Imaging Findings in Patients with Immune Checkpoint Inhibitor-Induced Arthritis

Immune checkpoint inhibitor (ICI)-induced arthritis is an increasingly recognized adverse event in patients with oncologic disease during immunotherapy. Four patterns are well described, including rheumatoid arthritis (RA)-like, polymyalgia rheumatica (PMR)-like, psoriatic arthritis (PsA)-like, and oligo-monoarthritis, among others. Despite better clinical recognition of these syndromes, information about the main imaging findings is limited. Methods: We conducted a retrospective observational study including all adult patients referred to the Rheumatology Department of a single-center due to ICI-induced arthritis who underwent imaging studies [ultrasound (US), magnetic resonance imaging (MRI), and (18)F-FDG PET/CT)] between January 2017 and January 2022. Results: Nineteen patients with ICI-induced arthritis with at least one diagnostic imaging assessment were identified (15 US, 4 MRI, 2 (18)F-FDG PET/CT). Most patients were male (84.2%), with a median age at inclusion of 73 years. The main underlying diagnoses for ICI treatment were melanoma in five cases. The distribution of ICI-induced arthritis was as follows: PMR-like (5, 26.2%), RA-like (4, 21.1%), PsA-like (4, 21.1%), and others (6, 31.6%). All RA-like patients had US findings indistinguishable from conventional RA patients. In addition, 3/5 (60%) of PMR-like patients had significant involvement of the hands and wrists. Abnormal findings on MRI or PET-CT were reported by clinical symptoms. No erosions or myofascitis were seen. Conclusions: ICI-induced arthritis patients present inflammatory patterns on imaging studies similar to conventional inflammatory arthropathies, and therefore these syndromes should be followed carefully and treated according to these findings

Precision mass measurements on neutron-rich rare-earth isotopes at JYFLTRAP - reduced neutron pairing and implications for the rr-process calculations

The rare-earth peak in the $r$-process abundance pattern depends sensitively on both the astrophysical conditions and subtle changes in nuclear structure in the region. This work takes an important step elucidating the nuclear structure and reducing the uncertainties in $r$-process calculations via precise atomic mass measurements at the JYFLTRAP double Penning trap. $^{158}$Nd, $^{160}$Pm, $^{162}$Sm, and $^{164-166}$Gd have been measured for the first time and the precisions for $^{156}$Nd, $^{158}$Pm, $^{162,163}$Eu, $^{163}$Gd, and $^{164}$Tb have been improved considerably. Nuclear structure has been probed via two-neutron separation energies $S_{2n}$ and neutron pairing energy metrics $D_n$. The data do not support the existence of a subshell closure at $N=100$. Neutron pairing has been found to be weaker than predicted by theoretical mass models. The impact on the calculated $r$-process abundances has been studied. Substantial changes resulting in a smoother abundance distribution and a better agreement with the solar $r$-process abundances are observed.Comment: 8 pages, 4 figures, accepted for publication in Physical Review Letter

Control and soft sensing strategies for a wastewater treatment plant using a neuro-genetic approach

During the last years, machine learning-based control and optimization systems are playing an important role in the operation of wastewater treatment plants in terms of reduced operational costs and improved effluent quality. In this paper, a machine learning-based control strategy is proposed for optimizing both the consumption and the number of regulation violations of a biological wastewater treatment plant. The methodology proposed in this study uses neural networks as a soft-sensor for on-line prediction of the effluent quality and as an identification model of the plant dynamics, all under a neuro-genetic optimum model-based control approach. The complete scheme was tested on a simulation model of the activated sludge process of a large-scale municipal wastewater treatment plant running under the GPS-X simulation frame and validated with operational gathered data, showing optimal control performance by minimizing operational costs while satisfying the effluent requirements, thus reducing the investment in expensive sensor devices.info:eu-repo/semantics/publishedVersio

High Sensitivity C Reactive Protein in Patients with Rheumatoid Arthritis Treated with Antibodies against IL-6 or Jak Inhibitors: A Clinical and Ultrasonographic Study

Background: We examined whether high-sensitivity CRP (hsCRP) reflected the inflammatory disease status evaluated by clinical and ultrasound (US) parameters in RA patients receiving IL-6 receptor antibodies (anti-IL-6R) or JAK inhibitors (JAKi). Methods: We conducted a cross-sectional study of patients with established RA receiving anti-IL-6R (tocilizumab, sarilumab) or JAKi (tofacitinib, baricitinib). Serum hsCRP and US synovitis in both hands were measured. Associations between hsCRP and clinical inflammatory activity were evaluated using composite activity indices. The association between hsCRP and US synovitis was analyzed. Results: 63 (92% female) patients (42 anti- IL-6R and 21 JAKi) were included, and the median disease duration was 14.4 (0.2–37.5) years. Most patients were in remission or had low levels of disease. Overall hsCRP values were very low, and significantly lower in anti-IL-6R patients (median 0.04 mg/dL vs. 0.16 mg/dL). Anti-IL-6R (82.4%) patients and 48% of JAKi patients had very low hsCRP levels (≤0.1 mg/dL) (p = 0.002). In the anti-IL-6R group, hsCRP did not correlate with the composite activity index or US synovitis. In the JAKi group, hsCRP moderately correlated with US parameters (r = 0.5) but not clinical disease activity, and hsCRP levels were higher in patients with US synovitis (0.02 vs. 0.42 mg/dL) (p = 0.001). Conclusion: In anti-IL-6R RA-treated patients, hsCRP does not reflect the inflammatory disease state, but in those treated with JAKi, hsCRP was associated with US synovitis

The Advanced LIGO Photon Calibrators

The two interferometers of the Laser Interferometry Gravitaional-wave Observatory (LIGO) recently detected gravitational waves from the mergers of binary black hole systems. Accurate calibration of the output of these detectors was crucial for the observation of these events, and the extraction of parameters of the sources. The principal tools used to calibrate the responses of the second-generation (Advanced) LIGO detectors to gravitational waves are systems based on radiation pressure and referred to as Photon Calibrators. These systems, which were completely redesigned for Advanced LIGO, include several significant upgrades that enable them to meet the calibration requirements of second-generation gravitational wave detectors in the new era of gravitational-wave astronomy. We report on the design, implementation, and operation of these Advanced LIGO Photon Calibrators that are currently providing fiducial displacements on the order of $10^{-18}$ m/$\sqrt{\textrm{Hz}}$ with accuracy and precision of better than 1 %.Comment: 14 pages, 19 figure

Plasma calprotectin as a biomarker of ultrasound synovitis in rheumatoid arthritis patients receiving IL-6 antagonists or JAK inhibitors

To analyse the accuracy of plasma calprotectin in patients with rheumatoid arthritis (RA) receiving monoclonal antibodies against IL-6 receptors (anti-rIL-6) or JAK inhibitors (JAKis) in detecting ultrasound (US) synovitis and compare it with acute phase reactants [high-sensitivity C-reactive protein (hs-CRP) and ESR].An observational cross-sectional study of RA patients receiving anti-rIL-6 (tocilizumab or sarilumab) or JAKi, (baricitinib or tofacitinib) was made. Plasma calprotectin for the diagnosis of US synovitis [synovial hypertrophy grade (SH)???2 plus power Doppler signal (PD)???1] was analysed using receiver operating characteristic curves (ROCs). The performance of ESR and hs-CRP was also studied. The three ROC curves were compared to determine which had the highest discriminatory power. Associations between plasma calprotectin and US scores were made using correlation analysis.Sixty-three RA patients were included. Mean plasma calprotectin levels were significantly higher in patients with US synovitis than in those without (0.89?±?0.85 vs 0.30?±?0.12 ?g/ml; p?=?0.0003). A moderate correlation between calprotectin and all US scores (HS score Rho?=?0.479; PD score Rho?=?0.492; and global score Rho?=?0.495) was found. The discriminatory capacity of plasma calprotectin showed an AUC of 0.795 (95% CI: 0.687-0.904). The AUC of hs-CRP and ESR was 0.721 and 0.564, respectively. hs-CRP serum levels showed a low positive correlation with the three US scores (Rho?<?0.40). After analysis according to the drugs administered, the correlation disappeared in patients receiving anti-rIL-6.Plasma calprotectin may be a sensitive biomarker of synovial inflammation in RA patients treated with anti-rIL-6 or JAKi.© The Author(s), 2022

The synovial and blood monocyte DNA methylomes mirror prognosis, evolution and treatment in early arthritis

Identifying predictive biomarkers at early stages of early inflammatory arthritis is crucial for starting appropriate therapies to avoid poor outcomes. Monocytes and macrophages, largely associated with arthritis, are contributors and sensors of inflammation through epigenetic modifications. In this study, we investigated associations between clinical features and DNA methylation in blood and synovial fluid (SF) monocytes in a prospective cohort of early inflammatory arthritis patients. Undifferentiated arthritis (UA) blood monocyte DNA methylation profiles exhibited significant alterations in comparison with those from healthy donors. We identified additional differences both in blood and SF monocytes after comparing UA patients grouped by their future outcomes, good versus poor. Patient profiles in subsequent visits revealed a reversion towards a healthy level in both groups, those requiring disease-modifying antirheumatic drugs (DMARDs) and those that remitted spontaneously. Changes in disease activity between visits also impacted DNA methylation, partially concomitant in the SF of UA and in blood monocytes of rheumatoid arthritis patients. Epigenetic similarities between arthritis types allow a common prediction of disease activity. Our results constitute a resource of DNA methylation-based biomarkers of poor prognosis, disease activity and treatment efficacy in early untreated UA patients for the personalized clinical management of early inflammatory arthritis patients

New constraints on the Al 25 (p,γ) reaction and its influence on the flux of cosmic γ rays from classical nova explosions

The astrophysical Al25(p,γ)Si26 reaction represents one of the key remaining uncertainties in accurately modeling the abundance of radiogenic Al26 ejected from classical novae. Specifically, the strengths of key proton-unbound resonances in Si26, that govern the rate of the Al25(p,γ) reaction under explosive astrophysical conditions, remain unsettled. Here, we present a detailed spectroscopy study of the Si26 mirror nucleus Mg26. We have measured the lifetime of the 3+, 6.125-MeV state in Mg26 to be 19(3)fs and provide compelling evidence for the existence of a 1- state in the T=1,A=26 system, indicating a previously unaccounted for=1 resonance in the Al25(p,γ) reaction. Using the presently measured lifetime, together with the assumption that the likely 1- state corresponds to a resonance in the Al25+p system at 435.7(53) keV, we find considerable differences in the Al25(p,γ) reaction rate compared to previous works. Based on current nova models, we estimate that classical novae may be responsible for up to ≈15% of the observed galactic abundance of Al26.This work was supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics, under Contract No. DEAC02-06CH11357 and Grants No. DEFG02-94-ER40834, No. DEFG02-97-ER41041, No. DEFG02-97-ER41043, and No. DE-FG02-93ER4077. U.K. personnel were supported by the Science and Technologies Facilities Council (STFC). This work was partially supported by the Spanish MINECO Grant No. AYA2017-86274-P, by the E.U. FEDER funds, and by the AGAUR/Generalitat de Catalunya Grant No. SGR-661/2017. This article benefited from discussions within the “ChETEC” COST Action (Grant No. CA16117). This research used resources of ANL's ATLAS facility, which is a DOE Office of Science User facility