Bronchial mucosal mast cells in asymptomatic smokers relation to structure, lung function and emphysema

AbstractThe pathologic mechanisms of chronic obstructive pulmonary disease (COPD) most certainly involves neutrophil granulocytes, cytotoxic T-cells, macophages and mast cells. The aim of this study was to investigate the relation between the number of mast cells in different compartments in bronchial biopsies of central proximal airways to structural changes, lung function tests and emphysema detected by high resolution computed tomography (HRCT).Twenty nine asymptomatic smoking and 16 never-smoking men from a population study were recruited. Central bronchial biopsies were stained to identify mast cells by immunohistochemistry. The number of mast cells in the epithelium, lamina propria and smooth muscle as well as epithelial integrity and thickness of the tenascin and laminin layer were determined.Smokers had increased numbers of mast cells in all compartments (P<0.001). Structural changes were correlated to mast cell numbers with the closest associations to mast cell numbers in the smooth muscle [epithelial integrity (Rs=−0.48, P=0.008), laminin layer (Rs=0.63, P=0.0002), tenascin layer (Rs=0.40, P=0.03)]. Similar correlations between mast cells and lung function tests were seen [functional residual capacity (FRC) (Rs=0.60, P=0.0006), total lung capacity (TLC) (Rs=0.44, P=0.02) and residual volume (RV) (Rs=0.41, P=0.03)]. No correlations could be detected between mast cells and FEV1 or to emphysema.Smoking is associated with an increase of mast cells in all compartments of the bronchial mucosa, including smooth muscle, and this is related to altered airway structure and function

Improving business processes of service companies

This article considers the problem of improving business process through analysis “Highlighting areas of concern”. In the process, we formulated a number of requirements that should meet the functionality of the information system and highlighted advantages of the"Selection concerns" method

How equitable is vocational rehabilitation in Sweden? A review of evidence on the implementation of a national policy framework

Purpose. Under the national framework law in Sweden, all eligible people should have equal chances of receiving vocational rehabilitation. We aimed to review the evidence on (1) whether access to vocational rehabilitation is equitable in practice and (2) whether the outcomes vary for different groups in the population. Method. Systematic review of studies in Sweden that reported diagnostic or socio-demographic characteristics of people offered or taking up rehabilitation programmes and outcomes of such programmes for different diagnostic and socio-demographic groups. Searches of 11 relevant electronic databases, 15 organisational websites, citation searching and contact with experts in the field, for the period 1990–2009. Results. A total of 11 studies were included in the final review, six of which addressed review question (1) and seven addressed review question (2). All the six observational studies of access reported biased selection into vocational rehabilitation: greater likelihood for men, younger people, those with longer-term sick leave, those with lower income, employed rather than unemployed people and those with musculoskeletal and mental disorders or alcohol abuse. Having had a rehabilitation investigation also increased the likelihood of receiving vocational rehabilitation. Differential outcome of rehabilitation was reported in seven studies: outcomes were better for men, younger people, employed individuals, those with shorter sick leave and those with higher income. Selection into vocational rehabilitation was perceived as important for successful outcomes, but success also depended on the state of the local labour market. Conclusions. There is evidence of socio-demographic differences in access to and outcomes of vocational rehabilitation in Sweden, even though the national framework law is meant to apply to everyone. Few studies have deliberately measured differential access or outcomes, and there is a need for this kind of equity analysis of population-wide policies. Studies evaluating the effects of vocational rehabilitation must consider selection into the programmes for adequate interpretation of impact results

Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin

Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Swedish social insurance officers' experiences of difficulties in assessing applications for disability pensions – an interview study

<p>Abstract</p> <p>Background</p> <p>In this study the focus is on social insurance officers judging applications for disability pensions. The number of applications for disability pension increased during the late 1990s, which has resulted in an increasing number of disability pensions in Sweden. A more restrictive attitude towards the clients has however evolved, as societal costs have increased and governmental guidelines now focus on reducing costs. As a consequence, the quantitative and qualitative demands on social insurance officers when handling applications for disability pensions may have increased. The aim of this study was therefore to describe the social insurance officers' experiences of assessing applications for disability pensions after the government's introduction of stricter regulations.</p> <p>Methods</p> <p>Qualitative methodology was employed and a total of ten social insurance officers representing different experiences and ages were chosen. Open-ended interviews were performed with the ten social insurance officers. Data was analysed with inductive content analysis.</p> <p>Results</p> <p>Three themes could be identified as problematic in the social insurance officers' descriptions of dealing with the applications in order to reach a decision on whether the issue qualified applicants for a disability pension or not: 1. Clients are heterogeneous. 2. Ineffective and time consuming waiting for medical certificates impede the decision process. 3. Perspectives on the issue of work capacity differed among different stakeholders. The backgrounds of the clients differ considerably, leading to variation in the quality and content of applications. Social insurance officers had to make rapid decisions within a limited time frame, based on limited information, mainly on the basis of medical certificates that were often insufficient to judge work capacity. The role as coordinating actor with other stakeholders in the welfare system was perceived as frustrating, since different stakeholders have different goals and demands. The social insurance officers experience lack of control over the decision process, as regulations and other stakeholders restrict their work.</p> <p>Conclusion</p> <p>A picture emerges of difficulties due to disharmonized systems, stakeholder-bound goals causing some clients to fall between two stools, or leading to unnecessary waiting times, which may limit the clients' ability to take an active part in a constructive process. Increased communication with physicians about how to elaborate the medical certificates might improve the quality of certificates and thereby reduce the clients waiting time.</p

Now Daddy’s Changing Diapers and Mommy’s Making Her Career - Evaluating a Generous Parental Leave Regulation Using a Natural Experiment

Over the last decades many OECD countries introduced parental leave regulations in order to counteract low and decreasing birth rates. In general, these regulations aim at making parenthood more attractive and more compatible with a working career, especially for women. The recent German Elterngeld reform is one example: By replacing 67 per cent of prepartum parental labor earnings for up to 14 months after birth of the child - if both father and mother take up the transfer - it intends to i) smooth or prevent households' earnings decline postpartum, ii) make childbearing attractive for working women while iii) keeping them close to the labor market, and iv) incentivize fathers to participate in childcare. We evaluate the reform by using a natural experiment created by the quick legislative process of the Elterngeld reform: Comparing outcomes of parents with children born shortly after and before the coming into effect of the law on 1 January 2007 yields unbiased estimates of the reform effects, because at the time when these children were conceived none of the parents knew that the regulation would be in force by the time their child is born. Our results are based on unique data from the official evaluation of the reform, which we conducted for the German government, and they show that the reform has been generally successful in attaining its objectives. In particular, we find a significant decrease in mothers' employment probability during the 12 months after giving birth, and a significant increase in mothers' employment probability after the Elterngeld transfer expires

MARCS model atmospheres

In this review presented at the Symposium A stellar journey in Uppsala, June 2008, I give my account of the historical development of the MARCS code from the first version published in 1975 and its premises to the 2008 grid. It is shown that the primary driver for the development team is the science that can be done with the models, and that they constantly strive to include the best possible physical data. A few preliminary comparisons of M star model spectra to spectrophotometric observations are presented. Particular results related to opacity effects are discussed. The size of errors in the spectral energy distribution (SED) and model thermal stratification are estimated for different densities of the wavelength sampling. The number of points used in the MARCS 2008 grid (108000) is large enough to ensure errors of only a few K in all models of the grid, except the optically very thin layers of metal-poor stars. Errors in SEDs may reach about 10% locally in the UV. The published sampled SEDs are thus appropriate to compute synthetic broad-band photometry, but higher resolution spectra will be computed in the near future and published as well on the MARCS site (marcs.astro.uu.se). Test model calculations with TiO line opacity accounted for in scattering show an important cooling of the upper atmospheric layers of red giants. Rough estimates of radiative and collisional time scales for electronic transitions of TiO indicate that scattering may well be the dominant mechanism in these lines. However models constructed with this hypothesis are incompatible with optical observations of TiO (Arcturus) or IR observations of OH (Betelgeuse), although they may succeed in explaining H2O line observations. More work is needed in that direction.Comment: Review talk at the conference "A stellar journey" held in Uppsala, June 2008. In press in Physica Scripta, eds. Paul Barklem, Andreas Korn, and Bertrand Ple

Early type stars at high galactic latitudes I. Ten young massive B-type stars

We present the results of quantitative spectral analyses of ten apparently normal B-type stars. These stars were found to be young massive B-type stars at distances of z=2.6 to 7.6 kpc from the galactic plane based on their positions in the (Teff, log g) diagram, normal abundance patterns and/or large projected rotational velocities. We discuss formation scenarios (runaway star scenarios versus a scenario for star formation in the halo) by comparing times-of-flight and evolutionary time scales. For all stars (except SB 357 and HS 1914+7139) both the scales are similar, indicating that the stars could have formed in the galactic disk and been ejected from there soon aftertheir birth. Derived ejection velocities range from 130 km/s to 440 km/s and may be used to constrain models for ejection mechanisms. Using new proper motion measurements we show that PHL 346, which was considered the most likely candidate for a young B-type star born in the halo, can be explained as a runaway star from the galactic plane.Comment: 11 pages, 5 eps-files, accepted for publication in Astronomy and Astrophysic