Erenumab in chronic migraine: Patient-reported outcomes in a randomized double-blind study.

OBJECTIVE: To determine the effect of erenumab, a human monoclonal antibody targeting the calcitonin gene-related peptide receptor, on health-related quality of life (HRQoL), headache impact, and disability in patients with chronic migraine (CM). METHODS: In this double-blind, placebo-controlled study, 667 adults with CM were randomized (3:2:2) to placebo or erenumab (70 or 140 mg monthly). Exploratory endpoints included migraine-specific HRQoL (Migraine-Specific Quality-of-Life Questionnaire [MSQ]), headache impact (Headache Impact Test-6 [HIT-6]), migraine-related disability (Migraine Disability Assessment [MIDAS] test), and pain interference (Patient-Reported Outcomes Measurement Information System [PROMIS] Pain Interference Scale short form 6b). RESULTS: Improvements were observed for all endpoints in both erenumab groups at month 3, with greater changes relative to placebo observed at month 1 for many outcomes. All 3 MSQ domains were improved from baseline with treatment differences for both doses exceeding minimally important differences established for MSQ-role function-restrictive (≥3.2) and MSQ-emotional functioning (≥7.5) and for MSQ-role function-preventive (≥4.5) for erenumab 140 mg. Changes from baseline in HIT-6 scores at month 3 were -5.6 for both doses vs -3.1 for placebo. MIDAS scores at month 3 improved by -19.4 days for 70 mg and -19.8 days for 140 mg vs -7.5 days for placebo. Individual-level minimally important difference was achieved by larger proportions of erenumab-treated participants than placebo for all MSQ domains and HIT-6. Lower proportions of erenumab-treated participants had MIDAS scores of severe (≥21) or very severe (≥41) or PROMIS scores ≥60 at month 3. CONCLUSIONS: Erenumab-treated patients with CM experienced clinically relevant improvements across a broad range of patient-reported outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT02066415. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CM, erenumab treatment improves HRQoL, headache impact, and disability

Revealing the Ionization Properties of the Magellanic Stream using Optical Emission

The Magellanic Stream, a gaseous tail that trails behind the Magellanic Clouds, could replenish the Milky Way with a tremendous amount of gas if it reaches the Galactic disk before it evaporates into the halo. To determine how the Magellanic Stream's properties change along its length, we have conducted an observational study of the H-alpha emission, along with other optical warm ionized gas tracers, toward 39 sight lines. Using the Wisconsin H-alpha Mapper telescope, we detect H-alpha emission brighter than 30 - 50 mR in 26 of our 39 sight lines. This H-alpha emission extends more than 2-degree away from the HI emission. By comparing H-alpha and [OI] intensities, we find that regions with log NHI = 19.5 - 20.0 are 16 - 67% ionized. Most of the H-alpha intensities along the Magellanic Stream are much higher than expected if the primary ionization source is photoionization from Magellanic Clouds, the Milky Way, and the extragalactic background. We find that the additional contribution from self ionization through a "shock cascade" that results as the Stream plows through the halo might be sufficient to reproduce the underlying level of H-alpha emission along the Stream. In the sparsely sampled region below the South Galactic Pole, there exists a subset of sight lines with uncharacteristically bright emission, which suggest that gas is being ionized further by an additional source that could be a linked to energetic processes associated with the Galactic center.Comment: Accepted for publication in the Astrophysical Journal on Nov 8, 201

Quantitative assessment of chronic lung disease of infancy using computed tomography

The aims of this study were to determine whether infants and toddlers with chronic lung disease of infancy (CLDI) have smaller airways and lower lung density compared with full-term healthy controls. Multi-slice computed tomography (CT) chest scans were obtained at elevated lung volumes during a brief respiratory pause in sedated infants and toddlers;38 CLDI were compared with 39 full-term controls. For CLDI subjects, gestational age at birth ranged from 25 to 29 weeks. Airway size was measured for the trachea and the next three to four generations into the right lower lobe;lung volumes and tissue density were also measured. The relationship between airway size and airway generation differed between the CLDI and full-term groups;the sizes of the first and second airway generations were larger in the shorter CLDI than in the shorter full-term subjects. The increased size in the airways in the CLDI subjects was associated with increasing mechanical ventilation time in the neonatal period. CLDI subjects had a greater heterogeneity of lung density compared with full-term subjects. Our results indicate that quantitative analysis of multi-slice CT scans at elevated volumes provides important insights into the pulmonary pathology of infants and toddlers with CLDI

An Introduction to Gas Accretion onto Galaxies

Evidence for gas accretion onto galaxies can be found throughout the universe. In this chapter, I summarize the direct and indirect signatures of this process and discuss the primary sources. The evidence for gas accretion includes the star formation rates and metallicities of galaxies, the evolution of the cold gas content of the universe with time, numerous indirect indicators for individual galaxies, and a few direct detections of inflow. The primary sources of gas accretion are the intergalactic medium, satellite gas and feedback material. There is support for each of these sources from observations and simulations, but the methods with which the fuel ultimately settles in to form stars remain murky.Comment: 14 pages, 5 figures, Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe

Serum MicroRNA-21 as a Biomarker for Allergic Inflammatory Disease in Children

MicroRNAs (miRs) have emerged as useful biomarkers for different disease states, including allergic inflammatory diseases such as asthma and eosinophilic esophagitis (EoE). Serum miRs are a possible non-invasive method for diagnosis of such diseases. We focused on microRNA-21 (miR-21) levels in serum, in order to assess the feasibility of using this gene as a non-invasive biomarker for these diseases in the clinic, as well as to better understand the expression pattern of miR-21 in allergic inflammation. We used quantitative PCR (QPCR) to assay miR-21 and other control miRs in esophageal biopsies from EoE patients and serum samples from EoE and asthma patients. Serum levels of miR-21 were significantly elevated in patients with asthma, whereas serum miR-21 levels were not associated with the presence of allergen-specific IgE (i.e. atopy). Esophageal biopsies showed a large elevation of miR-21 in EoE and an increase in miR-21 in EoE serum. Control U6 miR did not vary between asthma and control patients, however EoE serum had significantly decreased U6 microRNA compared to controls. The decreased U6 in EoE sera did not completely account for the relative increase in miR-21 in the sera of EoE patients. We report for the first time that miR-21 is elevated in the sera of both asthma and EoE patients. We find no relation between serum miR-21 levels and atopy. Our results thus suggest miR-21 is a novel biomarker for human allergic inflammatory diseases

Two Mathematically Equivalent Versions of Maxwell's Equations

This paper is a review of the canonical proper-time approach to relativistic mechanics and classical electrodynamics. The purpose is to provide a physically complete classical background for a new approach to relativistic quantum theory. Here, we first show that there are two versions of Maxwell's equations. The new version fixes the clock of the field source for all inertial observers. However now, the (natural definition of the effective) speed of light is no longer an invariant for all observers, but depends on the motion of the source. This approach allows us to account for radiation reaction without the Lorentz-Dirac equation, self-energy (divergence), advanced potentials or any assumptions about the structure of the source. The theory provides a new invariance group which, in general, is a nonlinear and nonlocal representation of the Lorentz group. This approach also provides a natural (and unique) definition of simultaneity for all observers. The corresponding particle theory is independent of particle number, noninvariant under time reversal (arrow of time), compatible with quantum mechanics and has a corresponding positive definite canonical Hamiltonian associated with the clock of the source. We also provide a brief review of our work on the foundational aspects of the corresponding relativistic quantum theory. Here, we show that the standard square-root and the Dirac equations are actually two distinct spin-$\tfrac{1}{2}$ particle equations.Comment: Appeared: Foundations of Physic

Measuring kinetic coefficients by molecular dynamics simulation of zone melting

Molecular dynamics simulations are performed to measure the kinetic coefficient at the solid-liquid interface in pure gold. Results are obtained for the (111), (100) and (110) orientations. Both Au(100) and Au(110) are in reasonable agreement with the law proposed for collision-limited growth. For Au(111), stacking fault domains form, as first reported by Burke, Broughton and Gilmer [J. Chem. Phys. {\bf 89}, 1030 (1988)]. The consequence on the kinetics of this interface is dramatic: the measured kinetic coefficient is three times smaller than that predicted by collision-limited growth. Finally, crystallization and melting are found to be always asymmetrical but here again the effect is much more pronounced for the (111) orientation.Comment: 8 pages, 9 figures (for fig. 8 : [email protected]). Accepted for publication in Phys. Rev.