Abstract
From 2022 March 18 to 21, NOAA Active Region (AR) 12967 was tracked simultaneously by Solar Orbiter at 0.35 au and Hinode/EIS at Earth. During this period, strong blueshifted plasma upflows ...were observed along a thin, dark corridor of open magnetic field originating at the AR’s leading polarity and continuing toward the southern extension of the northern polar coronal hole. A potential field source surface model shows large lateral expansion of the open magnetic field along the corridor. Squashing factor
Q
-maps of the large-scale topology further confirm super-radial expansion in support of the S-web theory for the slow wind. The thin corridor of upflows is identified as the source region of a slow solar wind stream characterized by ∼300 km s
−1
velocities, low proton temperatures of ∼5 eV, extremely high density >100 cm
−3
, and a short interval of moderate Alfvénicity accompanied by switchback events. When the connectivity changes from the corridor to the eastern side of the AR, the in situ plasma parameters of the slow solar wind indicate a distinctly different source region. These observations provide strong evidence that the narrow open-field corridors, forming part of the S-web, produce some extreme properties in their associated solar wind streams.
Aims. The Spectral Imaging of the Coronal Environment (SPICE) instrument is a high-resolution imaging spectrometer operating at extreme ultraviolet wavelengths. In this paper, we present the concept, ...design, and pre-launch performance of this facility instrument on the ESA/NASA Solar Orbiter mission.
Methods. The goal of this paper is to give prospective users a better understanding of the possible types of observations, the data acquisition, and the sources that contribute to the instrument’s signal.
Results. The paper discusses the science objectives, with a focus on the SPICE-specific aspects, before presenting the instrument’s design, including optical, mechanical, thermal, and electronics aspects. This is followed by a characterisation and calibration of the instrument’s performance. The paper concludes with descriptions of the operations concept and data processing.
Conclusions. The performance measurements of the various instrument parameters meet the requirements derived from the mission’s science objectives. The SPICE instrument is ready to perform measurements that will provide vital contributions to the scientific success of the Solar Orbiter mission.
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Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is ...unclear.
We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients.
An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes U-BIOPRED cohorts) by means of hierarchical clustering. IL-6TS–specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens.
Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS–high asthma with increased epithelial expression of IL-6TS–inducible genes in the absence of systemic inflammation. The IL-6TS–high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1β, IL-8, and IL-1β.
Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management.
We reviewed patient choice ...to follow HCP advice to adjust asthma treatment in a UK-based randomised, controlled, single-blind (study participant), multicentre, parallel group 48-week clinical study comparing biomarker-directed treatment adjustment with standard care in severe asthma.
Of 1572 treatment advisories (291 participants), instructions were followed in 1377 cases (87.6%). Patients were more likely to follow advice to remain on treatment (96.7%) than to either reduce (70.3%) or increase (67.1%) their treatment, with 64% of patients following all treatment advice. Multivariate analysis associated belonging to an ethnic minority group (OR 3.10, 95% CI 1.68-5.73) and prior study medication changes (two or more changes: OR 2.77, 95% CI 1.51-5.10) with failure to follow treatment advice. In contrast, emergency room attendance in the prior year (OR 0.54, 95% CI 0.32-0.92) was associated with following treatment advice. The largest effect was seen with transition onto or off oral corticosteroids (OR 29.28, 95% CI 16.07-53.36) when compared with those requested to maintain treatment. Centre was also an important determinant regarding the likelihood of patients to follow treatment advice.
Belonging to an ethnic minority group and multiple prior treatment adjustments were associated with not following HCP treatment advice. Patients also responded differently to HCP advice across UK specialist centres. These findings have implications for the generalisability of models of care in severe asthma and require further focused studies.
This book is a study of the uses of adjectives in different constructions, and of the problems that arise in their analysis, both in terms of syntactic theory and philosophy of grammar. The history ...of English has been one in which their uses in the attributive and predicative positions have increasingly diverged. This raises problems in general for the definition of the category, and for analyses that have tried to relate one use to another, by syntactic transformations or other devices. It also raises problems in individual positions, which concern in particular the basic structure of noun phrases and the justification for binary constituents; the status of the copular and its uses in the progressive; the indeterminacy of what were once described as raised constructions; and the function of postmodifying adjectives and adjective phrases in relation to others. The nature of these problems is often as much theoretical, or philosophical, as factual.
Patients with difficult-to-control asthma consume 50-60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence ...demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called 'T2-low asthma' and have a minimal response to corticosteroid therapy. Adjustment of corticosteroid treatment using sputum eosinophil counts from induced sputum has demonstrated reduced severe exacerbation rates and optimized corticosteroid dose. However, it has been challenging to move induced sputum into the clinical setting. There is therefore a need to examine novel algorithms to target appropriate levels of corticosteroid treatment in difficult asthma, particularly in T2-low asthmatics. This study examines whether a composite non-invasive biomarker algorithm predicts exacerbation risk in patients with asthma on high-dose inhaled corticosteroids (ICS) (± long-acting beta agonist) treatment, and evaluates the utility of this composite score to facilitate personalized biomarker-specific titration of corticosteroid therapy.
Patients recruited to this pragmatic, multi-centre, single-blinded randomised controlled trial are randomly allocated into either a biomarker controlled treatment advisory algorithm or usual care group in a ratio of 4:1. The primary outcome measure is the proportion of patients with any reduction in ICS or oral corticosteroid dose from baseline to week 48. Secondary outcomes include the rate of protocol-defined severe exacerbations per patient per year, time to first severe exacerbation from randomisation, dose of inhaled steroid at the end of the study, cumulative dose of inhaled corticosteroid during the study, proportion of patients on oral corticosteroids at the end of the study, proportion of patients who decline to progress to oral corticosteroids despite composite biomarker score of 2, frequency of hospital admission for asthma, change in the 7-item Asthma Control Questionnaire (ACQ-7), Asthma Quality of Life Questionnaire (AQLQ), forced expiratory volume in 1 s (FEV1), exhaled nitric oxide, blood eosinophil count, and periostin levels from baseline to week 48. Blood will also be taken for whole blood gene expression; serum, plasma, and urine will be stored for validation of additional biomarkers.
Multi-centre trials present numerous logistical issues that have been addressed to ensure minimal bias and robustness of study conduct.
ClinicalTrials.gov, NCT02717689 . Registered on 16 March 2016.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This study offers a fresh approach to the theory and practice of poetry criticism from a narratological perspective. Arguing that lyric poems share basic constituents with narrative fiction, the ...authors utilize the advanced techniques of narratology to invigorate the field of poetic theory and methodology while demonstrating the fruitfulness of this approach by detailed analyses of canonical English poems.
Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for ...the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples.
We sought to identify gene profiles associated with adult-onset severe asthma.
This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways.
Significant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma.
Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The magnetic activity of the Sun directly impacts the Earth and human life. Likewise, other stars will have an impact on the habitability of planets orbiting these host stars. Although the magnetic ...field at the surface of the Sun is reasonably well characterised by observations, the information on the magnetic field in the higher atmospheric layers is mainly indirect. This lack of information hampers our progress in understanding solar magnetic activity. Overcoming this limitation would allow us to address four paramount long-standing questions: (1) How does the magnetic field couple the different layers of the atmosphere, and how does it transport energy? (2) How does the magnetic field structure, drive and interact with the plasma in the chromosphere and upper atmosphere? (3) How does the magnetic field destabilise the outer solar atmosphere and thus affect the interplanetary environment? (4) How do magnetic processes accelerate particles to high energies? New ground-breaking observations are needed to address these science questions. We suggest a suite of three instruments that far exceed current capabilities in terms of spatial resolution, light-gathering power, and polarimetric performance: (a) A large-aperture UV-to-IR telescope of the 1-3 m class aimed mainly to measure the magnetic field in the chromosphere by combining high spatial resolution and high sensitivity. (b) An extreme-UV-to-IR coronagraph that is designed to measure the large-scale magnetic field in the corona with an aperture of about 40 cm. (c) An extreme-UV imaging polarimeter based on a 30 cm telescope that combines high throughput in the extreme UV with polarimetry to connect the magnetic measurements of the other two instruments. Placed in a near-Earth orbit, the data downlink would be maximised, while a location at L4 or L5 would provide stereoscopic observations of the Sun in combination with Earth-based observatories. This mission to measure the magnetic field will finally unlock the driver of the dynamics in the outer solar atmosphere and thereby will greatly advance our understanding of the Sun and the heliosphere.
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