Chronic urticaria in the real‐life clinical practice setting in the UK: results from the non‐interventional multicentre AWARE study

Abstract Background Chronic urticaria (CU) is a skin condition characterised by repeated occurrence of itchy wheals and/or angioedema for >6 weeks. Aim To provide data demonstrating the real‐life burden of CU in the UK. Methods This UK subset of the worldwide, prospective, non‐interventional AWARE study included patients aged 18–75 years diagnosed with H1‐antihistamine (H1‐AH)‐refractory chronic spontaneous urticaria (CSU) for >2 months. Baseline characteristics, disease activity, treatments, comorbidities and healthcare resource use were documented. Quality of life, work productivity and activity impairment were assessed. Results Baseline analysis included 252 UK patients. Mean age and body mass index were 45.0 years and 29.0 kg/m2, respectively. Most patients were female (77.8%) and had moderate/severe disease activity (mean Urticaria Activity Score over 7 days, 18.4) and a ‘spontaneous’ component to their CU (73.4% CSU; 24.6% CSU and chronic inducible urticaria). Common comorbidities included depression/anxiety (24.6%), asthma (23.8%) and allergic rhinitis (12.7%). A previous treatment was recorded for 57.9% of patients. Mean Dermatology Life Quality Index score was 9.5 and patients reported impairments in work productivity and activity. Healthcare resource use was high. Severity of CSU was associated with gender, obesity, anxiety and diagnosis. Only 28.5% of patients completed all nine study visits, limiting analysis of long‐term treatment patterns and disease impact. Conclusions Adult H1‐AH‐refractory CU patients in the UK reported high rates of healthcare resource use and impairment in quality of life, work productivity and activity at baseline. The differing structures of UK healthcare may explain the high study discontinuation rates versus other countries

The role of morphine in regulation of cancer cell growth

Morphine is considered the “gold standard” for relieving pain and is currently one of the most effective drugs available clinically for the management of severe pain associated with cancer. In addition to its use in the treatment of pain, morphine appears to be important in the regulation of neoplastic tissue. Although morphine acts directly on the central nervous system to relieve pain, its activities on peripheral tissues are responsible for many of the secondary complications. Therefore, understanding the impact, other than pain control, of morphine on cancer treatment is extremely important. The effect of morphine on tumor growth is still contradictory, as both growth-promoting and growth-inhibiting effects have been observed. Accumulating evidence suggests that morphine can affect proliferation and migration of tumor cells as well as angiogenesis. Various signaling pathways have been suggested to be involved in these extra-analgesic effects of morphine. Suppression of immune system by morphine is an additional complication. This review provides an update on the influence of morphine on the growth and migration potential of tumor cells

Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case-control diagnostic accuracy study (DIPSOC study).

BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed

A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals

A protective vaccine against HIV-1 will likely require the elicitation of a broadly neutralizing antibody (bNAb) response. Although the development of an immunogen that elicits such antibodies remains elusive, a proportion of HIV-1 infected individuals evolve broadly neutralizing serum responses over time, demonstrating that the human immune system can recognize and generate NAbs to conserved epitopes on the virus. Understanding the specificities that mediate broad neutralization will provide insight into which epitopes should be targeted for immunogen design and aid in the isolation of broadly neutralizing monoclonal antibodies from these donors. Here, we have used a number of new and established technologies to map the bNAb specificities in the sera of 19 donors who exhibit among the most potent cross-clade serum neutralizing activities observed to date. The results suggest that broad and potent serum neutralization arises in most donors through a limited number of specificities (1–2 per donor). The major targets recognized are an epitope defined by the bNAbs PG9 and PG16 that is associated with conserved regions of the V1, V2 and V3 loops, an epitope overlapping the CD4 binding site and possibly the coreceptor binding site, an epitope sensitive to a loss of the glycan at N332 and distinct from that recognized by the bNAb 2G12 and an epitope sensitive to an I165A substitution. In approximately half of the donors, key N-linked glycans were critical for expression of the epitopes recognized by the bNAb specificities in the sera

Anatomy of the sign-problem in heavy-dense QCD

QCD at finite densities of heavy quarks is investigated using the density-of-states method. The phase factor expectation value of the quark determinant is calculated to unprecedented precision as a function of the chemical potential. Results are validated using those from a reweighting approach where the latter can produce a significant signalto-noise ratio. We confirm the particle–hole symmetry at low temperatures, find a strong sign problem at intermediate values of the chemical potential, and an inverse Silver Blaze feature for chemical potentials close to the onset value: here, the phase-quenched theory underestimates the density of the full theory

Measurement of the W±Z boson pair-production cross section in pp collisions at √s=13TeV with the ATLAS detector

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Search for anomalous couplings in the W tb vertex from the measurement of double differential angular decay rates of single top quarks produced in the t-channel with the ATLAS detector

The electroweak production and subsequent decay of single top quarks is determined by the properties of the Wtb vertex. This vertex can be described by the complex parameters of an effective Lagrangian. An analysis of angular distributions of the decay products of single top quarks produced in the t -channel constrains these parameters simultaneously. The analysis described in this paper uses 4.6 fb−1 of proton-proton collision data at √s =7 TeV collected with the ATLAS detector at the LHC. Two parameters are measured simultaneously in this analysis. The fraction f 1 of decays containing transversely polarised W bosons is measured to be 0.37 ± 0.07 (stat.⊕syst.). The phase δ − between amplitudes for transversely and longitudinally polarised W bosons recoiling against left-handed b-quarks is measured to be −0.014π ± 0.036π (stat.⊕syst.). The correlation in the measurement of these parameters is 0.15. These values result in two-dimensional limits at the 95% confidence level on the ratio of the complex coupling parameters g R and V L, yielding Re[g R /V L] ∈ [−0.36, 0.10] and Im[g R /V L] ∈ [−0.17, 0.23] with a correlation of 0.11. The results are in good agreement with the predictions of the Standard Model

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions