross section and the asymmetry $A_\phi$, to an accuracy that will distinguish between different theoretical models, is feasible over most of the wide kinematic range accessible at Jefferson Lab.Comment: 54 pages and 24 figure

ATX-101 for reduction of submental fat: A phase III randomized controlled trial

BackgroundATX-101, an injectable form of deoxycholic acid, causes adipocytolysis when injected subcutaneously into fat.ObjectiveWe sought to evaluate the efficacy and safety of ATX-101.MethodsIn this phase III trial (REFINE-2), adults dissatisfied with their moderate or severe submental fat (SMF) were randomized to ATX-101 or placebo. Coprimary end points, evaluated at 12 weeks after last treatment, were composite improvements of 1 or more grades and 2 or more grades in SMF observed on both the validated Clinician- and Patient-Reported SMF Rating Scales. Other end points included magnetic resonance imaging–based assessment of submental volume, assessment of psychological impact of SMF, and additional patient-reported outcomes.ResultsAmong those treated with ATX-101 or placebo (n = 258/treatment group), 66.5% versus 22.2%, respectively, achieved a composite improvement of 1 or more grades (Mantel-Haenszel risk ratio 2.98; 95% confidence interval 2.31-3.85) and 18.6% versus 3.0% achieved a composite improvement of 2 or more grades in SMF (Mantel-Haenszel risk ratio 6.27; 95% confidence interval 2.91-13.52; P < .001 for both). Those treated with ATX-101 were more likely to achieve submental volume reduction confirmed by magnetic resonance imaging, greater reduction in psychological impact of SMF, and satisfaction with treatment (P < .001 for all). Overall, 85.7% of adverse events in the ATX-101 group and 76.9% in the placebo group were localized to the injection site.LimitationsFollow-up was limited to 44 weeks.ConclusionATX-101 is an alternative treatment for SMF reduction

Glassy Transition and Aging in a Model without Disorder

We study the off-equilibrium relaxational dynamics of the Amit-Roginsky $\phi^3$ field theory, for which the mode coupling approximation is exact. We show that complex phenomena such as aging and ergodicity breaking are present at low temperature, similarly to what is found in long range spin glasses. This is a generalization of mode coupling theory of the structural glass transition to off-equilibrium situations.Comment: 9 pages, 1 uuencoded figure, LaTex, preprint NORDITA 94/3

Reactive Oxygen Species Modulate Coronary Wall Shear Stress and Endothelial Function During Hyperglycemia

Hyperglycemia is associated with generation of reactive oxygen species (ROS), and this action may contribute to accelerated atherogenesis. We tested the hypothesis that hyperglycemia produces alterations in left anterior descending coronary artery (LAD) wall shear stress concomitant with endothelial dysfunction and ROS production in dogs (n = 12) instrumented for measurement of LAD blood flow, velocity, and diameter. Dogs were randomly assigned to receive vehicle (0.9% saline) or the superoxide dismutase mimetic 4- hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) and were administered intravenous infusions of d-glucose to achieve target blood glucose concentrations of 350 and 600 mg/dl (moderate and severe hyperglycemia, respectively). Endothelial function and ROS generation were assessed by coronary blood flow responses to acetylcholine (10, 30, and 100 ng/kg) and dihydroethidium fluorescence of myocardial biopsies, respectively. Indexes of wall shear stress were calculated with conventional fluid dynamics theory. Hyperglycemia produced dose-related endothelial dysfunction, increases in ROS production, and reductions in oscillatory shear stress that were normalized by tempol. The results suggest a direct association between hyperglycemia-induced ROS production, endothelial dysfunction, and decreases in oscillatory shear stress in vivo

Relativistic three-body bound states and the reduction from four to three dimensions

Beginning with an effective field theory based upon meson exchange, the Bethe-Salpeter equation for the three-particle propagator (six-point function) is obtained. Using the one-boson-exchange form of the kernel, this equation is then analyzed using time-ordered perturbation theory, and a three-dimensional equation for the propagator is developed. The propagator consists of a pre-factor in which the relative energies are fixed by the initial state of the particles, an intermediate part in which only global propagation of the particles occurs, and a post-factor in which relative energies are fixed by the final state of the particles. The pre- and post-factors are necessary in order to account for the transition from states where particles are off their mass shell to states described by the global propagator with all of the particle energies on shell. The pole structure of the intermediate part of the propagator is used to determine the equation for the three-body bound state: a Schr{\"o}dinger-like relativistic equation with a single, global Green's function. The role of the pre- and post-factors in the relativistic dynamics is to incorporate the poles of the breakup channels in the initial and final states. The derivation of this equation by integrating over the relative times rather than via a constraint on relative momenta allows the inclusion of retardation and dynamical boost corrections without introducing unphysical singularities.Comment: REVTeX, 21 pages, 4 figures, epsf.st

Bayes Wars Redivivus - An Exchange

An electronic exchange among 10 evidence scholars that began with a discussion of the restyled Federal Rules and grew into a significant restatement of debates in evidentiary scholarship over the last 50 years, touching on relevance, probative value, inference, Bayesianism and the foundations of evidence, with an introduction by Michael Risinger

Marine Genomics: A clearing-house for genomic and transcriptomic data of marine organisms

BACKGROUND: The Marine Genomics project is a functional genomics initiative developed to provide a pipeline for the curation of Expressed Sequence Tags (ESTs) and gene expression microarray data for marine organisms. It provides a unique clearing-house for marine specific EST and microarray data and is currently available at . DESCRIPTION: The Marine Genomics pipeline automates the processing, maintenance, storage and analysis of EST and microarray data for an increasing number of marine species. It currently contains 19 species databases (over 46,000 EST sequences) that are maintained by registered users from local and remote locations in Europe and South America in addition to the USA. A collection of analysis tools are implemented. These include a pipeline upload tool for EST FASTA file, sequence trace file and microarray data, an annotative text search, automated sequence trimming, sequence quality control (QA/QC) editing, sequence BLAST capabilities and a tool for interactive submission to GenBank. Another feature of this resource is the integration with a scientific computing analysis environment implemented by MATLAB. CONCLUSION: The conglomeration of multiple marine organisms with integrated analysis tools enables users to focus on the comprehensive descriptions of transcriptomic responses to typical marine stresses. This cross species data comparison and integration enables users to contain their research within a marine-oriented data management and analysis environment