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Showing papers by "Paul Morris published in 2016"


Journal ArticleDOI
01 Jan 2016-Heart
TL;DR: The adoption of CFD modelling signals a new era in cardiovascular medicine and a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges.
Abstract: 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.

296 citations


Journal ArticleDOI
TL;DR: Macrophages have a finite capacity for intracellular killing and fail to match sustained phagocytosis with sustained microbial killing when exposed to large inocula of S. aureus, and macrophages fail to engage apoptosis‐associated bacterial killing.
Abstract: Macrophages are critical effectors of the early innate response to bacteria in tissues. Phagocytosis and killing of bacteria are interrelated functions essential for bacterial clearance but the rate-limiting step when macrophages are challenged with large numbers of the major medical pathogen Staphylococcus aureus is unknown. We show that macrophages have a finite capacity for intracellular killing and fail to match sustained phagocytosis with sustained microbial killing when exposed to large inocula of S. aureus (Newman, SH1000 and USA300 strains). S. aureus ingestion by macrophages is associated with a rapid decline in bacterial viability immediately after phagocytosis. However, not all bacteria are killed in the phagolysosome, and we demonstrate reduced acidification of the phagolysosome, associated with failure of phagolysosomal maturation and reduced activation of cathepsin D. This results in accumulation of viable intracellular bacteria in macrophages. We show macrophages fail to engage apoptosis-associated bacterial killing. Ultittop mately macrophages with viable bacteria undergo cell lysis, and viable bacteria are released and can be internalized by other macrophages. We show that cycles of lysis and reuptake maintain a pool of viable intracellular bacteria over time when killing is overwhelmed and demonstrate intracellular persistence in alveolar macrophages in the lungs in a murine model.

90 citations


Journal ArticleDOI
TL;DR: How post-translational modifications of histone tails influence immune function to specific infectious diseases is explored and how emerging classes of pharmacological agents have been applied to models of infectious diseases and their potential to modulate key aspects of the immune response to bacterial infection and HIV therapy is discussed.

32 citations


Journal ArticleDOI
07 Oct 2016-PLOS ONE
TL;DR: In this paper, the authors examined the emotional origin of sympathy crying using functional thermal infrared imaging (FTII), a novel contactless measure of autonomic nervous system activity, and found that tears of sympathy are part of a complex autonomic interaction between the sympathetic and parasympathetic nervous systems, with the latter preceding the former.
Abstract: Sympathy crying is an odd and complex mixture of physiological and emotional phenomena. Standard psychophysiological theories of emotion cannot attribute crying to a single subdivision of the autonomic nervous system (ANS) and disagreement exists regarding the emotional origin of sympathy crying. The current experiment examines sympathy crying using functional thermal infrared imaging (FTII), a novel contactless measure of ANS activity. To induce crying female participants were given the choice to decide which film they wanted to cry to. Compared to baseline, temperature started increasing on the forehead, the peri-orbital region, the cheeks and the chin before crying and reached even higher temperatures during crying. The maxillary area showed the opposite pattern and a gradual temperature decrease was observed compared to baseline as a result of emotional sweating. The results suggest that tears of sympathy are part of a complex autonomic interaction between the sympathetic and the parasympathetic nervous systems, with the latter preceding the former. The emotional origin of the phenomenon seems to derive from subjective internal factors that relate to one’s personal experiences and attributes with tears arising in the form of catharses or as part of shared sadness.

25 citations


Journal ArticleDOI
TL;DR: The utility of an environmental omics approach to yield insights underlying phototrophic life as well as the interactions of the entire microbial community in an extreme environment is demonstrated.

16 citations


Journal ArticleDOI
TL;DR: The results showed that adults with ASD were less sensitive in making judgments about syllable stress relative to controls, and partial correlations revealed a key association of speech production abnormalities with stress perception sensitivity, rather than communicative ability.
Abstract: Purpose To date, the literature on perception of affective, pragmatic, and grammatical prosody abilities in autism spectrum disorders (ASD) has been sparse and contradictory. It is interesting to n...

11 citations


Journal ArticleDOI
TL;DR: To investigate the value of rotational coronary angiography (RoCA) in the context of percutaneous coronary intervention (PCI) planning, a large number of patients with a history of coronary artery disease are surveyed for RoCA use.
Abstract: Objectives To investigate the value of rotational coronary angiography (RoCA) in the context of percutaneous coronary intervention (PCI) planning. Background As a diagnostic tool, RoCA is associated with decreased patient irradiation and contrast use compared with conventional coronary angiography (CA) and provides superior appreciation of three-dimensional anatomy. However, its value in PCI remains unknown. Methods We studied stable coronary artery disease assessment and PCI planning by interventional cardiologists. Patients underwent either RoCA or conventional CA pre-PCI for planning. These were compared with the referral CA (all conventional) in terms of quantitative lesion assessment and operator confidence. An independent panel reanalyzed all parameters. Results Six operators performed 127 procedures (60 RoCA, 60 conventional CA, and 7 crossed-over) and assessed 212 lesions. RoCA was associated with a reduction in the number of lesions judged to involve a bifurcation (23 vs. 30 lesions, P < 0.05) and a reduction in the assessment of vessel caliber (2.8 vs. 3.0 mm, P < 0.05). RoCA improved confidence assessing lesion length (P = 0.01), percentage stenosis (P = 0.02), tortuosity (P < 0.04), and proximity to a bifurcation (P = 0.03), particularly in left coronary artery cases. X-ray dose, contrast agent volume, and procedure duration were not significantly different. Conclusions Compared with conventional CA, RoCA augments quantitative lesion assessment, enhances confidence in the assessment of coronary artery disease and the precise details of the proposed procedure, but does not affect X-ray dose, contrast agent volume, or procedure duration. © 2015 Wiley Periodicals, Inc.

5 citations


Proceedings Article
Paul Morris1
12 Jun 2016
TL;DR: This paper develops a new formal theory of dispatchability in terms of execution sequences, and exploits this to prove a characterization of dispatchable involving the structural properties of the STN graph.
Abstract: Dispatchability is an important property for the efficient execution of temporal plans where the temporal constraints are represented as a Simple Temporal Network (STN). It has been shown that every STN may be reformulated as a dispatch-able STN, and dispatchability ensures that the temporal constraints need only be satisfied locally during execution. Recently it has also been shown that Simple Temporal Networks with Uncertainty, augmented with wait edges, are Dynamically Controllable provided every projection is dispatchable. Thus, the dispatchability property has both theoretical and practical interest. One thing that hampers further work in this area is the underdeveloped theory. The existing definitions are expressed in terms of algorithms, and are less suitable for mathematical proofs. In this paper, we develop a new formal theory of dispatchability in terms of execution sequences. We exploit this to prove a characterization of dispatchability involving the structural properties of the STN graph. This facilitates the potential application of the theory to uncertainty reasoning.

4 citations


Journal ArticleDOI
TL;DR: The hypothesis that hypotestosteronaemia is not a consequence of angina pectoris or myocardial ischaemia is supported as well as the hypothesis that coronary revascularization has no sustained effect on androgen status.
Abstract: There is a clear association between low serum testosterone and coronary artery disease (CAD) in men. Hypotestosteronaemia is associated with accelerated atherosclerosis and a quarter of men with CAD are biochemically hypogonadal. Amongst those with CAD, hypotestosteronaemia is associated with increased mortality. Testosterone vasodilates coronary arteries, and exogenous testosterone reduces ischaemia. Whether hypotestosteronaemia is a cause or a consequence of CAD remains unanswered. The aim of this prospective observational study was to investigate whether coronary revascularization affected androgen status in men with stable angina pectoris. Twenty five men (mean age 62.7, SD 9.18) with angiographically significant CAD and symptomatic angina underwent full coronary revascularization by percutaneous coronary intervention. Androgen status and symptoms of angina, stress, depression and sexual function were assessed before, and at one and 6 months after the coronary revascularization. All patients underwent complete revascularization which was associated with a significant reduction in angina symptoms and ischaemia. No significant difference was seen in total testosterone (11.33 nmol/L baseline; 12.56, 1 month post; 13.04 at 6 months; p = 0.08). A significant and sustained rise in sex hormone-binding globulin was seen (33.99 nm/L baseline; 36.11 nm/L 1 month post PCI; 37.94 nm/L at 6 months; p = 0.03) Overall, there was no significant alteration in any other marker of androgen status including free testosterone or bioavailable testosterone. There was no change in symptoms of anxiety, depression or sexual function. Coronary revascularization has no sustained effect on androgen status. This supports the hypothesis that hypotestosteronaemia is not a consequence of angina pectoris or myocardial ischaemia.

4 citations


Book ChapterDOI
01 Jan 2016

1 citations


Proceedings Article
Paul Morris1
12 Feb 2016
TL;DR: In this article, the authors develop a new mathematical theory of dispatchability and its relationship to execution, including characterizations in terms of the structural properties of the Simple Temporal Networks with Uncertainty.
Abstract: Dispatchability is an important property for the efficient execution of temporal plans where the temporal constraints are represented as a Simple Temporal Network (STN). It has been shown that every STN may be reformulated as a dispatchable STN, and dispatchability ensures that the temporal constraints need only be satisfied locally during execution. Recently, it has also been shown that Simple Temporal Networks with Uncertainty, augmented with wait edges, are Dynamically Controllable provided every projection is dispatchable. Thus, dispatchability has considerable theoretical as well as practical significance. One thing that hampers further work in this area is the underdeveloped theory. Moreover, the existing foundation is inadequate in certain respects. In this paper, we develop a new mathematical theory of dispatchability and its relationship to execution. We also provide several characterizations of dispatchability, including characterizations in terms of the structural properties of the STN graph. This facilitates the potential application of the theory to other areas.


07 Oct 2016
TL;DR: The results suggest that tears of sympathy are part of a complex autonomic interaction between the sympathetic and the parasympathetic nervous systems, with the latter preceding the former.
Abstract: Sympathy crying is an odd and complex mixture of physiological and emotional phenomena. Standard psychophysiological theories of emotion cannot attribute crying to a single subdivision of the autonomic nervous system (ANS) and disagreement exists regarding the emotional origin of sympathy crying. The current experiment examines sympathy crying using functional thermal infrared imaging (FTII), a novel contactless measure of ANS activity. To induce crying female participantswere given the choice to decide which film they wanted to cry to. Compared to baseline, temperature started increasing on the forehead, the peri-orbital region, the cheeks and the chin before crying and reached even higher temperatures during crying. The maxillary area showed the opposite pattern and a gradual temperature decrease was observed compared to baseline as a result of emotional sweating. The results suggest that tears of sympathy are part of a complex autonomic interaction between the sympathetic and the parasympathetic nervous systems, with the latter preceding the former. The emotional origin of the phenomenon seems to derive from subjective internal factors that relate to one’s personal experiences and attributes with tears arising in the formof catharses or as part of shared sadness.

Patent
15 Dec 2016
TL;DR: In this paper, a computer-implemented method for determining fractional flow reserve (FFR) of a coronary artery and a computer system are provided, based upon a nonlinear impedance network having one or more characteristics based upon the pressure-flow relationship, and a measured proximal pressure of the coronary artery.
Abstract: A computer-implemented method for determining fractional flow reserve (FFR) of a coronary artery and a computer system are provided. Geometry data indicative of a geometry of a coronary system comprising the coronary artery are received;a 3D model of the coronary system is generated based on the geometry data; a pressure-flow relationship through at least a portion of the model is calculated based on steady-state analyses at a plurality of flow rates; the FFR is determined, based upon a non-linear impedance network having one or more characteristics based upon the pressure-flow relationship, and a measured proximal pressure of the coronary artery.