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CONCLUSION CPG should aid, but not replace, the health professional's clinical judgment in daily clinical patient management. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email [email protected] and deposition of tau in the brain characterizes frontotemporal dementia and Alzheimer's disease. Disease-associated mutations in the tau-encoding MAPT gene have enabled the generation of transgenic mouse models that recapitulate aspects of human neurodegenerative diseases, including tau hyperphosphorylation and neurofibrillary tangle formation. Here, we characterized the effects of transgenic P301S mutant human tau expression on neuronal network function in the murine hippocampus. Onset of progressive spatial learning deficits in P301S tau transgenic TAU58/2 mice were paralleled by long-term potentiation deficits and neuronal network aberrations during electrophysiological and EEG recordings. Gene-expression profiling just prior to onset of apparent deficits in TAU58/2 mice revealed a signature of immediate early genes that is consistent with neuronal network hypersynchronicity. We found that the increased immediate early gene activity was confined to neurons harbouring tau pathology, providing a cellular link between aberrant tau and network dysfunction. Taken together, our data suggest that tau pathology drives neuronal network dysfunction through hyperexcitation of individual, pathology-harbouring neurons, thereby contributing to memory deficits. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email [email protected] In SLE, heterogeneous clinical expression and activity may reflect diverse pathogenic and/or effector mechanisms. We investigated SLE heterogeneity by assessing the expression of three gene sets representative of type I IFN (IFN-I), polymorphonuclear neutrophil (PMN) and plasmablast (PB) signatures in a well-characterized, multidisciplinary cohort of SLE patients. We further assessed whether individual gene products could be representative of these three signatures. METHODS Whole blood, serum and clinical data were obtained from 140 SLE individuals. Gene expression was assessed by NanoString technology, using a panel of 37 probes to compute six IFN-I, one PMN and one PB scores. Protein levels were measured by ELISA. RESULTS Depending on the score, 45-50% of SLE individuals showed high IFN-I gene expression. All six IFN-I scores were significantly associated with active skin involvement, and two of six were associated with arthritis. IFN-induced Mx1 protein (MX1) level was correlated with IFN-I score (P less then 0.0001) and associated with a similar clinical phenotype. In all, 25% of SLE individuals showed high PMN gene expression, associated with SLE fever, serositis, leukopoenia and glucocorticoid use. PB gene expression was highly affected by immunosuppressant agents, with no association with SLE features. Combined IFN-I and PMN gene scores were significantly associated with high disease activity and outperformed anti-dsDNA and anti-C1q autoantibody and complement levels for predicting SLE activity. CONCLUSION IFN-I and PMN gene scores segregate with distinct SLE clinical features, and their combination may identify high disease activity. click here MX1 protein level performed similar to IFN-I gene expression. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email [email protected] The aims of this study were to identify homogeneous subgroups of knee and/or hip OA patients with distinct trajectories of the combination of pain and physical function (PF) over time and to determine the baseline factors associated with these trajectories. METHODS We used data from the Knee and Hip Osteoarthritis Long-term Assessment (KHOALA) cohort, a French population-based cohort of 878 patients with symptomatic knee and/or hip OA. Pain and PF were measured annually over 5 years with the Medical Outcomes Study Short Form 36 questionnaire. First, trajectory models were estimated with varying numbers of groups for each of the outcomes separately then fitted into a multi-trajectory model. We used multinomial logistic regression to determine the baseline characteristics associated with each trajectory. RESULTS Univariate four-class models were identified as most appropriate for pain and PF. Comparison of separate trajectories showed that 41% of patients included in the severe functional limitations trajectory did not belong to the more severe pain trajectory (Cramér's V statistic = 0.45). Group-based multi-trajectory modelling revealed four distinct trajectories of pain and PF. On multivariate analyses, female sex, older age, high Kellgren grade, low physical activity intensity, low psychosocial distress score (high distress) and low vitality score were associated with the more severe symptoms trajectory. CONCLUSION Over 5 years, we identified four distinct trajectories combining pain and PF. Management of weight, fatigue and psychosocial distress and the practice of physical activity seem important to maintain function and limit pain in patients with lower-limb OA. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email [email protected] In RA, Patient Acceptable Symptom State assesses disease from the patient's perspective, which does not correspond either to disease remission or to full control of disease impact. This study aims to explore the properties of a novel multilevel Patient Experienced Symptom State (PESS). METHODS This was a cross-sectional analysis of two datasets of patients with RA. PESS was assessed through the question 'Consider how your RA has affected you. If you remain in the coming months as you have been the last week, how would you rate your condition?', with five levels (from 'very bad' to 'very good'). Construct validity of PESS was assessed against validated disease activity [DAS28, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)] and impact measures [RA Impact of Disease (RAID) and modified HAQ]. Multiple pairwise comparisons between groups and receiver-operating characteristic curves with Youden Index were performed. RESULTS A total of 1407 patients [74% female, mean (s.