Clinical efficacy and safety of fluticasone propionate 1 mg twice daily administered via a HFA 134a pressurized metered dose inhaler to patients with severe asthma

A randomized, double-blind, cross-over study was conducted to assess the efficacy and safety of fluticasone propionate 1 mg twice daily administered via a pressurized metered dose inhaler (pMDI) containing the new non-chlorofluorocarbon (CFC) propellant (HFA 134a), or the established CFC propellants 11 and 12 in patients with severe asthma. The study comprised a 2-week run-in period followed by two 6-week treatment periods, with no washout period in between. One hundred and nineteen symptomatic adult patients with severe asthma, who were receiving inhaled beclomethasone 2–4 mg day−1 or equivalent, were randomized to treatment.Patients were randomized to one of two sequence groups (sequence 1: HFA 134a pMDI then CFC pMDI or sequence 2: CFC pMDI then HFA 134a pMDI). The sequence groups differed with respect to mean peak expiratory flow (PEF) at baseline; however, the magnitude of the increase in PEF from baseline during treatment was similar in the two sequence groups. Mean PEF at baseline was 334 l min−1 in sequence group 1 (HFA 134a→CFC pMDI) and this increased to 357 l min−1 and 366 l min−1 during treatment with the HFA 134a and CFC pMDI, respectively. In sequence group 2 (CFC→HFA 134a pMDI) mean PEF at baseline was 297 l min−1 and this increased to 336 l min−1 and 328 l min−1 during treatment with the HFA 134a and CFC pMDI, respectively.Based on an overall analysis of the two treatment groups at week 6, equivalence was demonstrated; the mean treatment difference (HFA 134a-CFC pMDI) in morning PEF was 0 l min−1 (90% confidence interval (CI), for difference between groups: −7, 6 l min−1). There was a comparable improvement in secondary efficacy variables, including clinic lung function measurements, in the two treatment groups. The incidence and type of most adverse events were similar in the two treatment groups. There was no difference in the adjusted geometric mean morning serum cortisol levels after treatment with the HFA 134a and CFC pMDI.Therefore, the fluticasone propionate HFA 134a pMDI constitutes a suitable replacement for the established CFC pMDI at a microgram equivalent dose

Conserved Class of Queen Pheromones Stops Social Insect Worker Reproduction

Dissertação de mestrado em Gestão, apresentada à Faculdade de Economia da Universidade de Coimbra, sob a orientação de Patrícia Pereira da SilvaEm 2011, a crise política e financeira de Portugal atingiu um nível crítico, levando à queda do governo, assim como ao pedido de ajuda à denominada Troika, constituída pelo (Fundo Monetário Internacional, Banco Central Europeu e Comunidade Europeia). As recomendações da Troika sobre a política energética Portuguesa basearam-se em torno de medidas que potenciem a eficiência energética, ou seja, medidas que permitam poupar e otimizar consumo de energia. No entanto, sobre as energias renováveis, foi pedida especial atenção, em particular, em tecnologias menos desenvolvidas (incluindo o fotovoltaico), nas quais se deverá efetuar uma análise rigorosa em termos de custos e consequências para o preço da energia. Outra das recomendações da Troika passou por uma revisão em baixo do preço pago pela tarifa (Feed-in tariff), com o intuito de que esse valor não produza compensações alegadamente excessivas para os investidores neste setor. Atendendo às novas constrições anteriormente apresentadas, e aos elevados custo de investimento que as Fontes de Energias Renováveis apresentam, nomeadamente, no setor fotovoltaico, a respetiva avaliação económica assume um papel primordial. É, assim, objetivo desta dissertação estimar da forma mais correta a rendibilidade do investimento, sendo, para tal, desenvolvida uma metodologia de análise de projetos de investimento, usando o método discounted cash flow (DCF) – Free Cash Flow to the firm, bem como, compreender e analisar quais os principais fatores que estão inerentes a um projeto de Fontes de Energia Renovável, nomeadamente, na análise do Levelized Cost Of Electricity (LCOE) e paridade com a rede elétrica. Deste modo, pretende-se uma reanálise do ponto de vista económico de projetos com origem em fontes de energia renovável

Herbivorous turtle ants obtain essential nutrients from a conserved nitrogen-recycling gut microbiome.

Nitrogen acquisition is a major challenge for herbivorous animals, and the repeated origins of herbivory across the ants have raised expectations that nutritional symbionts have shaped their diversification. Direct evidence for N provisioning by internally housed symbionts is rare in animals; among the ants, it has been documented for just one lineage. In this study we dissect functional contributions by bacteria from a conserved, multi-partite gut symbiosis in herbivorous Cephalotes ants through in vivo experiments, metagenomics, and in vitro assays. Gut bacteria recycle urea, and likely uric acid, using recycled N to synthesize essential amino acids that are acquired by hosts in substantial quantities. Specialized core symbionts of 17 studied Cephalotes species encode the pathways directing these activities, and several recycle N in vitro. These findings point to a highly efficient N economy, and a nutritional mutualism preserved for millions of years through the derived behaviors and gut anatomy of Cephalotes ants

Oviposition Preference and Offspring Performance In Container Breeding Mosquitoes: Evaluating the Effects of Organic Compounds and Laboratory Colonisation

1. The preference–performance hypothesis (PPH) predicts that organisms lacking parental care should oviposit in habitats that optimise offspring performance. Preference–performance relationships were investigated for the Asian tiger mosquito (Aedes albopictus Skuse) and the southern house mosquito (Culex quinquefasciatus Say) (Diptera: Culicidae), two medically important container-breeding species, in response to an organic chemical blend mimicking decaying plant matter. Additionally, the effects of long-term laboratory colonisation of Cx. quinquefasciatus using wild and laboratory strains were evaluated. 2. Oviposition bioassays were conducted by releasing gravid mosquitoes into field enclosures with automobile tires containing low and high concentrations of the chemical blend, and water controls. The offspring were then reared in water collected from the tires in which they were deposited. 3. Aedes albopictus and wild Cx. quinquefasciatus laid more eggs in the chemical blend than water controls but did not differentiate between the low and high concentrations. Conversely, laboratory Cx. quinquefasciatus only preferred the high concentration to the low concentration. No statistical associations between oviposition preference and larval survival were found, as the chemical blend did not affect survivorship of either species. 4. The oviposition preference for the chemical blend over water controls suggests that both species oviposit in the best available resource environment, but further studies are needed before conclusions regarding preference–performance relationships can be drawn. 5. It was found that long-term laboratory colonisation affects the oviposition behaviour in Cx. quinquefasciatus, suggesting that behavioural studies on laboratory strains are not always applicable to wild populations

Modeling DNA Structure, Elasticity and Deformations at the Base-pair Level

We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between neighboring base-pairs. The sugar-phosphate backbones are taken into account by semi-rigid harmonic springs with a non-zero spring length. The competition of these two interactions and the introduction of a simple geometrical constraint leads to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the Stack-of-Plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean squared base-pair step parameters. For the optimized model parameters we measured the critical force where the transition from B- to S-DNA occurs to be approximately $140{pN}$. We observe an overstretched S-DNA conformation with highly inclined bases that partially preserves the stacking of successive base-pairs.Comment: 15 pages, 25 figures. submitted to PR

Author Correction: Herbivorous turtle ants obtain essential nutrients from a conserved nitrogen-recycling gut microbiome.

The originally published version of the Supplementary Information file associated with this Article contained an error in Supplementary Figure 3. Panel b was inadvertently replaced with a duplicate of panel a. The error has now been fixed and the corrected version of the Supplementary Information PDF is available to download from the HTML version of the Article

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data