IMPORTANCE Botulinum toxin neuromodulators are an important treatment for facial synkinesis. Whether a difference in efficacy exists among the 3 different botulinum neuromodulators used in treating this condition remains unknown.OBJECTIVE To evaluate the effectiveness of 3 commercially available botulinum toxin neuromodulators in the treatment of facial synkinesis. DESIGN, SETTING, AND PARTICIPANTSIn this single-blind, 3-arm comparison randomized clinical trial, 28 patients at the Facial Nerve Center, University of Utah, Salt Lake City, were randomized to onabotulinumtoxinA, abobotulinumtoxinA, or incobotulinumtoxinA treatment. Each patient was given the Synkinesis Assessment Questionnaire (SAQ) to assess severity of synkinesis before treatment and 1, 2, and 4 weeks after treatment, and improvements were compared among the groups. Data were collected from July 3, 2012, to March 31, 2015.INTERVENTIONS Botulinum toxin type A neuromodulator (onabotulinumtoxinA, abobotulinumtoxinA, or incobotulinumtoxinA) injected into synkinetic areas of the face.MAIN OUTCOMES AND MEASURES Synkinesis assessed using the SAQ (score range, 20-100; lower scores indicate less severe synkinesis) before treatment and 1, 2, and 4 weeks after treatment.RESULTS A total of 28 patients (mean [SD] age, 49.1 [18.5] years; 8 [28.6%] male and 20 [71.4%] female), with 6 patients enrolled multiple times, received 38 treatments (15 onabotulinumtoxinA, 13 abobotulinumtoxinA, and 10 incobotulinumtoxinA). No significant difference existed in baseline pretreatment SAQ scores among the 3 groups. Mean (SD) SAQ score improvement at 4 weeks was 41% (31%) for the onabotulinumtoxinA, 42% (20%) for the abobotulinumtoxinA, and 17% (18%) for the incobotulinumtoxinA groups. No significant differences were noted in SAQ score improvements among the 3 groups at weeks 1 and 2 after treatment (week 1 mean improvements of 42% in the onabotulinumtoxinA, 45% in the abobotulinumtoxinA, and 26% in the incobotulinumtoxinA groups; P = .19; week 2 mean improvements of 43% in the onabotulinumtoxinA, 46% in the abobotulinumtoxinA, and 28% in the incobotulinumtoxinA groups; P = .20). The difference in mean SAQ score improvement for abobotulinumtoxinA vs incobotulinumtoxinA from pretreatment to 4 weeks after treatment was not significant (30 vs 12 points; P = .11) despite a significant difference in mean total SAQ score for abobotulinumtoxinA vs incobotulinumtoxinA (40.34 vs 58.00; P = .02).CONCLUSIONS AND RELEVANCE AbobotulinumtoxinA had similar efficacy to onabotulinumtoxinA and incobotulinumtoxinA for the management of facial synkinesis up to 4 weeks after treatment. IncobotulinumtoxinA had significantly less effect on SAQ score improvement than onabotulinumtoxinA at 4 weeks, perhaps because of the shorter duration of action. Shorter intervals between treatments or larger doses may be required when using incobotulinumtoxinA treatment for facial synkinesis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT03048383LEVEL OF EVIDENCE 1.

W e describe the data analysis and report the results of the final charge-ratio experiment using the Utah cosiiiic-ray muon deiector. Values for the charge ratio were obtained from least-squares fits to the observed beniiing.ang!e disi~ibutiuns. The fitting function was the result of folding the noise scattering distribution into the ideal loc:i!-spectrum bending distribution, with the charge ratio as a parameter of the fit. This method permitted a greater precision whiie circumventing the main causes of charge-ratio dilution. We obtain the average vaiue 1.378 .t 0.015 for muon momentum at production between 1 and 8 TeV/c, corresponding to a rnzdiari primary cosnzic-ray n~ornenium range 8-61 TcV,/t, With the results of chis experiment the charge ratio IS preciseiy known over about three decades of muon energy heginning around 10 GeV. Thus, we believe the cIiarge ratio can serve as a touchstone in determiiiing the hadronic interaction dynamics and composition of :he prirr~ary cosmic rays. Already approximate agreement has been obtained with experimental results from ixedidiclinns trrilizirrg the scaling-liiniring-fs:iginet~tation hypothesis arid constant composition of thc primary cosmic rays.

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In principle, there exists a second invariant in the fourth-order derivatives of~. However, in a system with translational invariance this term is identical with that given in (1).

We consider a cosmic-ray muon model in which a "directly produced" muon component with the same slope as the primary spectrum is added to the conventional pion-derived muons. It is found to be consistent with recent burst measurements, horizontalair-shower data, atmospheric gamma-ray fluxes, and muon spectrograph measurements. It may also explain the anomalous mu-less air showers. The model requires that the photonuclear cross section increase at very high energies.