A qualitative study exploring the health-related quality of life and symptomatic experiences of adults and adolescents with ulcerative colitis

Background: Ulcerative colitis (UC) often first presents during adolescence and early adulthood. Primary symptoms of UC are well known, yet similarities and differences of disease experience in adults and adolescents are not well characterized. Methods: To understand the health-related quality of life (HRQoL) and symptomatic experience of UC, in-depth interviews were conducted in the US with 21 adults (20–70 years) and 14 adolescents (12–17 years). Eligibility and medical history were confirmed by clinician report. A previously conducted literature review and resultant conceptual model informed the discussion guide to explore symptoms and HRQoL. Age appropriate creative tasks (“animal” task and collage) were employed to facilitate discussion. Transcripts and collages were subjected to thematic analysis using ATLAS.ti software. Results: Clinician-reported UC severity included 24% mild, 38% moderate, 38% severe among adults; and 64% mild, 29% moderate, 7% severe among adolescents. Among adults, 52% were female, 67% were white. Among adolescents, 50% were female, 71% were white. During analysis it was noted that all participants reported stomach/abdominal pain. Other key symptoms identified were frequent bowel movements, diarrhea, blood in stools, sudden need for bowel movement, stomach cramping, bloating, and feeling gassy/passing gas (?75% of participants). Key impacts identified were embarrassment, dietary limitations, having to plan around UC, worry/fear, anger, low mood/depression, and relationship with others, (?75% of participants). In creative tasks, animals were chosen to represent their UC and content included in the collages reflected the most commonly discussed themes from the interviews. Only adults discussed feeling dehydrated, while only adolescents discussed the impact of UC on school life. Conclusions: Open-ended interviews highlighted the HRQoL and symptomatic experiences of UC from the patient’s perspective, which were similar between adult and adolescent UC patients

The G0 Experiment: Apparatus for Parity-Violating Electron Scattering Measurements at Forward and Backward Angles

In the G0 experiment, performed at Jefferson Lab, the parity-violating elastic scattering of electrons from protons and quasi-elastic scattering from deuterons is measured in order to determine the neutral weak currents of the nucleon. Asymmetries as small as 1 part per million in the scattering of a polarized electron beam are determined using a dedicated apparatus. It consists of specialized beam-monitoring and control systems, a cryogenic hydrogen (or deuterium) target, and a superconducting, toroidal magnetic spectrometer equipped with plastic scintillation and aerogel Cerenkov detectors, as well as fast readout electronics for the measurement of individual events. The overall design and performance of this experimental system is discussed.Comment: Submitted to Nuclear Instruments and Method

Measurement of the νe and total 8B solar neutrino fluxes with the Sudbury Neutrino Observatory phase-III data set

This paper details the solar neutrino analysis of the 385.17-day phase-III data set acquired by the Sudbury Neutrino Observatory (SNO). An array of 3He proportional counters was installed in the heavy-water target to measure precisely the rate of neutrino-deuteron neutral-current interactions. This technique to determine the total active 8B solar neutrino flux was largely independent of the methods employed in previous phases. The total flux of active neutrinos was measured to be 5.54-0.31+0.33(stat.)-0.34+0.36(syst.)×106 cm-2 s-1, consistent with previous measurements and standard solar models. A global analysis of solar and reactor neutrino mixing parameters yielded the best-fit values of Δm2=7.59-0.21+0.19×10 -5eV2 and θ=34.4-1.2+1.3degrees

Exercise, diet, and skeletal muscle gene expression

BACKGROUND: Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. METHODS: In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. FINDINGS: Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response rate 89.7%; [effect size 87.4% (97.5% CI 82.9-91.8) vs placebo; 48.1% (41.2-55.0) vs etanercept]) and 336 (87.3%; [80.0% (74.4-85.7) vs placebo; 33.9% (27.0-40.7) vs etanercept]) patients; in the ixekizumab every 4 weeks group, by 269 (77.5%; [75.1% (69.5-80.8) vs placebo; 35.9% (28.2-43.6) vs etanercept]) and 325 (84.2%; [76.9% (71.0-82.8) vs placebo; 30.8% (23.7-37.9) vs etanercept]) patients; in the placebo group, by four (2.4%) and 14 (7.3%) patients; and in the etanercept group by 149 (41.6%) and 204 (53.4%) patients (all p<0.0001 vs placebo or etanercept). In the ixekizumab every 2 weeks group, sPGA 0/1 was achieved by 292 (response rate 83.2%; [effect size 80.8% (97.5% CI 75.6-86.0) vs placebo; 47.2% (39.9-54.4) vs etanercept]) and 310 (80.5%; [73.8% (67.7-79.9) vs placebo; 38.9% (31.7-46.1) vs etanercept]) patients; in the ixekizumab every 4 weeks group by 253 (72.9%; [70.5% (64.6-76.5) vs placebo; 36.9% (29.1-44.7) vs etanercept]) and 291 (75.4%; [68.7% (62.3-75.0) vs placebo; 33.8% (26.3-41.3) vs etanercept]) patients; in the placebo group by four (2.4%) and 13 (6.7%) patients; and in the etanercept group by 129 (36.0%) and 159 (41.6%) patients (all p<0.0001 vs placebo or etanercept). In combined studies, serious adverse events were reported in 14 (1.9%) of 734 patients given ixekizumab every 2 weeks, 14 (1.9%) of 729 given ixekizumab every 4 weeks, seven (1.9%) of 360 given placebo, and 14 (1.9%) of 739 given etanercept; no deaths were noted. INTERPRETATION: Both ixekizumab dose regimens had greater efficacy than placebo and etanercept over 12 weeks in two independent studies. These studies show that selectively neutralising interleukin 17A with a high affinity antibody potentially gives patients with psoriasis a new and effective biological therapy option. FUNDING: Eli Lilly and Co

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

The G0 experiment: Apparatus for parity-violating electron scattering measurements at forward and backward angles

In the G0 experiment, performed at Jefferson Lab, the parity-violating elastic scattering of electrons from protons and quasi-elastic scattering from deuterons is measured in order to determine the neutral weak currents of the nucleon. Asymmetries as small as 1 part-per-million in the scattering of a polarized electron beam are determined using a dedicated apparatus. It consists of specialized beam monitoring and control systems, a cryogenic hydrogen (or deuterium) target, and a superconducting, toroidal magnetic spectrometer equipped with plastic scintillation and aerogel Cherenkov detectors, as well as fast readout electronics for the measurement of individual events. The overall design and performance of this experimental system is discussed. © 2011 Elsevier B.V. All rights reserved.Articl

Measurement of the Cosmic Ray and Neutrino-Induced Muon Flux at the Sudbury Neutrino Observatory

Results are reported on the measurement of the atmospheric neutrino-induced muon flux at a depth of 2 kilometers below the Earth's surface from 1229 days of operation of the Sudbury Neutrino Observatory (SNO). By measuring the flux of through-going muons as a function of zenith angle, the SNO experiment can distinguish between the oscillated and un-oscillated portion of the neutrino flux. A total of 514 muon-like events are measured between -1 {le} cos {theta}{sub zenith} 0.4 in a total exposure of 2.30 x 10{sup 14} cm{sup 2} s. The measured flux normalization is 1.22 {+-} 0.09 times the Bartol three-dimensional flux prediction. This is the first measurement of the neutrino-induced flux where neutrino oscillations are minimized. The zenith distribution is consistent with previously measured atmospheric neutrino oscillation parameters. The cosmic ray muon flux at SNO with zenith angle cos {theta}{sub zenith} &gt; 0.4 is measured to be (3.31 {+-} 0.01 (stat.) {+-} 0.09 (sys.)) x 10{sup -10} {micro}/s/cm{sup 2}