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

Measuring and modelling the energy cost of reconfiguration in sensor networks [forthcoming]

As Wireless Sensor Networks (WSN) must operate for long periods on a limited power budget, estimating the energy cost of software operations is critical. Contemporary reconfiguration approaches for WSN allow for software evolution at various granularities; from reflashing of a complete software image, through replacement of complete applications, to the reconfiguration of individual software components. This paper contributes a generic model for measuring and modelling the energy cost of reconfiguration in WSN. We validate that this model is accurate in the face of different hardware platforms, software stacks and software encapsulation approaches. We have embedded this model in the LooCI middleware, resulting in the first energy aware reconfigurable component model for sensor networks. We evaluate our approach using two real-world WSN applications and demonstrate that our model predicts the energy cost of reconfiguration with 93% accuracy. Using this model we demonstrate that selecting the most appropriate software modularisation approach is key to minimising energy consumption

Levels and patterns of objectively assessed physical activity and compliance with different public health guidelines in university students

ArticleBackground Physical activity (PA) is associated with health enhancement. The aim of this study was to assess: 1) levels and patterns of PA in university students by using accelerometers; and 2) the percentage of fulfilment of PA recommendations for adults, according to different public health guidelines. Methods Observational cross-sectional study (Cuenca’s Adults Study) involving 296 (206 women) healthy Spanish university students aged 18–25 years old. Participants wore the ActiGraph GT1M accelerometer for seven consecutive days. Total PA, steps and time spent in sedentary time, light, moderate, vigorous, and moderate to vigorous PA (MVPA) was assessed, and the prevalence of sufficient PA was calculated according to various public health guidelines. Results No sex differences in total PA were found. University students were more sedentary during weekend days than weekdays (p<0.05). Only 30.3% of participants accumulated 30 min/day at least five days a week of MVPA. A total of 5.4% of students met the recommendation of 150 min/week of MVPA or 75 min/week of vigorous PA, in PA bouts of at least 10 min. using the same definition, but on five or more days a week, only 0.5% students were found to meet the recommendation. In addition, only 0.5% of students met the recommendation of 30 min/day of MVPA, at least five days a week and in bouts of at least 10 min. Finally, 28.1% of the students met the recommendation of 10,000 steps/day. Conclusions Our study shows a high incidence of sedentary time in university students. The number of students meeting PA recommendations significantly differed depending on the recommendation proposed. Specific strategies to promote PA in this population are necessary as well as an agreement as to which PA guidelines should be used.Fundación para la Investigación SanitariaMinistry of Health and Consumer AffairsInstituto de Salud Carlos IIIRed de Investigación en Actividades Preventivas y de Promoción de Salu

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

Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)

Background: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). // Patients and methods: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. // Results: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan–Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. // Conclusions: The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755)

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

High-precision mass measurements for the isobaric multiplet mass equation at A=52

Masses of Co-52, (52)Com, Fe-52, Fe-52(m), and Mn-52 have been measured with the JYFLTRAP double Penning trap mass spectrometer. The isobaric multiplet mass equation for the T = 2 quintet at A = 52 has been studied employing the new mass values. No significant breakdown (beyond the 3 sigma level) of the quadratic form of the IMME was observed (chi(2)/n = 2.4). The cubic coefficient was 6.0(32) keV (chi(2)/n = 1.1). The excitation energies for the isomer and the T = 2 isobaric analog state in Co-52 have been determined to be 374(13) keV and 2922(13) keV, respectively. The measured mass values for Co-52 and (52)Com are 29(10) keV and 16(15) keV higher, respectively, than obtained in a recent storage-ring experiment, and significantly lower than predicted by extrapolations. Consequently, this has an impact on the proton separation energies for Co-52 and Ni-53 relevant for the astrophysical rapid proton capture process. The Q value for the proton decay from the 19/2(-) isomer in Co-53 has been determined with an unprecedented precision, Q(p) = 1558.8(17) keV.Peer reviewe