Coronary artery remodelling, atherosclerosis and vascular function

OBJECTIVES: The aims of the thesis were to assess coronary artery remodelling and plaque load, and to determine whether this influences vascular and endothelial function in vivo in man.METHODS: Coronary artery remodelled segments were categorised using intravascular ultrasound (IVUS). Plaque type was characterised directly from spectral analysis of the radiofrequency ultrasound signal. Central arterial stiffness was assessed using non-invasive measures of arterial stiffness obtained by applanation tonometry of the radial, carotid and femoral artery. Coronary artery plaque volume was determined following computerised three-dimensional reconstruction of IVUS images obtained during a motorised pullback device. Coronary vessel area, arterial stiffness and vasomotor responses were determined using IVUS and Doppler Flow measurement and endothelial fibrinolytic responses by coronary sinus sampling during selective intracoronary infusions.RESULTS: Plaque characteristics Positively remodelled segments had a larger vessel area (16.5±1.1 mm2 vs. 8.7±0.9 mm2, p<0.01) and plaque area (7.3+1.1 mm2 vs. 4.4+0.8 mm2, p=0.05) than negatively remodelled segments. Both positive and negatively remodelled segments had a greater percentage of fibrous plaque (p<0.01) than calcified or lipid rich plaque. Comparing positively and negatively remodelled segments, there was no significant difference between the proportion of fibrous, calcified and lipid rich plaque. Comparisons with non-invasive measures Plaque volume positively correlated with carotid-radial pulse wave velocity (r=0.47, p=0.008) and appeared to correlate with carotid-femoral pulse wave velocity (r=0.34, p=0.07). Aortic augmentation (r=0.24, p=0.16), augmentation index (r=0.3, p=0.08), and pulse pressure (r=0.22, p=0.2) did 2 not significantly correlate with proximal coronary artery plaque volume. Structure and function In comparison to non- and positively remodelled segments, negatively remodelled segments had a higher stiffness index (67±16 vs. 33±5 and 38±8 respectively; p<0.02). A significant degree of preservation of vasodilatation to 10"6 M acetylcholine was evident in positively remodelled compared with negatively remodelled segments (p<0.05). Coronary blood flow increased with both substance P and sodium nitroprusside infusions (p<0.001), although coronary sinus plasma t-PA antigen and activity concentrations increased only during substance P infusion (p<0.006 for both). There was a significant inverse correlation between coronary artery plaque burden and the release of active t-PA (r=- 0.61, p=0.003).CONCLUSIONS: Pulse wave analysis may be a useful non-invasive surrogate marker for the extent of coronary atherosclerosis. Atherosclerotic risk factors and coronary plaque load are associated with impaired vasomotor and endogenous fibrinolytic function. Though plaque type was similar in remodelled types, negative remodelling was associated with more pronounced local vascular and endothelial dysfunction. These findings collectively suggest an important local interrelationship between coronary vascular structure and function that has implications for the pathophysiology of ischaemic heart disease

A (Bounded) Bestiary of Feynman Integral Calabi-Yau Geometries

We define the rigidity of a Feynman integral to be the smallest dimension over which it is non-polylogarithmic. We argue that massless Feynman integrals in four dimensions have a rigidity bounded by 2(L-1) at L loops, and we show that this bound may be saturated for integrals that we call marginal: those with (L+1)D/2 propagators in (even) D dimensions. We show that marginal Feynman integrals in D dimensions generically involve Calabi-Yau geometries, and we give examples of finite four-dimensional Feynman integrals in massless $\phi^4$ theory that saturate our predicted bound in rigidity at all loop orders.Comment: 5+2 pages, 11 figures, infinite zoo of Calabi-Yau manifolds. v2 reflects minor changes made for publication. This version is authoritativ

The Elliptic Double-Box Integral: Massless Amplitudes Beyond Polylogarithms

We derive an analytic representation of the ten-particle, two-loop double-box integral as an elliptic integral over weight-three polylogarithms. To obtain this form, we first derive a four-fold, rational (Feynman-)parametric representation for the integral, expressed directly in terms of dual-conformally invariant cross-ratios; from this, the desired form is easily obtained. The essential features of this integral are illustrated by means of a simplified toy model, and we attach the relevant expressions for both integrals in ancillary files. We propose a normalization for such integrals that renders all of their polylogarithmic degenerations pure, and we discuss the need for a new 'symbology' of iterated elliptic/polylogarithmic integrals in order to bring them to a more canonical form.Comment: 4+2 pages, 2 figures. Explicit results are included as ancillary files. v2: minor changes made for clarification; references adde

EVOLVING CONSERVATION EASEMENT MARKETS IN THE WEST

Land Economics/Use,

A Multiple Indicators, Multiple Causes Analysis of Farmers\u27 Information Use

A multiple indicators, multiple causes, or MIMIC, modeling framework can be used for analyzing a variety of farmer decision-making situations where multiple outcomes are possible. Example applications include analyses of farmer use of multiple information sources, management practices, or technologies. We applied the framework to analyze use of multiple information sources by beef cattle farmers. We provide measures of how farmer demographics, farm characteristics, and risk attitudes influenced farmer use of information from Extension, producer groups, popular press, the U.S. Department of Agriculture, the Internet, and other farmers. Education and greater willingness to take risk positively influenced information use among the farmers we studied. Our process has implications for broader use within Extension

All-Multiplicity Non-Planar MHV Amplitudes in sYM at Two Loops

We give a closed-form, prescriptive representation of all-multiplicity two-loop MHV amplitude integrands in fully-color-dressed (non-planar) maximally supersymmetric Yang-Mills theory.Comment: Corrected a sign mistake for the pentabox numerators (table IV). Minor improvements and references added in v2. 4+3 pages, 22 figures, 4 tables, infinity of new amplitudes. Ancillary files contain a Mathematica implementation of our resul

Rooting out letters:octagonal symbol alphabets and algebraic number theory

It is widely expected that NMHV amplitudes in planar, maximally supersymmetric Yang-Mills theory require symbol letters that are not rationally expressible in terms of momentum-twistor (or cluster) variables starting at two loops for eight particles. Recent advances in loop integration technology have made this an `experimentally testable' hypothesis: compute the amplitude at some kinematic point, and see if algebraic symbol letters arise. We demonstrate the feasibility of such a test by directly integrating the most difficult of the two-loop topologies required. This integral, together with its rotated image, suffices to determine the simplest NMHV component amplitude: the unique component finite at this order. Although each of these integrals involve algebraic symbol alphabets, the combination contributing to this amplitude is---surprisingly---rational. We describe the steps involved in this analysis, which requires several novel tricks of loop integration and also a considerable degree of algebraic number theory. We find dramatic and unusual simplifications, in which the two symbols initially expressed as almost ten million terms in over two thousand letters combine in a form that can be written in five thousand terms and twenty-five letters.Comment: 25 pages, 4 figures; detailed results available as ancillary file

Embedding Feynman integral (Calabi-Yau) geometries in weighted projective space

It has recently been demonstrated that Feynman integrals relevant to a wide range of perturbative quantum field theories involve periods of Calabi-Yaus of arbitrarily large dimension. While the number of Calabi-Yau manifolds of dimension three or higher is considerable (if not infinite), those relevant to most known examples come from a very simple class: degree-$2k$ hypersurfaces in $k$-dimensional weighted projective space $\mathbb{WP}^{1,\ldots,1,k}$. In this work, we describe some of the basic properties of these spaces and identify additional examples of Feynman integrals that give rise to hypersurfaces of this type. Details of these examples at three and four loops are included as ancillary files to this work.Comment: 44 pages, 31 figures; detailed examples given in ancillary file. Updated to reflect revisions for publicatio

Developing a hypothetical implementation framework of expectations for monitoring early signs of psychosis relapse using a mobile app: qualitative study

Background: Relapse is a common experience for people diagnosed with psychosis, which is associated with increased service costs and profound personal and familial distress. EMPOWER (Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery) is a peer worker–supported digital intervention that aims to enable service users to self-monitor their mental health with the aim of encouraging self-management and the shared use of personal data to promote relapse prevention. Digital interventions have not been widely used in relapse prevention and, therefore, little is currently known about their likely implementation—both within trials and beyond. Objective: Seeking the perspectives of all relevant stakeholder groups is recommended in developing theories about implementation because this can reveal important group differences in understandings and assumptions about whether and for whom the intervention is expected to work. However, the majority of intervention implementation research has been retrospective. This study aimed to discover and theoretically frame implementation expectations in advance of testing and synthesize these data into a framework. Methods: To develop a hypothetical implementation framework, 149 mental health professionals, carers, and people diagnosed with psychosis participated in 25 focus groups in both Australia and the United Kingdom. An interview schedule informed by the normalization process theory was used to explore stakeholders’ expectations about the implementation of the EMPOWER intervention. Data were analyzed using thematic analysis and then theoretically framed using the Medical Research Council guidelines for understanding the implementation of complex interventions. Results: All groups expected that EMPOWER could be successfully implemented if the intervention generated data that were meaningful to mental health staff, carers, and service users within their unique roles. However, there were key differences between staff, carers, and service users about what facilitators and barriers that stakeholders believe exist for intervention implementation in both the cluster randomized controlled trial stage and beyond. For example, service user expectations mostly clustered around subjective user experiences, whereas staff and carers spoke more about the impact upon staff interactions with service users. Conclusions: A hypothetical implementation framework synthesized from stakeholder implementation expectations provides an opportunity to compare actual implementation data gathered during an ongoing clinical trial, giving valuable insights into the accuracy of these stakeholders’ previous expectations. This is among the first studies to assess and record implementation expectations for a newly developed digital intervention for psychosis in advance of testing in a clinical trial