Comparison of four-times-a-day and twice-a-day dosing regimens in subjects requiring 1200 μg or less of budesonide to control mild to moderate asthma

AbstractThe aim of this study was to compare the efficacy, compliance and side-effects of budesonide administered twice daily (b.d.) and four times a day (q.d.) with a Turbuhaler® device in asthmatic subjects requiring ≤ 1200 μg daily. The randomized, parallel group study design included a 2-week baseline period followed by a 6–12-month treatment period. Subjects were assessed at regular intervals in hospital through FEV1, PC20 methacholine, adrenal function and throat swabs. They were asked to record their symptoms and PEF values morning and evening at home. An asthmatic flare-up, which was the main outcome resulting in a patient's termination of the study, was defined beforehand as (a) 25% or greater diurnal variability in PEF for 2 consecutive days, and/or (b) nocturnal awakenings due to asthma symptoms 2 days or more in the same week and/or (c) an increase (doubling or more) in the need for inhaled bronchodilator 2 days in the same week.Fifty-eight adult asthmatic subjects (20 males and 38 females) entered the study, one-half being randomly assigned to the b.d. regimen and one-half to the q.d. regimen. Fourteen subjects were on 400 μg, 15 subjects on 800 μg and 29 subjects on 1200 μg of budesonide daily. Seventeen flare-ups were recorded in the b.d. regimen group as opposed to 11 in the q.d. regimen (P=0·05), significant differences being found in the 800 and 1200 μg groups (a total of 13 flare-ups in the b.d. group and eight flare-ups in the q.d. group for the two doses, P=0·01). Kaplan-Meier survival analysis yielded similar results. There was no significant difference in FEV1, PC20 or cortisol levels during the study on either regimen. Throat symptoms and growth of Candida albicans were more common in the q.d. group. Compliance assessed by the number of times the Turbuhaler® device was actuated was significantly better in the b.d. group (95%) as compared with the q.d. group (83%). To conclude, administering inhaled budesonide with a Turbuhaler® device on a q.d. basis results in fewer flare-ups in spite of less satisfactory compliance and more common, local side-effects than on a b.d. regimen at daily doses of 800 and 1200 μg

Employment Expectations and Gross Flows by Type of Work Contract

There is growing interest in understanding firms’ temporary and permanent employment practices and how institutional changes shape them. Using data on Spanish establishments, we examine: (a) how employers adjust temporary and permanent job and worker flows to prior employment expectations, and (b) how the 1994 and 1997 labour reforms promoting permanent employment affected establishments’ employment practices. Generally, establishments’ prior employment expectations are realized through changes in all job and worker flows. However, establishments uniquely rely on temporary hires as a buffer to confront diminishing long-run employment expectations. None of the reforms significantly affected establishments’ net temporary or permanent employment flows.http://deepblue.lib.umich.edu/bitstream/2027.42/40032/3/wp646.pd

Expression of divIB of Bacillus subtilis during vegetative growth

Expression of the division initiation gene, divIB, of Bacillus subtilis vegetative growth was examined. lacZ fusion studies and transcription start point mapping have established that a sigma A promoter proximal to divIB is utilized in vivo. The -10 region of this promoter, which is located 93 bp upstream of the start codon, has been defined precisely by site-directed mutagenesis that destroys the promoter. Examination of transcripts by Northern (RNA) blotting has shown that there are at least two transcripts for divIB. The established proximal promoter was found to give rise to a very minor transcript which could not be convincingly demonstrated in wild-type cells but which became apparent upon insertion of a plasmid into the chromosome just upstream of this promoter. The major transcript for divIB originated from a site several kb upstream of the gene and is probably the same as the long polycistronic message also traversing the murD-spoVE-murG genes that was identified previously by others (A.D. Henriques, H. de Lencastre, and P.J. Piggot, Biochimie 74:735-748, 1992). Transcription from the proximal promoter alone, in an upstream-deletion mutant strain, provided sufficient DivIB for normal growth and division as well as sporulation

The beta Pictoris association: Catalog of photometric rotational periods of low-mass members and candidate members

We intended to compile the most complete catalog of bona fide members and candidate members of the beta Pictoris association, and to measure their rotation periods and basic properties from our own observations, public archives, and exploring the literature. We carried out a multi-observatories campaign to get our own photometric time series and collected all archived public photometric data time series for the stars in our catalog. Each time series was analyzed with the Lomb-Scargle and CLEAN periodograms to search for the stellar rotation periods. We complemented the measured rotational properties with detailed information on multiplicity, membership, and projected rotational velocity available in the literature and discussed star by star. We measured the rotation periods of 112 out of 117 among bona fide members and candidate members of the beta Pictoris association and, whenever possible, we also measured the luminosity, radius, and inclination of the stellar rotation axis. This represents to date the largest catalog of rotation periods of any young loose stellar association. We provided an extensive catalog of rotation periods together with other relevant basic properties useful to explore a number of open issues, such as the causes of spread of rotation periods among coeval stars, evolution of angular momentum, and lithium-rotation connection.Comment: Forthcoming article, Received: 20 June 2016 / Accepted: 09 September 2016; 40 pages, 2 figures. The online figures A1-A73 are available at CD

Factors Influencing Spatial Variability of Soil Apparent Electrical Conductivity

Soil apparent electrical conductivity (ECa) can be used as a precision farming diagnostic tool more efficiently if the factors influencing ECa spatial variability are understood. The objective of this study was to ascertain the causes of ECa spatial variability in soils developed in an environment with between 50 and 65 cm of annual rainfall. Soils at the research sites were formed on calcareous glacial till parent materials deposited approximately 10,000 years ago. Soil samples (0–15 cm) collected from at least a 60 by 60 m grid in four fields were analyzed for Olsen phosphorus (P) and potassium (K). Elevation was measured by a carrier phase single frequency DGPS and ECa was measured with an EM 38 (Geonics Ltd., ON, Canada) multiple times between 1995 and 1999. Apparent electrical conductivity contained spatial structure in all fields. Generally, the well drained soils in the summit areas and the poorly drained soil in the toeslope areas had low and high ECa values, respectively. The landscape differences in ECa were attributed to: (i) water leaching salts out of summit areas and capillary flow combined with seepage transporting water and salts from subsurface to surface soils in toeslope areas; (ii) lower water contents in summit than toeslope soils; and (iii) water erosion which transported surface soil from summit/shoulder areas to lower backslope/footslope areas. A conceptual model based on these findings was developed. In this model, topography followed a sine curve and ECa followed a cosine curve. Field areas that did not fit the conceptual model were: (i) areas containing old animal confinement areas; (ii) areas where high manure rates had been applied; and (iii) areas where soils were outside the boundary conditions of the model, i.e., soils not developed under relatively low rainfall conditions in calcareous glacial till with temperatures ranging between mesic and frigid. This research showed that the soil forming processes as well as agricultural management influenced ECa and that by understanding how landscape position influences salt loss and accumulation, water redistributions following precipitation, and erosion areas that do not fit the conceptual model can be identified. This information can be used to improve soil sampling strategies

Adherence to chronic medication in older populations: application of a common protocol among three European cohorts

Purpose: The purpose of this study was to evaluate and compare medication adherence to chronic therapies in older populations across different regions in Europe. Methods: This explorative study applied a harmonized method of data extraction and analysis from pharmacy claims databases of three European countries to compare medication adherence at a cross-country level. Data were obtained for the period between January 1, 2010, and December 31, 2011. Patients (aged >= 65 years) who newly initiated to oral antidiabetics, antihyperlipidemics, or antiosteoporotics were identified and followed for over a 12-month period. Main outcome measures were medication adherence (medication possession ratio, [MPR]; implementation) and persistence on index treatment. All country-specific data sets were prepared by employing a common data input model. Outcome measures were calculated for each country and pooled using random effect models. Results: In total, 39, 186 new users were analyzed. In pooled data from the three countries, suboptimal implementation (MPR <80%) was 52.45% (95% CI: 33.43-70.79) for antihyperlipidemics, 61.35% (95% CI: 52.83-69.22) for antiosteoporotics, and 30.33% (95% CI: 25.53-35.60) for oral antidiabetics. Similarly, rates of non-persistence (discontinuation) were 55.63% (95% CI: 35.24-74.29) for antihyperlipidemics, 60.24% (95% CI: 45.35-73.46) for antiosteoporotics, and 46.80% (95% CI: 36.40-57.4) for oral antidiabetics. Conclusion: Medication adherence was suboptimal with >50% of older people non-adherent to antihyperlipidemics and antiosteoporotics in the three European cohorts. However, the degree of variability in adherence rates among the three countries was high. A harmonized method of data extraction and analysis across health-related database in Europe is useful to compare medication-taking behavior at a cross-country level

Initial therapy, regimen change, and persistence in a spanish cohort of newly treated type 2 diabetes patients: A retrospective, observational study using real-world data

The World Health Organization considers the non-adherence to medication a significant issue with global impact, especially in chronic conditions such as type 2 diabetes. We aim to study antidiabetic treatment initiation, add-on, treatment switching, and medication persistence. We conducted an observational study on 4247 individuals initiating antidiabetic treatment between 2013 and 2014 in the EpiChron Cohort (Spain). We used Cox regression models to estimate the likelihood of non-persistence after a one-year follow-up, expressed as hazard ratios (HRs). Metformin was the most frequently used first-line antidiabetic (80% of cases); combination treatment was the second most common treatment in adults aged 40–79 years, while dipeptidyl peptidase-4 inhibitors were the second most common in individuals in their 80s and over, and in patients with renal disease. Individuals initiated on metformin were less likely to present addition and switching events compared with any other antidiabetic. Almost 70% of individuals initiated on monotherapy were persistent. Subjects aged 40 and over (HR 0.53–0.63), living in rural (HR 0.79) or more deprived areas (HR 0.77–0.82), or receiving polypharmacy (HR 0.84), were less likely to show discontinuation. Our findings could help identify the population at risk of discontinuation, and offer them closer monitoring for proper integrated management to improve prognosis and health outcomes

Human-carnivore relations: conflicts, tolerance and coexistence in the American West

Carnivore and humans live in proximity due to carnivore recovery efforts and ongoing human encroachment into carnivore habitats globally. The American West is a region that uniquely exemplifies these human-carnivore dynamics, however, it is unclear how the research community here integrates social and ecological factors to examine human-carnivore relations. Therefore, strategies promoting human-carnivore coexistence are urgently needed. We conducted a systematic review on human-carnivore relations in the American West covering studies between 2000 and 2018. We first characterized human-carnivore relations across states of the American West. Second, we analyzed similarities and dissimilarities across states in terms of coexistence, tolerance, number of ecosystem services and conflicts mentioned in literature. Third, we used Bayesian modeling to quantify the effect of social and ecological factors influencing the scientific interest on coexistence, tolerance, ecosystem services and conflicts. Results revealed some underlying biases in human-carnivore relations research. Colorado and Montana were the states where the highest proportion of studies were conducted with bears and wolves the most studied species. Non-lethal management was the most common strategy to mitigate conflicts. Overall, conflicts with carnivores were much more frequently mentioned than benefits. We found similarities among Arizona, California, Utah, and New Mexico according to how coexistence, tolerance, services and conflicts are addressed in literature. We identified percentage of federal/private land, carnivore family, social actors, and management actions, as factors explaining how coexistence, tolerance, conflicts and services are addressed in literature. We provide a roadmap to foster tolerance towards carnivores and successful coexistence strategies in the American West based on four main domains, (1) the dual role of carnivores as providers of both beneficial and detrimental contributions to people, (2) social-ecological factors underpinning the provision of beneficial and detrimental contributions, (3) the inclusion of diverse actors, and (4) cross-state collaborative management

First light of the VLT planet finder SPHERE. I. Detection and characterization of the sub-stellar companion GJ 758 B

GJ758 B is a brown dwarf companion to a nearby (15.76 pc) solar-type, metal-rich (M/H = +0.2 dex) main-sequence star (G9V) that was discovered with Subaru/HiCIAO in 2009. From previous studies, it has drawn attention as being the coldest (~600K) companion ever directly imaged around a neighboring star. We present new high-contrast data obtained during the commissioning of the SPHERE instrument at the VLT. The data was obtained in Y-, J-, H-, and Ks-bands with the dual-band imaging (DBI) mode of IRDIS, providing a broad coverage of the full near-infrared (near-IR) range at higher contrast and better spectral sampling than previously reported. In this new set of high-quality data, we report the re-detection of the companion, as well as the first detection of a new candidate closer-in to the star. We use the new 8 photometric points for an extended comparison of GJ758 B with empirical objects and 4 families of atmospheric models. From comparison to empirical object, we estimate a T8 spectral type, but none of the comparison object can accurately represent the observed near-IR fluxes of GJ758 B. From comparison to atmospheric models, we attribute a Teff = 600K $\pm$ 100K, but we find that no atmospheric model can adequately fit all the fluxes of GJ758 B. The photometry of the new candidate companion is broadly consistent with L-type objects, but a second epoch with improved photometry is necessary to clarify its status. The new astrometry of GJ758 B shows a significant proper motion since the last epoch. We use this result to improve the determination of the orbital characteristics using two fitting approaches, Least-Square Monte Carlo and Markov Chain Monte Carlo. Finally, we analyze the sensitivity of our data to additional closer-in companions and reject the possibility of other massive brown dwarf companions down to 4-5 AU. [abridged]Comment: 20 pages, 15 figures. Accepted for publication in A&