A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients

Introduction: Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited. Methods: We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non-immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, we quantified the ex vivo production of phospholipase A2 receptor (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, Strasberg, Germany]) and assessed the circulating antibody repertoire by phage immunoprecipitation sequencing (PhIP-Seq). Results: After adjusting for multiple testing, plasma cells and regulatory B cells (BREG) were significantly higher (P < 0.05) in MN patients compared with both control groups. The percentages of circulating plasma cells correlated with serum anti-PLA2R antibody levels (P = 0.042) and were associated with disease activity. Ex vivo-expanded PLA2R-specific IgG-producing plasmablasts generated from circulating PLA2R-specific memory B cells (mBCs) correlated with serum anti-PLA2R IgG antibodies (P < 0.001) in MN patients. Tumor necrosis factor-alpha (TNF-alpha) was the only significantly increased cytokine in MN patients (P < 0.05), whereas there was no significant difference across study groups in the autoantibody and antiviral antibody repertoire. Conclusion: This extensive phenotypic and functional immune characterization shows that autoreactive plasma cells are present in the circulation of MN patients, providing a new therapeutic target and a candidate biomarker of disease activity

Deficits in narrative abilities in child British Sign Language users with specific language impairment

This study details the first ever investigation of narrative skills in a group of 17 deaf signing children who have been diagnosed with disorders in their British Sign Language development compared with a control group of 17 deaf child signers matched for age, gender, education, quantity, and quality of language exposure and non-verbal intelligence. Children were asked to generate a narrative based on events in a language free video. Narratives were analysed for global structure, information content and local level grammatical devices, especially verb morphology. The language-impaired group produced shorter, less structured and grammatically simpler narratives than controls, with verb morphology particularly impaired. Despite major differences in how sign and spoken languages are articulated, narrative is shown to be a reliable marker of language impairment across the modality boundaries

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

Resounding meaning: a PERMA wellbeing profile of classical musicians

While music has been linked with enhanced wellbeing across a wide variety of contexts, the professional pursuit of a music career is frequently associated with poor psychological health. Most research has focused on assessing negative functioning, and to date, few studies have attempted to profile musicians’ wellbeing using a positive framework. This study aimed to generate a profile that represents indicators of optimal functioning among classical musicians. The PERMA model, which reconciles hedonic and eudaimonic wellbeing, was adopted and its five elements assessed with a sample of professional classical musicians: Positive Emotion, Engagement, Relationships, Meaning and Accomplishment. 601 participants (298 women, 303 men) engaged in careers as orchestral (n = 236), solo (n = 158), chamber (n = 112), and choral musicians (n = 36), as well as composers (n = 30) and conductors (n = 29), answered the PERMA-Profiler, a self-report questionnaire built to assess the five components of PERMA. Results point to high scores across all dimensions, with Meaning emerging as the highest rated dimension. Musicians scored significantly higher than general population indicators on Positive Emotion, Relationships and Meaning. When wellbeing is assessed as positive functioning and not the absence of illbeing, musicians show promising profiles. The reconciliation between these findings and the previous body of research pointing to the music profession as highly challenging for healthy psychological functioning is discussed. *** For a video summary of this article please see http://researchonline.rcm.ac.uk/id/eprint/1804/ **

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at root s = 8 TeV with the ATLAS detector (vol 75, 299, 2015)

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √s=8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT&gt;120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between EmissT&gt;150 GeV and EmissT&gt;700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presented

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements