Studies in many areas of particle and astroparticle physics require a good knowledge of hadron spectra produced at small angles to the primary particle direction, e.g. in the TeV energy range at the ...LHC. The present work is dedicated to development of a particle identification technique based on the transition radiation produced by highly relativistic particles. Dedicated experimental studies were carried out and simulation models were developed to reproduce experimental data obtained with different prototypes. On the basis of these studies, the possibility of making detectors able to provide hadron composition measurement with high accuracy and identify particles with high efficiency in the forward experiments at the LHC was demonstrated. Two concepts of large scale TRDs are proposed: the straw TRD and the GaAs/straw TRD. They allow the reconstruction of hadron spectra with accuracy about or below 1% and to identify particles with high efficiency in individual events. As an example, suppression of the combinatorial background was demonstrated for the D0→K−π+ and D̄0→K+π− decays.
Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses are important for therapeutics development. Here we ...describe a distinct class of broadly neutralizing human mAbs with protective capacity against three ebolaviruses infectious for humans: Ebola (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) viruses. We isolated mAbs from human survivors of ebolavirus disease and identified a potent mAb, EBOV-520, which bound to an epitope in the glycoprotein (GP) base region. EBOV-520 efficiently neutralized EBOV, BDBV, and SUDV and also showed protective capacity in relevant animal models of these infections. EBOV-520 mediated protection principally by direct virus neutralization and exhibited multifunctional properties. This study identified a potent naturally occurring mAb and defined key features of the human antibody response that may contribute to broad protection. This multifunctional mAb and related clones are promising candidates for development as broadly protective pan-ebolavirus therapeutic molecules.
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•Broad human antibody recognizes a quaternary site of vulnerability on ebolavirus GP•The antibody possesses pan-ebolavirus neutralizing and protective capacity•The antibody mediates protection principally by direct virus neutralization•The antibody uses several mechanisms for contributing to broad immunity
Ebola virus, a member of the Filoviridae family, causes severe disease in humans. Gilchuk et al. isolated and characterized broadly neutralizing human monoclonal antibodies active against all three clinically relevant ebolavirus species. Potent monoclonal antibody EBOV-520 binds to the glycoprotein base region, acts principally by direct virus neutralization, and exploits several mechanisms for contributing to pan-ebolavirus protective immunity.
ABSTRACT
Introduction/Aims
In traumatic nerve lesions (TNLs), motor unit potentials (MUPs) may be difficult to detect in early injury. Ultrasound‐guided electromyography (US‐EMG) can aid in ...identifying areas of muscle activation, but its sensitivity can be improved. In this study we compare the sensitivity of US‐EMG alone with US‐EMG after peripheral nerve stimulation (NC‐US‐EMG) to better identify active muscle regions.
Methods
In this prospective study, 32 patients with severe TNLs were evaluated with standard EMG (ST‐EMG), US‐EMG, and NC‐US‐EMG at baseline (T0), after 2 to 3 months (T1), and after 5 to 6 months (T2).
Results
NC‐US‐EMG was more sensitive in detecting MUPs compared with US‐EMG and ST‐EMG at T0 (19 patients vs 14 and 5 patients, respectively). In addition, both US‐guided techniques were more sensitive than ST‐EMG in detecting MUPs (ST‐EMG vs US‐EMG: P = .014; ST‐EMG vs NC‐US‐EMG: P = .003). At T1, ST‐EMG remained less sensitive NC‐US‐EMG (P = .019). No significant differences were observed among the three techniques at T2.
Discussion
In the evaluation of severe TNLs, the combination of peripheral nerve stimulation and US increases the sensitivity of EMG for MUP detection at baseline and 2 to 3 months postinjury.
See Editorial on pages 189‐190 in this issue
Pulsars are born with subsecond spin periods and slow by electromagnetic braking for several tens of millions of years, when detectable radiation ceases. A second life can occur for neutron stars in ...binary systems. They can acquire mass and angular momentum from their companions, to be spun up to millisecond periods and begin radiating again. We searched Fermi Large Area Telescope data for pulsations from all known millisecond pulsars (MSPs) outside of globular clusters, using rotation parameters from radio telescopes. Strong gamma-ray pulsations were detected for eight MSPs. The gamma-ray pulse profiles and spectral properties resemble those of young gamma-ray pulsars. The basic emission mechanism seems to be the same for MSPs and young pulsars, with the emission originating in regions far from the neutron star surface.
We present a detailed statistical analysis of the correlation between radio and gamma-ray emission of the active galactic nuclei (AGNs) detected by Fermi during its first year of operation, with the ...largest data sets ever used for this purpose. We use both archival interferometric 8.4 GHz data (from the Very Large Array and ATCA, for the full sample of 599 sources) and concurrent single-dish 15 GHz measurements from the Owens Valley Radio Observatory (OVRO, for a sub sample of 199 objects). Our unprecedentedly large sample permits us to assess with high accuracy the statistical significance of the correlation, using a surrogate data method designed to simultaneously account for common-distance bias and the effect of a limited dynamical range in the observed quantities. We find that the statistical significance of a positive correlation between the centimeter radio and the broadband (E > 100 MeV) gamma-ray energy flux is very high for the whole AGN sample, with a probability of <10--7 for the correlation appearing by chance. Using the OVRO data, we find that concurrent data improve the significance of the correlation from 1.6 X 10--6 to 9.0 X 10--8. Our large sample size allows us to study the dependence of correlation strength and significance on specific source types and gamma-ray energy band. We find that the correlation is very significant (chance probability < 10--7) for both flat spectrum radio quasars and BL Lac objects separately; a dependence of the correlation strength on the considered gamma-ray energy band is also present, but additional data will be necessary to constrain its significance.
The gamma -ray sky >100 MeV is dominated by the diffuse emissions from interactions of cosmic rays with the interstellar gas and radiation fields of the Milky Way. Observations of these diffuse ...emissions provide a tool to study cosmic-ray origin and propagation, and the interstellar medium. We present measurements from the first 21 months of the Fermi Large Area Telescope (Fermi-LAT) mission and compare with models of the diffuse gamma -ray emission generated using the GALPROP code. The models are fitted to cosmic-ray data and incorporate astrophysical input for the distribution of cosmic-ray sources, interstellar gas, and radiation fields. To assess uncertainties associated with the astrophysical input, a grid of models is created by varying within observational limits the distribution of cosmic-ray sources, the size of the cosmic-ray confinement volume (halo), and the distribution of interstellar gas. An all-sky maximum-likelihood fit is used to determine the X sub(CO) factor, the ratio between integrated CO-line intensity and H sub(2) column density, the fluxes and spectra of the gamma -ray point sources from the first Fermi-LAT catalog, and the intensity and spectrum of the isotropic background including residual cosmic rays that were misclassified as gamma -rays, all of which have some dependency on the assumed diffuse emission model. The models are compared on the basis of their maximum-likelihood ratios as well as spectra, longitude, and latitude profiles. We also provide residual maps for the data following subtraction of the diffuse emission models. The models are consistent with the data at high and intermediate latitudes but underpredict the data in the inner Galaxy for energies above a few GeV. Possible explanations for this discrepancy are discussed, including the contribution by undetected point-source populations and spectral variations of cosmic rays throughout the Galaxy. In the outer Galaxy, we find that the data prefer models with a flatter distribution of cosmic-ray sources, a larger cosmic-ray halo, or greater gas density than is usually assumed. Our results in the outer Galaxy are consistent with other Fermi-LAT studies of this region that used different analysis methods than employed in this paper.
Recent observations of supernova remnants (SNRs) hint that they accelerate cosmic rays to energies close to approximately 10¹⁵ electron volts. However, the nature of the particles that produce the ...emission remains ambiguous. We report observations of SNR W44 with the Fermi Large Area Telescope at energies between 2 x 10⁸ electron volts and 3 x10¹¹ electron volts. The detection of a source with a morphology corresponding to the SNR shell implies that the emission is produced by particles accelerated there. The gamma-ray spectrum is well modeled with emission from protons and nuclei. Its steepening above approximately 10⁹ electron volts provides a probe with which to study how particle acceleration responds to environmental effects such as shock propagation in dense clouds and how accelerated particles are released into interstellar space.
To assess immunogenicity of a heterologous fourth dose of an mRNA (BNT162b2) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in autoimmune rheumatic diseases (ARD) patients with ...poor/non-response to inactivated vaccine (Sinovac-CoronaVac).
A total of 164 ARD patients who were coronavirus disease 2019 (COVID-19) poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies-NAb) to the third dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) 3 months after last dose. IgG and NAb were evaluated before and after the fourth dose.
Significant increases were observed after the fourth dose in IgG (66.4 vs 95.1%, P < 0.001), NAb positivity (5.5 vs 83.5%, P < 0.001) and geometric mean titre (29.5 vs 215.8 AU/ml, P < 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after a fourth dose were more frequently under rituximab (P = 0.001). Negative NAb was associated with older age (P = 0.015), RA (P = 0.002), SSc (P = 0.026), LEF (P = 0.016) and rituximab use (P = 0.007). In multiple logistic regression analysis, prednisone dose ≥7.5 mg/day (OR = 0.34; P = 0.047), LEF (OR = 0.32, P = 0.036) and rituximab use (OR = 0.19, P = 0.022) were independently associated with negative NAb after the fourth vaccine dose.
This is the largest study to provide evidence of a remarkable humoral response after the fourth dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/non-response to the third dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose.
ClinicalTrials.gov, https://clinicaltrials.gov, CoronavRheum #NCT04754698.
To describe the role of the Diffusion Weighted Imaging (DWI) in the assessment of hepatocellular carcinoma (HCC).
Several electronic databases were evaluated in the present review. The search ...included articles published from January 2010 to May 2019. The references of all articles were also evaluated. All titles and abstracts were assessed, and only the studies of DWI in patients with HCC were retained.
HCC is the most common primitive hepatic cancer. The non-invasive radiological criteria for HCC diagnosis are based on the presence of the specific vascular profile characterized by contrast uptake during arterial phase, defined as arterial hyperenhancement, followed by washout in the venous/portal phase. However, arterial hyperenhancement and wash out appearance have a sensitivity rate of 50-60% in lesion smaller than 2 cm. Therefore, other functional parameters have been introduced in the detection and characterization of HCC nodules. DWI has been applied to liver imaging as an excellent tool for detection and characterization of focal liver lesions, increasing clinical confidence and decreasing false positives. The assessment of DW images can be done qualitatively and quantitatively, through the apparent diffusion coefficient (ADC) map. Intravoxel incoherent motion (IVIM) is a more sophisticated analysis, a biexponential model, to better defining the relationship between signal attenuation and increasing b value that separately reproduces tissue diffusivity and tissue perfusion. Traditionally DWI approach to analyze data is founded on the hypothesis that water molecules diffuse within a voxel following a single direction with a Gaussian behavior without any restriction. However, according to the presence of microstructures, water molecules within biologic tissues exhibits a non-Gaussian phenomena proposed by Jensen in 2005 called Diffusion Kurtosis Imaging (DKI). This approach assesses the kurtosis coefficient (K) that shows the deviance of diffusion from a Gaussian approach, and the diffusion coefficient (D) with the correction of non-Gaussian bias. DKI is an advanced DWI model that quantifies non-Gaussian behavior of diffusion and provides both a corrected ADC, as well as the excess kurtosis of tissue, a measure of the extent to which tissue diffusion deviates from a Gaussian pattern. It is believed that the DKI model is more sensitive to tissue microstructural complexity than standard DW.
DWI should be an integral part of study protocol for HCC patients, considering the great advantages due to DWI and DWI-based approaches in detection and characterization of HCC.
We present the second catalog of high-energy gamma -ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), derived from ...data taken during the first 24 months of the science phase of the mission, which began on 2008 August 4. Source detection is based on the average flux over the 24 month period. The second Fermi -LAT catalog (2FGL) includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms of power-law, exponentially cutoff power-law, or log-normal forms. Also included are flux measurements in five energy bands and light curves on monthly intervals for each source. Twelve sources in the catalog are modeled as spatially extended. We provide a detailed comparison of the results from this catalog with those from the first Fermi-LAT catalog (1FGL). Although the diffuse Galactic and isotropic models used in the 2FGL analysis are improved compared to the 1FGL catalog, we attach caution flags to 162 of the sources to indicate possible confusion with residual imperfections in the diffuse model. The 2FGL catalog contains 1873 sources detected and characterized in the 100 MeV to 100 GeV range of which we consider 127 as being firmly identified and 1171 as being reliably associated with counterparts of known or likely gamma -ray-producing source classes.
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