Biologic Sequencing in Systemic Lupus Erythematosus: After Secondary Non-response to Rituximab, Switching to Humanised Anti-CD20 Agent Is More Effective Than Belimumab

Background: Rituximab is commonly used for systemic lupus erythematosus (SLE) but secondary non-depletion and non-response (2NDNR) associated with anti-drug antibodies is a notable problem with repeat rituximab cycles. Other B cell-targeted therapies include other anti-CD20 monoclonal antibodies or belimumab. Objective: To compare efficacy of switching to alternative anti-CD20 agents vs. belimumab in SLE patients with 2NDNR to rituximab. Methods: One hundred and twenty five patients received rituximab and had evaluable data. 77/125 received repeat rituximab cycles. Of these, 14/77 (18%) had 2NDNR. 8/14 patients were switched to belimumab (CD20-to-belimumab group) and 6/14 patients were switched to an alternative humanised anti-CD20 agent (CD20-to-CD20 group, ocrelizumab n = 3, ofatumumab n = 2, obinutuzumab n = 1). Efficacy was assessed using the BILAG-2004, SLEDAI-2K, SRI-4, and daily prednisolone requirement at baseline and 6 months. Results: In the CD20-to-belimumab group, only one patient achieved an SRI-4 and 2/8 patients had new/worsening BILAG-2004 grade A for lupus nephritis. There was no improvement in SLEDAI-2K; median (IQR) was 11.0 (9.5–14.8) at baseline and 10 (9.5–15.5) at 6 months. Median (IQR) prednisolone dose increased from 7.5 mg (4.4–12.5) to 10 mg (6.3–10). In the CD20-to-CD20 group, all 6 patients achieved an SRI-4. Median (IQR) SLEDAI-2K improved from 16.0 (10.3–24.0) at baseline to 5.0 (2.5–6.0) at 6 months. Median (IQR) prednisolone dose decreased from 15 mg (15–15) to 10.5 mg (5.3–15.0). Conclusion: This is the first assessment of belimumab’s efficacy in a post-rituximab population. Our data suggests that patients with 2NDNR to rituximab, which constituted 11% of all patients initiated on this drug, should be switched within the same biologic class to another anti-CD20 agent

Measuring the perception of quality physical education in Latin American professionals

Um plano instável para o desenvolvimento de currículos e questões de apoio na educac¸ão física (PE) criou confusão entre os profissionais. O objetivo desta pesquisa é investigar os fatores percebidos como importantes no desenvolvimento da educac¸ão física de qualidade (QPE) por profissionais de países da América Latina (AL). Um questionário composto por 24 itens com base no QPE foi respondido por 468 profissionais coletados em 6 cidades da América Latina. Uma análise fatorial exploratória dos 24 itens usando extrac¸ão ML e rotac¸ão obliminar direta foram aplicados, e os 17 itens retidos foram agrupados em uma soluc¸ão de três fatores denominada Elementos de Desenvolvimento e Suporte para QPE na Escola (DSFQPE) ( = 0,935), Valor essencial do QPE (CVPE) ( = 0,890) e Arranjo Curricular das Atividades Físicas (CAPA) ( = 0,850). Os itens retidos indicaram propriedades excelentes e o referencial básico percebido pelos profissionais de EF em países da América Latina como importante na investigac¸ão do PEQ. © 2018 Colegio ´ Brasileiro de Ciencias ˆ do Esporte. Publicado por Elsevier Editora Ltda. Este e´ um artigo Open Access sob uma licenc¸a CC BY-NC-N

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Ten-item Internet Gaming Disorder Test (IGDT-10): measurement invariance and cross-cultural validation across seven language-based samples

Background and aims: The Ten-Item Internet Gaming Disorder Test (IGDT-10) is a short screening instrument developed to assess Internet gaming disorder (IGD) as proposed in the DSM-5, adopting a concise, clear, and consistent item-wording. According to initial studies conducted in 2014, the instrument showed promising psychometric characteristics. The present study tested the psychometric properties, including language and gender invariance, in a large international sample of online gamers. Methods: Data were collected from 7,193 participants comprising Hungarian (n=3,924), Iranian (n=791), English-speaking (n=754), French-speaking (n=421), Norwegian (n=195), Czech (n=496), and Peruvian (n=612) online gamers via gamingrelated websites and gaming-related social-networking-site groups. Results: A unidimensional factor structure provided a good fit to the data in all language-based samples. In addition, results indicated both language and gender invariance on the level of scalar invariance. Criterion and construct validity of the IGDT-10 was supported by its strong association with the Problematic Online Gaming Questionnaire and moderate association with weekly gaming time, psychopathological symptoms, and impulsivity. The proportions of each sample that met the cut-off score on the IGDT-10 varied between 1.61% and 4.48% in the individual samples, except for the Peruvian sample (13.44%). Conclusions: The IGDT-10 shows robust psychometric properties and appears suitable for conducting cross-cultural and gender comparisons across seven languages

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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 > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 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 presente

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques