62 research outputs found
The Strange Quark Contribution to the Proton's Magnetic Moment
We report a new determination of the strange quark contribution to the
proton's magnetic form factor at a four-momentum transfer Q2 = 0.1 (GeV/c)^2
from parity-violating e-p elastic scattering. The result uses a revised
analysis of data from the SAMPLE experiment which was carried out at the
MIT-Bates Laboratory. The data are combined with a calculation of the proton's
axial form factor GAe to determine the strange form factor GMs(Q2=0.1)=0.37 +-
0.20 +- 0.26 +- 0.07. The extrapolation of GMs to its Q2=0 limit and comparison
with calculations is also discussed.Comment: 6 pages, 1 figure, submitted to Phys. Lett.
Future Directions in Parity Violation: From Quarks to the Cosmos
I discuss the prospects for future studies of parity-violating (PV)
interactions at low energies and the insights they might provide about open
questions in the Standard Model as well as physics that lies beyond it. I cover
four types of parity-violating observables: PV electron scattering; PV hadronic
interactions; PV correlations in weak decays; and searches for the permanent
electric dipole moments of quantum systems.Comment: Talk given at PAVI 06 workshop on parity-violating interactions,
Milos, Greece (May, 2006); 10 page
Cryogenic magnetic coil and superconducting magnetic shield for neutron electric dipole moment searches
A magnetic coil operated at cryogenic temperatures is used to produce spatial, relative field gradients below 6 ppm/cm, stable for several hours. The apparatus is a prototype of the magnetic components for a neutron electric dipole moment (nEDM) search, which will take place at the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory using ultra-cold neutrons (UCN). That search requires a uniform magnetic field to mitigate systematic effects and obtain long polarization lifetimes for neutron spin precession measurements. This paper details upgrades to a previously described apparatus [1], particularly the introduction of super-conducting magnetic shielding and the associated cryogenic apparatus. The magnetic gradients observed are sufficiently low for the nEDM search at SNS
Physics of Solar Prominences: II - Magnetic Structure and Dynamics
Observations and models of solar prominences are reviewed. We focus on
non-eruptive prominences, and describe recent progress in four areas of
prominence research: (1) magnetic structure deduced from observations and
models, (2) the dynamics of prominence plasmas (formation and flows), (3)
Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and
large-scale patterns of the filament channels in which prominences are located.
Finally, several outstanding issues in prominence research are discussed, along
with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape
Strong evidences of hadron acceleration in Tycho's Supernova Remnant
Very recent gamma-ray observations of G120.1+1.4 (Tycho's) supernova remnant
(SNR) by Fermi-LAT and VERITAS provided new fundamental pieces of information
for understanding particle acceleration and non-thermal emission in SNRs. We
want to outline a coherent description of Tycho's properties in terms of SNR
evolution, shock hydrodynamics and multi-wavelength emission by accounting for
particle acceleration at the forward shock via first order Fermi mechanism. We
adopt here a quick and reliable semi-analytical approach to non-linear
diffusive shock acceleration which includes magnetic field amplification due to
resonant streaming instability and the dynamical backreaction on the shock of
both cosmic rays (CRs) and self-generated magnetic turbulence. We find that
Tycho's forward shock is accelerating protons up to at least 500 TeV,
channelling into CRs about the 10 per cent of its kinetic energy. Moreover, the
CR-induced streaming instability is consistent with all the observational
evidences indicating a very efficient magnetic field amplification (up to ~300
micro Gauss). In such a strong magnetic field the velocity of the Alfv\'en
waves scattering CRs in the upstream is expected to be enhanced and to make
accelerated particles feel an effective compression factor lower than 4, in
turn leading to an energy spectrum steeper than the standard prediction
{\propto} E^-2. This latter effect is crucial to explain the GeV-to-TeV
gamma-ray spectrum as due to the decay of neutral pions produced in nuclear
collisions between accelerated nuclei and the background gas. The
self-consistency of such an hadronic scenario, along with the fact that the
concurrent leptonic mechanism cannot reproduce both the shape and the
normalization of the detected the gamma-ray emission, represents the first
clear and direct radiative evidence that hadron acceleration occurs efficiently
in young Galactic SNRs.Comment: Minor changes. Accepted for publication in Astronomy & Astrophysic
Safety and efficacy of vanzacaftorâtezacaftorâdeutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials
Background
Elexacaftorâtezacaftorâivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing.
Methods
We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftorâtezacaftorâdeutivacaftor in participants with cystic fibrosis who were aged 18 years or older. A phase 2 randomised, double-blind, active-controlled study (VX18-561-101; April 17, 2019, to Aug 20, 2020) was carried out to compare deutivacaftor monotherapy with ivacaftor monotherapy in participants with CFTR gating mutations, following a 4-week ivacaftor monotherapy run-in period. Participants were randomly assigned to receive either ivacaftor 150 mg every 12 h, deutivacaftor 25 mg once daily, deutivacaftor 50 mg once daily, deutivacaftor 150 mg once daily, or deutivacaftor 250 mg once daily in a 1:1:2:2:2 ratio. The primary endpoint was absolute change in ppFEV1 from baseline at week 12. A phase 2 randomised, double-blind, controlled, proof-of-concept study of vanzacaftorâtezacaftorâdeutivacaftor (VX18-121-101; April 30, 2019, to Dec 10, 2019) was conducted in participants with cystic fibrosis and heterozygous for F508del and a minimal function mutation (F/MF genotypes) or homozygous for F508del (F/F genotype). Participants with F/MF genotypes were randomly assigned 1:2:2:1 to receive either 5 mg, 10 mg, or 20 mg of vanzacaftor in combination with tezacaftorâdeutivacaftor or a triple placebo for 4 weeks, and participants with the F/F genotype were randomly assigned 2:1 to receive either vanzacaftor (20 mg)âtezacaftorâdeutivacaftor or tezacaftorâivacaftor active control for 4 weeks, following a 4-week tezacaftorâivacaftor run-in period. Primary endpoints for part 1 and part 2 were safety and tolerability and absolute change in ppFEV1 from baseline to day 29. Secondary efficacy endpoints were absolute change from baseline at day 29 in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. These clinical trials are registered with ClinicalTrials.gov, NCT03911713 and NCT03912233, and are complete.
Findings
In study VX18-561-101, participants treated with deutivacaftor 150 mg once daily (n=23) or deutivacaftor 250 mg once daily (n=24) had mean absolute changes in ppFEV1 of 3·1 percentage points (95% CI â0·8 to 7·0) and 2·7 percentage points (â1·0 to 6·5) from baseline at week 12, respectively, versus â0·8 percentage points (â6·2 to 4·7) with ivacaftor 150 mg every 12 h (n=11); the deutivacaftor safety profile was consistent with the established safety profile of ivacaftor 150 mg every 12 h. In study VX18-121-101, participants with F/MF genotypes treated with vanzacaftor (5 mg)âtezacaftorâdeutivacaftor (n=9), vanzacaftor (10 mg)âtezacaftorâdeutivacaftor (n=19), vanzacaftor (20 mg)âtezacaftorâdeutivacaftor (n=20), and placebo (n=10) had mean changes relative to baseline at day 29 in ppFEV1 of 4·6 percentage points (â1·3 to 10·6), 14·2 percentage points (10·0 to 18·4), 9·8 percentage points (5·7 to 13·8), and 1·9 percentage points (â4·1 to 8·0), respectively, in sweat chloride concentration of â42·8 mmol/L (â51·7 to â34·0), â45·8 mmol/L (95% CI â51·9 to â39·7), â49·5 mmol/L (â55·9 to â43·1), and 2·3 mmol/L (â7·0 to 11·6), respectively, and in CFQ-R respiratory domain score of 17·6 points (3·5 to 31·6), 21·2 points (11·9 to 30·6), 29·8 points (21·0 to 38·7), and 3·3 points (â10·1 to 16·6), respectively. Participants with the F/F genotype treated with vanzacaftor (20 mg)âtezacaftorâdeutivacaftor (n=18) and tezacaftorâivacaftor (n=10) had mean changes relative to baseline (taking tezacaftorâivacaftor) at day 29 in ppFEV1 of 15·9 percentage points (11·3 to 20·6) and â0·1 percentage points (â6·4 to 6·1), respectively, in sweat chloride concentration of â45·5 mmol/L (â49·7 to â41·3) and â2·6 mmol/L (â8·2 to 3·1), respectively, and in CFQ-R respiratory domain score of 19·4 points (95% CI 10·5 to 28·3) and â5·0 points (â16·9 to 7·0), respectively. The most common adverse events overall were cough, increased sputum, and headache. One participant in the vanzacaftorâtezacaftorâdeutivacaftor group had a serious adverse event of infective pulmonary exacerbation and another participant had a serious rash event that led to treatment discontinuation. For most participants, adverse events were mild or moderate in severity.
Interpretation
Once-daily dosing with vanzacaftorâtezacaftorâdeutivacaftor was safe and well tolerated and improved lung function, respiratory symptoms, and CFTR function. These results support the continued investigation of vanzacaftorâtezacaftorâdeutivacaftor in phase 3 clinical trials compared with elexacaftorâtezacaftorâivacaftor.
Funding
Vertex Pharmaceuticals
Effect of Ivacaftor on Objective and Subjective Measures of Cough in Patients with Cystic Fibrosis
BACKGROUND AND OBJECTIVES: Cough is a major symptom in cystic fibrosis. Ivacaftor is a novel drug which targets the G551D mutation and has been demonstrated to improve lung function and weight in the long term. It also improves symptoms of extra-oesophageal reflux. We wanted to evaluate the effect of ivacaftor on cough in cystic fibrosis. METHODS: In two patients with cystic fibrosis the Hull Airway Reflux Questionnaire (HARQ) was completed and objective cough counts were measured prior to and within 4 weeks after initiation of treatment with ivacaftor. Spirometry was also undertaken and weight checked at these time frames. RESULTS: In the first patient the HARQ score decreased from 29 to 11 and objective cough counts from 29 to 9 cough events per hour. Similarly in the second patient the HARQ score decreased from 13 to 9 and objective cough count from 76 to 5 cough events per hour. There was no significant change in spirometric parameters or weight. CONCLUSION: We have observed early subjective and objective improvement in cough measures on treatment with ivacaftor. We suggest that this improvement could be attributed to improvement of gastro-intestinal function and that cough metrics could be used as early and accurate end points of drug efficacy
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