Sex differences in axial spondyloarthritis: data from a Portuguese spondyloarthritis cohort

Background: Axial spondyloarthritis (axSpA), particularly ankylosing spondylitis was historically considered a male’s disease and has been under-recognized in women. Emerging evidence reveals sex differences in pathophysiology, disease presentation and therapeutic efficacy. Objective: To identify differences between sexes in a Portuguese cohort of patients with axSpA regarding clinical manifestations, disease activity, functional capacity, patient related outcomes and presence of sacroiliitis on x-ray or magnetic resonance imaging. Methods: Patients with ≥18 years fulfilling the ASAS- Assessment of Spondyloarthritis International Society classification criteria for axSpA registered in the electronic Rheumatic Diseases Portuguese Register (Reuma.pt) were included in this multicentric cross-sectional study. Sociodemographic data, clinical features and imaging were collected from the first record in Reuma.pt. These variables were compared between sexes using Mann-Whitney test and Chi-Square test. Variables with a significant association with variable sex were considered in the multiple variable analysis to adjust the sex effect on the outcome variables. Statistical analysis was performed with R version 4.0.2 and p<0.05 was considered statistically significant. Results: A total of 1995 patients were included, 1114 (55.9%) men and 881 (44.1%) women. Men had an earlier disease onset (25.1 vs 28.4, p<0.001), were younger at diagnosis (26.9 vs 30.4, p<0.001) and were more frequently smokers (32.1% vs 15.7%, p<0.001). Comparing to women, men had worse Bath Ankylosing Spondylitis Metrological Index scores (4.0 vs 3.4, p<0.001), higher levels of C-Reactive Protein (10.5 vs 6.9 mg/L, p<0.001) and were more often Human Leukocyte Antigen-B27 positive (67.8% vs 54%, p<0.001). In contrast, women more frequently had inflammatory bowel disease (8.8% vs 4.9%, p=0.004), higher levels of erythrocyte sedimentation rate (25.0 vs 21.0mm/h, p=0.003) and worse patient-related outcomes- Bath Ankylosing Spondylitis Disease Activity Index (5.7 vs 4.5, p<0.001), Patient Global Assessment (60.0 vs 50.0, p<0.001) and fatigue (6.2 vs 5.0, p<0.001). Discussion: In this large multicentric study from a Portuguese axSpA cohort, we confirmed sex differences in patients with axSpA. This work brings awareness to these differences, resulting in less underdiagnosis and misdiagnosis, optimizing treatment strategies, and improving outcomes in axSpA.publishe

Preoperative evaluation of pulmonary artery morphology and pulmonary circulation in neonates with pulmonary atresia - usefulness of MR angiography in clinical routine

BACKGROUND: To explore the role of contrast-enhanced magnetic resonance angiography (CE-MRA) in clinical routine for evaluating neonates with pulmonary atresia (PA) and to describe their pulmonary artery morphology and blood supply.CE-MRA studies of 15 neonates with PA (12 female; median weight: 2900 g) were retrospectively evaluated by two radiologists in consensus. Each study was judged to be either diagnostic or non-diagnostic depending on the potential to evaluate pulmonary artery morphology and pulmonary blood supply. In those cases where surgery or conventional angiocardiography was performed results were compared. RESULTS: CE-MRA was considered diagnostic in 87%. Pulmonary artery morphology was classified as "confluent with (n = 1) and without (n = 1) main pulmonary artery", "non-confluent" (n = 6) or "absent" (n = 7). Source of pulmonary blood supply was "a persistent arterial duct" (n = 12), "a direct" (n = 22) or "indirect (n = 9) aortopulmonary collateral artery (APCA)" or "an APCA from the ascending aorta" (n = 2). In no patient were there any additional findings at surgery or conventional angiocardiography which would have changed the therapeutic or surgical approach. CONCLUSIONS: CE-MRA is a useful diagnostic tool for the preoperative evaluation of the morphology of pulmonary arteries and blood supply in neonates with PA. In most cases diagnostic cardiac catheterization can be avoided

Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma

Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.

BACKGROUND: Germline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers. METHODS: A retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses. RESULTS: Tumour risks analysis provided novel penetrance estimates and genotype-phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%). CONCLUSIONS: Overall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype-tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers

Measurement of the Spectroscopy of Orbitally Excited B Mesons at LEP

We measure the masses, decay widths and relative production rate of orbitally excited B mesons using 1.25 million hadronic Z decays recorded by the L3 detector. B-meson candidates are inclusively reconstructed and combined with charged pions produced at the primary event vertex. An excess of events above the expected background in the B\pi mass spectrum in the region 5.6-5.8 GeV is interpreted as resulting from the decay B_u,d^** -> B^(*)\pi, where B_u,d^** denotes a mixture of l=1 B-meson states containing a u or a d quark. A fit to the mass spectrum yields the masses and decay widths of the B_1^* and B_2^* spin states, as well as the branching fraction for the combination of l=1 states. In addition, evidence is presented for the existence of an excited B-meson state or mixture of states in the region 5.9-6.0 GeV

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN