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Agents that block the renin–angiotensin system (RAS) improve glucoregulation in the metabolic syndrome disorder. We evaluated the effects of egg white hydrolysate (EWH), previously shown to modulate the protein abundance of RAS component in vivo, on glucose homeostasis in diet-induced insulin-resistant rats. Sprague–Dawley rats were fed a high-fat diet (HFD) for 6 weeks to induce insulin resistance. They were then randomly divided into four groups receiving HFD or HFD supplemented with different concentrations of EWH (1, 2 and 4 %) for another 6 weeks in the first trial. In the second trial, insulin-resistant rats were divided into two groups receiving only HFD or HFD+4 % EWH for 6 weeks. Glucose homeostasis was assessed by oral glucose tolerance and insulin tolerance tests. Insulin signalling and protein abundance of RAS components, gluconeogenesis enzymes and PPARγ were evaluated in muscle, fat and liver. Adipocyte morphology and inflammatory markers were evaluated. In vivo administration of EWH increased insulin sensitivity, improved oral glucose tolerance (P < 0·0001) and reduced systemic inflammation (P < 0·05). EWH potentiated insulin-induced Akt phosphorylation in muscle (P = 0·0341) and adipose tissue (P = 0·0276), but minimal differences in the protein abundance of tissue RAS components between the EWH and control groups were observed. EWH treatment also reduced adipocyte size (P = 0·0383) and increased PPARγ2 protein abundance (P = 0·0237). EWH treatment yielded positive effects on the inflammatory profile, glucose tolerance, insulin sensitivity and adipocyte differentiation in HFD-induced insulin resistance rats. The involvement of local RAS activity requires further investigation.
Accelerating innovation translation is a priority for improving healthcare and health. Although dissemination and implementation (D&I) research has made significant advances over the past decade, it has attended primarily to the implementation of long-standing, well-established practices and policies. We present a conceptual architecture for speeding translation of promising innovations as candidates for iterative testing in practice. Our framework to Design for Accelerated Translation (DART) aims to clarify whether, when, and how to act on evolving evidence to improve healthcare. We view translation of evidence to practice as a dynamic process and argue that much evidence can be acted upon even when uncertainty is moderately high, recognizing that this evidence is evolving and subject to frequent reevaluation. The DART framework proposes that additional factors – demand, risk, and cost, in addition to the evolving evidence base – should influence the pace of translation over time. Attention to these underemphasized factors may lead to more dynamic decision-making about whether or not to adopt an emerging innovation or de-implement a suboptimal intervention. Finally, the DART framework outlines key actions that will speed movement from evidence to practice, including forming meaningful stakeholder partnerships, designing innovations for D&I, and engaging in a learning health system.
Modelling of Solar Energetic Particles (SEPs) is usually carried out by means of the 1D focused transport equation and the same approach is adopted within several SEP Space Weather forecasting frameworks. We present an alternative approach, based on test particle simulations, which naturally describes 3D particle propagation. The SPARX forecasting system is an example of how test particle simulations can be used in real time in a Space Weather context. SPARX is currently operational within the COMESEP Alert System. The performance of the system, which is triggered by detection of a solar flare of class >M1.0 is evaluated by comparing forecasts for flare events between 1997 and 2017 with actual SEP data from the GOES spacecraft.
Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA–MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA–MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA–MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.
Mental health research funding priorities in high-income countries must balance longer-term investment in identifying neurobiological mechanisms of disease with shorter-term funding of novel prevention and treatment strategies to alleviate the current burden of mental illness. Prioritising one area of science over others risks reduced returns on the entire scientific portfolio.
Endothelial dysfunction and arterial stiffness are early predictors of CVD. Intervention studies have suggested that diet is related to vascular health, but most prior studies have tested individual foods or nutrients and relied on small samples of younger adults. The purpose of the present study was to examine the relationships between adherence to the 2010 Dietary Guidelines for Americans and vascular health in a large cross-sectional analysis. In 5887 adults in the Framingham Heart Study Offspring and Third Generation cohorts, diet quality was quantified with the 2010 Dietary Guidelines Adherence Index (DGAI-2010). Endothelial function was assessed via brachial artery ultrasound and arterial stiffness via arterial tonometry. In age-, sex- and cohort-adjusted analyses, a higher DGAI-2010 score (greater adherence) was modestly associated with a lower resting flow velocity, hyperaemic response, mean arterial pressure, carotid–femoral pulse wave velocity (PWV), and augmentation index, but not associated with resting arterial diameter or flow-mediated dilation (FMD). In multivariable models adjusting for cardiovascular risk factors, only the association of a higher DGAI-2010 score with a lower baseline flow velocity and augmentation index persisted (β = − 0·002, P= 0·003 and β = − 0·05 ± 0·02, P< 0·001, respectively). Age-stratified multivariate-adjusted analyses suggested that the relationship of higher DGAI-2010 scores with lower mean arterial pressure, PWV and augmentation index was more pronounced among adults younger than 50 years. Better adherence to the 2010 Dietary Guidelines for Americans, particularly in younger adults, is associated with a lower peripheral blood flow velocity and arterial wave reflection, but not FMD. The present results suggest a link between adherence to the Dietary Guidelines and favourable vascular health.
In this final chapter we focus on the interactions between convection, magnetic fields and rotation in stars that, like our Sun, possess deep outer convection zones, with the aim of relating theory to observations. Following on from the treatment of planetary dynamos in Chapter 7, we begin by considering the large-scale fields that are responsible for the solar cycle and survey attempts to model solar and stellar dynamos, ranging from mean-field dynamo theory to the results of the latest massive computations (Charbonneau 2010).
Then we turn to small-scale behaviour at the solar surface. Over the past two decades detailed observations – from the ground, from the stratosphere and from space – have revealed a wealth of detailed information about the structure and properties of magnetic features on the Sun and on other magnetically active stars. Although the idealized theoretical models that we have described in previous chapters do explain the general behaviour of magnetic fields at the surface of a vigorously convecting star, any more detailed confrontation of theory with observations demands a more precise description of the stellar plasma. Two properties are particularly important. The first is the role of ionization: in the Sun, hydrogen is ionized just below the visible photosphere, with resulting changes to the equation of state and the value of γ that affect the superadiabatic gradient and lead to the presence of a deep convection zone (Stix 2002).
The last thirty years have seen great leaps forward in the subject of magnetoconvection. Computational techniques can now explain exotic nonlinear behaviour, transition to chaos and the formation of structures that can be observed on the surface of the Sun. Here, two leading experts present the current state of knowledge of the subject. They provide a mathematical and numerical treatment of the interactions between electrically conducting fluids and magnetic fields that lead to the complex structures and rich behaviour observed on the Sun and other stars, as well as in the interiors of planets like the Earth. The authors' combined analytical and computational approach provides a model for the study of a wide range of related problems. The discussion includes bifurcation theory, chaotic behaviour, pattern formation in two and three dimensions, and applications to geomagnetism and to the properties of sunspots and other features at the solar surface.
The original motivation for studying magnetoconvection came from the interplay between magnetic fields and convection that is observed in sunspots. Since then this subject has developed into a fascinating and important topic in its own right. We therefore decided to write a comprehensive monograph that would cover all aspects of magnetoconvection from the viewpoint of applied mathematics, and as a branch of astrophysical (or geophysical) fluid dynamics. Thus we shall emphasize the role of nonlinear dynamics, and focus on idealized model problems rather than on ambitious realistic simulations.
The properties of convection in an electrically conducting fluid with an imposed magnetic field are interesting not only in themselves but also as the richest example of double-diffusive behaviour. Linear theory allows both steady and oscillatory solutions, while theoretical descriptions of nonlinear behaviour demonstrate the power of bifurcation theory, with examples of bifurcation sequences that lead to chaos, as well as of group-theoretic applications to pattern selection. These mathematical results can all be related to carefully constructed numerical experiments.
Although we shall adopt an applied mathematical approach, our discussion is particularly relevant to the behaviour of magnetic fields at the surface of the Sun, which are now being observed in unprecedented detail, both from the ground and from space. Convection also interacts with magnetic fields in the solar interior, as it does in other stars, and is a key component of solar and stellar dynamos.
We have seen that convection may set in at either a Hopf or a pitchfork bifurcation, giving rise to branches of nonlinear oscillatory or steady motion. In this chapter we consider weakly and mildly nonlinear behaviour, in regimes that are accessible to an analytical approach, without having to rely on large-scale computation. Our treatment relies on mathematical developments in nonlinear dynamics – a subject that has its roots in the work of Poincaré more than a century ago but has grown explosively during the past few decades. In what follows we shall adopt a straightforward approach that is aimed at traditional applied mathematicians rather than at experts in nonlinear mathematics. Magnetoconvection provides a rich and fascinating demonstration of the power of bifurcation theory, and of its ability to explain a wide range of interactions between branches of solutions that may be stable or unstable, steady, oscillatory or chaotic.
We shall confine our attention here to idealized models of Boussinesq magnetoconvection, and focus on two-dimensional behaviour. In subsequent chapters these restrictions will be progressively relaxed. We shall mainly be concerned with imposed magnetic fields that are vertical, but horizontal fields will be considered briefly in the final subsection. As in Section 3.1.4, we assume that the velocity u and the magnetic field B are confined to the xz-plane and independent of y.
In this chapter we penetrate further into the nonlinear domain, relying principally on the results of careful numerical experiments, and confining our attention to the simplest and most thoroughly studied configurations. Our primary aim is to extract qualitative understanding from the computations. Once interpreted, they provide a basis for investigating the more complicated structures and patterns that will be treated later in the book.
We begin by extending the mildly nonlinear results in Chapter 4 to cover convection in a rectangular box when the magnetic Reynolds number is large and the magnetic field becomes dynamically important. Then we study the analogous problem in a cylindrical domain with axial symmetry imposed. Next we return to Cartesian models and to the chaotic behaviour that was introduced in Section 4.3, in order to confirm that the Shilnikov effect is present in the full system; in addition, we find a regime with Lorenz-like chaos. Thereafter we consider the effects of relaxing the lateral constraints and thereby allowing travelling waves, together with steady convection in tilted cells and vigorous pulsating waves. That leads us to consider patterns of convection in extended regions, where rolls are modulated at longer wavelengths and localized (or isolated) states can appear. Then we proceed to the strong field limit, and consider behaviour when cells are vertically elongated and very slender. Finally, we discuss the effects of inclined magnetic fields on nonlinear convection.
In this chapter we introduce the effects of rotation into the study of magnetoconvection. While these effects can safely be neglected when discussing the dynamics of the solar photosphere, since typical timescales are much less than a solar day, the large-scale motions occurring deeper in the solar convection zone and in the Earth's liquid core are strongly affected by rotation. Indeed, rotation would appear to be a crucial ingredient in the dynamo mechanisms that are responsible for the geomagnetic field and the solar magnetic cycle. A full discussion of dynamo theory is outside the scope of this book (though see, for example, Dormy and Soward 2007) but we shall discuss dynamo models in which convection plays a prominent role. As such, we shall depart later in this chapter from consideration of convective flows in simple planar models and in addition discuss what happens in spherical geometries.
A necessary preliminary to understanding the complex interaction of magnetic fields with rotating convection is a discussion of the rotating, nonmagnetic case. This is first done in a Cartesian geometry. Then the effect of a vertical magnetic field is introduced. We restrict ourselves to the problem of convection in a layer rotating about a vertical axis. Then we can discuss the effects of a vertical magnetic field (this makes comparison with previous chapters easier, but such a configuration is not one that can readily be recognized in nature).