Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Media justice: Madeleine McCann, intermediatization and "trial by media" in the British press

Three-year-old Madeleine McCann disappeared on 3 May 2007 from a holiday apartment in Portugal. Over five years and multiple investigations that failed to solve this abducted child case, Madeleine and her parents were subject to a process of relentless ‘intermediatization’. Across 24–7 news coverage, websites, documentaries, films, YouTube videos, books, magazines, music and artworks, Madeleine was a mediagenic image of innocence and a lucrative story. In contrast to Madeleine’s media sacralization, the representation of her parents, Kate and Gerry McCann, fluctuated between periods of vociferous support and prolonged and libellous ‘trial by media’. This article analyses how the global intermediatization of the ‘Maddie Mystery’ fed into and fuelled the ‘trial by media’ of Kate and Gerry McCann in the UK press. Our theorization of ‘trial by media’ is developed and refined through considering its legal limitations in an era of ‘attack journalism’ and unprecedented official UK inquiries into press misconduct and criminality

(Correcting) misdiagnoses of asthma: A cost effectiveness analysis

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The prevalence of physician-diagnosed-asthma has risen over the past three decades and misdiagnosis of asthma is potentially common. Objective: to determine whether a secondary-screening-program to establish a correct diagnosis of asthma in those who report a physician diagnosis of asthma is cost effective.Method: Randomly selected physician-diagnosed-asthmatic subjects from 8 Canadian cities were studied with an extensive diagnostic algorithm to rule-in, or rule-out, a correct diagnosis of asthma. Subjects in whom the diagnosis of asthma was excluded were followed up for 6-months and data on asthma medications and heath care utilization was obtained. Economic analysis was performed to estimate the incremental lifetime costs associated with secondary screening of previously diagnosed asthmatic subjects. Analysis was from the perspective of the Canadian healthcare system and is reported in Canadian dollars.Results: Of 540 randomly selected patients with physician diagnosed asthma 150 (28%; 95%CI 19-37%) did not have asthma when objectively studied. 71% of these misdiagnosed patients were on some asthma medications. Incorporating the incremental cost of secondary-screening for the diagnosis of asthma, we found that the average cost savings per 100 individuals screened was $35,141 (95$4,588-$69,278).Conclusion: Cost savings primarily resulted from lifetime costs of medication use averted in those who had been misdiagnosed.This work was funded by the Canadian Institute of Health Research, Canada and the University Of Ottawa Division Of Respiratory Medicine

Six-dimensional (1,0) effective action of F-theory via M-theory on Calabi-Yau threefolds

The six-dimensional effective action of F-theory compactified on a singular elliptically fibred Calabi-Yau threefold is determined by using an M-theory lift. The low-energy data are derived by comparing a circle reduction of a general six-dimensional (1,0) gauged supergravity theory with the effective action of M-theory on the resolved Calabi-Yau threefold. The derivation includes six-dimensional tensor multiplets for which the (anti-) self-duality constraints are imposed on the level of the five-dimensional action. The vector sector of the reduced theory is encoded by a non-standard potential due to the Green-Schwarz term in six dimensions. This Green-Schwarz term also contains higher curvature couplings which are considered to establish the full map between anomaly coefficients and geometry. F-/M-theory duality is exploited by moving to the five-dimensional Coulomb branch after circle reduction and integrating out massive vector multiplets and matter hypermultiplets. The associated fermions then generate additional Chern-Simons couplings at one-loop. Further couplings involving the graviphoton are induced by quantum corrections due to excited Kaluza-Klein modes. On the M-theory side integrating out massive fields corresponds to resolving the singularities of the Calabi-Yau threefold, and yields intriguing relations between six-dimensional anomalies and classical topology.Comment: 55 pages, v2: typos corrected, discussion of loop corrections improve

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality

Evidence for F(uzz) Theory

We show that in the decoupling limit of an F-theory compactification, the internal directions of the seven-branes must wrap a non-commutative four-cycle S. We introduce a general method for obtaining fuzzy geometric spaces via toric geometry, and develop tools for engineering four-dimensional GUT models from this non-commutative setup. We obtain the chiral matter content and Yukawa couplings, and show that the theory has a finite Kaluza-Klein spectrum. The value of 1/alpha_(GUT) is predicted to be equal to the number of fuzzy points on the internal four-cycle S. This relation puts a non-trivial restriction on the space of gauge theories that can arise as a limit of F-theory. By viewing the seven-brane as tiled by D3-branes sitting at the N fuzzy points of the geometry, we argue that this theory admits a holographic dual description in the large N limit. We also entertain the possibility of constructing string models with large fuzzy extra dimensions, but with a high scale for quantum gravity.Comment: v2: 66 pages, 3 figures, references and clarifications adde

Conformal Quivers and Melting Molecules

Quiver quantum mechanics describes the low energy dynamics of a system of wrapped D-branes. It captures several aspects of single and multicentered BPS black hole geometries in four-dimensional $\mathcal{N} = 2$ supergravity such as the presence of bound states and an exponential growth of microstates. The Coulomb branch of an Abelian three node quiver is obtained by integrating out the massive strings connecting the D-particles. It allows for a scaling regime corresponding to a deep AdS$_2$ throat on the gravity side. In this scaling regime, the Coulomb branch is shown to be an $SL(2,\mathbb{R})$ invariant multi-particle superconformal quantum mechanics. Finally, we integrate out the strings at finite temperature---rather than in their ground state---and show how the Coulomb branch `melts' into the Higgs branch at high enough temperatures. For scaling solutions the melting occurs for arbitrarily small temperatures, whereas bound states can be metastable and thus long lived. Throughout the paper, we discuss how far the analogy between the quiver model and the gravity picture, particularly within the AdS$_2$ throat, can be taken.Comment: 49 pages, 16 figure

Identifying Causal Risk Factors for Violence among Discharged Patients

This study was funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0407-10500)