Imaging as an End Point in Ischemia Trials

Imaging of cardiac function and anatomy has advanced at an exponential rate over the past two decades. Our ability to quantitatively assess the degree of myocardial ischemia and accurately define the vascular anatomy using noninvasive techniques is greater than ever before. Current advances is cardiac imaging are allowing us to more safely assess patients for myocardial ischemia and better understand the prognostic implications of our findings. This review summarizes the current state of knowledge in cardiac imaging for the assessment of cardiac ischemia with a focus on the use of cardiac MRI

Re-evaluating the changing geographies of climate activism and the state in the post-climate emergency era in the build-up to COP26

A key aim of much climate activism is to enhance climate ambition and hold local and national governments, as well as global governance forums like the United Nations (UN), to account for the ways in which they implement and monitor climate policy across society to reverse long-term climate change. In recent years new local forms of climate activism, particularly at the urban scale, have taken a more prominent role in this. Although place-based, such local forms of climate activism are at the same time multi-scalar in orientation and strategic focus. This is particularly true in the UK where climate activism has prompted a number of local councils to declare climate emergencies, providing a mechanism by which they can become locally accountable in the delivery of their climate action plans, whilst at the same time holding national government to prior and future commitments to global climate governance. Using interview data with experts working on climate emergency declarations research across the UK, we critically discuss four key themes that have underpinned and catalysed the changing geographies of civil-state relationships within the climate emergency and what this may mean for future global climate governance under the UNFCCC Conferences of the Parties (COP). We argue that decision-makers at COP26 need to take greater heed of the significance of this new broader urban climate activism and its role in geopolitically mobilising more equitable, democratic and inclusive forms of climate governance which give citizens and civil society more credence within global climate policy decision-making processes that have been up to now, dominated by national state discourses

Radial Lattice Quantization of 3D ϕ4\phi^4 Field Theory

The quantum extension of classical finite elements, referred to as quantum finite elements ({\bf QFE})~\cite{Brower:2018szu,Brower:2016vsl}, is applied to the radial quantization of 3d $\phi^4$ theory on a simplicial lattice for the $\mathbb R \times \mathbb S^2$ manifold. Explicit counter terms to cancel the one- and two-loop ultraviolet defects are implemented to reach the quantum continuum theory. Using the Brower-Tamayo~\cite{Brower:1989mt} cluster Monte Carlo algorithm, numerical results support the QFE ansatz that the critical conformal field theory (CFT) is reached in the continuum with the full isometries of $\mathbb R \times \mathbb S^2$ restored. The Ricci curvature term, while technically irrelevant in the quantum theory, is shown to dramatically improve the convergence opening, the way for high precision Monte Carlo simulation to determine the CFT data: operator dimensions, trilinear OPE couplings and the central charge.Comment: 8 pages, 7 figure

Molecular Gas in the Lensed Lyman Break Galaxy cB58

We have used the IRAM Plateau de Bure Interferometer to map CO(3-2) emission from the gravitationally lensed Lyman break galaxy MS1512-cB58. This is the first detection of a molecular emission line in any Lyman break system; its integrated intensity implies a total molecular gas mass of 6.6e9 Msun, while its width implies a dynamical mass of 1.0e10 csc^2i Msun (for a flat Lambda=0.7 cosmology). These estimates are in excellent concordance with nearly all parameters of the system measured at other wavelengths, and yield a consistent picture of past and future star formation with no obvious discrepancies requiring explanation by differential lensing. In particular, we find that the age and remaining lifetime of the current episode of star formation are likely to be similar; the surface densities of star formation and molecular gas mass are related by a Schmidt law; and the fraction of baryonic mass already converted into stars is sufficient to account for the observed enrichment of the interstellar medium to 0.4 Zsun. Barring substantial gas inflow or a major merger, the stars forming in the current episode will have mass and coevality at z=0 similar to those of a spiral bulge. Assuming cB58 is a typical Lyman break galaxy apart from its magnification, its global parameters suggest that the prescriptions for star formation used in some semi-analytic models of galaxy evolution require moderate revision, although the general prediction that gas mass fraction should increase with redshift is validated. [abridged]Comment: 41 pages, 6 figures, accepted by Ap

Informing UK governance of resilience to climate risks: improving the local evidence-base

International assessments of evidence on climate change (e.g. Intergovernmental Panel on Climate Change, IPCC) or national climate change risk assessments (e.g. UK Climate Change Risk Assessment, CCRA) do not offer a sufficiently granular perspective on climate impacts to adequately inform governance of resilience to climate risks at the local level. Using an analysis of UK decision-makers managing and responding to heatwaves and flood risks, this paper argues how more robust local evidence is needed to inform decision-making regarding adaptation options for enhancing local resilience. We identify evidence gaps and issues relating to local climate change impacts, including sources and quality of evidence used, adequacy and accessibility of evidence available, ill-communicated evidence and conflicting or misused evidence. A lack of appreciation regarding how scientific evidence and personal judgement can mutually enhance the quality of decision-making underpins all of these gaps. Additionally, we find that the majority of evidence currently used is reductively based upon socio-economic and physical characteristics of climate risks. We argue that a step change is needed in local climate resilience that moves beyond current physical and socio-economic risk characterisation to a more inclusive co-constitution of social and politically defined climate risks at the local scale that are better aligned with the local impacts felt and needs of stakeholders

Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms

BackgroundAsthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear.ObjectiveWe performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients.MethodsSixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed.ResultsSignificant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and ??-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms.ConclusionThe evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies

Influence of Sex-Based Differences in Cardiac Phenotype on Atrial Fibrillation Recurrence in Patients Undergoing Pulmonary Vein Isolation

BackgroundPulmonary vein isolation (PVI) is a commonly engaged therapy for symptomatic atrial fibrillation (AF). Prior studies have documented elevated AF recurrence rates among females vs. males. Sex-specific mechanisms underlying this phenomenon are poorly understood. This prospective cohort study aimed to evaluate the sex-based differences in cardiac phenotype and their influence on (AF) recurrence following first-time PVI.MethodsA total of 204 consecutive patients referred for first-time PVI and 101 healthy subjects were prospectively studied by cardiovascular magnetic resonance (CMR) imaging. Multi-chamber volumetric and functional measures were assessed by sex-corrected Z-score analyses vs. healthy subjects. Patients were followed for a median of 2.6 years for the primary outcome of clinical AF recurrence. Multivariable analyses adjusting for age and comorbidities were performed to identify independent predictors of AF recurrence.ResultsAF recurrence following first PVI occurred in 41% of males and 59% of females (p = 0.03). Females were older with higher prevalence of hypertension and thyroid disorders. Z-score-based analyses revealed significantly reduced ventricular volumes, greater left atrial (LA) volumes, and reduced LA contractility in females vs. males. Multivariable analysis revealed each of LA minimum and pre-systolic volumes and booster EF Z-scores to be independently associated with AF recurrence, providing respective hazard ratios of 1.10, 1.19, and 0.89 (p = 0.001, 0.03, and 0.01).ConclusionAmong patients referred for first time PVI, females were older and demonstrated significantly poorer LA contractile health vs. males, the latter independently associated with AF recurrence. Assessment of LA contractile health may therefore be of value to identify female patients at elevated risk of AF recurrence. Factors influencing female patient referral for PVI at more advanced stages of atrial disease warrant focused investigation