The serological diagnosis of staphylococcal infective endocarditis

Objectives: Establishing the diagnosis of infective endocarditis (IE) can be difficult when blood cultures remain sterile or echocardiography is inconclusive. Staphylococcus aureus is a common aetiological microorganism in IE and is associated with severe valvular destruction and increased mortality. Early diagnosis using culture and antibiotic independent tests would be preferable to allow prompt antibiotic administration. We have developed and evaluated 2 serological assays for the rapid identification of a staphylococcal aetiology in infective endocarditis. The assays measure IgG against whole cells of S. aureus and IgG against lipid S, a novel extracellular antigen released by Gram-positive microorganisms. Methods: Serum was collected from 130 patients with IE and 94 control patients. IgG against whole cells of S. aureus and against lipid S was measured by enzyme linked immunosorbent assay (ELISA). Results: Anti-lipid S IgG titres were higher in IE caused by Gram-positive microorganisms than in controls (p < 0.0001) and higher in staphylococcal IE than in both controls and IE caused by other microorganisms (p = 0.0003). Anti-whole cell staphylococcal IgG was significantly higher in serum from patients with staphylococcal IE than in IE caused by other microorganisms and control samples (p < 0.0001). Conclusion: High anti-whole cell IgG titres are predictive of a staphylococcal aetiology in IE. Elevated serum anti-lipid S IgG titres are predictive of Gram-positive infection compared to controls, very high titres being associated with staphylococcal IE. © 2005 The British Infection Society.

The development of filamentous fungi in submerged culture

During the 24 hour period following inoculation, aggregation of spores and sporelings can have an important effect on the subsequent growth of filamentous fungi in submerged culture. This early phase of growth does not appear to have received much attention, and it was for this reason that the author's research was started. The aggregation, germination and early growth of the filamentous fungus Aspergillus niger have been followed in aerated tower fermenters, by microscopic examination. By studying many individual sporelings it has been possible to estimate the specific growth rate and germination times, and then to assess the branching characteristics of the fungus over a period of from 1 to 10 hours after germination. The results have been incorporated into computer models to simulate the development of the physical structure of individual and aggregated sporelings. Following germination, and an initial rapid growth phase, fungi were found to grow exponentially: in the case of A.niger the mean germination time was about 5 hours and the doubling time was as short as 1.5 hours. Branching also followed an exponential pattern and appeared to be related to hyphal length. Using a simple hypothesis for growth along with empirical parameters, typical fungal structures were generated using the computer models : these compared well with actual sporelings observed under the microscope. Preliminary work suggested that the techniques used in this research could be successfully applied to a range of filamentous fungi.

Entrepreneurship and the informal economy: a study of Ukraine's hidden enterprise culture

How many entrepreneurs start-up their business ventures conducting some or all of their trade in the informal economy? The aim of this paper is to answer this key question that has been seldom addressed using data from 600 face-to-face structured interviews conducted in Ukraine in late 2005 and early 2006. Analyzing the 331 entrepreneurs identified (i.e., individuals starting-up an enterprise in the past three years), just 10 percent operate on a wholly legitimate basis, while 39 percent have a license to trade and/or have registered their business but conduct a portion of their trade in the informal economy, and 51 percent operate unregistered enterprises and conduct all of their trade on an off-the-books basis. Given that some 90 percent of all business start-ups operate partially or wholly in the informal economy, and that 40 percent of all respondents depend on the informal economy as either their principal or secondary contributor to their livelihoods, the paper concludes by considering the wider implications of these findings both for further research and public policy.

The casing layer in the culture of Agaricus bisporus, the cultivated mushroom

The casing layer is an essential component of the system employed in the culture of Agaricus bisporus. The literature appropriate to the casing layer is fully reviewed, including aspects relating to fructification and morphogenesis in A.bisporus, together with an appraisal of the various media employed, their properties and functions, and the commercial significance of the casing layer. Equipment is described for use in experiments in mushroom culture, based on a scaled-down version of normal growing technique, allowing the analysis of both weights and number of fruitbodies forming, which was useful in assessing the effects of different casing treatments. The basic steps in the production of fruitbodies in A.bisporus.are described, including a photographic study of the colonisation of casing and fructification. Various alterations to the physical structure of peat/chalk casing mixtures were found to have an effect on fructification; those causing an opening-out of the casing structure tended to give better yields, especially in the early stages of production. It was shown that, in order to obtain greater yield through casing amendment, fructification must be stimulated, giving increased numbers of fruitbodies, disproportionate to their total weight and consequently of lower mean weight. A synthetic casing medium based on the light glass-like mineral, perlite, was developed. The best formula obtained was -.1 part perlite: 1 part montmorillonite clay (by weight): 3 parts 0.01% glucose solution. Perlite/montmorillonite casing could be improved by adding compost colonised by mycelium of A.bisporus, or adding a peat-chalk casing extract. Perlite was also found to be suitable for admixture with the standard casing medium and a mixture of equal parts by volume performed as well as the peat/chalk casing normally used.

Scale-up of human mesenchymal stem cell culture:current technologies and future challenges

Regenerative medicine technologies have the potential to revolutionise human healthcare. However, whilst science has revealed the potential, and early products have shown the power of such therapies, there is now a need for the long-term supply of human stem cells in sufficient numbers to create reproducible and cost effective therapeutic products. The industrial platforms to be developed for human cell culture are in some ways analogous to those already developed for biopharmaceutical production using mammalian cells at large scales. However, there are a number of unique challenges that need to be addressed, largely because the quality of the cell is paramount, rather than the proteins that they express. © 2013 Elsevier Ltd.

Development of a co-culture model of the human lungs for toxicity testing and identification of biomarkers of inhalation toxicity

The airway epithelium is the first point of contact in the lung for inhaled material, including infectious pathogens and particulate matter, and protects against toxicity from these substances by trapping and clearance via the mucociliary escalator, presence of a protective barrier with tight junctions and initiation of a local inflammatory response. The inflammatory response involves recruitment of phagocytic cells to neutralise and remove and invading materials and is oftern modelled using rodents. However, development of valid in vitro airway epithelial models is of great importance due to the restrictions on animal studies for cosmetic compound testing implicit in the 7th amendment to the European Union Cosmetics Directive. Further, rodent innate immune responses have fundamental differences to human. Pulmonary endothelial cells and leukocytes are also involved in the innate response initiated during pulmonary inflammation. Co-culture models of the airways, in particular where epithelial cells are cultured at air liquid interface with the presence of tight junctions and differentiated mucociliary cells, offer a solution to this problem. Ideally validated models will allow for detection of early biomarkers of response to exposure and investigation into inflammatory response during exposure. This thesis describes the approaches taken towards developing an in vitro epithelial/endothelial cell model of the human airways and identification biomarkers of response to exposure to xenobiotics. The model comprised normal human primary microvascular endothelial cells and the bronchial epithelial cell line BEAS-2B or normal human bronchial epithelial cells. BEAS-2B were chosen as their characterisation at air liquid interface is limited but they are robust in culture, thereby predicted to provide a more reliable test system. Proteomics analysis was undertaken on challenged cells to investigate biomarkers of exposure. BEAS-2B morphology was characterised at air liquid interface compared with normal human bronchial epithelial cells. The results indicate that BEAS-2B cells at an air liquid interface form tight junctions as shown by expression of the tight junction protein zonula occludens-1. To this author’s knowledge this is the first time this result has been reported. The inflammatory response of BEAS-2B (measured as secretion of the inflammatory mediators interleukin-8 and -6) air liquid interface mono-cultures to Escherichia coli lipopolysaccharide or particulate matter (fine and ultrafine titanium dioxide) was comparable to published data for epithelial cells. Cells were also exposed to polymers of “commercial interest” which were in the nanoparticle range (and referred to particles hereafter). BEAS-2B mono-cultures showed an increased secretion of inflammatory mediators after challenge. Inclusion of microvascular endothelial cells resulted in protection against LPS- and particle- induced epithelial toxicity, measured as cell viability and inflammatory response, indicating the importance of co-cultures for investigations into toxicity. Two-dimensional proteomic analysis of lysates from particle-challenged cells failed to identify biomarkers of toxicity due to assay interference and experimental variability. Separately, decreased plasma concentrations of serine protease inhibitors, and the negative acute phase proteins transthyretin, histidine-rich glycoprotein and alpha2-HS glycoprotein were identified as potential biomarkers of methyl methacrylate/ethyl methacrylate/butylacrylate treatment in rats.

The influence of organizational and national culture on new product performance

The authors conduct a meta-analysis on the combined influence of organizational and national culture on new product performance. For this purpose, they refer to the effectiveness of value congruency and develop a conceptual model describing the fit between organizational culture types as suggested by the competing values framework and national culture, as described by Hofstede's cultural dimensions. The meta-analysis is based on 489 effect sizes taken from 123 manuscripts. The findings show that organizations with a market culture show the highest new product performance, while hierarchy-type organizations show the lowest performance. The influence of national culture variables supports the effect of value congruency, and shows that in individualistic cultures the impact of a clan culture decreases, the impact of an adhocracy culture type decreases with uncertainty avoidance, and the influence of a hierarchy culture type increases with power distance. The superior effect of a market culture type can be matched by other organizational orientations, but in particular national cultures only. The combined findings underline the importance for firms that seek to improve the success rate of new products on international markets to consider the fit of a national culture with a firm's organizational culture.