Upper airways colonisation of Streptococcus pneumoniae in adults aged 60 years and older: A systematic review of prevalence and individual participant data meta-analysis of risk factors

Background: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous. Methods: This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study. Findings: Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0–39% by conventional culture methods and 3–23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26–4•21 and OR 7•72, 95% CI 1•15–51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12–2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27–2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27–0•70). Interpretation: Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups. Funding: No funding was required

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies $E>E_{th}=5.5\times 10^{19}$ eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at $E>E_{th}$ are heavy nuclei with charge $Z$, the proton component of the sources should lead to excesses in the same regions at energies $E/Z$. We here report the lack of anisotropies in these directions at energies above $E_{th}/Z$ (for illustrative values of $Z=6,\ 13,\ 26$). If the anisotropies above $E_{th}$ are due to nuclei with charge $Z$, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory

The advent of the Auger Engineering Radio Array (AERA) necessitates the development of a powerful framework for the analysis of radio measurements of cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air shower radio emission in coincidence with the surface particle detectors and fluorescence telescopes of the Pierre Auger Observatory, the radio analysis functionality had to be incorporated in the existing hybrid analysis solutions for fluoresence and surface detector data. This goal has been achieved in a natural way by extending the existing Auger Offline software framework with radio functionality. In this article, we lay out the design, highlights and features of the radio extension implemented in the Auger Offline framework. Its functionality has achieved a high degree of sophistication and offers advanced features such as vectorial reconstruction of the electric field, advanced signal processing algorithms, a transparent and efficient handling of FFTs, a very detailed simulation of detector effects, and the read-in of multiple data formats including data from various radio simulation codes. The source code of this radio functionality can be made available to interested parties on request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to author list and references in v

Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory

We present the results of searches for dipolar-type anisotropies in different energy ranges above $2.5\times 10^{17}$ eV with the surface detector array of the Pierre Auger Observatory, reporting on both the phase and the amplitude measurements of the first harmonic modulation in the right-ascension distribution. Upper limits on the amplitudes are obtained, which provide the most stringent bounds at present, being below 2% at 99% $C.L.$ for EeV energies. We also compare our results to those of previous experiments as well as with some theoretical expectations.Comment: 28 pages, 11 figure

Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

Bounds on the density of sources of ultra-high energy cosmic rays from the Pierre Auger Observatory

We derive lower bounds on the density of sources of ultra-high energy cosmic rays from the lack of significant clustering in the arrival directions of the highest energy events detected at the Pierre Auger Observatory. The density of uniformly distributed sources of equal intrinsic intensity was found to be larger than similar to (0.06 – 5) x 10(-4) Mpc(-3) at 95% CL, depending on the magnitude of the magnetic defections. Similar bounds, in the range (0.2 – 7) x 10(-4) Mpc(-3), were obtained for sources following the local matter distribution.We are very grateful to the following agencies and organizations for financial support,: Comision Nacional de Energia Atomica, Fundacion Antorchas, Gobierno De La, Provincia de Ailendoza. Municipalidad de Malargile. INDM floldings and Valle Las Lenas, in gratitude for their continuing cooperation over land access. Argentina; the Australian Research Council; Conselho Nacional de Desenvolvimento Cientifico e 'Tecnologico (CNPq), Financiadora de Estudos e Projetos (FINEP), Fundacdo de Amparo a Pesquisa do Est ado de Rio de Janeiro (FAP HRJ), Fundacdo de Amparo Pesquisa do Estado de Sdo Paulo (FAPESP), Ministerio de Ciencia e Tecnologia (IVICT), Brazil; AVCR AVOZ10100502 and AVOZ10100522, GAAV KJB100100904, AISMT-CR LA08016, LG11044, 1VIEB111003, MSAI0021620859, LA08015, TACR TA01010517 and GA U.K. 119810, Czech Republic; Centre de Calcul I-N2P3/CNRS, Centre National de la -Recherche Scientifique ((1 NRS), Conseil Regional Ile-de-France, f)epartement, Physique Nuclealre et Corpusculaire (I N( Departement Sciences de l'Univers (SDU-INSU/CNRS), France; Bundesministerium fur Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DITG), Finanzministerium Baden-Wurttemberg, flelmholtz-Gemeinschaft Deutscher Forschungszentren Ministerium fur Wissenschaft und Forschung, Nordrhein-Westfalen, Ministerimn fur Wissenschaft, Forschung und Kunst, Baden-WUrttemberg, Germany; Istituto Nazion ale di Fisica Nucleare (INFN), Ministero dell'Istruzione, delhLniversita e della Ricerca (MIUR), Italy: Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico; Ministerie van Onden s Cultuur on NVetenschap Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO), Stichting voor Rmdamenteel Onderzoek der Materie (FOM), Netherlands; Ministry of Science and Higher Education, Grant Nos. N N202 200239 and N N202 207238, Poland; Portuguese national funds and FEDER funds within COMPETE - Programa Operacional Factores de Competitividade through Fundacao para a Ciencia e a Tecnologia, Portugal; Romanian Authority for Scientific Research ANCS, CNDI-UEFISETD1 partnership projects nr.20/2012 and nr.194/2012, project nr.1 /ASPERA2/20I2 ERA-NET and PN-IIRU-PD-2011-3-0145-17, Romania; Ministry for Higher Education, Science, and 'Technology, Slovenian Research Agency, Slovenia; Comunidad de Madrid, FEDER funds, Ministerio de Ciencia e Innovacion and Consolider-Ingenio 2010 (( PAN), X unta de Galicia Spain; Science and Technology Facilities Council, United kingdom; Department of Luergy, Contract Nos. DE-ACO2-07(11-111359, DE-FR02-04E1(41300, DE-FG02-99E1(41107, National Science Foundation, Grant No. 0450696, The Grainger Foundation U.S.A.; NAFOSTED, Vietnam; Marie Curie-IRSES/HPLANET, European Particle Physics Latin American Network, European Union 7th Frarneworlc Program. Grant No. IIRSES-2009-GA-246806; and UNESCO.Peer reviewe

Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids

We would like to thank the members of the Neuroscience Research Domain at ICVS for all the helpful discussions and suggestions. We are especially thankful to the animal facility caretakers, and to Drs Sara Silva, António Melo and Ana Paula Silva and Dieter Fischer for their helpStress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, and are more responsive to the psychostimulatory actions of morphine. These animals presented prominent changes in the nucleus accumbens (NAcc), a key component of the mesolimbic reward circuitry; specifically, cell numbers and dopamine (DA) levels were significantly reduced, whereas DA receptor 2 (Drd2) mRNA expression levels were markedly upregulated in the NAcc. Interestingly, repeated morphine exposure significantly downregulated Drd2 expression in iuGC-exposed animals, in parallel with increased DNA methylation of the Drd2 gene. Administration of a therapeutic dose of L-dopa reverted the hypodopaminergic state in the NAcc of iuGC animals, normalized Drd2 expression and prevented morphine-induced hypermethylation of the Drd2 promoter. In addition, L-dopa treatment promoted dendritic and synaptic plasticity in the NAcc and, importantly, reversed drug-seeking behavior. These results reveal a new mechanism through which drug-seeking behaviors may emerge and suggest that a brief and simple pharmacological intervention can restrain these behaviors in vulnerable individuals.This work was supported by the Institute for the Study of Affective Neuroscience (ISAN). AJR, BC and MC were supported by Fundação para a Ciência e Tecnologia (FCT) fellowship

Protection of flunarizine on cerebral mitochondria injury induced by cortical spreading depression under hypoxic conditions

A rat cortical spreading depression (CSD) model was established to explore whether cerebral mitochondria injury was induced by CSD under both normoxic and hypoxic conditions and whether flunarizine had a protective effect on cerebral mitochondria. SD rats, which were divided into seven groups, received treatment as follows: no intervention (control Group I); 1 M NaCl injections (Group II); 1 M KCl injections (Group III); intraperitoneal flunarizine (3 mg/kg) 30 min before KCl injections (Group IV); 14% O2 inhalation before NaCl injections (Group V); 14% O2 inhalation followed by KCl injections (Group VI); 14% O2 inhalation and intraperitoneal flunarizine followed by KCl injections (Group VII). Following treatment, brains were removed for the analysis of mitochondria transmembrane potential (MMP) and oxidative respiratory function after recording the number, amplitude and duration of CSD. The duration of CSD was significantly longer in Group VI than that in Group III. The number and duration of CSD in Group VII was significantly lower than that in Group VI. MMP in Group VI was significantly lower than that in Group III, and MMP in Group VII was significantly higher than that in Group VI. State 4 respiration in Group VI was significantly higher than that in Group III, and state 3 respiration in Group VII was significantly higher than that in Group VI. Respiration control of rate in Group VII was also significantly higher than that in Group VI. Thus, we concluded that aggravated cerebral mitochondria injury might be attributed to CSD under hypoxic conditions. Flunarizine can alleviate such cerebral mitochondria injury under both normoxic and hypoxic conditions