Use of Secukinumab in a Cohort of Erythrodermic Psoriatic Patients: A Pilot Study

Erythrodermic psoriasis (EP) is a dermatological emergency and its treatment with secukinumab is still controversial. Furthermore, no data exist regarding the prognostic value of drug abuse in such a condition. We performed a multi-center, international, retrospective study, enrolling a sample of EP patients (body surface area > 90%) who were treated with secukinumab (300 mg) during the study period from December 2015 to December 2018. Demographics and clinical data were collected. Drug abuses were screened and, specifically, smoking status (packages/year), cannabis use (application/week) and alcoholism-tested with the Alcohol Use Disorders Identification Test (AUDIT)-were assessed. All patients were followed for up to 52 weeks. We enrolled 13 EP patients, nine males, and four females, with a median age of 40 (28-52) years. Patients na\uefve to biologic therapy were 3/13. Regarding drug use, seven patients had a medium-high risk of alcohol addiction, three used cannabis weekly, and seven were smokers with a pack/year index of 295 (190-365). The response rate to secukinumab was 10/13 patients with a median time to clearance of three weeks (1.5-3). No recurrences were registered in the 52-week follow-up and a Psoriasis Area Severity Index (PASI) score of 90 was achieved. The entire cohort of non-responders (n = 3) consumed at least two drugs of abuse (alcohol, smoking or cannabis). Non-responders were switched to ustekinumab and obtained a PASI 100 in 24 weeks. However, given our observed number of patients using various drugs in combination with secukinumab in EP, further studies are needed to ascertain drug abuse prevalence in a larger EP cohort. Secukinumab remains a valid, effective and safe therapeutic option for EP

Seasonal, interannual and decadal variability of tropospheric ozone in the North Atlantic: comparison of UM-UKCA and remote sensing observations for 2005–2018

Tropospheric ozone is an important component of the Earth system as it can affect both climate and air quality. In this work, we use observed tropospheric column ozone derived from the Ozone Monitoring Instrument (OMI) and Microwave Limb Sounder (MLS) OMI-MLS, in addition to OMI ozone retrieved in discrete vertical layers, and compare it to tropospheric ozone from UM-UKCA simulations (which utilize the Unified Model, UM, coupled to UK Chemistry and Aerosol, UKCA). Our aim is to investigate recent changes (2005–2018) in tropospheric ozone in the North Atlantic region, specifically its seasonal, interannual and decadal variability, and to understand what factors are driving such changes. The model exhibits a large positive bias (greater than 5 DU or ∼ 50 %) in the tropical upper troposphere: through sensitivity experiments, time series correlation, and comparison with the Lightning Imaging Sensor and Optical Transient Detector lightning flash dataset, the model positive bias in the tropics is attributed to shortcomings in the convection and lightning parameterizations, which overestimate lightning flashes in the tropics relative to mid-latitudes. Use of OMI data, for which vertical averaging kernels and a priori information are available, suggests that the model negative bias (6–10 DU or ∼ 20 %) at mid-latitudes, relative to OMI-MLS tropospheric column, could be the result of vertical sampling. Ozone in the North Atlantic peaks in spring and early summer, with generally good agreement between the modelled and observed seasonal cycle. Recent trends in tropospheric ozone were investigated: whilst both observational datasets indicate positive trends of ∼ 5 % and ∼ 10 % in North Atlantic ozone, the modelled ozone trends are much closer to zero and have large uncertainties. North Atlantic ozone interannual variability (IAV) in the model was found to be correlated to the IAV of ozone transported to the North Atlantic from the stratosphere (R=0.77) and emission of NOx from lightning in the tropics (R=0.72). The discrepancy between modelled and observed trends for 2005–2018 could be linked to the model underestimating lower stratospheric ozone trends and associated stratosphere to troposphere transport. Modelled tropospheric ozone IAV is driven by IAV of tropical emissions of NOx from lightning and IAV of ozone transport from the stratosphere; however, the modelled and observed IAV differ. To understand the IAV discrepancy we investigated how modelled ozone and its drivers respond to large-scale modes of variability. Using OMI height-resolved data and model idealized tracers, we were able to identify stratospheric transport of ozone into the troposphere as the main driver of the dynamical response of North Atlantic ozone to the Arctic Oscillation (AO) and the North Atlantic Oscillation (NAO). Finally, we found that the modelled ozone IAV is too strongly correlated to the El Niño–Southern Oscillation (ENSO) compared to observed ozone IAV. This is again linked to shortcomings in the lightning flashes parameterization, which underestimates (overestimates) lightning flash production in the tropics during positive (negative) ENSO events

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

OBJECTIVE: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. METHODS: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. RESULTS: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. CONCLUSION: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Desempenho produtivo de porta-enxertos de macieira da série Geneva em solo de replantio

The objective of this work was to identify rootstocks with competitive agronomic potential to substitute those currently used in Southern Brazil for the Galaxy and Fuji Suprema apple scion cultivars cultivated on replanting soils. The experiment was carried out in the municipality of Lebon Regis, in the state of Santa Catarina, Brazil, from the 2009/2010 to the 2014/2015 crop season, in a randomized complete block design, with four replicates. The yield performance of the 'Galaxy' and 'Fuji Suprema' scions grafted on the G.056, G.202, G.213, G.814, G.896, G.969, M.9, and Marubakaido/M.9 rootstocks was evaluated. G.896 and G.814 stood out due to their superior annual and cumulative fruit yields, as well as to their greater yield regularity, although they showed lower ability of dwarfing the scion. The greatest average fruit weight of 'Galaxy' was obtained on G.056 and G.213. For 'Fuji Suprema', G.969 promoted smaller fruits, whereas the other rootstocks did not differ. All the evaluated rootstocks produced less suckers than Marubakaido/M.9 and less burrknots than M.9 and Marubakaido/M.9. In general, on replanting soil conditions, G.202 is promising among dwarfing rootstocks, mainly for 'Fuji Suprema'. G.056, G.814, and G.896 also stand out, and the two first are more specific for 'Fuji Suprema'.O objetivo deste trabalho foi identificar porta-enxertos com potencial agronômico competitivo para substituir os tradicionalmente usados no Sul do Brasil para as cultivares-copa de macieira Galaxy e Fuji Suprema cultivadas em solo de replantio. O experimento foi conduzido em Lebon Regis, no Estado de Santa Catarina, nas safras de 2009/2010 a 2014/2015, em delineamento experimental de blocos ao acaso, com quatro repetições. Avaliou-se o desempenho agronômico das copas 'Galaxy' e 'Fuji Suprema', enxertadas sobre G.056, G.202, G.213, G.814, G.896, G.969, M.9 e Marubakaido/M.9. G.896 e G.814 se destacaram pelas produções de frutos anual e acumulada superiores, bem como pela maior regularidade produtiva, embora tenham apresentado menor capacidade ananizante sobre a copa. As maiores massas médias de frutos de 'Galaxy' foram obtidas sobre G.056 e G.213. Para 'Fuji Suprema', G.969 proporcionou frutos menores, enquanto os demais porta-enxertos não diferiram entre si. Todos os porta-enxertos avaliados rebrotaram menos que Marubakaido/M.9 e produziram menos “burrknots” que M.9 e Marubakaido/M.9. No geral, nas condições de solo de replantio, G.202 mostra ser promissor entre os porta-enxertos ananizantes, principalmente para 'Fuji Suprema'. Destacam-se também G.056, G.814 e G.896, sendo os dois primeiros mais específicos para 'Fuji Suprema'

Search for heavy Majorana or Dirac neutrinos and right-handed W gauge bosons in final states with charged leptons and jets in pp collisions at √s = 13 TeV with the ATLAS detector

A search for heavy right-handed Majorana or Dirac neutrinos NR and heavy right-handed gauge bosons WR is performed in events with energetic electrons or muons, with the same or opposite electric charge, and energetic jets. The search is carried out separately for topologies of clearly separated final-state products (“resolved” channel) and topologies with boosted final states with hadronic and/or leptonic products partially overlapping and reconstructed as a large-radius jet (“boosted” channel). The events are selected from pp collision data at the LHC with an integrated luminosity of 139 fb−1 collected by the ATLAS detector at √s = 13 TeV. No significant deviations from the Standard Model predictions are observed. The results are interpreted within the theoretical framework of a left-right symmetric model, and lower limits are set on masses in the heavy righthanded WR boson and NR plane. The excluded region extends to about m(WR) = 6.4 TeV for both Majorana and Dirac NR neutrinos at m(NR) < 1 TeV. NR with masses of less than 3.5 (3.6) TeV are excluded in the electron (muon) channel at m(WR) = 4.8 TeV for the Majorana neutrinos, and limits of m(NR) up to 3.6 TeV for m(WR) = 5.2 (5.0) TeV in the electron (muon) channel are set for the Dirac neutrinos. These constitute the most stringent exclusion limits to date for the model considered

Observation of four-top-quark production in the multilepton final state with the ATLAS detector

This paper presents the observation of four-top-quark (tt¯tt¯) production in proton-proton collisions at the LHC. The analysis is performed using an integrated luminosity of 140 fb−1 at a centre-of-mass energy of 13 TeV collected using the ATLAS detector. Events containing two leptons with the same electric charge or at least three leptons (electrons or muons) are selected. Event kinematics are used to separate signal from background through a multivariate discriminant, and dedicated control regions are used to constrain the dominant backgrounds. The observed (expected) significance of the measured tt¯tt¯ signal with respect to the standard model (SM) background-only hypothesis is 6.1 (4.3) standard deviations. The tt¯tt¯ production cross section is measured to be 22.5+6.6−5.5 fb, consistent with the SM prediction of 12.0±2.4 fb within 1.8 standard deviations. Data are also used to set limits on the three-top-quark production cross section, being an irreducible background not measured previously, and to constrain the top-Higgs Yukawa coupling and effective field theory operator coefficients that affect tt¯tt¯ production

Search for single production of vector-like T quarks decaying into Ht or Zt in pp collisions at s√ = 13 TeV with the ATLAS detector

This paper describes a search for the single production of an up-type vector-like quark (T) decaying as T → Ht or T → Zt. The search utilises a dataset of pp collisions at s√ = 13 TeV collected with the ATLAS detector during the 2015–2018 data-taking period of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Data are analysed in final states containing a single lepton with multiple jets and b-jets. The presence of boosted heavy resonances in the event is exploited to discriminate the signal from the Standard Model background. No significant excess above the Standard Model expectation is observed, and 95% CL upper limits are set on the production cross section of T quarks in different decay channels. The results are interpreted in several benchmark scenarios to set limits on the mass and universal coupling strength (κ) of the vector-like quark. For singlet T quarks, κ values above 0.53 are excluded for all masses below 2.3 TeV. At a mass of 1.6 TeV, κ values as low as 0.35 are excluded. For T quarks in the doublet scenario, where the production cross section is much lower, κ values above 0.72 are excluded for all masses below 1.7 TeV, and this exclusion is extended to κ above 0.55 for low masses around 1.0 TeV

Search for excited τ-leptons and leptoquarks in the final state with τ-leptons and jets in pp collisions at s√ = 13 TeV with the ATLAS detector

A search is reported for excited τ-leptons and leptoquarks in events with two hadronically decaying τ-leptons and two or more jets. The search uses proton-proton (pp) collision data at s√ = 13 TeV recorded by the ATLAS experiment during the Run 2 of the Large Hadron Collider in 2015–2018. The total integrated luminosity is 139 fb−1. The excited τ-lepton is assumed to be produced and to decay via a four-fermion contact interaction into an ordinary τ-lepton and a quark-antiquark pair. The leptoquarks are assumed to be produced in pairs via the strong interaction, and each leptoquark is assumed to couple to a charm or lighter quark and a τ-lepton. No excess over the background prediction is observed. Excited τ-leptons with masses below 2.8 TeV are excluded at 95% CL in scenarios with the contact interaction scale Λ set to 10 TeV. At the extreme limit of model validity where Λ is set equal to the excited τ-lepton mass, excited τ-leptons with masses below 4.6 TeV are excluded. Leptoquarks with masses below 1.3 TeV are excluded at 95% CL if their branching ratio to a charm quark and a τ-lepton equals 1. The analysis does not exploit flavour-tagging in the signal region

Measurement of the cross-sections of the electroweak and total production of a Zγ pair in association with two jets in pp collisions at √s = 13 TeV with the ATLAS detector

This Letter presents the measurement of the fiducial and differential cross-sections of the electroweak production of a Zγ pair in association with two jets. The analysis uses 140 fb−1 of LHC proton–proton collision data taken at √s = 13 TeV recorded by the ATLAS detector during the years 2015–2018. Events with a Z boson candidate decaying into either an e+e− or μ+μ− pair, a photon and two jets are selected. The electroweak component is extracted by requiring a large dijet invariant mass and by using the information about the centrality of the system and is measured with an observed and expected significance well above five standard deviations. The fiducial pp → Zγ jj cross-section for the electroweak production is measured to be 3.6 ± 0.5 fb. The total fiducial cross-section that also includes contributions where the jets arise from strong interactions is measured to be 16.8+2.0 −1.8 fb. The results are consistent with the Standard Model predictions. Differential cross-sections are also measured using the same events and are compared with parton-shower Monte Carlo simulations. Good agreement is observed between data and predictions