The promotion of local wellbeing: A primer for policymakers

There is growing interest among policymakers in the promotion of wellbeing as an objective of public policy. In particular, local authorities have been given powers to undertake action to promote wellbeing in their area. Recent advances in the academic literature on wellbeing are giving rise to an increasingly detailed picture of the factors that determine people’s subjective wellbeing (how they think and feel about their lives). However, the concept of subjective wellbeing is poorly understood within local government and much of the evidence base is extremely recent. I therefore review the literature on the definition, measurement, and determinants of wellbeing, and discuss some of its implications for local public policy

Quantum theory of massless (p,0)-forms

We describe the quantum theory of massless (p,0)-forms that satisfy a suitable holomorphic generalization of the free Maxwell equations on Kaehler spaces. These equations arise by first-quantizing a spinning particle with a U(1)-extended local supersymmetry on the worldline. Dirac quantization of the spinning particle produces a physical Hilbert space made up of (p,0)-forms that satisfy holomorphic Maxwell equations coupled to the background Kaehler geometry, containing in particular a charge that measures the amount of coupling to the U(1) part of the U(d) holonomy group of the d-dimensional Kaehler space. The relevant differential operators appearing in these equations are a twisted exterior holomorphic derivative and its hermitian conjugate (twisted Dolbeault operators with charge q). The particle model is used to obtain a worldline representation of the one-loop effective action of the (p,0)-forms. This representation allows to compute the first few heat kernel coefficients contained in the local expansion of the effective action and to derive duality relations between (p,0) and (d-p-2,0)-forms that include a topological mismatch appearing at one-loop.Comment: 32 pages, 3 figure

Two Years Later: Journals Are Not Yet Enforcing the ARRIVE Guidelines on Reporting Standards for Pre-Clinical Animal Studies

There is growing concern that poor experimental design and lack of transparent reporting contribute to the frequent failure of pre-clinical animal studies to translate into treatments for human disease. In 2010, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were introduced to help improve reporting standards. They were published in PLOS Biology and endorsed by funding agencies and publishers and their journals, including PLOS, Nature research journals, and other top-tier journals. Yet our analysis of papers published in PLOS and Nature journals indicates that there has been very little improvement in reporting standards since then. This suggests that authors, referees, and editors generally are ignoring guidelines, and the editorial endorsement is yet to be effectively implemented

Molecular motors robustly drive active gels to a critically connected state

Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages, 8 figure

Edaphic, structural and physiological contrasts across Amazon Basin forest-savanna ecotones suggest a role for potassium as a key modulator of tropical woody vegetation structure and function

Sampling along a precipitation gradient in tropical South America extending from ca. 0.8 to 2.0 m ag-1, savanna soils had consistently lower exchangeable cation concentrations and higher C/N ratios than nearby forest plots. These soil differences were also reflected in canopy averaged leaf traits with savanna trees typically having higher leaf mass per unit area but lower mass-based nitrogen (Nm) and potassium (Km). Both Nm and Km also increased with declining mean annual precipitation (PA), but most area-based leaf traits such as leaf photosynthetic capacity showed no systematic variation with PA or vegetation type. Despite this invariance, when taken in conjunction with other measures such as mean canopy height, area-based soil exchangeable potassium content, [K]sa , proved to be an excellent predictor of several photosynthetic properties (including 13C isotope discrimination). Moreover, when considered in a multivariate context with PA and soil plant available water storage capacity (θP) as covariates, [K]sa also proved to be an excellent predictor of stand-level canopy area, providing drastically improved fits as compared to models considering just PA and/or θP. Neither calcium, nor magnesium, nor soil pH could substitute for potassium when tested as alternative model predictors (ΔAIC > 10). Nor for any model could simple soil texture metrics such as sand or clay content substitute for either [K]sa or θP. Taken in conjunction with recent work in Africa and the forests of the Amazon Basin, this suggests-in combination with some newly conceptualised interacting effects of PA and θP also presented here-a critical role for potassium as a modulator of tropical vegetation structure and function.Natural Environment Research Council (NERC) TROBIT Consortium projectCNPqRoyal Society of London - Wolfson Research Merit Awar

External validation of the Ottawa subarachnoid hemorrhage clinical decision rule in patients with acute headache ☆

We aim to externally validate the Ottawa subarachnoid hemorrhage (OSAH) clinical decision rule. This rule identifies patients with acute nontraumatic headache who require further investigation. We conducted a medical record review of all patients presenting to the emergency department (ED) with headache from January 2011 to November 2013. Per the OSAH rule, patients with any of the following predictors require further investigation: age 40 years or older, neck pain, stiffness or limited flexion, loss of consciousness, onset during exertion, or thunderclap. The rule was applied following the OSAH rule criteria. Patients were followed up for repeat visits within 7 days of initial presentation. Data were electronically harvested from the electronic medical record and manually abstracted from individual patient charts using a standardized data abstraction form. Calibration between trained reviewers was performed periodically. A total of 5034 ED visits with acute headache were reviewed for eligibility. There were 1521 visits that met exclusion criteria, and 3059 had headache of gradual onset or time to maximal intensity greater than or equal to 1 hour. The rule was applied to 454 patients (9.0%). There were 9 cases of subarachnoid hemorrhage (SAH), yielding an incidence of 2.0% (95% confidence interval [CI], 1.0%-3.9%) in the eligible cohort. The sensitivity for SAH was 100% (95% CI, 62.9%-100%); specificity, 7.6% (95% CI, 5.4%-10.6%); positive predictive value, 2.1% (95% CI 1.0%-4.2%); and negative predictive value, 100% (95% CI, 87.4%-100%). The OSAH rule was 100% sensitive for SAH in the eligible cohort. However, its low specificity and applicability to only a minority of ED patients with headache (9%) reduce its potential impact on practice

Logarithmic Corrections to Extremal Black Hole Entropy from Quantum Entropy Function

We evaluate the one loop determinant of matter multiplet fields of N=4 supergravity in the near horizon geometry of quarter BPS black holes, and use it to calculate logarithmic corrections to the entropy of these black holes using the quantum entropy function formalism. We show that even though individual fields give non-vanishing logarithmic contribution to the entropy, the net contribution from all the fields in the matter multiplet vanishes. Thus logarithmic corrections to the entropy of quarter BPS black holes, if present, must be independent of the number of matter multiplet fields in the theory. This is consistent with the microscopic results. During our analysis we also determine the complete spectrum of small fluctuations of matter multiplet fields in the near horizon geometry.Comment: LaTeX file, 52 pages; v2: minor corrections, references adde

Spacelike Singularities and Hidden Symmetries of Gravity

We review the intimate connection between (super-)gravity close to a spacelike singularity (the "BKL-limit") and the theory of Lorentzian Kac-Moody algebras. We show that in this limit the gravitational theory can be reformulated in terms of billiard motion in a region of hyperbolic space, revealing that the dynamics is completely determined by a (possibly infinite) sequence of reflections, which are elements of a Lorentzian Coxeter group. Such Coxeter groups are the Weyl groups of infinite-dimensional Kac-Moody algebras, suggesting that these algebras yield symmetries of gravitational theories. Our presentation is aimed to be a self-contained and comprehensive treatment of the subject, with all the relevant mathematical background material introduced and explained in detail. We also review attempts at making the infinite-dimensional symmetries manifest, through the construction of a geodesic sigma model based on a Lorentzian Kac-Moody algebra. An explicit example is provided for the case of the hyperbolic algebra E10, which is conjectured to be an underlying symmetry of M-theory. Illustrations of this conjecture are also discussed in the context of cosmological solutions to eleven-dimensional supergravity.Comment: 228 pages. Typos corrected. References added. Subject index added. Published versio

Quantum Gravity in 2+1 Dimensions: The Case of a Closed Universe

In three spacetime dimensions, general relativity drastically simplifies, becoming a ``topological'' theory with no propagating local degrees of freedom. Nevertheless, many of the difficult conceptual problems of quantizing gravity are still present. In this review, I summarize the rather large body of work that has gone towards quantizing (2+1)-dimensional vacuum gravity in the setting of a spatially closed universe.Comment: 61 pages, draft of review for Living Reviews; comments, criticisms, additions, missing references welcome; v2: minor changes, added reference

Epidermal growth factor receptor kinase domain mutations are rare in salivary gland carcinomas

Activating mutations within the epidermal growth factor (EGFR) tyrosine kinase domain identify non-small cell lung cancer patients with improved clinical response to tyrosine kinase inhibitor therapy. Recently, we identified two EGFR mutations in a cohort of 25 salivary gland carcinomas (SGCs) by screening the tumour samples for the both most common hotspot mutations in exons 19 and 21 by allele-specific PCR. Here, we present a comprehensive sequencing analysis of the entire critical EGFR tyrosine kinase domain in 65 SGC of the main histopathological types. We found EGFR mutations in the tyrosine kinase domain to be a rare event in SGCs. No additional mutations other than the two known exon 19 deletions (c.2235_2249del15) in a mucoepidermoid carcinoma and an adenoid cystic carcinoma have been detected. Other putative predictive markers for EGFR-targeted therapy in SGCs might be relevant and should be investigated