A associação salmeterol//fluticasona é mais eficaz do que a fluticasona e o montelukast oral na asma

RESUMO: Em todo o mundo, as taxas de morbilidade e mortalidade relacionadas com a asma têm vindo a aumentar. Segundo as normas intervencionais (Guidelines), os objectivos do manejamento da asma brônquica devem ser o controlo de sintomas e a prevenção das exacerbações e consequente melhoria da qualidade de vida do doente asmático. à amplamente aceite que a terapêutica corticosteróide inalada é o tratamento preventivo disponível mais eficaz devido ao seu papel anti-inflamatório. No caso de doentes que permanecem sintomáticos sob corticoterapia por via inalatória, a associação de β2 agonista de longa acção com o salmeterol traduzse numa melhoria da função pulmonar e controlo dos sintomas mais significativa do que a observada com a duplicação da dose de corticosteróides. Está comprovada a eficácia da combinação de β2 agonistas de longa acção e corticosteróides inalados no tratamento da inflamação e disfunção do músculo liso â mecanismos fisiopatológicos envolvidos na asma.Não é ainda perfeitamente clara a vantagem da adição de antileucotrienos embora existam diversos estudos que evidenciam uma modesta melhoria da função pulmonar e dos sintomas diários quando esta classe de fármacos é associada à corticoterapia inalada.A análise actual compara a eficácia clínica de associação do salmeterol e do montelukast à corticoterapia por via inalatória (propionato de fluticasona) em adultos com asma que estão sintomáticas apesar da terapêutica referida.Foi efectuado um estudo multicêntrico, randomizado, duplamente cego, com um grupo controlo, englobando indivíduos asmáticos com idadeâ¥15 anos medicados com corticóides inalados durante, pelo menos, as 4 semanas que antecederam o estudo. Apresentavam obstrução das vias aéreas reversível após inalação de um β2 agonista de curta acção numa dose â¤800 μg (â FEV1â¥15%).Foram excluídos os doentes com infecções respiratórias, exacerbações requerendo hospitalização nas últimas 4 semanas, submetidos a corticoterapia oral ou endovenosa nesse período ou mais de 2 vezes nas últimas 12 semanas, fumadores UMA>10, mulheres grávidas ou em período de amamentação e doentes cuja terapêutica de manutenção foi alterada nas últimas semanas.Após um período de run-in de 4 semanas, os doentes foram submetidos durante 12 semanas à associação salmeterol/ propionato de fluticasona 50/100 μg duas vezes/dia ou propionato de fluticasona 100 μg duas vezes/dia e montelukast 10 mg uma vez/dia. Os doentes registaram diariamente os scores de sintomas, o PEF matinal e o uso de terapêutica de alívio.Foram observados às 4, 8 e 12 semanas de tratamento, tendo a função pulmonar sido avaliada nessas datas. Foi feito o levantamento das exacerbações que foram classificadas em ligeira (terapêutica de alívioâ¥3 inalações/ dia em relação ao basal em 2 dias consecutivos), moderada (requerendo CT oral e/ ou antibióticos) ou grave (necessitando de hospitalização).Foi monitorizada a segurança e tolerabilidade do tratamento através do registo dos efeitos adversos em cada visita clínica. Nestas foi efectuada observação pela ORL.Foram avaliados 1168 doentes, tendo sido 725 submetidos a terapêutica (356 salmeterol/ propionato de fluticasona e 369 a propionato de fluticasona e montelukast). A compliance foi elevada em ambos os grupos: 96% e 97%, respectivamente.Após 12 semanas de tratamento, o aumento do PEF matinal foi significativamente superior no grupo salmeterol/ fluticasona (36 L/min) em comparação com o 2.º grupo (19 L/min; p<0,001). A melhoria do FEV foi também significativamente maior no grupo salmeterol/fluticasona (p<0,001). A associação permite um melhor controlo dos sintomas diurnos e nocturnos, sendo as exacerbações mais raras e o uso da terapêutica de alívio menor. Ambos os tratamentos foram bem tolerados. A satisfação com os resultados obtidos com a terapêutica instituída foi superior no 1º grupo (92,9% versus 83,8%; p<0,005). A melhoria da função pulmonar observada após a administração de associação salmeterol/ fluticasona foi significativamente superior em relação à verificada com a corticoterapia inalada e o montelukast. COMENTÃRIO: Os resultados deste estudo revelaram que a associação salmeterol/ propionato de fluticasona (50 μg/ 100 μg) em 2 tomas/dia durante 12 semanas era mais eficaz que propionato de fluticasona 10 μg duas vezes/dia e montelukast 10 μg uma vez/dia no tratamento de doentes com asma moderada ou grave. A associação traduz-se numa melhoria significativamente superior da função pulmonar, dos scores de sintomas e numa redução da frequência das exacerbações.Este estudo foi efectuado para demonstrar os benefícios da associação de β2 agonistas de longa duração (salmeterol) ou anti-leucotrienos (montelukast) à corticoterapia por via inalatória em doentes sintomáticos.Os critérios de inclusão implicaram que se tratasse de indivíduos asmáticos com sintomatologia e requerendo aumento da terapêutica de manutenção. A reversibilidade com a administração de salbutamol podia potencialmente favorecer o grupo salmeterol/ fluticasona. No entanto, este critério de selecção é fundamental para o correcto diagnóstico de asma e foi utilizado em numerosas análises retrospectivas. O período de 12 semanas é suficiente para demonstrar o máximo efeito do salmeterol e do montelukast, o que já tinha sido provado anteriormente.A redução da frequência da exacerbação de asma é importante na diminuição da morbilidade e mortalidade dos doentes asmáticos, melhorando a sua qualidade de vida e reduzindo os custos associados à doença.Numerosos estudos revelaram que a associação de salmeterol/corticóides inalados tem maiores benefícios clínicos do que a administração deste fármaco e anti-leucotrienos, traduzindo-se num menor número de visitas ao Serviço de Urgência e diminuição do uso de terapêutica de alívio.No estudo actual, a diferente eficácia não pode ser atribuída à diferença na compliance, visto esta ter sido elevada em ambos os grupos. Está, também, provado que o uso da terapêutica múltipla em dispositivos diferentes e várias tomas diárias contribui para uma má compliance.Em resumo, nos doentes sintomáticos sob doses baixas de corticóides inalados, ambas as terapêuticas são eficazes, embora no 1.º grupo os benefícios sejam significativamente superiores. Estes resultados estão de acordo com estudos realizados anteriormente com montelukast e zafirlukast e confirma que a associação salmeterol/fluticasona é a opção preferencial para doentes não controlados com a corticoterapia inalada. Palavras-chave: Salmeterol propionato de fluticasona, associação terapêutica, asma, montelukas

Constraints on the high-density nuclear equation of state from the phenomenology of compact stars and heavy-ion collisions

A new scheme for testing nuclear matter equations of state (EsoS) at high densities using constraints from neutron star phenomenology and a flow data analysis of heavy-ion collisions is suggested. An acceptable EoS shall not allow the direct Urca process to occur in neutron stars with masses below $1.5~M_{\odot}$, and also shall not contradict flow and kaon production data of heavy-ion collisions. Compact star constraints include the mass measurements of 2.1 +/- 0.2 M_sun (1 sigma level) for PSR J0751+1807, of 2.0 +/- 0.1 M_sun from the innermost stable circular orbit for 4U 1636-536, the baryon mass - gravitational mass relationships from Pulsar B in J0737-3039 and the mass-radius relationships from quasiperiodic brightness oscillations in 4U 0614+09 and from the thermal emission of RX J1856-3754. This scheme is applied to a set of relativistic EsoS constrained otherwise from nuclear matter saturation properties with the result that no EoS can satisfy all constraints simultaneously, but those with density-dependent masses and coupling constants appear most promising.Comment: 15 pages, 8 figures, 5 table

Periodic orbit spectrum in terms of Ruelle--Pollicott resonances

Fully chaotic Hamiltonian systems possess an infinite number of classical solutions which are periodic, e.g. a trajectory ``p'' returns to its initial conditions after some fixed time tau_p. Our aim is to investigate the spectrum tau_1, tau_2, ... of periods of the periodic orbits. An explicit formula for the density rho(tau) = sum_p delta (tau - tau_p) is derived in terms of the eigenvalues of the classical evolution operator. The density is naturally decomposed into a smooth part plus an interferent sum over oscillatory terms. The frequencies of the oscillatory terms are given by the imaginary part of the complex eigenvalues (Ruelle--Pollicott resonances). For large periods, corrections to the well--known exponential growth of the smooth part of the density are obtained. An alternative formula for rho(tau) in terms of the zeros and poles of the Ruelle zeta function is also discussed. The results are illustrated with the geodesic motion in billiards of constant negative curvature. Connections with the statistical properties of the corresponding quantum eigenvalues, random matrix theory and discrete maps are also considered. In particular, a random matrix conjecture is proposed for the eigenvalues of the classical evolution operator of chaotic billiards

Job Crafting via Decreasing Hindrance Demands:The Motivating Role of Interdependence Misfit and the Facilitating Role of Autonomy

Job crafting theory suggests that misalignment between an employee’s preferred and actual amount of job characteristics acts as a motivational trigger for job crafting. We test this unexplored, yet key proposition underlying job crafting theory. To do so, however, we take a more comprehensive misfit perspective than previously applied, evaluating person-job undersupply and oversupply. We propose that task interdependence misfit motivates a reductive form of job crafting, decreasing hindrance demands. We also propose that low autonomy mitigates the misfit to decreasing hindrance demands relationship. To empirically evaluate this direction, we employ moderated polynomial regression and response surface analysis. Study 1 (N = 159 English-speaking respondents) findings suggest that task interdependence misfit (both undersupply and oversupply) is positively related to decreasing hindrance demands. Study 2 (N = 363 Dutch-speaking respondents) findings replicate and support our misfit hypothesis. Further, as expected, low levels of autonomy neutralize the relationship between task interdependence misfit and decreasing hindrance demands. Theoretical and practical implications regarding the misfit-as-motivation hypothesis, and the simultaneous investigation of job crafting facilitators (i.e., autonomy) and motivators (i.e., misfit) are discussed

Cold uniform matter and neutron stars in the quark-mesons-coupling model

A new density dependent effective baryon-baryon interaction has been recently derived from the quark-meson-coupling (QMC) model, offering impressive results in application to finite nuclei and dense baryon matter. This self-consistent, relativistic quark-level approach is used to construct the Equation of State (EoS) and to calculate key properties of high density matter and cold, slowly rotating neutron stars. The results include predictions for the maximum mass of neutron star models, together with the corresponding radius and central density, as well the properties of neutron stars with mass of order 1.4 $M_\odot$. The cooling mechanism allowed by the QMC EoS is explored and the parameters relevant to slow rotation, namely the moment of inertia and the period of rotation investigated. The results of the calculation, which are found to be in good agreement with available observational data, are compared with the predictions of more traditional EoS. The QMC EoS provides cold neutron star models with maximum mass 1.9--2.1 M$_\odot$, with central density less than 6 times nuclear saturation density ($n_{0}= 0.16 {\rm fm}^{-3}$) and offers a consistent description of the stellar mass up to this density limit. In contrast with other models, QMC predicts no hyperon contribution at densities lower than $3n_0$, for matter in $\beta$-equilibrium. At higher densities, $\Xi^{-,0}$ and $\Lambda$ hyperons are present

Heavy ion collisions with non-equilibrium Dirac-Brueckner mean fields

The influence of realistic interactions on the reaction dynamics in intermediate energy heavy ion collisions is investigated. The mean field in relativistic transport calculations is derived from microscopic Dirac-Brueckner (DB) self-energies, taking non-equilibrium effects, in particular the anisotropy of the local phase space configurations, into account. Thus this approach goes beyond the local density approximation. A detailed analysis of various in-plane and out-of-plane flow observables is presented for Au on Au reactions at incident energies ranging from 250 to 800 A.MeV and the results are compared to recent measurements of the FOPI collaboration. An overall good agreement with in-plane flow data and a reasonable description of the out-of-plane emission is achieved. For these results the intrinsic momentum dependence of the non-equilibrium mean fields is important. On the other hand, the local density approximation with the same underlying DB forces as well as a standard non-linear version of the $\sigma\omega$ model are less successful in describing the present data. This gives evidence of the applicability of self energies derived from the DB approach to nuclear matter also far from saturation and equilibrium.Comment: 63 pages Latex, using Elsevier style, 20 ps-figures, to appear in Nucl. Phys.

Life and Liesegang: Outcrop-Scale Microbially Induced Diagenetic Structures and Geochemical Self-Organization Phenomena Produced by Oxidation of Reduced Iron

The Kanab Wonderstone is sandstone (Shinarump Member, Chinle Formation) that is cemented and stained with iron oxide. The iron-oxide cementation and staining in these rocks have been considered examples of the Liesegang phenomenon, but we will show that they comprise a microbially induced structure. The spacing of bands of iron-oxide stain follow the Jablczynski spacing law (wherein the spacing between bands of iron-oxide stain increases as one traverses a series of bands) characteristic of Liesegang. Bands of iron-oxide cement exhibit more variable spacing and exhibit a weak but significant correlation between band thickness and distance between bands of cement. The pore-filling cement contains morphotypes that are similar in size and habit to those exhibited by microaerophilic iron-oxidizing bacteria. Other disseminated iron-oxide mineralization occurs as rhombohedra interpreted to be pseudomorphs after siderite. We interpret the cement to be produced by microbially mediated oxidation of siderite (a typical early diagenetic mineral in fluvial sandstones). Iron-oxidizing bacteria colonized the redox interface between siderite-cemented sand and porous sandstone. Microbes oxidized aqueous Fe(II), generating acid that caused siderite dissolution. The iron-oxide cement is the microbial product of a geochemical drive for organization; whereas the iron-oxide stain is true Liesegang. Together, they comprise a distinctive microbially induced structure with high preservation potential. Key Words: Biosignatures—Iron oxides—Diagenesis—Iron-oxidizing bacteria—Shinarump

The rate of colonization by macro-invertebrates on artificial substrate samplers

The influence of exposure time upon macro-invertebrate colonization on modified Hester-Dendy substrate samplers was investigated over a 60-day period. The duration of exposure affected the number of individuals, taxa and community diversity. The numbers of individuals colonizing the samplers reached a maximum after 39 days and then began to decrease, due to the emergence of adult insects. Coefficients of variation for the four replicate samples retrieved each sampling day fluctuated extensively throughout the study. No tendencies toward increasing or decreasing coefficients of variation were noted with increasing time of sampler exposure. The number of taxa colonizing the samplers increased throughout the study period. The community diversity index was calculated for each sampling day and this function tended to increase throughout the same period. This supports the hypothesis that an exposure period of 6 weeks, as recommended by the United States Environmental Protection Agency, may not always provide adequate opportunity for a truly representative community of macro-invertebrates to colonize multiplate samplers. Many of the taxa were collected in quite substantial proportions after periods of absence or extreme sparseness. This is attributed to the growth of periphyton and the collection of other materials that created food and new habitats suitable for the colonization of new taxa. Investigation of the relationship between ‘equitability’ and length of exposure revealed that equitability did not vary like diversity with increased time of exposure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72073/1/j.1365-2427.1979.tb01522.x.pd

Metal enrichment processes

There are many processes that can transport gas from the galaxies to their environment and enrich the environment in this way with metals. These metal enrichment processes have a large influence on the evolution of both the galaxies and their environment. Various processes can contribute to the gas transfer: ram-pressure stripping, galactic winds, AGN outflows, galaxy-galaxy interactions and others. We review their observational evidence, corresponding simulations, their efficiencies, and their time scales as far as they are known to date. It seems that all processes can contribute to the enrichment. There is not a single process that always dominates the enrichment, because the efficiencies of the processes vary strongly with galaxy and environmental properties.Comment: 18 pages, 8 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 17; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke