Osteoimmunology of Spondyloarthritis

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA

The AMS Star Tracker thermal qualification overview

Four different thermal-vacuum tests were performed on AMICA Star Tracker (AST) in the period March-July 2006 in the space simulator of the SERMS laboratory in TerniItaly. Each of these tests was designed to verify different AST camera design features. The Thermal Balance test was conceived to validate the thermo-elastic model of the instrument and the active and passive thermal control subsystems. The Thermal Vacuum Cycling test was conceived to validate the AST electronics operative and survival temperature limits under vacuum conditions. The worst hot and cold operative and survival limits of the lens and filters in the AST optical system were assessed by means of the "Sun in the lens" and Lens Cold tests

Mirror system of the RICH detector of the NA62 experiment

A large RICH detector is used in NA62 to suppress the muon contamination in the charged pion selection by a factor 100 in the momentum range between 15 and 35 GeV/c. The detector consists of a 17 m long tank (vessel), filled with neon gas at atmospheric pressure. Cherenkov light is reflected by a mosaic of 20 spherical mirrors with 17 m focal length, placed at the downstream end, and collected by 1952 photomultipliers (PMTs) placed at the upstream end. In this paper the characterization of the mirrors before installation and the mirror support system are described. The mirror installation procedure and the laser alignment are also illustrated

OP0223 DEVELOPMENT AND PRELIMINARY VALIDATION OF ULTRASONOGRAPHIC DISEASE ACTIVITY AND DAMAGE SCORES IN PSORIATIC ARTHRITIS PATIENTS: RESULTS FROM THE UPSTREAM (ULTRASOUND IN PSORIATIC ARTHRITIS TREATMENT) STUDY

Background:The UPSTREAM (NCT03330769) is a 24-month multi-center prospective cohort study that primarily aims to evaluate the additional value of musculoskeletal ultrasound (msk-US) over clinical examination in predicting 6-month minimal disease activity in Psoriatic Arthritis (PsA). (1)Objectives:To develop and preliminarily validate an activity msk-US score and a damage msk-US score for PsA using the UPSTREAM database.Methods:Patients classified with PsA according to CASPAR criteria and starting a new course of therapy for clinically active peripheral joint disease were eligible. The information regarding objectives, study design, clinical and US assessment has already been published (1). The msk-US examination was performed in 42 joints, 36 tendons, 12 entheses and 2 bursae defined through a web-based exercise (2). The sonographic elementary lesions were allocated to disease activity [i.e. synovitis (sy), tenosynovitis (ts), peritendinitis (pt), bursitis (bs) all evaluated both in Grey Scale (GS) and Power Doppler (PD) and active enthesitis (en)] and to damage (i.e. joint erosion, bone proliferation, tendon tear, enthesophyte, calcification and irregular enthesis bone profile). Hands and feet X-ray were assessed using the modified Sharp-Van der Heijde (mSVH) score. A principal component (PC) analysis (PCA) was performed for each score and the number of PCs was defined by means of parallel analysis using baseline data. Each PC was normalized (n) taking into account the proportion between the observed value (e.g. sy-GS count) and the maximum expected value (e.g. 42 for sy-GS). Spearman' correlation was used to investigate the construct and discrimination validity of the new scores.Results:Between February 2017 and May 2020, 312 PsA patients (155 men), with a mean (SD) age of 52.8 13.4, were enrolled from 19 centers; 22 expert sonographers were involved with substantial agreement for US lesions evaluated (k ≥0.7). The median [IQR] disease duration was 1.3 [0.1-6.1] years and the median [IQR] tender joint and swollen joint counts were 6 [3-13] and 2 [1-5], respectively. The weight derived from PCA for each sonographic lesions and the final equation for calculating the scores are reported in Figure 1 (1A activity and 1B damage). The final msk-US activity score [n(ts-GS + ts-PD)*2.87] + [n(bs-GS + bs-PD)*1.76] + [n(pt-GS + pt-PD)*1.43] + [n(active en)*1.00] + [n(sy-GS)*0.83] + [n(sy-PD)*0.45] has the best construct and discrimination validities according to a significant correlation with all clinical variables usually related to clinical activity (Table 1). The msk-US damage score correlated with mSVH score, HAQ and other clinical variables (Table 1).Table 1.VariablesMsk-US activity scoreMsk-US damage scoreSpearman correlationP-valueSpearman correlationP-valueESR0.1960.0020.0750.235CRP0.209<0.0010.0680.254TJC0.338<0.0010.286<0.001SJC0.338<0.0010.0720.221Dactylitis count0.284<0.001-0.0610.306LEI0.1940.0010.214<0.001Physician GA0.150.0120.0160.793Patient GA activity0.1380.018-0.0730.221Patient GA pain0.1990.001-0.0270.648HAQ0.238<0.0010.1460.014BASDAI0.237<0.0010.1750.003PSAID-90.70.0040.1480.013DAPSA0.392<0.0010.228<0.001Sharp van Der Heijde score0.1150.20.2660.003Figure 1.Conclusion:These newly developed and preliminary validated msk-US activity and damage scores could be used in patients with PsA in the context of observational and controlled trials.References:[1]Canzoni M et al. BMJ Open. 2018;8:e021942.[2]Zabotti A et al. Ann Rheum Dis 2018;77:1537–1538.Acknowledgements:Alberto Batticciotto; Oscar Massimiliano Epis; Luisa Arcarese; Luca Navarini; Marta Caprioli; Mirco Magnani; Roberta Ramonda; Marco Amedeo CimminoDisclosure of Interests:Alen Zabotti: None declared, Matteo Piga: None declared, Anna Zanetti: None declared, Marco Canzoni: None declared, nicola boffini: None declared, valentina picerno: None declared, Giovanni Zanframundo: None declared, Ettore Silvagni: None declared, Ivan Giovannini: None declared, BERND RAFFEINER: None declared, Palma Scolieri: None declared, Paola Mancini: None declared, Simone Parisi: None declared, Alessandra Bortoluzzi Grant/research support from: GSK, Garifallia Sakellariou Consultant of: Consultant for Abbvie and Novartis, Orazio De Lucia: None declared, Ilaria Tinazzi: None declared, Fabiana Figus: None declared, Luca Idolazzi Speakers bureau: Received grants as speaker for Eli Lilly, UCB, Celgene, MSD, Abbvie, Novartis, Paid instructor for: Paid instructor for UCB during Product specialist Meeting, Mariagrazia Lorenzin: None declared, Sara Zandonella Callegher: None declared, Alberto Cauli: None declared, Greta Carrara: None declared, Carlo Alberto Scirè: None declared, Annamaria Iagnocco: None declare

A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01

The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics experiment that will study cosmic rays in the $\sim 100 \mathrm{MeV}$ to $1 \mathrm{TeV}$ range and will be installed on the International Space Station (ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected $10^8$ cosmic ray triggers. Part of the \emph{Mir} space station was within the AMS-01 field of view during the four day \emph{Mir} docking phase of this flight. We have reconstructed an image of this part of the \emph{Mir} space station using secondary $\pi^-$ and $\mu^-$ emissions from primary cosmic rays interacting with \emph{Mir}. This is the first time this reconstruction was performed in AMS-01, and it is important for understanding potential backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor stylistic and grammer change

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan–Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8–91.5%) at month 12, 78.8% (95% CI: 78.8–85.2%) at month 24, 63.8% (95% CI: 55.1–73.8%) at month 36, and 59.9% (95% CI: 55.1–73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results

Apremilast retention rate in clinic practice:observations from an Italian multi-center study

Objective There are few real-world setting studies focused on apremilast efectiveness (i.e., retention rate) in psoriatic arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention ratein real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and thefactors related to treatment persistence. Methods In ffteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan–Meier curve and the Coxanalysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value&lt;0.05 was considered statistically signifcant. Results The 356 enrolled patients (median age 60 [interquartile range IQR 52–67] yrs; male prevalence 42.7%) median observation period was 17 [IQR 7–34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefcacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefcacy (19%). Age and oligo-articular phenotype were related to treatment persistence (respectively hazard ratio 0.98 IQR 0.96–0.99; p=0.048 and 0.54 IQR 0.31–0.95; p=0.03). Conclusion Almost three-ffths of PsA patients receiving apremilast were still in treatment after 3 years. This study confrmed its efectiveness and safety profle. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbiditi

Ponte et stratégie de la reproduction chez les femelles du tacaud Trisopterus luscus (Gadidés) du plateau continental de la Galice, nord-ouest de l'Espagne

[EN] Pouting, Trisopterus luscus is harvested commercially on the Galician shelf by the Spanish inshore artisanal fleet. In spite of a substantial decrease in pouting catches, fishery regulations are limited to size length restrictions. This study provides biological data including length-at-maturity based on histological methods, seasonal maturation, spawning and fecundity. A collection 443 females, from 17 to 42 cm in total length, were sampled from landings (December 2003 to December 2004). Pouting length-at-maturity was estimated as 19.2 cm on average. Pouting females in spawning condition were observed throughout the year and the number of developing oocytes ranged from 20 000 to 1 327 000. Peak spawning was observed between February and April, which correlated well with trends in gonadosomatic index, and inverse to condition factor and hepatosomatic index. Histological examination of the gonads revealed that pouting ovarian development organization is asynchronous, and fecundity is probably determinate.[FR] Le tacaud, Trisopterus luscus est pêché par la flotte artisanale espagnole. En dépit d'une diminution substantielle des captures de tacaud, la pêche est réglementée uniquement à partir d'une taille minimum commerciale. Cette étude fournit des données biologiques comprenant la taille à maturité sexuelle basée sur l'histologie, la maturation saisonnière, la ponte et la fécondité. Un échantillon de 443 femelles, de 17 à 42 cm longueur totale, est examiné à partir des débarquements durant une année (de décembre 2003 à décembre 2004). La taille moyenne à maturité sexuelle est estimée à 19,2 cm. Les femelles de tacaud en condition de ponte sont observée tout au long de l'année et le nombre d'ovocytes s'étend de 20 000 to 1 327 000 par individu. Les pics de ponte sont observés entre février et avril, ce qui est bien corrélé avec l'évolution du rapport gonado-somatique et inverse de celle du facteur de condition et du rapport hépato-somatique. L'étude histologique révèle que le développement ovarien chez le tacaud est asynchrone, et que la fécondité est probablement déterminée.Peer reviewe

High statistics measurement of the positron fraction in primary cosmic rays of 0.5-500 GeV with the alpha magnetic spectrometer on the international space station

A precision measurement by AMS of the positron fraction in primary cosmic rays in the energy range from 0.5 to 500 GeV based on 10.9 million positron and electron events is presented. This measurement extends the energy range of our previous observation and increases its precision. The new results show, for the first time, that above &sim;200GeV the positron fraction no longer exhibits an increase with energy.</p