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Aims Ischaemic heart disease results from insufficient coronary blood flow. Direct measurement of absolute flow (mL/min) is feasible, but has not entered routine clinical practice in most catheterization laboratories. Interventional cardiologists, therefore, rely on surrogate markers of flow. Recently, we described a computational fluid dynamics (CFD) method for predicting flow that differentiates inlet, side branch, and outlet flows during angiography. In the current study, we evaluate a new method that regionalizes flow along the length of the artery. Methods and results Three-dimensional coronary anatomy was reconstructed from angiograms from 20 patients with chronic coronary syndrome. All flows were computed using CFD by applying the pressure gradient to the reconstructed geometry. Side branch flow was modelled as a porous wall boundary. Side branch flow magnitude was based on morphometric scaling laws with two models: a homogeneous model with flow loss along the entire arterial length; and a regionalized model with flow proportional to local taper. Flow results were validated against invasive measurements of flow by continuous infusion thermodilution (Coroventis™, Abbott). Both methods quantified flow relative to the invasive measures: homogeneous (r 0.47, P 0.006; zero bias; 95% CI −168 to +168 mL/min); regionalized method (r 0.43, P 0.013; zero bias; 95% CI −175 to +175 mL/min). Conclusion During angiography and pressure wire assessment, coronary flow can now be regionalized and differentiated at the inlet, outlet, and side branches. The effect of epicardial disease on agreement suggests the model may be best targeted at cases with a stenosis close to side branches.

Aims Angiography-derived fractional flow reserve (angio-FFR) permits physiological lesion assessment without the need for an invasive pressure wire or induction of hyperaemia. However, accuracy is limited by assumptions made when defining the distal boundary, namely coronary microvascular resistance (CMVR). We sought to determine whether machine learning (ML) techniques could provide a patient-specific estimate of CMVR and therefore improve the accuracy of angio-FFR. Methods and results Patients with chronic coronary syndromes underwent coronary angiography with FFR assessment. Vessel-specific CMVR was computed using a three-dimensional computational fluid dynamics simulation with invasively measured proximal and distal pressures applied as boundary conditions. Predictive models were created using non-linear autoregressive moving average with exogenous input (NARMAX) modelling with computed CMVR as the dependent variable. Angio-FFR (VIRTUheart™) was computed using previously described methods. Three simulations were run: using a generic CMVR value (Model A); using ML-predicted CMVR based upon simple clinical data (Model B); and using ML-predicted CMVR also incorporating echocardiographic data (Model C). The diagnostic (FFR ≤ or >0.80) and absolute accuracies of these models were compared. Eighty-four patients underwent coronary angiography with FFR assessment in 157 vessels. The mean measured FFR was 0.79 (±0.15). The diagnostic and absolute accuracies of each personalized model were: (A) 73% and ±0.10; (B) 81% and ±0.07; and (C) 89% and ±0.05, P Conclusion The accuracy of angio-FFR was dependent in part upon CMVR estimation. Personalization of CMVR from standard clinical data resulted in a significant reduction in angio-FFR error.

Fractional flow reserve (FFR) is the current gold standard invasive assessment of coronary artery disease (CAD). FFR reports coronary blood flow (CBF) as a fraction of a hypothetical and unknown normal value. Although used routinely to diagnose CAD and guide treatment, how accurately FFR predicts actual CBF changes remains unknown. In this study, we compared fractional CBF with absolute CBF (aCBF, in ml min−1), measured with a computational method during standard angiography and pressure wire assessment, on 203 diseased arteries (143 patients). We found a substantial correlation between the two measurements (r = 0.89 and Cohen’s kappa = 0.71). Concordance between fractional and absolute CBF reduction was high when FFR was >0.80 (91%) but reduced when FFR was ≤0.80 (81%), 0.70–0.80 (68%) and, particularly, 0.75–0.80 (62%). Discordance was associated with coronary microvascular resistance, vessel diameter and mass of myocardium subtended, all factors to which FFR is agnostic. Assessment of aCBF complements FFR and may be valuable to assess CBF, particularly in cases within the FFR ‘gray zone’.

BackgroundInternational guidelines for the treatment of patients with pulmonary arterial hypertension (PAH) recommend the use of risk stratification to optimise therapy to achieve and maintain a low-risk profile. However, recommended methods require hospital-based investigations. We sought to develop a method for daily, remote risk evaluation.MethodsConsecutive patients (n=5820) with pulmonary hypertension (PH) were identified from the ASPIRE registry and stepwise Cox regression applied to identify parameters associated with survival. A physiological risk score was applied to all patients and survival assessed by the Kaplan-Meier method. Physical activity was measured in patients with PAH implanted with insertable cardiac monitors (ICM, n=80) to provide a remote measure of exercise capacity. In patients with PAH and implanted pulmonary artery pressure (PAP) monitor and ICM (n=28) we undertook a time-stratified bidirectional case–crossover study to determine the physiology of therapeutic escalation (TE) and clinical worsening and a remote physiological risk score applied to the data.ResultsAge, male sex, PH aetiology, WHO functional class (FC), incremental shuttle walk-distance (ISWD), heart rate reserve (HRR) and total pulmonary resistance (TPR) as independent predictors of survival. Mortality increased with each decile of baseline physiological risk (pConclusionRemote risk evaluation may facilitate personalised medicine and proactive management. The physiological risk score accurately stratifies patients with PH and may be applied to remote monitoring data for early evaluation of clinical efficacy and detection of clinical worsening.

Aims Over the last ten years, virtual Fractional Flow Reserve (vFFR) has improved the utility of Fractional Flow Reserve (FFR), a globally recommended assessment to guide coronary interventions. Although the speed of vFFR computation has accelerated, techniques utilising full 3D computational fluid dynamics (CFD) solutions rather than simplified analytical solutions still require significant time to compute. Methods and results This study investigated the speed, accuracy and cost of a novel 3D-CFD software method based upon a graphic processing unit (GPU) computation, compared with the existing fastest central processing unit (CPU)-based 3D-CFD technique, on 40 angiographic cases. The novel GPU simulation was significantly faster than the CPU method (median 31.7 s (Interquartile Range (IQR) 24.0–44.4s) vs. 607.5 s (490–964 s), P < 0.0001). The novel GPU technique was 99.6% (IQR 99.3–99.9) accurate relative to the CPU method. The initial cost of the GPU hardware was greater than the CPU (£4080 vs. £2876), but the median energy consumption per case was significantly less using the GPU method (8.44 (6.80–13.39) Wh vs. 2.60 (2.16–3.12) Wh, P < 0.0001). Conclusion This study demonstrates that vFFR can be computed using 3D-CFD with up to 28-fold acceleration than previous techniques with no clinically significant sacrifice in accuracy.

Building a visual overview of temporal event sequences with an optimal level-of-detail (i.e. simplified but informative) is an ongoing challenge - expecting the user to zoom into every important aspect of the overview can lead to missing insights. We propose a technique to build a multilevel overview of event sequences, whose granularity can be transformed across sequence clusters (vertical level-of-detail) or longitudinally (horizontal level-of-detail), using hierarchical aggregation and a novel cluster data representation Align-Score-Simplify. By default, the overview shows an optimal number of sequence clusters obtained through the average silhouette width metric - then users are able to explore alternative optimal sequence clusterings. The vertical level-of-detail of the overview changes along with the number of clusters, whilst the horizontal level-of-detail refers to the level of summarization applied to each cluster representation. The proposed technique has been implemented into a visualization system called Sequence Cluster Explorer (Sequen-C) that allows multilevel and detail-on-demand exploration through three coordinated views, and the inspection of data attributes at cluster, unique sequence, and individual sequence level. We present two case studies using real-world datasets in the healthcare domain: CUREd and MIMIC-III; which demonstrate how the technique can aid users to obtain a summary of common and deviating pathways, and explore data attributes for selected patterns., Comment: This is the author's version of the article to be published in IEEE Transactions on Visualization and Computer Graphics

Objective\ud \ud We aim to validate four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) peak velocity tracking methods for measuring the peak velocity of mitral inflow against Doppler echocardiography.\ud \ud \ud \ud Method\ud \ud Fifty patients were recruited who had 4D flow CMR and Doppler Echocardiography. After transvalvular flow segmentation using established valve tracking methods, peak velocity was automatically derived using three-dimensional streamlines of transvalvular flow. In addition, a static-planar method was used at the tip of mitral valve to mimic Doppler technique.\ud \ud \ud \ud Results\ud \ud Peak E-wave mitral inflow velocity was comparable between TTE and the novel 4D flow automated dynamic method (0.9 ± 0.5 vs 0.94 ± 0.6 m/s; p = 0.29) however there was a statistically significant difference when compared with the static planar method (0.85 ± 0.5 m/s; p = 0.01). Median A-wave peak velocity was also comparable across TTE and the automated dynamic streamline (0.77 ± 0.4 vs 0.76 ± 0.4 m/s; p = 0.77). A significant difference was seen with the static planar method (0.68 ± 0.5 m/s; p = 0.04). E/A ratio was comparable between TTE and both the automated dynamic and static planar method (1.1 ± 0.7 vs 1.15 ± 0.5 m/s; p = 0.74 and 1.15 ± 0.5 m/s; p = 0.5 respectively). Both novel 4D flow methods showed good correlation with TTE for E-wave (dynamic method; r = 0.70; P < 0.001 and static-planar method; r = 0.67; P < 0.001) and A-wave velocity measurements (dynamic method; r = 0.83; P < 0.001 and static method; r = 0.71; P < 0.001). The automated dynamic method demonstrated excellent intra/inter-observer reproducibility for all parameters.\ud \ud \ud \ud Conclusion\ud \ud Automated dynamic peak velocity tracing method using 4D flow CMR is comparable to Doppler echocardiography for mitral inflow assessment and has excellent reproducibility for clinical use.

Aims Coronary artery stents have profound effects on arterial function by altering fluid flow mass transport and wall shear stress. We developed a new integrated methodology to analyse the effects of stents on mass transport and shear stress to inform the design of haemodynamically-favourable stents. Methods and results Stents were deployed in model vessels followed by tracking of fluorescent particles under flow. Parallel analyses involved high-resolution micro-computed tomography scanning followed by computational fluid dynamics simulations to assess wall shear stress distribution. Several stent designs were analysed to assess whether the workflow was robust for diverse strut geometries. Stents had striking effects on fluid flow streamlines, flow separation or funnelling, and the accumulation of particles at areas of complex geometry that were tightly coupled to stent shape. CFD analysis revealed that stents had a major influence on wall shear stress magnitude, direction and distribution and this was highly sensitive to geometry. Conclusions Integration of particle tracking with CFD allows assessment of fluid flow and shear stress in stented arteries in unprecedented detail. Deleterious flow perturbations, such as accumulation of particles at struts and non-physiological shear stress, were highly sensitive to individual stent geometry. Novel designs for stents should be tested for mass transport and shear stress which are important effectors of vascular health and repair.

Nearly half of all patients with angina have non-obstructive coronary artery disease (ANOCA); this is an umbrella term comprising heterogeneous vascular disorders, each with disparate pathophysiology and prognosis. Approximately two-thirds of patients with ANOCA have coronary microvascular disease (CMD). CMD can be secondary to architectural changes within the microcirculation or secondary to vasomotor dysfunction. An inability of the coronary vasculature to augment blood flow in response to heightened myocardial demand is defined as an impaired coronary flow reserve (CFR), which can be measured non-invasively, using imaging, or invasively during cardiac catheterisation. Impaired CFR is associated with myocardial ischaemia and adverse cardiovascular outcomes.The CMD workstream is part of the cardiovascular partnership between the British Heart Foundation and The National Institute for Health Research in the UK and comprises specialist cardiac centres with expertise in coronary physiology assessment. This document outlines the two main modalities (thermodilution and Doppler techniques) for estimation of coronary flow, vasomotor testing using acetylcholine, and outlines a standard operating procedure that could be considered for adoption by national networks. Accurate and timely disease characterisation of patients with ANOCA will enable clinicians to tailor therapy according to their patients’ coronary physiology. This has been shown to improve patients’ quality of life and may lead to improved cardiovascular outcomes in the long term.

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance imaging (MRI) is an emerging technique used for intra-cardiac blood flow assessment. The role of 4D flow cardiovascular MRI in the assessment of trans-valvular flow in patients with atrial fibrillation (AF) has not previously been assessed. The purpose of this study was to assess the feasibility, image quality, and internal validity of 4D flow cardiovascular MRI in the quantification of trans-valvular flow in patients with AF. Methods: Patients with AF and healthy controls in sinus rhythm underwent cardiovascular MRI, including 4D flow studies. Quality assurance checks were done on the raw data and streamlines. Consistency was investigated by trans-valvular flow assessment between the mitral valve (MV) and the aortic valve (AV). Results: Eight patients with AF (88% male, mean age 62±13 years, mean heart rate (HR) 83±16 beats per minute (bpm)) were included and compared with ten healthy controls (70% male, mean age 41±20 years, mean HR 68.5±9 bpm). All scans were of either good quality with minimal blurring artefacts, or excellent quality with no artefacts. No significant bias was observed between the AV and MV stroke volumes in either healthy controls (–4.8, 95% CI –15.64 to 6.04; P=0.34) or in patients with AF (1.64, 95% CI –4.7 to 7.94; P=0.56). A significant correlation was demonstrated between MV and AV stroke volumes in both healthy controls (r=0.87, 95% CI 0.52 to 0.97; P=0.001) and in AF patients (r=0.82, 95% CI 0.26 to 0.97; P=0.01). Conclusions: In patients with AF, 4D flow cardiovascular MRI is feasible with good image quality, allowing for quantification of trans-valvular flow.

"various communities within multinational Canada adhere to different understandings of the nation, and, further, these same communities are at differing stages in their negotiation of an ethnic or civic form of nationalism. Multiculturalism emerged in the context of socially and historically determined paradigms of the nation and nationalism; these same forces must figure in its re-evaluation....this paper identifies five “communities” in Canada as fields of comparative literary inquiry. The implicit assumption here is that recognition of the preoccupations of these collectives vis-a-vis the nation will precede any attempt to arrive at what Hayden King referred to as “a cohesive and honest narrative” about the Canadian nation."

This study sought to assess the ability of a novel virtual coronary intervention (VCI) tool based on invasive angiography to predict the patient's physiological response to stenting.Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is associated with improved clinical and economic outcomes compared with angiographic guidance alone. Virtual (v)FFR can be calculated based upon a 3-dimensional (3D) reconstruction of the coronary anatomy from the angiogram, using computational fluid dynamics (CFD) modeling. This technology can be used to perform virtual stenting, with a predicted post-PCI FFR, and the prospect of optimized treatment planning.Patients undergoing elective PCI had pressure-wire-based FFR measurements pre- and post-PCI. A 3D reconstruction of the diseased artery was generated from the angiogram and imported into the VIRTUheart workflow, without the need for any invasive physiological measurements. VCI was performed using a radius correction tool replicating the dimensions of the stent deployed during PCI. Virtual FFR (vFFR) was calculated pre- and post-VCI, using CFD analysis. vFFR pre- and post-VCI were compared with measured (m)FFR pre- and post-PCI, respectively.Fifty-four patients and 59 vessels underwent PCI. The mFFR and vFFR pre-PCI were 0.66 ± 0.14 and 0.68 ± 0.13, respectively. Pre-PCI vFFR deviated from mFFR by ±0.05 (mean Δ = -0.02; SD = 0.07). The mean mFFR and vFFR post-PCI/VCI were 0.90 ± 0.05 and 0.92 ± 0.05, respectively. Post-VCI vFFR deviated from post-PCI mFFR by ±0.02 (mean Δ = -0.01; SD = 0.03). Mean CFD processing time was 95 s per case.The authors have developed a novel VCI tool, based upon the angiogram, that predicts the physiological response to stenting with a high degree of accuracy.

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards ‘digital patient’ or ‘virtual physiological human’ representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges.

Fractional flow reserve (FFR) is the “gold standard” for assessing the physiological significance of coronary artery disease during invasive coronary angiography. FFR-guided percutaneous coronary intervention improves patient outcomes and reduces stent insertion and cost; yet, due to several practical and operator related factors, it is used in

The degree of infestation by New Zealand sooty beech scale insects (Ultracoelostoma assimile, Homoptera: Margarodidae) varies dramatically among adjacent southern beech trees (Nothofagus spp., Fagaceae), but has previously been assumed to be uniformly or randomly distributed within individual host trees. In this study, a full-census survey was conducted from ground level to canopy level on 14 naturally occurring, canopy-dominant red beech (Nothofagus fusca) trees (size range 38.7-107.6 cm diameter at breast height) to determine the degree of within-tree heterogeneity in herbivore density. 2. The within-tree distribution of the sooty beech scale was vertically stratified and highly heterogeneous, with the greatest densities occurring on bark surfaces in the canopy rather than on the trunk, and on the lower rather than upper sides of the branches. The spatial distribution was strongly negatively correlated with trunk and branch diameter, and increasing bark thickness (as a function of diameter) provides a plausible explanation for differences in the establishment and population density of sooty beech scale insects with trunk and branch size. Furthermore, there was a significant change in the spatial distribution of scale insect populations on trunks and branches of trees of increasing diameter at breast height. This indicates a strong temporal component to the spatial dynamics of the sooty beech scale insect driven by changing host phenology. Future studies on phytophagous insects infesting large host trees need to consider more explicitly changes in population dynamics through space and time. 3. Because of the high degree of within-tree heterogeneity in population density, the total population size of scale insects on an individual tree could not be predicted from any measure of population density low on the trunk. However, the dry weight biomass of sooty mould fungi growing on the ground beneath infested trees was a remarkably accurate predictor of the total popula- tion size of scale insects. The use of sooty mould fungi as a relative measure of population size could be incorporated into studies of other honeydew-producing

A 3D+t description of the coronary tree is important for diagnosis of coronary artery disease and therapy planning. In this paper, we propose a method for finding 3D+t points on coronary artery tree given tracked 2D+t point locations in X-ray rotational angiography images. In order to cope with the ill-posedness of the problem, we use a bilinear model of ventricle as a spatio-temporal constraint on the nonrigid structure of the coronary artery. Based on an energy minimization formulation, we estimate i) bilinear model parameters, ii) global rigid transformation between model and X-ray coordinate systems, and iii) correspondences between 2D coronary artery points on X-ray images and 3D points on bilinear model. We validated the algorithm using a software coronary artery phantom.

Vladimir Nabokov began his illustrious literary career as a Russian poet. This simple comment bears stating if for no other reason than to draw attention to an aspect of Nabokov's writing which is often neglected. The author of many unpublished poems and a considerable number of published ones in several volumes which span his career, Nabokov retained a life-long interest in poetry. Indeed, Nabokov's oeuvre is symmetrically and suggestively contained within the matching bookends of two volumes of poetry-his first publication of 1916 and his final, posthumously published work of 1979-both entitled simply Stikhi. Despite the prominent presence of poetry in his oeuvre, criticism has accorded Nabokov's poetry far less attention than his prose. Possible reasons for this relative neglect are close at hand. Foremost amongst these must be Nabokov's brilliance as a writer of prose. Whatever the relative merits of his poetry-and as we shall see below, judging the aesthetic quality of his poetry is not an unproblematic undertaking-the startling quality of his prose contributes to the diminishing of his achievements in other artistic realms. Relatedly, Nabokov's poetry suffers obscurity in part as a result of historical and linguistic circumstance. Published in Russian and often in emigre journals with limited circulation, much of Nabokov's poetry bore the same undeserved fate which afflicted much of emigre Russia's astounding artistic output between the wars. In transferring the bulk of his artistic activities to English and prose, Nabokov began the process of winning a larger audience for his art. In making this move, however, he seemed to leave behind the language and genre which helped to form his art and which introduced him to his first extended readership. It is to this art form and audience that I would like to return in the following paper. With this study, I intend to make a limited contribution to the larger topic of a much needed critical assessment of the place of poetry in Nabokov's oeuvre. Here I wish to undertake a partial examination of the response to Nabokov the poet in emigre criticism from the early 1920s, when Nabokov first began to appear as a regularly published poet, until 1956 and the appearance of Gleb Struve's Russkaia literatura v izgnanii (Russian Literature in Exile).2 My reasons for concluding this survey in 1956 are essentially twofold. By 1956, Nabokov was a well established English language prose writer, who no longer sought an extended audience for the occasional Russian poems he continued to write. Secondly, Struve's seminal account of emigre Russian literature offers a synthesising interpretation of this particular cultural phenomenon which, in its very conclusiveness, seems to suggest a historical point of closure. With regard to an appraisal of Nabokov's role and value as a poet, Stuve's sensitive assessment also had something of a finalising, and in this sense restricting, function. In the final analysis, Struve's influential interpretation judged Nabokov to be a prose writer who wrote poetry until he switched to the medium better suited to his skills. Rather than placing Nabokov's efforts in prose and poetry on a continuum of related abilities, the two realms were conceived of as separate and even conflicting in his art. Already in 1956, Struve looked back on Nabokov's poetic production as if on a closed chapter in Nabokov's writing. Since then, critical reception of Nabokov's poetry has been effectively entombed in the perception of it as the immature expression of his artistic ability, cut off by language and artistic mode from the remainder of his oeuvre. As much by accident as design, this interpretation, while undoubtedly not intended to be restrictive, has remained the dominant approach to Nabokov the poet and has yet to be systematically examined. As the totality of his oeuvre makes clear, however, Nabokov retained a life-long interest in poetry. His numerous fictional and non-fictional works continually return, in the most diverse ways, to poetry. …