Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2).

BACKGROUND: Patients with high-frequency episodic migraine (HFEM) have a greater disease burden than those with low-frequency episodic migraine (LFEM). Acute treatment overuse increases the risk of migraine chronification in patients with HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile. Here, we investigate whether there are differences in galcanezumab efficacy in patients with LFEM or with HFEM. METHODS: Data were pooled from two double-blind, placebo-controlled phase 3 trials; EVOLVE-1 and EVOLVE-2. Patients were 18-65 years old, experienced 4-14 monthly migraine headache days (MHDs) for ≥1 year prior, with onset at \u3c 50 years of age. Migraine headaches were tracked via electronic patient-reported outcome system and randomization was stratified by low (LFEM; 4-7 monthly MHDs) or high (HFEM; 8-14 monthly MHDs) frequency. Subgroup analysis compared the HFEM and LFEM subgroups with a linear or generalized linear mixed model repeated measures approach. RESULTS: The intent-to-treat patients (N = 1773) had a mean age of 41.3 years, were mostly white (75%), female (85%), and 66% of patients had HFEM. In both the LFEM and HFEM subgroups, the overall (Months 1-6) and monthly changes from baseline in monthly MHDs and monthly MHDs with acute medication use compared with placebo were statistically significantly reduced for galcanezumab 120-mg and 240-mg. Galcanezumab (120-mg and 240-mg) significantly decreased the overall and monthly MHDs with nausea and/or vomiting, and with photophobia and phonophobia versus placebo in patients with LFEM or HFEM. In both subgroups, the mean overall (Months 1-6) and monthly percentages of patients with ≥50%, ≥75%, and 100% reduction in monthly MHDs from baseline were statistically significantly greater in patients receiving either dose of galcanezumab versus placebo. Galcanezumab (120-mg and 240-mg) significantly improved the Migraine-Specific Quality of Life Questionnaire role function-restrictive domain score as well as the Migraine Disability Assessment total score versus placebo for patients with LFEM or HFEM. There were no significant subgroup-by-treatment interactions. CONCLUSIONS: Galcanezumab was as effective in patients with HFEM as in those with LFEM. Associated symptoms, quality of life, and disability were similarly improved in patients with HFEM or LFEM. TRIAL REGISTRATION: NCT02614183 , NCT02614196

Maxwell equations in matrix form, squaring procedure, separating the variables, and structure of electromagnetic solutions

The Riemann -- Silberstein -- Majorana -- Oppenheimer approach to the Maxwell electrodynamics in vacuum is investigated within the matrix formalism. The matrix form of electrodynamics includes three real 4 \times 4 matrices. Within the squaring procedure we construct four formal solutions of the Maxwell equations on the base of scalar Klein -- Fock -- Gordon solutions. The problem of separating physical electromagnetic waves in the linear space \lambda_{0}\Psi^{0}+\lambda_{1}\Psi^{1}+\lambda_{2}\Psi^{2}+ lambda_{3}\Psi^{3} is investigated, several particular cases, plane waves and cylindrical waves, are considered in detail.Comment: 26 pages 16 International Seminar NCPC, May 19-22, 2009, Minsk, Belaru

Generalized Gravi-Electromagnetism

A self consistant and manifestly covariant theory for the dynamics of four charges (masses) (namely electric, magnetic, gravitational, Heavisidian) has been developed in simple, compact and consistent manner. Starting with an invariant Lagrangian density and its quaternionic representation, we have obtained the consistent field equation for the dynamics of four charges. It has been shown that the present reformulation reproduces the dynamics of individual charges (masses) in the absence of other charge (masses) as well as the generalized theory of dyons (gravito - dyons) in the absence gravito - dyons (dyons). key words: dyons, gravito - dyons, quaternion PACS NO: 14.80H

Evaluation of an epigenetic assay for predicting repeat prostate biopsy outcome in African American men

OBJECTIVE: To evaluate an epigenetic assay performed on tissue from negative prostate biopsies in a group of African American (AA) men undergoing repeat biopsy, and to compare accuracy for predicting repeat biopsy outcome to prior studies conducted in predominantly Caucasian populations. MATERIALS AND METHODS: The study population consisted of 211 AA men from 7 urology centers across the United States; all of whom were undergoing 12-core transrectal ultrasound-guided repeat biopsy within 30 months from a negative index biopsy. All biopsy cores from the negative index biopsy were profiled for the epigenetic biomarkers GSTP1, APC, and RASSF1 using ConfirmMDx for Prostate Cancer (MDxHealth, Irvine, CA). RESULTS: Upon repeat biopsy, 130 of 211 subjects (62%) had no prostate cancer (PCa) detected and 81 of 211 (38%) were diagnosed with PCa. Of the subjects with PCa, 54 (67%) were diagnosed with Gleason score (GS) = 7 disease. For detection of PCa at repeat biopsy, ConfirmMDx sensitivity was 74.1% and specificity was 60.0%, equivalent to prior studies (P = .235 and .697, respectively). For detection of GS >= 7 PCa, sensitivity was 78% and specificity was 53%. The negative predictive values for detection of all PCa and GS >= 7 PCa were 78.8% and 94.2%, respectively. CONCLUSION: In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy. Results were consistent with previous studies from predominantly Caucasian populations. Therefore, the ConfirmMDx assay is a useful tool for risk stratification of AA men who had an initial negative biopsy

Availability of High Quality TRMM Ground Validation Data from Kwajalein, RMI: A Practical Application of the Relative Calibration Adjustment Technique

Since the Tropical Rainfall Measuring Mission (TRMM) satellite launch in November 1997, the TRMM Satellite Validation Office (TSVO) at NASA Goddard Space Flight Center (GSFC) has been performing quality control and estimating rainfall from the KPOL S-band radar at Kwajalein, Republic of the Marshall Islands. Over this period, KPOL has incurred many episodes of calibration and antenna pointing angle uncertainty. To address these issues, the TSVO has applied the Relative Calibration Adjustment (RCA) technique to eight years of KPOL radar data to produce Ground Validation (GV) Version 7 products. This application has significantly improved stability in KPOL reflectivity distributions needed for Probability Matching Method (PMM) rain rate estimation and for comparisons to the TRMM Precipitation Radar (PR). In years with significant calibration and angle corrections, the statistical improvement in PMM distributions is dramatic. The intent of this paper is to show improved stability in corrected KPOL reflectivity distributions by using the PR as a stable reference. Inter-month fluctuations in mean reflectivity differences between the PR and corrected KPOL are on the order of 1-2 dB, and inter-year mean reflectivity differences fluctuate by approximately 1 dB. This represents a marked improvement in stability with confidence comparable to the established calibration and uncertainty boundaries of the PR. The practical application of the RCA method has salvaged eight years of radar data that would have otherwise been unusable, and has made possible a high-quality database of tropical ocean-based reflectivity measurements and precipitation estimates for the research community

Quaternion Analysis for Generalized Electromagnetic Fields of Dyons in Isotropic Medium

Quaternion analysis of time dependent Maxwell's equations in presence of electric and magnetic charges has been developed and the solutions for the classical problem of moving charges (electric and magnetic) are obtained in unique, simple and consistent manner

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease

Helicity, polarization, and Riemann-Silberstein vortices

Riemann-Silberstein (RS) vortices have been defined as surfaces in spacetime where the complex form of a free electromagnetic field given by F=E+iB is null (F.F=0), and they can indeed be interpreted as the collective history swept out by moving vortex lines of the field. Formally, the nullity condition is similar to the definition of "C-lines" associated with a monochromatic electric or magnetic field, which are curves in space where the polarization ellipses degenerate to circles. However, it was noted that RS vortices of monochromatic fields generally oscillate at optical frequencies and are therefore unobservable while electric and magnetic C-lines are steady. Here I show that under the additional assumption of having definite helicity, RS vortices are not only steady but they coincide with both sets of C-lines, electric and magnetic. The two concepts therefore become one for waves of definite frequency and helicity. Since the definition of RS vortices is relativistically invariant while that of C-lines is not, it may be useful to regard the vortices as a wideband generalization of C-lines for waves of definite helicity.Comment: 5 pages, no figures. Submitted to J of Optics A, special issue on Singular Optics; minor changes from v.

Maxwell Equations in Complex Form of Majorana - Oppenheimer, Solutions with Cylindric Symmetry in Riemann S_{3} and Lobachevsky H_{3} Spaces

Complex formalism of Riemann - Silberstein - Majorana - Oppenheimer in Maxwell electrodynamics is extended to the case of arbitrary pseudo-Riemannian space - time in accordance with the tetrad recipe of Tetrode - Weyl - Fock - Ivanenko. In this approach, the Maxwell equations are solved exactly on the background of static cosmological Einstein model, parameterized by special cylindrical coordinates and realized as a Riemann space of constant positive curvature. A discrete frequency spectrum for electromagnetic modes depending on the curvature radius of space and three parameters is found, and corresponding basis electromagnetic solutions have been constructed explicitly. In the case of elliptical model a part of the constructed solutions should be rejected by continuity considerations. Similar treatment is given for Maxwell equations in hyperbolic Lobachevsky model, the complete basis of electromagnetic solutions in corresponding cylindrical coordinates has been constructed as well, no quantization of frequencies of electromagnetic modes arises.Comment: 39 page

Effect of the human immunodeficiency virus type 1 reverse transcriptase polymorphism Leu-214 on replication capacity and drug susceptibility

A negative association between polymorphism Leu-214 and type-1 thymidine analogue mutations (TAM1) and a positive association with a clinically favorable virological response to thymidine analogue-based combination antiretroviral therapy have been described. In this study, the impact of Leu-214 on replication capacity and resistance to zidovudine (ZDV) of viruses containing TAM1 or TAM2 was determined. Leu-214 decreased the growth rate of viruses bearing Tyr-215, as well as their resistance to ZDV. This observation was confirmed by structural and molecular modeling data, suggesting a regulatory role for Leu-214 in the emergence and phenotypic resistance of TAM1