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This study presented the first light curve analysis of the OP Boo and V0511 Cam binary stars, which was conducted in the frame of the Binary Systems of South and North (BSN) Project. Photometric ground-based observations were conducted with standard filters at two observatories in the Czech Republic. We computed a new ephemeris for each of the systems using our extracted times of minima, TESS data, and additional literature. Linear fits for O-C diagrams of both systems were considered using the Markov Chain Monte Carlo (MCMC) method. The light curves were analyzed using the Wilson-Devinney (WD) binary code combined with the Monte Carlo (MC) simulation. The light curve solutions of both target systems required a cold starspot. The absolute parameters of the systems were calculated by using a P-M parameter relationship. The positions of the systems were also depicted on the Hertzsprung-Russell (HR), P-L, logMtot-logJ0, and T-M diagrams. The second component in both systems is determined to be a more massive and hotter star. Therefore, it can be concluded that both systems are W-type contact binary systems.

We present the first release of the Czech Variable star catalogue that currently contains 1228 stars whose variability was discovered by 60 Czech observers. The catalogue contains confirmed variable stars of various types, but also candidates. We give precise coordinates, cross identification with other catalogues, information about constellation, variability type, brightness, light elements, name of the discoverer and year of discovery. In eighty-eight percent of stars the variability type is estimated, for more than 60 % of the stars the light ephemerides are given.

In order to bring quantum networks into the real world, we would like to determine the requirements of quantum network protocols including the underlying quantum hardware. Because detailed architecture proposals are generally too complex for mathematical analysis, it is natural to employ numerical simulation. Here we introduce NetSquid, the NETwork Simulator for QUantum Information using Discrete events, a discrete-event based platform for simulating all aspects of quantum networks and modular quantum computing systems, ranging from the physical layer and its control plane up to the application level. We study several use cases to showcase NetSquid’s power, including detailed physical layer simulations of repeater chains based on nitrogen vacancy centres in diamond as well as atomic ensembles. We also study the control plane of a quantum switch beyond its analytically known regime, and showcase NetSquid’s ability to investigate large networks by simulating entanglement distribution over a chain of up to one thousand nodes. Implementing large-scale quantum networks is one of the challenges at the core of quantum communication. Here, the authors present NetSquid, a quantum network simulator that allows studying how such networks can be built, including physical hardware modelling, modularity, scalability, and examples.

ObjectivesThe Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint (SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation.MethodsThe literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC).ResultsNo revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97).ConclusionThe ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.

ObjectivesTo review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA).MethodsThe Assessment in SpondyloArthritis International Society (ASAS) MRI working group conducted a consensus exercise to review the definition of a positive MRI for inclusion in the ASAS classification criteria of axial SpA. Existing definitions and new data relevant to the MRI diagnosis and classification of sacroiliitis and spondylitis in axial SpA, published since the ASAS definition first appeared in print in 2009, were reviewed and discussed. The precise wording of the existing definition was examined in detail and the data and a draft proposal were presented to and voted on by the ASAS membership.ResultsThe clear presence of bone marrow oedema on MRI in subchondral bone is still considered to be the defining observation that determines the presence of active sacroiliitis. Structural damage lesions seen on MRI may contribute to a decision by the observer that inflammatory lesions are genuinely due to SpA but are not required to meet the definition. The existing definition was clarified adding guidelines and images to assist in the application of the definition.ConclusionThe definition of a positive MRI for classification of axial SpA should continue to primarily depend on the imaging features of ‘active sacroiliitis’ until more data are available regarding MRI features of structural damage in the sacroiliac joint and MRI features in the spine and their utility when used for classification purposes.

Treatment options for recurrent glioblastoma are scarce, with second-line chemotherapy showing only modest activity against the tumour. Despite the absence of well controlled trials, bevacizumab is widely used in the treatment of recurrent glioblastoma. Nonetheless, whether the high response rates reported after treatment with this drug translate into an overall survival benefit remains unclear. We report the results of the first randomised controlled phase 2 trial of bevacizumab in recurrent glioblastoma. The BELOB trial was an open-label, three-group, multicentre phase 2 study undertaken in 14 hospitals in the Netherlands. Adult patients (≥18 years of age) with a first recurrence of a glioblastoma after temozolomide chemoradiotherapy were randomly allocated by a web-based program to treatment with oral lomustine 110 mg/m2 once every 6 weeks, intravenous bevacizumab 10 mg/kg once every 2 weeks, or combination treatment with lomustine 110 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Randomisation of patients was stratified with a minimisation procedure, in which the stratification factors were centre, Eastern Cooperative Oncology Group performance status, and age. The primary outcome was overall survival at 9 months, analysed by intention to treat. A safety analysis was planned after the first ten patients completed two cycles of 6 weeks in the combination treatment group. This trial is registered with the Nederlands Trial Register (www.trialregister.nl, number NTR1929). Between Dec 11, 2009, and Nov 10, 2011, 153 patients were enrolled. The preplanned safety analysis was done after eight patients had been treated, because of haematological adverse events (three patients had grade 3 thrombocytopenia and two had grade 4 thrombocytopenia) which reduced bevacizumab dose intensity; the lomustine dose in the combination treatment group was thereafter reduced to 90 mg/m2. Thus, in addition to the eight patients who were randomly assigned to receive bevacizumab plus lomustine 110 mg/m2, 51 patients were assigned to receive bevacizumab alone, 47 to receive lomustine alone, and 47 to receive bevacizumab plus lomustine 90 mg/m2. Of these patients, 50 in the bevacizumab alone group, 46 in the lomustine alone group, and 44 in the bevacizumab and lomustine 90 mg/m2 group were eligible for analyses. 9-month overall survival was 43% (95% CI 29–57) in the lomustine group, 38% (25–51) in the bevacizumab group, 59% (43–72) in the bevacizumab and lomustine 90 mg/m2 group, 87% (39–98) in the bevacizumab and lomustine 110 mg/m2 group, and 63% (49–75) for the combined bevacizumab and lomustine groups. After the reduction in lomustine dose in the combination group, the combined treatment was well tolerated. The most frequent grade 3 or worse toxicities were hypertension (13 [26%] of 50 patients in the bevacizumab group, three [7%] of 46 in the lomustine group, and 11 [25%] of 44 in the bevacizumab and lomustine 90 mg/m2 group), fatigue (two [4%], four [9%], and eight [18%]), and infections (three [6%], two [4%], and five [11%]). At the time of this analysis, 144/148 (97%) of patients had died and three (2%) were still on treatment. The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies. However, the results in the bevacizumab alone group do not justify further studies of this treatment. Roche Nederland and KWF Kankerbestrijding.

Background: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research. Design: Prospective, multicenter, multinational, cross-sectional study. Methods and analyses: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information. Ethics: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885.

The JAK pathway is a potential therapeutic target in ankylosing spondylitis. This study assessed the efficacy and safety of upadacitinib, a selective JAK1 inhibitor, in patients with ankylosing spondylitis. This multicentre, randomised, double-blind, placebo-controlled, two-period, parallel-group, phase 2/3 study, SELECT-AXIS 1, enrolled adults in 62 sites in 20 countries. Eligible patients had active ankylosing spondylitis, fulfilled modified New York criteria, were previously untreated with biological disease-modifying antirheumatic drugs, and had inadequate response to at least two or intolerance or contraindication to non-steroidal anti-inflammatory drugs. Patients were randomly assigned 1:1 using interactive response technology to take oral upadacitinib 15 mg once daily or oral placebo for the 14-week period 1; only period 1 data are reported here. The primary endpoint was the composite outcome measure of the Assessment of SpondyloArthritis international Society 40 response at week 14. Analyses were done in the full analysis set of patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03178487. Between Nov 30, 2017, and Oct 15, 2018, 187 patients were randomly assigned to upadacitinib 15 mg (93 patients) or to placebo (94 patients), and 178 (95%) patients (89 in the upadacitinib group and 89 in the placebo group) completed period 1 on study drug (by the completion date of Jan 21, 2019). Significantly more patients had an Assessment of SpondyloArthritis international Society 40 response in the upadacitinib group versus in the placebo group at week 14 (48 [52%] of 93 patients vs 24 [26%] of 94 patients; p=0·0003; treatment difference 26% [95% CI 13–40]). Adverse events were reported in 58 (62%) of 93 patients in the upadacitinib group versus 52 (55%) of 94 in the placebo group. The most common adverse event in the upadacitinib group was increased creatine phosphokinase (eight [9%] of 93 patients in the upadacitinib group vs two [2%] of 94 patients with placebo). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported; one serious adverse event was reported in each group. Upadacitinib 15 mg was efficacious and well tolerated in patients with active ankylosing spondylitis who had an inadequate response or contraindication to non-steroidal anti-inflammatory drugs. These data support the further investigation of upadacitinib for the treatment of axial spondyloarthritis. AbbVie.

Monocytes and neutrophils from the myeloid lineage contribute to multiple sclerosis (MS), but the dynamics of myelopoiesis during MS are unclear. Here we uncover a disease stage-specific relationship between lifestyle, myelopoiesis and neuroinflammation. In mice with relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE), myelopoiesis in the femur, vertebrae and spleen is elevated prior to disease onset and during remission, preceding the peaks of clinical disability and neuroinflammation. In progressive EAE (P-EAE), vertebral myelopoiesis rises steadily throughout disease, while femur and splenic myelopoiesis is elevated early before waning later during disease height. In parallel, sleep disruption or hyperlipidemia and cardiometabolic syndrome augment M-CSF generation and multi-organ myelopoiesis to worsen P-EAE clinical symptoms, neuroinflammation, and spinal cord demyelination, with M-CSF blockade abrogating these symptoms. Lastly, results from a previous trial show that Mediterranean diet restrains myelopoietic activity and myeloid lineage progenitor skewing and improves clinical symptomology of MS. Together, our data suggest that myelopoiesis in MS is dynamic and dependent on disease stage and location, and that lifestyle factors modulate disease by influencing M-CSF-mediated myelopoiesis. Myeloid cells contribute to the etiology of multiple sclerosis (MS), but the dynamics of myelopoiesis during disease progression is still unclear. Here the authors show, in both mouse models and clinical data, that myelopoiesis is differentially regulated via M-CSF modulation in different organs at distinct stages of MS, with diet and lifestyle being potential modifiers.

The placental thickness (PTh) is an ultrasonographic measurement commonly used to assess the placenta. The study aimed to determine selected factors influencing PTh in 2D prenatal ultrasonographic examination. It might have a special value in difficult cases for interpretation when PTh is above or below the reference values. In this retrospective study, we analysed the results of foetal ECHO examination of 2833 foetuses performed between June 2016 and December 2019 in our single unit. 596 healthy foetuses older than 12 weeks of gestation from singleton pregnancies were enrolled in the study. The following parameters were used in the further analysis: placental implantation site, gestational age according to the last menstrual period (LMP) and foetal biometry (FB); maternal weight, height, and body mass index (BMI) at the time of examination; and PTh. PTh was affected by its location: posterior 33 mm vs. anterior 30 mm ( < 0.001). Moreover, its thickness significantly correlated with gestational age according to FB ( = 0.386, < 0.001), LMP ( = 0.369, < 0.001), maternal weight ( = 0.192, < 0.001), height ( = 0.125, = 0.002), and BMI ( = 0.147, < 0.001), but not with maternal age ( = 0.050, = 0.219). A linear regression model based on these data explained the 16.38% variability of the tested subjects ( < 0.001). Our observations suggest that maternal weight correlated more strongly with PTh than maternal BMI. For PTh evaluation, it is important to pay attention to the placental implantation site - the posterior placenta was thicker than the anterior placenta. Moreover, PTh variability remains largely unknown; therefore, further research in this field is needed.