Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with D

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Mass distribution in our Galaxy

This article summarizes recent work on the luminosity and mass distribution of the Galactic bulge and disk, and on the mass of the Milky Way's dark halo. A new luminosity model consistent with the COBE NIR data and the apparent magnitude distributions of bulge clump giant stars has bulge/bar length of \simeq 3.5\kpc, axis ratios of 1:(0.3-0.4):0.3, and short disk scale-length (\simeq 2.1\kpc). Gas-dynamical flows in the potential of this model with constant M/L fit the terminal velocities in $10\deg\le |l| \le 50\deg$ very well. The luminous mass distribution with this M/L is consistent with the surface density of known matter near the Sun, but still underpredicts the microlensing optical depth towards the bulge. Together, these facts argue strongly for a massive, near-maximal disk in our $\sim L^\ast$, Sbc spiral Galaxy. While the outer rotation curve and global mass distribution are not as readily measured as in similar spiral galaxies, the dark halo mass estimated from satellite velocities is consistent with a flat rotation curve continuing on from the luminous mass distribution

Bayesian astrostatistics: a backward look to the future

This perspective chapter briefly surveys: (1) past growth in the use of Bayesian methods in astrophysics; (2) current misconceptions about both frequentist and Bayesian statistical inference that hinder wider adoption of Bayesian methods by astronomers; and (3) multilevel (hierarchical) Bayesian modeling as a major future direction for research in Bayesian astrostatistics, exemplified in part by presentations at the first ISI invited session on astrostatistics, commemorated in this volume. It closes with an intentionally provocative recommendation for astronomical survey data reporting, motivated by the multilevel Bayesian perspective on modeling cosmic populations: that astronomers cease producing catalogs of estimated fluxes and other source properties from surveys. Instead, summaries of likelihood functions (or marginal likelihood functions) for source properties should be reported (not posterior probability density functions), including nontrivial summaries (not simply upper limits) for candidate objects that do not pass traditional detection thresholds.Comment: 27 pp, 4 figures. A lightly revised version of a chapter in "Astrostatistical Challenges for the New Astronomy" (Joseph M. Hilbe, ed., Springer, New York, forthcoming in 2012), the inaugural volume for the Springer Series in Astrostatistics. Version 2 has minor clarifications and an additional referenc

Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP)

BACKGROUND: Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. The intravenous (IV) N-acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively unchanged. This involves 3 different infusion regimens (dose and time) lasting over 20 hours. The same weight-related dose of NAC is used irrespective of paracetamol dose. Complications include frequent nausea and vomiting, anaphylactoid reactions and dosing errors. We designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard NAC and a modified, shorter, regimen. METHODS/DESIGN: We designed a double-blind trial using a 2 × 2 factorial design involving four parallel groups. Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was stratified on: paracetamol dose, perceived risk factors, and time to presentation. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions and end of treatment liver function documented. Where clinically necessary further doses of NAC were administered as per standard UK protocols at the end of the first antidote course. DISCUSSION: This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first attempt to formally examine new methods of administering IV NAC in paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new NAC regimen. In addition as anaphylactoid response appears related to plasma concentrations of both NAC and paracetamol anaphylactoid reactions should be less likely. This study is not powered to assess the relative efficacy of the two NAC regimens, however it will give useful information to power future studies. As the first formal randomised clinical trial in this patient group in over 30 years this study will also provide information to support further studies in patients in paracetamol overdose, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk. TRIAL REGISTRATION: EudraCT number 2009-017800-10, ClinicalTrials.gov IdentifierNCT0105027

Accelerated swell testing of artificial sulfate bearing lime stabilised cohesive soils

This paper reports on the physico-chemical response of two lime stabilised sulfate bearing artificial soils subject to the European Accelerated Volumetric Swell Test (EN13286-49). At various intervals during the test, a specimen was removed and subject to compositional and microstructural analysis. Ettringite was formed by both soils types, but with significant differences in crystal morphology. Ettringite crystals formed from kaolin based soils were very small, colloidal in size and tended to form on the surface of other particles. Conversely, those formed from montmorillonite were relatively large and typically formed away from the surface in the pore solution. It was concluded that the mechanism by which ettringite forms is determined by the hydroxide ion concentration in the pore solution and the fundamental structure of the bulk clay. In the kaolin soil, ettringite forms by a topochemical mechanism and expands by crystal swelling. In the montmorillonite soil, it forms by a through-solution mechanism and crystal growth

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

Surveillance programs for detection and characterization of emergent pathogens and antimicrobial resistance: results from the Division of Infectious Diseases, UNIFESP

Several epidemiological changes have occurred in the pattern of nosocomial and community acquired infectious diseases during the past 25 years. Social and demographic changes possibly related to this phenomenon include a rapid population growth, the increase in urban migration and movement across international borders by tourists and immigrants, alterations in the habitats of animals and arthropods that transmit disease, as well as the raise of patients with impaired host defense abilities. Continuous surveillance programs of emergent pathogens and antimicrobial resistance are warranted for detecting in real time new pathogens, as well as to characterize molecular mechanisms of resistance. In order to become more effective, surveillance programs of emergent pathogens should be organized as a multicenter laboratory network connected to the main public and private infection control centers. Microbiological data should be integrated to guide therapy, adapting therapy to local ecology and resistance patterns. This paper presents an overview of data generated by the Division of Infectious Diseases, Federal University of São Paulo, along with its participation in different surveillance programs of nosocomial and community acquired infectious diseases.Várias alterações epidemiológicas ocorreram no perfil das doenças infecciosas hospitalares e comunitárias nos últimos 25 anos. Mudanças sociais e demográficas possivelmente relacionadas com esse fenômeno incluem o rápido crescimento populacional, o aumento da migração urbana e deslocamento através de fronteiras internacionais por turistas e imigrantes, alterações nos habitats de animais e artrópodes que transmitem doença assim como o aumento no número de pacientes com deficiências nas respostas de defesa. Os programas contínuos de vigilância de patógenos emergentes e resistência antimicrobiana são necessários para a detecção em tempo real de novos patógenos assim como para caracterizar mecanismos moleculares de resistência. Para serem mais efetivos, os programasde vigilância dos patógenos emergentes devem ser organizados em uma rede de laboratórios multicêntricos ligados aos principais centros de controle de infecções, públicos e privados. Os dados microbiológicos devem ser integrados a guias terapêuticos adaptando práticas terapêuticas à ecologia local eaos padrões de resistência. O artigo apresenta uma revisão dos dados gerados pela Disciplina de Infectologia, Universidade Federal de São Paulo (UNIFESP), contemplando sua participação nos diferentes programas de vigilância de doenças infecciosas hospitalares e adquiridas na comunidade.Universidade Federal de São Paulo (UNIFESP) Departamento de Medicina Divisão de Doenças InfecciosasUniversidade Federal de São Paulo (UNIFESP) Departamento de Microbiologia, Imunologia e ParasitologiaUNIFESP, Depto. de Medicina Divisão de Doenças InfecciosasUNIFESP, Depto. de Microbiologia, Imunologia e ParasitologiaSciEL

Cytokine and Protein Markers of Leprosy Reactions in Skin and Nerves: Baseline Results for the North Indian INFIR Cohort

Leprosy affects skin and peripheral nerves. Although we have effective antibiotics to treat the mycobacterial infection, a key part of the disease process is the accompanying inflammation. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called ‘reactions’. These reactions are associated with worsening of the nerve damage. We recruited a cohort of 303 newly diagnosed leprosy patients in North India with the aim of understanding and defining the pathological processes better. We took skin and nerve biopsies from patients and examined them to define which molecules and mediators of inflammation were present. We found high levels of the cytokines Tumour Necrosis Factor alpha, Transforming Growth Factor beta and inducible Nitric Oxide Synthase in biopsies from patients with reactions. We also found high levels of bacteria and inflammation in the nerves. These experiments tell us that we need to determine which other molecules are present and to explore ways of switching off the production of these pro-inflammatory molecules