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BackgroundIdentifying pre-clinical phases of rheumatoid arthritis (RA) is challenging. Musculoskeletal ultrasound (US) is more sensitive than clinical assessment for the detection of synovitis. US abnormalities have been associated with subsequent joint inflammation in patients with anti-citrullinated peptide antibodies (ACPA) without clinical synovitis (SJ)1.ObjectivesTo identify US abnormalities associated with the recognized phases of RA development2 in individuals at increased risk for RA.MethodsThis is a nested cohort study within an ongoing prospective study of individuals genetically at risk of developing RA, namely first degree relatives of patients with RA (FDR). Individuals without clinical evidence of RA were enrolled, and then followed-up yearly. We included in this analysis all individuals with available ACPA status (anti-CCP 2, 3.0, or 3.1) and US assessment. The US examination was conducted according to the validated SONAR score3 and performed by US trained rheumatologists blinded to clinical and biological data. According to previous publications4, inflammatory activity on US (active US) was defined as a Bmode score ≥9 and at least one synovitis of grade 2 or 3, or a Doppler score ≥2. We used logistic regression to analyze univariable and multivariable associations between US findings and specific phases preceding RA development and other patient characteristics.ResultsA total of 269 FDRs were analyzed, of which 97 (36%) had an active US as defined above. Individuals with an active US tended to be older (years median (IQR): 51 (41–59) vs 47 (35–57), OR: 1.0, 95% CI: 1.0–1.0, p<0.05), with no difference in sex, body mass index and tobacco smoking. In univariable analyses, there was a strong correlation between an active US and the presence of 'unclassified arthritis' (≥1 SJ on physical examination) (OR:2.6, 95% CI:1.4–4.9). No association was demonstrated with genetic risk factors (presence of shared epitope), systemic autoimmunity (ACPA positivity) or self reported symptoms in the absence of arthralgia or SJ (Table 1). In the multivariable analyses, the relation between US and 'unclassified arthritis' remained significant (OR:2.4, 95% CI:1.3–4.5).ConclusionsIn individuals at risk of RA, active US was strongly associated with the presence of “unclassified arthritis”. There was no association between US findings and earlier identified phases of RA development. These data suggest that in individuals at increased risk for RA, without obvious disease, US may identify imminent RA. These findings support the usefulness of US in a screening strategy for imminent RA.ReferencesNam JL et al. Ann Rheum Dis. 2016 Jan 22.Gerlag DM et al. Ann Rheum Dis. 2012 May;71(5):638–41. 3.Zufferey P. Joint Bone Spine 2014;81(3):222–7. 4.Zufferey P et al. Swiss Med Wkly.2013;143.Disclosure of InterestNone declared

BackgroundMany controversies exist about the role of sex hormones and reproductive factors in the development of rheumatoid arthritis (RA). Post-menopause is a period of important hormonal and immunologic changes and has been associated with increased risk of seronegative-RA (1). Earlier age at menopause has been associated with increased risk of RA (2), therefore factors related to menopause may be relevant for the development of preclinical phases of RA.ObjectivesTo study the association between reproductive and menopausal factors and the risk of development systemic autoimmunity associated with RA, in particular of anti-citrullinated protein antibodies (ACPA), in women at increased risk for RA.MethodsThis is a nested cohort study within an ongoing prospective study of individuals genetically at risk of developing RA, namely first degree relatives of patients with RA (FDRs). Individuals without clinical evidence of RA were enrolled, and followed-up yearly with clinical and laboratory assessments. We included all women with available ACPA status (anti-CCP 2, 3.1 or 3.0). Reproductive and menopausal factors were self-reported. We operationally defined perimenopausal women as those with recent menopause (<3 years) or aged between 47 to 53 years with menopause-related symptoms. Total ovulatory years were estimated by substracting the age at menarche from the age at menopause minus one year for every childbirth and the total years of oral contraceptive use as previously described (3). We used logistic regression to analyze univariable and multivariable associations between ACPA-positivity and menopause factors.ResultsOf the 809 FDR women analyzed, 50 (6%) were ACPA-positive and had a median age of 46 (interquartile range (IQR): 34–56) years. Characteristics of FDR women are shown in Table 1. In univariable analysis, older age, ≥1 tender joint on examination, post-menopausal status and total ovulatory years were significantly associated with ACPA positivity. Perimenopausal status tended to be associated with ACPA status (OR:1.8, 95%CI:0.9–3.4), but did not reach significance. Other menopausal factors, such as age at menopause, earlier menopause or surgical menopause were not associated with ACPA positivity. Due to high correlation between age and menopausal status (r=0.73), we included tobacco smoking, post-menopausal status and having ≥1 tender joint on examination in the multivariable adjusted analyses, post-menopausal status and ≥1 tender joint on examination remained independently associated with ACPA positivity.ConclusionsPost-menopausal FDR women have an increased risk of ACPA positivity, suggesting menopausal hormonal changes are associated with the development of ACPAs, which may be linked to previously described increase of pro-inflammatory cytokines during menopause (4).ReferencesBengtsson C, et al. Arthritis Rheumatol 2014;66:S1261.Beydoun HA, et al. Menopause 2013;20:930–5.Costenbader KH, et al 2007; 56(4):1251–62.Kim OY, et al. Age 2012;34:415–2.Disclosure of InterestNone declared

BackgroundIn genetically susceptible individuals, environmental factors induce a pathological activation of the immune system that may eventually lead to systemic autoimmunity and subsequent clinical manifestations. Different risk factors may be relevant for the development of this systemic autoimmunity, representing one of the phases preceding the onset of rheumatoid arthritis (RA) (1).ObjectivesTo identify predictors for the development of systemic autoimmunity associated with RA in individuals genetically at increased risk.MethodsThis is an ongoing prospective cohort study of individuals at increased risk of developing RA, namely first degree relatives of patients with autoimmune diseases (FDRs). Individuals without clinical evidence of RA were enrolled and followed-up yearly. We included all individuals with available anti-citrullinated protein antibodies (ACPA) status (anti-CCP 2, 3.0, or 3.1). We used logistic regression to analyze univariable and multivariable associations between ACPA positivity and putative risk factors or symptoms, including the Connective Tissue Disease Screening Questionnaire (CSQ), 3 or more positive responses represented possible RA (2).ResultsA total of 1064 of FDRs were analyzed, of which 57 (5%) were ACPA-positive. FDRs had a median age of 45 (interquartile range (IQR): 34–56) years, 76% were female, 25% had at least one self-reported episode of joint swelling, however on examination only 12% had ≥1 swollen joint (Table 1). In univariable analyses, ACPA-positivity was associated with older age, female sex, tender joints (self reported, ≥1 on examination and mean count), mean swollen joint count, CSQ score and self-reported symptoms associated with possible RA by CSQ. Other variables such as tobacco smoking, alcohol consumption, obesity or tooth loss were not significantly associated with ACPA status. In women, ACPA-positivity was significantly associated with age (OR: 1.1, 95%CI: 1.0–1.1), but not in men (OR: 1.0, 95%CI: 0.9–1.1). In the multivariable adjusted analysis, older age and self-reported symptoms associated with possible RA by CSQ remained independently associated with ACPA positivity. Female sex and tobacco smoking ever had a strong but not significant association.ConclusionsIn individuals at high risk for RA, the development of ACPAs was associated with older age and self-reported symptoms related with possible RA. We found a trend for an association between female sex and tobacco smoking with ACPA positivity, which did however not reach statistical significance. These findings suggest similar risk factors for the development of ACPAs and for classifiable RA, suggesting that the development of ACPAs is a valid proxy for RA development.ReferencesGerlag DM et al. Ann Rheum Dis. 2012; 71(5): 638–41.Karlson EW, et al. Ann Epidemiol 1995;5:297–302.Disclosure of InterestNone declared

Cristóbal de Virués's La gran Semíramis features characters, images, and ideas that may be interpreted as grotesque. Recognizing this potential in the text, director Diego Chiri integrates visual and conceptual elements of this aesthetic into his 2015 Repertorio Español production of the play. In fact, three different types of grotesque are evident in the text and in Chiri's production, and all of them help to reconcile opposing, apparently contradictory ideas in the work. The ambivalent, simultaneous repulsion and attraction prompted by the abject, as conceived by Julia Kristeva, helps sustain in tension divergent views of the characters. Images and actions are subjected to processes of distortion, transformation, degradation, and parody, in the spirit of Mikhail Bakhtin's grotesque realism. The playwright and director reveal the machinations of power to be grotesque when wielded by vile sovereigns, as defined by Michel Foucault, and sanctioned by weak-minded administrators. An analysis of the Roman chronicles of Semiramis from which Virués draws his action reveals how, contrary to his sources, he has chosen to magnify the alleged controversial aspects of her persona to the extent that they overshadow her heroism. Virués's treatment of material from classical historians Diodorus and Justinus is characterized by the simultaneity of different modes of interpreting and representing the body and sexuality, and suggests that he participates in the processes of distortion and degradation that have typified the production of the Semiramis myth, itself grotesque, throughout the centuries.

Background Diagnosing rheumatoid arthritis (RA) early and identifying pre-clinical RA has become a high-stakes undertaking. In RA patients, musculoskeletal ultrasound (US) is more sensitive than clinical assessment for synovitis detection. Whether US is associated with joint involvement in healthy individuals at increased risk for RA is unknown. Objectives To assess the value of US to detect specific phases leading to the development of RA in a healthy population at increased risk of RA. Methods This study is nested within an ongoing prospective cohort study of healthy first-degree relatives of RA patients (FDRs), who had no established rheumatic disease at inclusion. Data collection included health questionnaires, physical examination and blood tests, including inflammatory markers, HLA-DR genotyping, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP2) levels by ELISA. A standardized US examination was performed according to the OMERACT criteria: synovitis was scored in B-mode and Doppler by a semi-quantitative scale ranging from 0 to 3 on MCPs and PIPs 2 to 5, wrists, olecranon fossa and knees. A composite endpoint of either presence of auto-antibodies (RF-IgM, RF-IgA or anti-CCP2) or at least one swollen joint on physical examination was chosen (group 1). To test if US was independently associated with the primary end point, we used logistic regression, adjusting for potential confounders such as age, sex, body mass index, Caucasian race and smoking. Results One hundred consecutive healthy FDRs were included in this analysis. Baseline characteristics were similar between the two groups except for swollen joints and RF by definition (table 1). Doppler activity was detected significantly more often in group 1 (60%) than in the control group (34%) (p=0.05, adjusted OR: 3.02 (95%CI: 0.82 – 11.1). The mean Doppler score was also significantly higher in group 1: 1.46 compared to 0.62 (p=0.02, adjusted OR: 1.64 (95%CI: 1.01 – 2.66)). However, neither the presence of synovitis grade 2 or 3 on B-mode (47% versus 42%, p=0.76) nor the median B-mode score (6 (IQR: 4 – 9) versus 6 (IQR: 4 – 10), p=0.75) allowed to discriminate the two groups. Conclusions Doppler signal on US was associated with the presence of auto-antibodies or clinical signs of synovitis, thus identifying early signs of arthritis in a population at risk to develop RA. Disclosure of Interest None Declared

Abstract The decays B+ → J/ψπ+π − K+ are studied using a data set corresponding to an integrated luminosity of 9 fb −1 collected with the LHCb detector in proton-proton collisions between 2011 and 2018. Precise measurements of the ratios of branching fractions with the intermediate ψ2(3823), χc1(3872) and ψ(2S) states are reported. The values are B B + → ψ 2 3823 K + × B ψ 2 3823 → J / ψπ + π − B B + → χ c 1 3872 K + × B χ c 1 3872 → J / ψπ + π − = 3.56 ± 0.67 ± 0.11 × 10 − 2 , B B + → ψ 2 3823 K + × B ψ 2 3823 → J / ψπ + π − B B + → ψ 2 S K + × B ψ 2 S → J / ψπ + π − = 1.31 ± 0.25 ± 0.04 × 10 − 3 , B B + → χ c 1 3872 K + × B χ c 1 3872 → J / ψπ + π − B B + → ψ 2 S K + × B ψ 2 S → J / ψπ + π − = 3.69 ± 0.07 ± 0.06 × 10 − 2 , $$ {\\displaystyle \\begin{array}{c}\\frac{{\\mathcal{B}}_{{\\mathrm{B}}^{+}\\to {\\uppsi}_2(3823){\\mathrm{K}}^{+}}\\times {\\mathcal{B}}_{\\uppsi_2(3823)\\to \\mathrm{J}/{\\uppsi \\uppi}^{+}{\\uppi}^{-}}}{{\\mathcal{B}}_{{\\mathrm{B}}^{+}\\to {\\upchi}_{\\mathrm{c}1}(3872){\\mathrm{K}}^{+}}\\times {\\mathcal{B}}_{\\upchi_{\\mathrm{c}1}(3872)\\to \\mathrm{J}/{\\uppsi \\uppi}^{+}{\\uppi}^{-}}}=\\left(3.56\\pm 0.67\\pm 0.11\\right)\\times {10}^{-2},\\\ {}\\frac{{\\mathcal{B}}_{{\\mathrm{B}}^{+}\\to {\\uppsi}_2(3823){\\mathrm{K}}^{+}}\\times {\\mathcal{B}}_{\\uppsi_2(3823)\\to \\mathrm{J}/{\\uppsi \\uppi}^{+}{\\uppi}^{-}}}{{\\mathcal{B}}_{{\\mathrm{B}}^{+}\\to \\uppsi \\left(2\\mathrm{S}\\right){\\mathrm{K}}^{+}}\\times {\\mathcal{B}}_{\\uppsi \\left(2\\mathrm{S}\\right)\\to \\mathrm{J}/{\\uppsi \\uppi}^{+}{\\uppi}^{-}}}=\\left(1.31\\pm 0.25\\pm 0.04\\right)\\times {10}^{-3},\\\ {}\\frac{{\\mathcal{B}}_{\\mathrm{B}+\\to {\\upchi}_{\\mathrm{c}1}(3872){\\mathrm{K}}^{+}}\\times {\\mathcal{B}}_{\\upchi_{\\mathrm{c}1}(3872)\\to \\mathrm{J}/{\\uppsi \\uppi}^{+}{\\uppi}^{-}}}{{\\mathcal{B}}_{{\\mathrm{B}}^{+}\\to \\uppsi \\left(2\\mathrm{S}\\right){\\mathrm{K}}^{+}}\\times {\\mathcal{B}}_{\\uppsi \\left(2\\mathrm{S}\\right)\\to \\mathrm{J}/{\\uppsi \\uppi}^{+}{\\uppi}^{-}}}=\\left(3.69\\pm 0.07\\pm 0.06\\right)\\times {10}^{-2},\\end{array}} $$ where the first uncertainty is statistical and the second is systematic. The decay of B+ → ψ2(3823)K+ with ψ2(3823) → J/ψπ+π − is observed for the first time with a significance of 5.1 standard deviations. The mass differences between the ψ2(3823), χc1(3872) and ψ(2S) states are measured to be m χ c 1 3872 − m ψ 2 3823 = 47.50 ± 0.53 ± 0.13 MeV / c 2 , m ψ 2 3823 − m ψ 2 2 S = 137.98 ± 0.53 ± 0.14 MeV / c 2 , m χ c 1 3872 − m ψ 2 2 S = 185.49 ± 0.06 ± 0.03 MeV / c 2 , $$ {\\displaystyle \\begin{array}{c}{m}_{\\upchi_{\\mathrm{c}1}(3872)}-{m}_{\\uppsi_2(3823)}=47.50\\pm 0.53\\pm 0.13\\;\\mathrm{MeV}/{c}^2,\\\ {}{m}_{\\uppsi_2(3823)}-{m}_{\\uppsi_2\\left(2\\mathrm{S}\\right)}=137.98\\pm 0.53\\pm 0.14\\;\\mathrm{MeV}/{c}^2,\\\ {}{m}_{\\upchi_{\\mathrm{c}1}(3872)}-{m}_{\\uppsi_2\\left(2\\mathrm{S}\\right)}=185.49\\pm 0.06\\pm 0.03\\;\\mathrm{MeV}/{c}^2,\\end{array}} $$ resulting in the most precise determination of the χc1(3872) mass. The width of the ψ2(3823) state is found to be below 5.2 MeV at 90% confidence level. The Breit-Wigner width of the χc1(3872) state is measured to be Γ χ c 1 3872 BW = 0.96 − 0.18 + 0.19 ± 0.21 MeV $$ {\\Gamma}_{\\upchi_{\\mathrm{c}1}(3872)}^{\\mathrm{BW}}={0.96}_{-0.18}^{+0.19}\\pm 0.21\\;\\mathrm{MeV} $$ which is inconsistent with zero by 5.5 standard deviations.

A bstract A measurement of the Ξ cc + + mass is performed using data collected by the LHCb experiment between 2016 and 2018 in pp collisions at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 5 . 6 fb − 1 . The Ξ cc + + candidates are reconstructed via the decay modes Ξ cc + + → Λ c + K − π + π + and Ξ cc + + → Ξ c + π + . The result, 3621 . 55 ± 0 . 23 (stat) ± 0 . 30 (syst) MeV/ c 2 , is the most precise measurement of the Ξ cc + + mass to date.

Using proton-proton collision data, corresponding to an integrated luminosity of 9 fb −1 , collected with the LHCb detector between 2011 and 2018, a new narrow charmonium state, the X(3842) resonance, is observed in the decay modes$$ \\mathrm{X}(3842)\\to {D}^0{\\overline{D}}^0 $$X 3842 → D 0 D ¯ 0 and X(3842) → D + D − . The mass and the natural width of this state are measured to be$$ \\begin{array}{l}{m}_{X(3842)}=3842.71\\pm 0.16\\pm 0.12\\ MeV/{c}^2,\\hfill \\\ {}{\\varGamma}_{X(3842)}=2.79\\pm 0.51\\pm 0.35\\ MeV,\\hfill \\end{array} $$m X 3842 = 3842.71 ± 0.16 ± 0.12 M e V / c 2 , Γ X 3842 = 2.79 ± 0.51 ± 0.35 M e V , where the first uncertainty is statistical and the second is systematic. The observed mass and narrow natural width suggest the interpretation of the new state as the unobserved (spin-3 ψ 3 1 3 D 3 ) charmonium state. In addition, prompt hadroproduction of the ψ (3770) and χ 2 (3930) states is observed for the first time, and the parameters of these states are measured to be$$ \\begin{array}{l}{m}_{\\psi (3770)}=3778.1\\pm 0.7\\pm 0.6\\ MeV/{c}^2,\\hfill \\\ {}{m}_{\\chi_2(3930)}=3921.9\\pm 0.6\\pm 0.2\\ MeV/{c}^2,\\hfill \\\ {}{\\varGamma}_{\\chi_2(3930)}=36.6 \\pm 1.9 \\pm 0.9\\ MeV,\\hfill \\end{array} $$m ψ 3770 = 3778.1 ± 0.7 ± 0.6 M e V / c 2 , m χ 2 3930 = 3921.9 ± 0.6 ± 0.2 M e V / c 2 , Γ χ 2 3930 = 36.6 ± 1.9 ± 0.9 M e V , where the first uncertainty is statistical and the second is systematic.

During 2011 the LHCb experiment at CERN collected 1.0 fb −1 of pp collisions. Due to the large heavy quark production cross-sections, these data provide unprecedented samples of heavy flavoured hadrons. The first results from LHCb have made a significant impact on the flavour physics landscape and have definitively proved the concept of a dedicated experiment in the forward region at a hadron collider. This document discusses the implications of these first measurements on classes of extensions to the Standard Model, bearing in mind the interplay with the results of searches for on-shell production of new particles at ATLAS and CMS. The physics potential of an upgrade to the LHCb detector, which would allow an order of magnitude more data to be collected, is emphasised.