The Italian Society of Rheumatology clinical practice guidelines for the management of large vessel vasculitis.

OBJECTIVE: Since of the last publication of last recommendations on primary large-vessel vasculitis (LVV) endorsed by the Italian Society of Rheumatology (SIR) in 2012, new evidence emerged regarding the diagnosis and the treatment with conventional and biologic immunosuppressive drugs. The associated potential change of clinical care supported the need to update the original recommendations. METHODS: Using the grading of recommendations assessment, development and evaluation (GRADE)-ADOLOPMENT framework, a systematic literature review was performed to update the evidence supporting the European Alliance of Associations for Rheumatology (EULAR) guidelines on LVV as reference. A multidisciplinary panel of 12 expert clinicians, a trained nurse, and a patients' representative discussed the recommendation in cooperation with an Evidence Review Team. Sixty-one stakeholders were consulted to externally review and rate the recommendations. RESULTS: Twelve recommendations were formulated. A suspected diagnosis of LVV should be confirmed by imaging or histology. In active GCA or TAK, the prompt commencement of high dose of oral glucocorticoids (40-60 mg prednisone-equivalent per day) is strongly recommended to induce clinical remission. In selected patients with GCA (e.g., refractory or relapsing disease or patients at risk of glucocorticoid related adverse effects) the use of an adjunctive therapy (tocilizumab or methotrexate) is recommended. In all patients diagnosed with TAK, adjunctive therapies, such as conventional synthetic or biological immunosuppressants, should be given in combination with glucocorticoids. CONCLUSIONS: The new set of SIR recommendations was formulated in order to provide a guidance on both diagnosis and treatment of patients suspected of or with a definite diagnosis of LVV.

Erratum: "Inference of the Local Interstellar Spectra of Cosmic-Ray Nuclei Z ⩽ 28 with the GALPROP-HELMOD Framework" (2020, ApJS, 250, 27).

[This corrects the article PMC8549769.].

The Discovery of a Low-energy Excess in Cosmic-Ray Iron: Evidence of the Past Supernova Activity in the Local Bubble.

Since its launch, the Alpha Magnetic Spectrometer-02 (AMS-02) has delivered outstanding quality measurements of the spectra of cosmic-ray (CR) species ( p ¯ , e ±, and nuclei, 1H-8O, 10Ne, 12Mg, 14Si) which resulted in a number of breakthroughs. One of the latest long-awaited surprises is the spectrum of 26Fe just published by AMS-02. Because of the large fragmentation cross section and large ionization energy losses, most of CR iron at low energies is local and may harbor some features associated with relatively recent supernova (SN) activity in the solar neighborhood. Our analysis of the new AMS-02 results, together with Voyager 1 and ACE-CRIS data, reveals an unexpected bump in the iron spectrum and in the Fe/He, Fe/O, and Fe/Si ratios at 1-2 GV, while a similar feature in the spectra of He, O, and Si and in their ratios is absent, hinting at a local source of low-energy CRs. The found excess extends the recent discoveries of radioactive 60Fe deposits in terrestrial and lunar samples and in CRs. We provide an updated local interstellar spectrum (LIS) of iron in the energy range from 1 MeV nucleon-1 to ~10 TeV nucleon-1. Our calculations employ the GALPROP-HELMOD framework, which has proved to be a reliable tool in deriving the LIS of CR p ¯ , e -, and nuclei Z ⩽ 28.

Deciphering the Local Interstellar Spectra of Secondary Nuclei with the Galprop/Helmod Framework and a Hint for Primary Lithium in Cosmic Rays.

Local interstellar spectra (LIS) of secondary cosmic-ray (CR) nuclei, lithium, beryllium, boron, and partially secondary nitrogen, are derived in the rigidity range from 10 MV to ~200 TV using the most recent experimental results combined with state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. The lithium spectrum appears somewhat flatter at high energies compared to other secondary species, which may imply a primary lithium component. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. An iterative maximum-likelihood method is developed that uses GALPROP-predicted LIS as input to HelMod, which provides the modulated spectra for specific time periods of the selected experiments for the model-data comparison. The proposed LIS accommodates the low-energy interstellar spectra measured by Voyager 1, the High Energy Astrophysics Observatory-3 (HEAO-3), and the Cosmic Ray Isotope Spectrometer on board of the Advanced Composition Explorer (ACE/CRIS), as well as the high-energy observations by the Payload for Antimatter Matter Exploration and Light-nuclei Astrophysics (PAMELA), Alpha Magnetic Spectrometer-02 (AMS-02), and earlier experiments that are made deep in the heliosphere. The interstellar and heliospheric propagation parameters derived in this study are consistent with our earlier results for propagation of CR protons, helium, carbon, oxygen, antiprotons, and electrons.

Inference of the Local Interstellar Spectra of Cosmic-Ray Nuclei Z ⩽ 28 with the GalProp-HelMod Framework.

Composition and spectra of Galactic cosmic rays (CRs) are vital for studies of high-energy processes in a variety of environments and on different scales, for interpretation of γ-ray and microwave observations, for disentangling possible signatures of new phenomena, and for understanding of our local Galactic neighborhood. Since its launch, AMS-02 has delivered outstanding-quality measurements of the spectra of p ¯ , e ±, and nuclei: 1H-8O, 10Ne, 12Mg, 14Si. These measurements resulted in a number of breakthroughs; however, spectra of heavier nuclei and especially low-abundance nuclei are not expected until later in the mission. Meanwhile, a comparison of published AMS-02 results with earlier data from HEAO-3-C2 indicates that HEAO-3-C2 data may be affected by undocumented systematic errors. Utilizing such data to compensate for the lack of AMS-02 measurements could result in significant errors. In this paper we show that a fraction of HEAO-3-C2 data match available AMS-02 measurements quite well and can be used together with Voyager 1 and ACE-CRIS data to make predictions for the local interstellar spectra (LIS) of nuclei that are not yet released by AMS-02. We are also updating our already-published LIS to provide a complete set from 1H-28Ni in the energy range from 1 MeV nucleon-1 to ~100-500 TeV nucleon-1, thus covering 8-9 orders of magnitude in energy. Our calculations employ the GalProp-HelMod framework, which has proved to be a reliable tool in deriving the LIS of CR p ¯ , e -, and nuclei 1H-8O.

HelMod in the Works: From Direct Observations to the Local Interstellar Spectrum of Cosmic-Ray Electrons.

The local interstellar spectrum (LIS) of cosmic-ray (CR) electrons for the energy range 1 MeV to 1 TeV is derived using the most recent experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. An iterative maximum-likelihood method is developed that uses GALPROP-predicted LIS as input to HelMod, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The optimized HelMod parameters are then used to adjust GALPROP parameters to predict a refined LIS with the procedure repeated subject to a convergence criterion. The parameter optimization uses an extensive data set of proton spectra from 1997 to 2015. The proposed CR electron LIS accommodates both the low-energy interstellar spectra measured by Voyager 1 as well as the high-energy observations by PAMELA and AMS-02 that are made deep in the heliosphere; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The interstellar and heliospheric propagation parameters derived in this study agree well with our earlier results for CR protons, helium nuclei, and anti-protons propagation and LIS obtained in the same framework.

Deciphering the Local Interstellar Spectra of Primary Cosmic-Ray Species with helmod.

Local interstellar spectra (LIS) of primary cosmic ray (CR) nuclei, such as helium, oxygen, and mostly primary carbon are derived for the rigidity range from 10 MV to ~200 TV using the most recent experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and helmod, are combined into a single framework that is used to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. The developed iterative maximum-likelihood method uses GALPROP-predicted LIS as input to helmod, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The interstellar and heliospheric propagation parameters derived in this study are consistent with our prior analyses using the same methodology for propagation of CR protons, helium, antiprotons, and electrons. The resulting LIS accommodate a variety of measurements made in the local interstellar space (Voyager 1) and deep inside the heliosphere at low (ACE/CRIS, HEAO-3) and high energies (PAMELA, AMS-02).

Solution of Heliospheric Propagation: Unveiling the Local Interstellar Spectra of Cosmic-ray Species.

Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with the data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range.

Validation of a pretreatment delivery quality assurance method for the CyberKnife Synchrony system.

PURPOSE: To evaluate the geometric and dosimetric accuracies of the CyberKnife Synchrony respiratory tracking system (RTS) and to validate a method for pretreatment patient-specific delivery quality assurance (DQA). METHODS: An EasyCube phantom was mounted on the ExacTrac gating phantom, which can move along the superior-inferior (SI) axis of a patient to simulate a moving target. The authors compared dynamic and static measurements. For each case, a Gafchromic EBT3 film was positioned between two slabs of the EasyCube, while a PinPoint ionization chamber was placed in the appropriate space. There were three steps to their evaluation: (1) the field size, the penumbra, and the symmetry of six secondary collimators were measured along the two main orthogonal axes. Dynamic measurements with deliberately simulated errors were also taken. (2) The delivered dose distributions (from step 1) were compared with the planned ones, using the gamma analysis method. The local gamma passing rates were evaluated using three acceptance criteria: 3% local dose difference (LDD)/3 mm, 2%LDD/2 mm, and 3%LDD/1 mm. (3) The DQA plans for six clinical patients were irradiated in different dynamic conditions, to give a total of 19 cases. The measured and planned dose distributions were evaluated with the same gamma-index criteria used in step 2 and the measured chamber doses were compared with the planned mean doses in the sensitive volume of the chamber. RESULTS: (1) A very slight enlargement of the field size and of the penumbra was observed in the SI direction (on average <1 mm), in line with the overall average CyberKnife system error for tracking treatments. (2) Comparison between the planned and the correctly delivered dose distributions confirmed the dosimetric accuracy of the RTS for simple plans. The multicriteria gamma analysis was able to detect the simulated errors, proving the robustness of their method of analysis. (3) All of the DQA clinical plans passed the tests, both in static and dynamic conditions. No statistically significant differences were found between static and dynamic cases, confirming the high degree of accuracy of the Synchrony RTS. CONCLUSIONS: The presented methods and measurements verified the mechanical and dosimetric accuracy of the Synchrony RTS. Their method confirms the fact that the RTS, if used properly, is able to treat a moving target with great precision. By combining PinPoint ion chamber, EBT3 films, and gamma evaluation of dose distributions, their DQA method robustly validated the effectiveness of CyberKnife and Synchrony system.

Electronic portal imaging registration in breast cancer radiotherapy verification: analysis of inter-observer agreement among different categories of health practitioners.

Electronic portal imaging (EPI) is commonly used to identify and correct for inter-fraction variability in tangential breast irradiation. Based on the institutional policy, EPI registration is performed by either radiation oncologist or therapist. Little data is available on the inter-observer agreement in EPI registration among different health practitioners. The aim of our study was to analyze inter-observer agreement among radiation oncologists and therapists in the evaluation of EPI for breast cancer radiotherapy verification. EPI data of 40 patients treated with tangential fields were independently reviewed by a radiation oncologist (on-line, just before treatment) and off-line by junior and senior therapists. Displacement of each EPI image with respect to the digital reconstructed radiographs (DRRs) was quantified using manual EPI registration based on bony marks with the corresponding DRRs. Agreement between observers was evaluated using weighted Cohen's Kappa statistics. In 95% out of 720 EPI-DRR comparisons, the EPI-DRR misalignment was < 5 mm. The difference between observers was < 2 mm in 666 (92.5%) out of all 720 delta values. High inter-observer agreement was found, with weighted Cohen's Kappa values attesting evaluation overlaps ranging from moderate (among therapists) to almost perfect (among radiation oncologist and therapists). The high agreement among the observers demonstrated the precision of breast localization using EPI. These findings suggest that routine EPI-based patient set-up verification in breast cancer radiotherapy can be safely entrusted to trained therapists (supervision should be assured based on the local tasks definition). Our study might be useful in quality assurance and in the optimization of workload in the radiotherapy departments. They might allow for wider implementation of complex and evolving radiotherapy technologies.

Disseminated transmissible venereal tumour associated with Leishmaniasis in a dog.

This report addresses an atypical transmissible venereal tumour in an 8-year-old bitch that was pluriparous and seropositive for leishmaniasis. There were ascites and a serosanguineous discharge from the vulva, but no lesions on the external genital mucosa. An aspirate of the peritoneal fluid showed mononuclear round cells characteristic of transmissible venereal tumour (TVT). Exploratory laparotomy revealed light red, granulomatous structures in the peritoneum, omentum, spleen, liver and uterine horns. Cytological and histopathological tests confirmed the diagnosis of intra-abdominal TVT. Dissemination of the TVT to several organs inside the abdominal cavity probably resulted from immunosuppression caused by leishmaniasis, which favoured the presence and aggressiveness of TVT.

Detection of Pneumocystis spp. in lung samples from pigs in Brazil.

The genus Pneumocystis is composed of opportunistic fungi currently considered as specific pulmonary pathogens in humans and other mammals. In pigs, Pneumocystis pneumonia (PcP) could create significant economical losses due to its detrimental effects on growth, food conversion, and carcass/viscera condemnation. This study revealed that Pneumocystis organisms could be detected by Grocott's staining or immunohistochemistry in 36.9% of 564 slaughtered pigs from two geographic regions of Brazil. The prevalence of positive cases was 39.9% and 33.9% in pigs slaughtered in Rio Grande do Sul (RS) and Mato Grosso (MT) states, respectively. Among the positive cases in RS, Pneumocystis organisms were observed in 41.9% of 33 histologically normal lungs, and in 58.0% of lungs presenting with histological lesions. In contrast, the prevalence in MT in normal and abnormal lungs was 36.3% and 63.5%, respectively. Major histopathological findings in lungs of infected animals were bronchointerstitial pneumonia (47.6%), suggestive of enzootic pneumonia, and interstitial pneumonia (37.9%), compatible with PcP. The results of this survey strengthened the interest of detecting fungal pathogens, in addition to other infectious agents, and evaluating their financial impact on Brazilian pig industry. Preventive and/or therapeutic strategies should be developed in order to minimize the incidence of respiratory fungal infections in pigs and associated economic losses.