Objective
To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis (RA).
Methods
Synovial biopsy ...specimens and demographic and clinical data were collected from 2 RA cohorts (n = 329), one of patients with untreated early RA (n = 165) and one of patients with established RA with an inadequate response to tumor necrosis factor inhibitors (TNFi‐IR; n = 164). Synovial tissue was subjected to hematoxylin and eosin and immunohistochemical staining and semiquantitative assessment for the degree of synovitis (on a scale of 0–9) and of CD20+ B cell infiltrate (on a scale of 0–4). B cell scores were validated by digital image analysis and B cell lineage–specific transcript analysis (RNA‐Seq) in the early RA (n = 91) and TNFi‐IR (n = 127) cohorts. Semiquantitative CD20 scores were used to classify patients as B cell rich (≥2) or B cell poor (<2).
Results
Semiquantitative B cell scores correlated with digital image analysis quantitative measurements and B cell lineage–specific transcripts. B cell–rich synovitis was present in 35% of patients in the early RA cohort and 47.7% of patients in the TNFi‐IR cohort (P = 0.025). B cell–rich patients showed higher levels of disease activity and seropositivity for rheumatoid factor and anti–citrullinated protein antibody in early RA but not in established RA, while significantly higher histologic synovitis scores in B cell–rich patients were demonstrated in both cohorts.
Conclusion
We describe a robust semiquantitative histologic B cell score that closely replicates the quantification of B cells by digital or molecular analyses. Our findings indicate an ongoing B cell–rich synovitis, which does not seem to be captured by standard clinimetric assessment, in a larger proportion of patients with established RA than early RA.
Accurate measurements of physical processes in high energy frontier experiments demand exceptional spatial, temporal, and energy precision to discern the physics behind high-energy particle jets. ...Calorimeters, like other detection systems, must be able to meet these increasingly challenging performance requirements. In the prospective TeV-scale Muon Collider, the primary hurdle in designing detectors and devising event reconstruction algorithms is the challenge posed by Beam-Induced Background (BIB). Nevertheless, it is conceivable to mitigate the impact of BIB on the Muon Collider's calorimeter by capitalizing on certain characteristics and ensuring key features such as high granularity, precise timing, longitudinal segmentation, and superior energy resolution. This is what the here described Research and Development is trying to achieve with an innovative semi-homogeneous electromagnetic calorimeter constructed from stackable and interchangeable modules composed of lead fluoride crystals (PbF2). These modules are equipped with surface-mount UV-extended Silicon Photomultipliers (SiPMs) and are collectively referred to as the Crilin calorimeter (CRystal calorImeter with Longitudinal INformation). The challenge lies in making sure this calorimeter can operate effectively within an extremely harsh radiation environment, enduring an annual neutron flux of <inline-formula> <tex-math notation="LaTeX">10^{14}~n_{1\text {MeV}}/\text {cm}^{2} </tex-math></inline-formula> and a total ionizing dose (TID) of 10 kGy. In this article, the radiation tolerance measured in several irradiation campaigns is discussed, and the timing performances during a test beam at CERN-H2 with 120-GeV electrons. Additionally, a description of the latest prototype, Proto-1, is provided together with the results of the latest low-energy beam test at the LNF beam test facility (BTF) with 450 MeV electrons.
In modern experiment, a high granularity is required in order to distinguish signal particles from background and to solve the substructures necessary for jet identification. Time of arrival ...measurements in the calorimeter could play an important role in HL-LHC, since a high number of pile-up collisions is expected, and the timing could be used to assign clusters to the corresponding interaction vertex. In a Muon Collider, the timing could be used to remove signals produced by beam-induced background, asynchronous with respect to the bunch crossing. The calorimeter energy resolution is also fundamental to measure the kinematic properties of jets: a finely segmented calorimeter design should be favored in order to solve the jet substructure. However, this contrasts with the requirement for high timing resolution even for signal events involving low energy deposits, such as in the case of high impulse muons. Our proposed design, the Crilin calorimeter, is a semi-homogeneous calorimeter based on Lead Fluoride (PbF
2
) Crystals readout by surface-mount UV-extended Silicon Photomultipliers (SiPMs). In this paper, the development of a small prototype consisting of 2 layers of 3 × 3 crystals each is reported along with the relative results.
Aims/hypothesis
Endothelium-derived factors are thought to be physiological modulators of large artery stiffness. The aim of the study was to investigate whether endothelial function could be a ...determinant of arterial stiffness in essential hypertensive patients, in relation with the concomitant presence of type 2 diabetes mellitus.
Methods
The study included 341 participants (84 hypertensive patients with and 175 without type 2 diabetes mellitus, 82 matched controls). Brachial artery endothelium-dependent flow-mediated dilation (FMD) was determined by high-resolution ultrasound and computerised edge detection system. Applanation tonometry was used to measure carotid–femoral pulse wave velocity (PWV).
Results
Hypertensive patients with diabetes had higher PWV (10.1 ± 2.3 m/s vs 8.6 ± 1.4 m/s,
p
< 0.001) and lower FMD (3.51 ± 2.07 vs 5.16 ± 2.96%,
p
< 0.001) than non-diabetic hypertensive patients, who showed impaired vascular function when compared with healthy participants (7.9 ± 1.6 m/s and 6.68 ± 3.67%). FMD was significantly and negatively correlated to PWV only in hypertensive diabetic patients (
r
= −0.456,
p
< 0.001), but not in hypertensive normoglycaemic patients (
r
= −0.088,
p
= 0.248) or in healthy participants (
r
= 0.008,
p
= 0.946). Multivariate analysis demonstrated that, in the diabetic group, FMD remained an independent predictor of PWV after adjustment for confounders (
r
2
= 0.083,
p
= 0.003). Subgroup analysis performed in non-diabetic hypertensive patients revealed that neither obesity nor the metabolic syndrome affected the relationship between FMD and PWV.
Conclusions/interpretation
Endothelial dysfunction is a determinant of aortic stiffness in hypertensive diabetic patients but not in hypertensive patients without diabetes. These results suggest that type 2 diabetes mellitus on top of hypertension might worsen arterial compliance by endothelium-related mechanisms.
We illustrate the proposal, nicknamed LAGRANGE, to use spacecraft, located at the Sun–Earth Lagrange points, as a physical reference frame. Performing time of flight measurements of electromagnetic ...signals traveling on closed paths between the points, we show that it would be possible: (a) to refine gravitational time delay knowledge due both to the Sun and the Earth; (b) to detect the gravito-magnetic frame dragging of the Sun, so deducing information about the interior of the star; (c) to check the possible existence of a galactic gravitomagnetic field, which would imply a revision of the properties of a dark matter halo; (d) to set up a relativistic positioning and navigation system at the scale of the inner solar system. The paper presents estimated values for the relevant quantities and discusses the feasibility of the project analyzing the behavior of the space devices close to the Lagrange points.
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