Graphie: A network-based visual interface for the UK's primary legislation [version 1; peer review: 2 approved]

Background: legislation.gov.uk is a platform that enables users to explore and navigate the many sections of the UK’s legal corpus through its well-designed searching and browsing features. However, there is room for improvement as it lacks the ability to easily move between related sections or Acts and only presents a text-only rendering of provisions. With Graphie, our novel navigational tool (graphie.quantlaw.co.uk), we aim to address this limitation by presenting alternative visualizations of legal documents using both text and graphs. Methods: The building block of Graphie is Sofia, an offline data pipeline designed to support different data visualizations by parsing and modelling data provided by legislation.gov.uk in open access form. Results: Graphie provides a network representation of the hierarchical structure of an Act of Parliament, which is typically organized in a tree-like fashion according to the content and information contained in each sub-branch. Nodes in Graphie represent sections of an Act (or individual provisions), while links embody the hierarchical connections between them. The legal map provided by Graphie is easily navigable by hovering on nodes, which are also color-coded and numbered to provide easily accessible information about the underlying content. The full textual content of each node is also available on a dedicated hyperlinked canvas. Conclusions: While we focus on the Housing Act 2004 for illustrative purposes, our platform is scalable, versatile, and provides users with a unified toolbox to visualize and explore the UK legal corpus in a fast and user-friendly way

Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms

AbstractBackgroundMethylnaltrexone, a selective peripheral acting mu-opioid receptor antagonist, alleviates the constipating effects of opioids without affecting centrally mediated analgesia.ObjectivesTo assess the effect of subcutaneous (SC) methylnaltrexone injection on patient-reported constipation symptoms and pain scores.MethodsA total of 469 subjects on opioids for chronic non-malignant pain with opioid-induced constipation were randomized to methylnaltrexone SC with once daily (QD) or every other day (QOD) dosing or placebo for 4 weeks. Constipation symptoms and pain were assessed using the patient assessment of constipation–symptoms (PAC-SYM) questionnaire and a 11-point scale, respectively, at baseline, Day 14 and Day 28. Change from baseline in PAC-SYM and pain scores were compared between methylnaltrexone and placebo arms at Day 28 using analysis of covariance, with treatment group as factor and baseline score as covariate.ResultsA majority of patients were women (60%), average age was 49 years old, and back pain (60%) was the primary pain condition. At Day 28, the methylnaltrexone SC QD group showed a significant improvement over placebo for rectal symptoms (−0.56 vs. –0.30; P < 0.05), stool symptoms (−0.76 vs. –0.43; P < 0.001) and global scores (−0.62 vs. –0.37; P < 0.001). Improvement in stool symptoms (−0.69 vs.−0.43; P < 0.05) and the global scores (−0.52 vs. –0.37; P < 0.05) were significantly greater than placebo in the methylnaltrexone QOD group. Differences in change from baseline in abdominal symptoms and pain scores between the methylnaltrexone SC QD or QOD dosing arms and placebo were not significant.ConclusionThe results of our study indicate significant improvement in constipation symptoms with methylnaltrexone QD or QOD dosing compared to placebo without a significant effect on pain scores

RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p

Measurement of the nuclear modification factor for muons from charm and bottom hadrons in Pb+Pb collisions at 5.02 TeV with the ATLAS detector

Heavy-flavour hadron production provides information about the transport properties and microscopic structure of the quark-gluon plasma created in ultra-relativistic heavy-ion collisions. A measurement of the muons from semileptonic decays of charm and bottom hadrons produced in Pb+Pb and pp collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV with the ATLAS detector at the Large Hadron Collider is presented. The Pb+Pb data were collected in 2015 and 2018 with sampled integrated luminosities of 208 mu b(-1) and 38 mu b(-1), respectively, and pp data with a sampled integrated luminosity of 1.17 pb(-1) were collected in 2017. Muons from heavy-flavour semileptonic decays are separated from the light-flavour hadronic background using the momentum imbalance between the inner detector and muon spectrometer measurements, and muons originating from charm and bottom decays are further separated via the muon track's transverse impact parameter. Differential yields in Pb+Pb collisions and differential cross sections in pp collisions for such muons are measured as a function of muon transverse momentum from 4 GeV to 30 GeV in the absolute pseudorapidity interval vertical bar eta vertical bar &lt; 2. Nuclear modification factors for charm and bottom muons are presented as a function of muon transverse momentum in intervals of Pb+Pb collision centrality. The bottom muon results are the most precise measurement of b quark nuclear modification at low transverse momentum where reconstruction of B hadrons is challenging. The measured nuclear modification factors quantify a significant suppression of the yields of muons from decays of charm and bottom hadrons, with stronger effects for muons from charm hadron decays

A search for an unexpected asymmetry in the production of e+μ− and e−μ+ pairs in proton-proton collisions recorded by the ATLAS detector at root s = 13 TeV

This search, a type not previously performed at ATLAS, uses a comparison of the production cross sections for e(+)mu(-) and e(-)mu(+) pairs to constrain physics processes beyond the Standard Model. It uses 139 fb(-1) of proton-proton collision data recorded at root s = 13 TeV at the LHC. Targeting sources of new physics which prefer final states containing e(+)mu(-) and e(-)mu(+), the search contains two broad signal regions which are used to provide model-independent constraints on the ratio of cross sections at the 2% level. The search also has two special selections targeting supersymmetric models and leptoquark signatures. Observations using one of these selections are able to exclude, at 95% confidence level, singly produced smuons with masses up to 640 GeV in a model in which the only other light sparticle is a neutralino when the R-parity-violating coupling lambda(23)(1)' is close to unity. Observations using the other selection exclude scalar leptoquarks with masses below 1880 GeV when g(1R)(eu) = g(1R)(mu c) = 1, at 95% confidence level. The limit on the coupling reduces to g(1R)(eu) = g(1R)(mu c) = 0.46 for a mass of 1420 GeV

Differential cross-section measurements of the production of four charged leptons in association with two jets using the ATLAS detector

Differential cross-sections are measured for the production of four charged leptons in association with two jets. These measurements are sensitive to final states in which the jets are produced via the strong interaction as well as to the purely-electroweak vector boson scattering process. The analysis is performed using proton-proton collision data collected by ATLAS at √s = 13 TeV and with an integrated luminosity of 140 fb−1. The data are corrected for the effects of detector inefficiency and resolution and are compared to state-of-the-art Monte Carlo event generator predictions. The differential cross-sections are used to search for anomalous weak-boson self-interactions that are induced by dimension-six and dimension-eight operators in Standard Model effective field theory

Information retrieval and structural complexity of legal trees

We introduce a model for the retrieval of information hidden in legal texts. These are typically organised in a hierarchical (tree) structure, which a reader interested in a given provision needs to explore down to the "deepest" level (articles, clauses,...). We assess the structural complexity of legal trees by computing the mean first-passage time a random reader takes to retrieve information planted in the leaves. The reader is assumed to skim through the content of a legal text based on their interests/keywords, and be drawn towards the sought information based on keywords affinity, i.e. how well the Chapters/Section headers of the hierarchy seem to match the informational content of the leaves. Using randomly generated keyword patterns, we investigate the effect of two main features of the text -- the horizontal and vertical coherence -- on the searching time, and consider ways to validate our results using real legal texts. We obtain numerical and analytical results, the latter based on a mean-field approximation on the level of patterns, which lead to an explicit expression for the complexity of legal trees as a function of the structural parameters of the model. Policy implications of our results are briefly discussed.Comment: 47 pages, 17 figure

An Integrated Safety Summary of Omadacycline, a Novel Aminomethylcycline Antibiotic

Omadacycline is a semisynthetic tetracycline antibiotic. Phase III clinical trial results have shown that omadacycline has an acceptable safety profile in the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Similar to most tetracyclines, transient nausea and vomiting and low-magnitude increases in liver aminotransferases were the most frequent treatment-emergent adverse events in phase III studies but were not treatment limiting. Package insert warnings and precautions for omadacycline include tooth discoloration; enamel hypoplasia; inhibition of bone growth following use in late pregnancy, infancy, or childhood up to 8 years of age; an imbalance in mortality (2%, compared with 1% in moxifloxacin-treated patients) was observed in the phase III study in patients with community-acquired bacterial pneumonia. Omadacycline has no effect on the QT interval, and its affinity for muscarinic M2 receptors resulted in transient heart rate increases following dosing