Experimental and quantitative imaging techniques in interstitial lung disease.

Interstitial lung diseases (ILDs) are a heterogeneous group of conditions, with a wide and complex variety of imaging features. Difficulty in monitoring, treating and exploring novel therapies for these conditions is in part due to the lack of robust, readily available biomarkers. Radiological studies are vital in the assessment and follow-up of ILD, but currently CT analysis in clinical practice is qualitative and therefore somewhat subjective. In this article, we report on the role of novel and quantitative imaging techniques across a range of imaging modalities in ILD and consider how they may be applied in the assessment and understanding of ILD. We critically appraised evidence found from searches of Ovid online, PubMed and the TRIP database for novel and quantitative imaging studies in ILD. Recent studies have explored the capability of texture-based lung parenchymal analysis in accurately quantifying several ILD features. Newer techniques are helping to overcome the challenges inherent to such approaches, in particular distinguishing peripheral reticulation of lung parenchyma from pleura and accurately identifying the complex density patterns that accompany honeycombing. Robust and validated texture-based analysis may remove the subjectivity that is inherent to qualitative reporting and allow greater objective measurements of change over time. In addition to lung parenchymal feature quantification, pulmonary vessel volume analysis on CT has demonstrated prognostic value in two retrospective analyses and may be a sign of vascular changes in ILD which, to date, have been difficult to quantify in the absence of overt pulmonary hypertension. Novel applications of existing imaging techniques, such as hyperpolarised gas MRI and positron emission tomography (PET), show promise in combining structural and functional information. Although structural imaging of lung tissue is inherently challenging in terms of conventional proton MRI techniques, inroads are being made with ultrashort echo time, and dynamic contrast-enhanced MRI may be used for lung perfusion assessment. In addition, inhaled hyperpolarised 129Xenon gas MRI may provide multifunctional imaging metrics, including assessment of ventilation, intra-acinar gas diffusion and alveolar-capillary diffusion. PET has demonstrated high standard uptake values (SUVs) of 18F-fluorodeoxyglucose in fibrosed lung tissue, challenging the assumption that these are 'burned out' and metabolically inactive regions. Regions that appear structurally normal also appear to have higher SUV, warranting further exploration with future longitudinal studies to assess if this precedes future regions of macroscopic structural change. Given the subtleties involved in diagnosing, assessing and predicting future deterioration in many forms of ILD, multimodal quantitative lung structure-function imaging may provide the means of identifying novel, sensitive and clinically applicable imaging markers of disease. Such imaging metrics may provide mechanistic and phenotypic information that can help direct appropriate personalised therapy, can be used to predict outcomes and could potentially be more sensitive and specific than global pulmonary function testing. Quantitative assessment may objectively assess subtle change in character or extent of disease that can assist in efficacy of antifibrotic therapy or detecting early changes of potentially pneumotoxic drugs involved in early intervention studies

Effects of Pore Walls and Randomness on Phase Transitions in Porous Media

We study spin models within the mean field approximation to elucidate the topology of the phase diagrams of systems modeling the liquid-vapor transition and the separation of He$^3$--He$^4$ mixtures in periodic porous media. These topologies are found to be identical to those of the corresponding random field and random anisotropy spin systems with a bimodal distribution of the randomness. Our results suggest that the presence of walls (periodic or otherwise) are a key factor determining the nature of the phase diagram in porous media.Comment: REVTeX, 11 eps figures, to appear in Phys. Rev.

Diagnostic accuracy of CT pulmonary angiography in suspected pulmonary hypertension

Objectives Computed tomography (CT) pulmonary angiography is widely used in patients with suspected pulmonary hypertension (PH). However, the diagnostic and prognostic significance remains unclear. The aim of this study was to (a) build a diagnostic CT model and (b) test its prognostic significance. Methods Consecutive patients with suspected PH undergoing routine CT pulmonary angiography and right heart catheterisation (RHC) were identified. Axial and reconstructed images were used to derive CT metrics. Multivariate regression analysis was performed in the derivation cohort to identify a diagnostic CT model to predict mPAP ≥ 25 mmHg (the existing ESC guideline definition of PH) and > 20 mmHg (the new threshold proposed at the 6th World Symposium on PH). In the validation cohort, sensitivity, specificity and compromise CT thresholds were identified with receiver operating characteristic (ROC) analysis. The prognostic value of the CT model was assessed using Kaplan-Meier analysis. Results Between 2012 and 2016, 491 patients were identified. In the derivation cohort (n = 247), a CT model was identified including pulmonary artery diameter, right ventricular outflow tract thickness, septal angle and left ventricular area. In the validation cohort (n = 244), the model was diagnostic, with an area under the ROC curve of 0.94/0.91 for mPAP ≥ 25/> 20 mmHg respectively. In the validation cohort, 93 patients died; mean follow-up was 42 months. The diagnostic thresholds for the CT model were prognostic, log rank, all p < 0.01. Discussion In suspected PH, a diagnostic CT model had diagnostic and prognostic utility

Hyperpolarised 129-xenon diffusion-weighted MRI for assessing lung microstructure in IPF

Background Hyperpolarised 129-xenon (129Xe) magnetic resonance imaging (MRI) shows promise in monitoring the progression of idiopathic pulmonary fibrosis (IPF) due to the lack of ionising radiation and the ability to quantify functional impairment. Diffusion-weighted (DW)-MRI with hyperpolarised gases can provide information about lung microstructure. The aims were to compare 129Xe DW-MRI measurements with pulmonary function tests (PFTs), and to assess whether they can detect early signs of disease progression in patients with newly diagnosed IPF. Methods This is a prospective, single-centre, observational imaging study of patients presenting with IPF to Northern General Hospital (Sheffield, UK). Hyperpolarised 129Xe DW-MRI was performed at 1.5 T on a whole-body General Electric HDx scanner and PFTs were performed on the same day as the MRI scan. Results There was an increase in global 129Xe apparent diffusion coefficient (ADC) between the baseline and 12-month visits (mean 0.043 cm2·s−1, 95% CI 0.040–0.047 cm2·s−1 versus mean 0.045 cm2·s−1, 95% CI 0.040–0.049 cm2·s−1; p=0.044; n=20), with no significant change in PFTs over the same time period. There was also an increase in 129Xe ADC in the lower zone (p=0.027), and an increase in 129Xe mean acinar dimension in the lower zone (p=0.033) between the baseline and 12-month visits. 129Xe DW-MRI measurements correlated strongly with diffusing capacity of the lung for carbon monoxide (% predicted), transfer coefficient of the lung for carbon monoxide (KCO) and KCO (% predicted). Conclusions 129Xe DW-MRI measurements appear to be sensitive to early changes of microstructural disease that are consistent with progression in IPF at 12 months. As new drug treatments are developed, the ability to quantify subtle changes using 129Xe DW-MRI could be particularly valuable

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

The APEX Large CO Heterodyne Orion Legacy Survey (ALCOHOLS): I. Survey overview

Context: The Orion molecular cloud complex harbours the nearest Giant Molecular Clouds (GMCs) and the nearest site of high-mass star formation. Its young star and protostar populations are thoroughly characterized. The region is therefore a prime target for the study of star formation. Aims: Here, we verify the performance of the SuperCAM 64 pixel heterodyne array on the Atacama Pathfinder Experiment (APEX). We give a descriptive overview of a set of wide-field CO(3-2) spectral line cubes obtained towards the Orion GMC complex, aimed at characterizing the dynamics and structure of the extended molecular gas in diverse regions of the clouds, ranging from very active sites of clustered star formation in Orion B to comparatively quiet regions in southern Orion A. In a future publication, we will characterize the full population of protostellar outflows and their feedback over an entire GMC. Methods: We present a 2.7 square degree (130 pc2) mapping survey in the 12CO(3-2) transition, obtained using SuperCAM on APEX at an angular resolution of 1900 (7600 AU or 0.037 pc at a distance of 400 pc), covering the main sites of star formation in the Orion B cloud (L 1622, NGC 2071, NGC 2068, Ori B9, NGC 2024, and NGC 2023), and a large patch in the southern part of the L 1641 cloud in Orion A. Results: We describe CO integrated line emission and line moment maps and position-velocity diagrams for all survey fields and discuss a few subregions in some detail. Evidence for expanding bubbles is seen with lines splitting into double components, often in areas of optical nebulosities, most prominently in the NGC 2024 H ii region, where we argue that the bulk of the molecular gas is in the foreground of the H ii region. High CO(3-2)/CO(1-0) line ratios reveal warm CO along the western edge of the Orion B cloud in the NGC 2023/NGC 2024 region facing the IC 434 H ii region. We see multiple, well separated radial velocity cloud components towards several fields and propose that L 1641-S consists of a sequence of clouds at increasingly larger distances. We find a small, seemingly spherical cloud, which we term ’Cow Nebula’ globule, north of NGC 2071. We confirm that we can trace high velocity line wings out to the ’extremely high velocity’ regime in protostellar molecular outflows for the NGC 2071-IR outflow and the NGC 2024 CO jet, and identify the protostellar dust core FIR4 (rather than FIR5) as the true driving source of the NGC 2024 monopolar outflow

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements

A search for resonances decaying into a Higgs boson and a new particle X in the XH → qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson (H) and a new particle (X) is reported, utilizing 36.1 fb−1 of proton–proton collision data at collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle X is assumed to decay to a pair of light quarks, and the fully hadronic final state is analysed. The search considers the regime of high XH resonance masses, where the X and H bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of XH mass versus X mass is scanned for evidence of a signal, over a range of XH resonance mass values between 1 TeV and 4 TeV, and for X particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of XH and X masses, on the production cross-section of the resonance

Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio