Giant cell arteritis is a granulomatous vasculitis of the aorta and its branches that causes blindness, stroke, and aortic aneurysm. CD4 T cells are key pathogenic regulators, instructed by vessel ...wall dendritic cells to differentiate into vasculitic T cells. The unique pathways driving this dendritic cell-T-cell interaction are incompletely understood, but may provide novel therapeutic targets for a disease in which the only established therapy is long-term treatment with high doses of corticosteroids.
Immunohistochemical and gene expression analyses of giant cell arteritis-affected temporal arteries revealed abundant expression of the NOTCH receptor and its ligands, Jagged1 and Delta1. Cleavage of the NOTCH intracellular domain in wall-infiltrating T cells indicated ongoing NOTCH pathway activation in large-vessel vasculitis. NOTCH activation did not occur in small-vessel vasculitis affecting branches of the vasa vasorum tree. We devised 2 strategies to block NOTCH pathway activation: γ-secretase inhibitor treatment, preventing nuclear translocation of the NOTCH intracellular domain, and competing for receptor-ligand interactions through excess soluble ligand, Jagged1-Fc. In a humanized mouse model, NOTCH pathway disruption had strong immunosuppressive effects, inhibiting T-cell activation in the early and established phases of vascular inflammation. NOTCH inhibition was particularly effective in downregulating Th17 responses, but also markedly suppressed Th1 responses.
Blocking NOTCH signaling depleted T cells from the vascular infiltrates, implicating NOTCH- NOTCH ligand interactions in regulating T-cell retention and survival in vessel wall inflammation. Modulating the NOTCH signaling cascade emerges as a promising new strategy for immunosuppressive therapy of large-vessel vasculitis.
The β-decay half-lives of 110 neutron-rich isotopes of the elements from _{37}Rb to _{50}Sn were measured at the Radioactive Isotope Beam Factory. The 40 new half-lives follow robust systematics and ...highlight the persistence of shell effects. The new data have direct implications for r-process calculations and reinforce the notion that the second (A≈130) and the rare-earth-element (A≈160) abundance peaks may result from the freeze-out of an (n,γ)⇄(γ,n) equilibrium. In such an equilibrium, the new half-lives are important factors determining the abundance of rare-earth elements, and allow for a more reliable discussion of the r process universality. It is anticipated that universality may not extend to the elements Sn, Sb, I, and Cs, making the detection of these elements in metal-poor stars of the utmost importance to determine the exact conditions of individual r-process events.
Abstract
Background
Paramedics need to be in good physical health to be able to respond to emergencies. We hypothesized that near misses by paramedics and unanticipated incidents that cause no harm ...may be associated with presenteeism during emergency rescues.
Aims
To examine the association between presenteeism and near misses among paramedics.
Methods
A cross-sectional study was conducted among 254 paramedics using a self-administered questionnaire. Presenteeism was measured using the work functioning impairment scale (WFun).
Results
Twelve per cent of respondents experienced high work function impairment indicating presenteeism. The rate of near-miss experiences steadily increased with increasing work function impairment among paramedics (WFun score category: middle, odds ratio (OR) 3.62, 95% confidence interval (CI) 1.62–8.11; high, OR 4.36, 95% CI 1.37–13.84; very high, OR 8.62, 95% CI 2.09–35.48).
Conclusions
This study demonstrated a positive relationship between impaired work function indicating presenteeism and near misses among paramedics. This suggests that presenteeism may be associated with errors that have the potential to cause serious accidents. Improved access to treatment for frequent health problems may reduce the number of incidents among paramedics.
To investigate the effect of deep learning on the diagnostic performance of radiologists and radiology residents in detecting breast cancers on computed tomography (CT).
In this retrospective study, ...patients undergoing contrast-enhanced chest CT between January 2010 and December 2020 using equipment from two vendors were included. Patients with confirmed breast cancer were categorised as the training (n=201) and validation (n=26) group and the testing group (n=30) using processed CT images from either vendor. The trained deep-learning model was applied to test group patients with (30 females; mean age = 59.2 ± 15.8 years) and without (19 males, 21 females; mean age = 64 ± 15.9 years) breast cancer. Image-based diagnostic performance of the deep-learning model was evaluated with the area under the receiver operating characteristic curve (AUC). Two radiologists and three radiology residents were asked to detect malignant lesions by recording a four-point diagnostic confidence score before and after referring to the result from the deep-learning model, and their diagnostic performance was evaluated using jackknife alternative free-response receiver operating characteristic analysis by calculating the figure of merit (FOM).
The AUCs of the trained deep-learning model on the validation and test data were 0.976 and 0.967, respectively. After referencing with the result of the deep learning model, the FOMs of readers significantly improved (reader 1/2/3/4/5: from 0.933/0.962/0.883/0.944/0.867 to 0.958/0.968/0.917/0.947/0.900; p=0.038).
Deep learning can help radiologists and radiology residents detect breast cancer on CT.
Aharonov-Bohm (AB) oscillations are studied for a parallel-coupled vertical double quantum dot with a common source and drain electrode. We observe AB oscillations of current via a one-electron ...bonding state as the ground state and an antibonding state as the excited state. As the center gate voltage becomes more negative, the oscillation period is clearly halved for both the bonding and antibonding states, and the phase changes by half a period for the antibonding state. This result can be explained by a calculation that takes account of the indirect interdot coupling via the two electrodes.
We analyze the full-counting statistics of the electric heat current flowing in a two-terminal quantum conductor whose temperature is probed by a third electrode ("probe electrode"). In particular we ...demonstrate that the cumulant-generating function obeys the fluctuation theorem in the presence of a constant magnetic field. The analysis is based on the scattering matrix of the three-terminal junction (comprising the two electronic terminals and the probe electrode), and a separation of time scales: it is assumed that the rapid charge transfer across the conductor and the rapid relaxation of the electrons inside the probe electrode give rise to much slower energy fluctuations in the latter. This separation allows for a stochastic treatment of the probe dynamics, and the reduction of the three-terminal setup to an effective two-terminal one. Expressions for the lowest nonlinear transport coefficients, e.g., the linear-response heat-current noise and the second nonlinear thermal conductance, are obtained and explicitly shown to preserve the symmetry of the fluctuation theorem for the two-terminal conductor. The derivation of our expressions, which is based on the transport coefficients of the three-terminal system explicitly satisfying the fluctuation theorem, requires full calculations of vertex corrections.
Suppression of the occurrence of remanent vortices is necessary to improve the quality factor of superconducting resonators. In particular, the flux-expulsion dynamics in Nb during cooling has become ...of major interest to researchers focusing on superconducting cavities. To study the vortex states and their behavior in high-purity cavity-grade Nb, we used a magneto-optical imaging technique to perform real-space observations of the magnetic field distributions during the field-cooling and field-scanning processes. In the field-cooling process, the distributions were observed to undergo phase separation into vortex and Meissner regions, as would be expected in an intermediate mixed state (IMS). The vortex regions in the IMS, such as vortex bundles, tend to be larger in higher fields, in contrast to the Meissner regions, which experience shrinkage. In the field-scanning process, domelike field profiles, which indicate a geometrical barrier with very weak bulk pinning, were observed. The existence of the IMS suggests that cavity-grade Nb is in a type-II/1 superconductor regime, in which attractive interaction between vortices at a length scale of the penetration depth is crucial for the behavior of vortices.
•Controversial results in literature about non-thermal effects of electric fields.•Unreliable methods and assumptions can compromise results and conclusions.•Control and distribution of temperature ...and electric field are key factors.•Comparison with conventional process must be fair.•Depending on field frequency, effects may be subtle and difficult to assess.
The use of microwave and ohmic heating in food processing has the advantage of a fast volumetric heating due to ionic and dielectric mechanisms, depending on field frequency. One topic that has been under debate is whether or not the electric field has a non-thermal effect that enhances the inactivation of microorganisms and enzymes. Numerous studies with controversial have been conducted using different approaches, experimental designs and methodologies. This review discusses important factors for accurately assessing non-thermal effects, such as distribution and control of electric field and temperature, measurement of time temperature history, sample homogeneity, fair comparison with conventional processed samples. Current theories for non-thermal inactivation of enzymes (structure and functionally changes) and micro-organisms (cell membrane changes) are also reviewed.
•Steady state crack velocity of delayed hydride cracking in Zircaloy-2 was analyzed.•A large stress peak is induced at an end of hydride by volume expansion of hydride.•Hydrogen diffuses to the ...stress peak, thereby accelerating steady hydride growth.•Crack velocity was estimated from the calculated hydrogen flux into the stress peak.•There was good agreement between calculation results and experimental data.
Delayed hydride cracking (DHC) of Zircaloy-2 is one possible mechanism for the failure of boiling water reactor fuel rods in ramp tests at high burnup. Analyses were made for hydrogen diffusion around a crack tip to estimate the crack velocity of DHC in zirconium alloys, placing importance on effects of precipitation of δ-hydride. The stress distribution around the crack tip is significantly altered by precipitation of hydride, which was strictly analyzed using a finite element computer code. Then, stress-driven hydrogen diffusion under the altered stress distribution was analyzed by a differential method. Overlapping of external stress and hydride precipitation at a crack tip induces two stress peaks; one at a crack tip and the other at the front end of the hydride precipitate. Since the latter is larger than the former, more hydrogen diffuses to the front end of the hydride precipitate, thereby accelerating hydride growth compared with that in the absence of the hydride. These results indicated that, after hydride was formed in front of the crack tip, it grew almost steadily accompanying the interaction of hydrogen diffusion, hydride growth and the stress alteration by hydride precipitation. Finally, crack velocity was estimated from the calculated hydrogen flux into the crack tip as a function of temperature, stress intensity factor and material strength. There was qualitatively good agreement between calculation results and experimental data.
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