302 research outputs found
Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial
Introduction: Several studies have described prognostic value of serum neurofilament light chain (sNfL) at the group level in relapsing multiple sclerosis (RMS) patients. Here, we aimed to explore the temporal association between sNfL and development of subclinical disease activity as assessed by magnetic resonance imaging (MRI) at the group level and evaluate the potential of sNfL as a biomarker for capturing subclinical disease activity in individual RMS patients. Methods: In the 12-week APLIOS study, patients (N = 284) received subcutaneous ofatumumab 20 mg. Frequent sNfL sampling (14 time points over 12 weeks) and monthly MRI scans enabled key analyses including assessment of the group-level temporal relationship of sNfL levels with on-study subclinical development of gadolinium-enhancing (Gd +)T1 lesions. Prognostic value of baseline sNfL ("high" vs. "low") level for subsequent on-study clinical relapse or Gd + T1 activity was assessed. Individual patient-level development of on-study Gd + T1 lesions wascompared across three predictors: baseline Gd + T1 lesion number, baseline sNfL ("high" vs. "low"), and time-matched sNfL. Results: In patients developing Gd + T1 lesions at week 4 (absent at baseline), sNfL levels increased during the month preceding the week-4 MRI scan and then gradually decreased back to baseline. High versus low baseline sNfL conferred increased risk of subsequent on-study clinical relapse or Gd + T1 activity (HR, 2.81; p < 0.0001) in the overall population and, notably, also in the patients without baseline Gd + T1 lesions (HR, 2.48; p = 0.0213). Individual patient trajectories revealed a marked difference in Gd + T1 lesions between patients with the ten highest vs. lowest baseline sNfL levels (119 vs. 19 lesions). Prognostic value of baseline or time-matched sNfL for on-study Gd + T1 lesions was comparable to that of the number of baseline MRI Gd + T1 lesions. Conclusions: sNfL measurement may have utility in capturing and monitoring subclinical disease activity in RMS patients. sNfL assessments could complement regular MRI scans and may provide an alternative when MRI assessment is not feasible. ClinicalTrials.gov: NCT03560739. Classification of Evidence: This study provides class I evidence that serum neurofilament light may be used as a biomarker for monitoring subclinical disease activity in relapsing multiple sclerosis patients, as shown by its elevation in the weeks preceding the development of new gadolinium-enhancing T1 lesion activity
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Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study
Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion
Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter
Showers produced by positive hadrons in the highly granular CALICE
scintillator-steel analogue hadron calorimeter were studied. The experimental
data were collected at CERN and FNAL for single particles with initial momenta
from 10 to 80 GeV/c. The calorimeter response and resolution and spatial
characteristics of shower development for proton- and pion-induced showers for
test beam data and simulations using Geant4 version 9.6 are compared.Comment: 26 pages, 16 figures, JINST style, changes in the author list, typos
corrected, new section added, figures regrouped. Accepted for publication in
JINS
Shower development of particles with momenta from 15 GeV to 150 GeV in the CALICE scintillator-tungsten hadronic calorimeter
We present a study of showers initiated by electrons, pions, kaons, and
protons with momenta from 15 GeV to 150 GeV in the highly granular CALICE
scintillator-tungsten analogue hadronic calorimeter. The data were recorded at
the CERN Super Proton Synchrotron in 2011. The analysis includes measurements
of the calorimeter response to each particle type as well as measurements of
the energy resolution and studies of the longitudinal and radial shower
development for selected particles. The results are compared to Geant4
simulations (version 9.6.p02). In the study of the energy resolution we include
previously published data with beam momenta from 1 GeV to 10 GeV recorded at
the CERN Proton Synchrotron in 2010.Comment: 35 pages, 21 figures, 8 table
Hadron shower decomposition in the highly granular CALICE analogue hadron calorimeter
The spatial development of hadronic showers in the CALICE scintillator-steel
analogue hadron calorimeter is studied using test beam data collected at CERN
and FNAL for single positive pions and protons with initial momenta in the
range from 10 to 80 GeV/c. Both longitudinal and radial development of hadron
showers are parametrised with two-component functions. The parametrisation is
fit to test beam data and simulations using the QGSP_BERT and FTFP_BERT physics
lists from Geant4 version 9.6. The parameters extracted from data and simulated
samples are compared for the two types of hadrons. The response to pions and
the ratio of the non-electromagnetic to the electromagnetic calorimeter
response, h/e, are estimated using the extrapolation and decomposition of the
longitudinal profiles.Comment: 38 pages, 19 figures, 5 tables; author list changed; submitted to
JINS
Performance of the first prototype of the CALICE scintillator strip electromagnetic calorimeter
A first prototype of a scintillator strip-based electromagnetic calorimeter
was built, consisting of 26 layers of tungsten absorber plates interleaved with
planes of 45x10x3 mm3 plastic scintillator strips. Data were collected using a
positron test beam at DESY with momenta between 1 and 6 GeV/c. The prototype's
performance is presented in terms of the linearity and resolution of the energy
measurement. These results represent an important milestone in the development
of highly granular calorimeters using scintillator strip technology. This
technology is being developed for a future linear collider experiment, aiming
at the precise measurement of jet energies using particle flow techniques
Differential (2+1) Jet Event Rates and Determination of alpha_s in Deep Inelastic Scattering at HERA
Events with a (2+1) jet topology in deep-inelastic scattering at HERA are
studied in the kinematic range 200 < Q^2< 10,000 GeV^2. The rate of (2+1) jet
events has been determined with the modified JADE jet algorithm as a function
of the jet resolution parameter and is compared with the predictions of Monte
Carlo models. In addition, the event rate is corrected for both hadronization
and detector effects and is compared with next-to-leading order QCD
calculations. A value of the strong coupling constant of alpha_s(M_Z^2)=
0.118+- 0.002 (stat.)^(+0.007)_(-0.008) (syst.)^(+0.007)_(-0.006) (theory) is
extracted. The systematic error includes uncertainties in the calorimeter
energy calibration, in the description of the data by current Monte Carlo
models, and in the knowledge of the parton densities. The theoretical error is
dominated by the renormalization scale ambiguity.Comment: 25 pages, 6 figures, 3 tables, submitted to Eur. Phys.
The Time Structure of Hadronic Showers in highly granular Calorimeters with Tungsten and Steel Absorbers
The intrinsic time structure of hadronic showers influences the timing
capability and the required integration time of hadronic calorimeters in
particle physics experiments, and depends on the active medium and on the
absorber of the calorimeter. With the CALICE T3B experiment, a setup of 15
small plastic scintillator tiles read out with Silicon Photomultipliers, the
time structure of showers is measured on a statistical basis with high spatial
and temporal resolution in sampling calorimeters with tungsten and steel
absorbers. The results are compared to GEANT4 (version 9.4 patch 03)
simulations with different hadronic physics models. These comparisons
demonstrate the importance of using high precision treatment of low-energy
neutrons for tungsten absorbers, while an overall good agreement between data
and simulations for all considered models is observed for steel.Comment: 24 pages including author list, 9 figures, published in JINS
Infrastructure for Detector Research and Development towards the International Linear Collider
The EUDET-project was launched to create an infrastructure for developing and
testing new and advanced detector technologies to be used at a future linear
collider. The aim was to make possible experimentation and analysis of data for
institutes, which otherwise could not be realized due to lack of resources. The
infrastructure comprised an analysis and software network, and instrumentation
infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture
Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA
The multiplicity structure of the hadronic system X produced in
deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic
system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY
vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant
mass M_X of the system X. Results are presented on multiplicity distributions
and multiplicity moments, rapidity spectra and forward-backward correlations in
the centre-of-mass system of X. The data are compared to results in e+e-
annihilation, fixed-target lepton-nucleon collisions, hadro-produced
diffractive final states and to non-diffractive hadron-hadron collisions. The
comparison suggests a production mechanism of virtual photon dissociation which
involves a mixture of partonic states and a significant gluon content. The data
are well described by a model, based on a QCD-Regge analysis of the diffractive
structure function, which assumes a large hard gluonic component of the
colourless exchange at low Q^2. A model with soft colour interactions is also
successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first
submission - omitted bibliograph
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