In vivo measurement of regional variation in anterior scleral resistance to Schiotz indentation

Purpose: Recent studies indicate that ocular and scleral rigidity is pertinent to our understanding of glaucoma, age related macular degeneration and the development and pathogenesis of myopia. The principal method of measuring ocular rigidity is by extrapolation of data from corneal indentation tonometry (Ko) using Friedenwald’s transformation algorithms. Using scleral indentation (Schiotz tonometry) we assess whether regional variations in resistance to indentation occur in vivo across the human anterior globe directly, with reference to the deflection of Schiotz scale readings. Methods: Data were collected from both eyes of 26 normal young adult subjects with a range of refractive error (mean spherical equivalent ± S.D. of -1.77 D ± 3.28 D, range -10.56 to +4.38 D). Schiotz tonometry (5.5 g & 7.5 g) was performed on the cornea and four scleral quadrants; supero-temporal (ST) and -nasal (SN), infero-temporal (IT) and -nasal (IN) approximately 8 mm posterior to the limbus. Results: Values of Ko (mm3)-1 were consistent with those previously reported (mean 0.0101 ± 0.0082, range 0.0019–0.0304). In regards to the sclera, significant differences (p < 0.001) were found across quadrants with indentation readings for both loads between means for the cornea and ST; ST and SN; ST and IT, ST and IN. Mean (±S.D.) scale readings for 5.5 g were: cornea 5.93 ± 1.14, ST 8.05 ± 1.58, IT 7.03 ± 1.86, SN 6.25 ± 1.10, IN 6.02 ± 1.49; and 7.5 g: cornea 9.26 ± 1.27, ST 11.56 ± 1.65, IT 10.31 ± 1.74, SN 9.91 ± 1.20, IN 9.50 ± 1.56. Conclusions: Significant regional variation was found in the resistance of the anterior sclera to indentation produced by the Schiotz tonometer.

Are lipid ratios less susceptible to change with systemic inflammation than individual lipid components in patients with rheumatoid arthritis?

Rheumatoid arthritis (RA) associates with excess cardiovascular risk and there is a need to assess that risk. However, individual lipid levels may be influenced by disease activity and drug use, whereas lipid ratios may be more robust. A cross-sectional cohort of 400 consecutive patients was used to establish factors that influenced individual lipid levels and lipid ratios in RA, using multiple regression models. A further longitudinal cohort of 550 patients with RA was used to confirm these findings, using generalized estimating equations. Cross-sectionally, higher C-reactive protein (CRP) levels correlated with lower levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol ([HDL-C] P = .015), whereas lipid ratios did not correlate with CRP. The findings were broadly replicated in the longitudinal data. In summary, the effects of inflammation on individual lipid levels may underestimate lipid-associated cardiovascular disease (CVD) risk in RA, thus lipid ratios may be more appropriate for CVD risk stratification in RA.

Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis

Background: Activated factor XIII (FXIIIa), a transglutaminase, introduces fibrin-fibrin and fibrin-inhibitor cross-links, resulting in more mechanically stable clots. The impact of cross-linking on resistance to fibrinolysis has proved challenging to evaluate quantitatively. Methods: We used a whole blood model thrombus system to characterize the role of cross-linking in resistance to fibrinolytic degradation. Model thrombi, which mimic arterial thrombi formed in vivo, were prepared with incorporated fluorescently labeled fibrinogen, in order to allow quantification of fibrinolysis as released fluorescence units per minute. Results: A site-specific inhibitor of transglutaminases, added to blood from normal donors, yielded model thrombi that lysed more easily, either spontaneously or by plasminogen activators. This was observed both in the cell/platelet-rich head and fibrin-rich tail. Model thrombi from an FXIII-deficient patient lysed more quickly than normal thrombi; replacement therapy with FXIII concentrate normalized lysis. In vitro addition of purified FXIII to the patient's preprophylaxis blood, but not to normal control blood, resulted in more stable thrombi, indicating no further efficacy of supraphysiologic FXIII. However, addition of tissue transglutaminase, which is synthesized by endothelial cells, generated thrombi that were more resistant to fibrinolysis; this may stabilize mural thrombi in vivo. Conclusions: Model thrombi formed under flow, even those prepared as plasma 'thrombi', reveal the effect of FXIII on fibrinolysis. Although very low levels of FXIII are known to produce mechanical clot stability, and to achieve ?-dimerization, they appear to be suboptimal in conferring full resistance to fibrinolysis.

Characterisation of resistance to ß-lactam antibiotics in a population of Haemophilus influenzae

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Adaptive resistance to biocides in Salmonella enterica and Escherichia coli O157 and cross-resistance to antimicrobial agents

The mechanisms by which bacteria resist killing by antibiotics and biocides are still poorly defined, although repeated exposure to sublethal concentrations of antibacterial agents undoubtedly contributes to their development. This study aimed both to investigate the potential of Salmonella enterica and Escherichia coli O157 for adaptive resistance to commonly used biocides and to determine any cross-resistance to antibiotics. Strains were repeatedly passaged in media containing increasing concentrations of a biocide or antibiotic until adaptive resistance was obtained. A wide panel of antimicrobial agents was then screened by using the adapted strain to determine cross-resistance, if any. Adaptive resistance was readily achieved for both S. enterica and E. coli O157. Cross-resistance in adaptively resistant S. enterica varied with the serotype; Salmonella enterica serovar Enteritidis expressed cross-resistance to chloramphenicol, whereas Salmonella enterica serovar Typhimurium expressed cross-resistance to chlorhexidine. Benzalkonium chloride-resistant Salmonella enterica serovar Virchow showed elevated resistance to chlorhexidine; however, chlorhexidine-resistant Salmonella serovar Virchow did not demonstrate reciprocal cross-resistance to benzalkonium chloride, suggesting specific rather than generic resistance mechanisms. E. coli O157 strains acquired high levels of resistance to triclosan after only two sublethal exposures and, when adapted, repeatedly demonstrated decreased susceptibilities to various antimicrobial agents, including chloramphenicol, erythromycin, imipenem, tetracycline, and trimethoprim, as well as to a number of biocides. These observations raise concern over the indiscriminate and often inappropriate use of biocides, especially triclosan, in situations where they are unnecessary, whereby they may contribute to the development of microbial resistance mechanisms.

An investigation into the acceptance of online banking in Saudi Arabia

Although a regional leader, Internet banking in Saudi Arabia is yet to be fully utilised as a value-adding tool to improve customer relationships and achieve cost advantages. The aim of this study was to identify the factors that encourage customers to adopt online banking in Saudi Arabia. The research constructs were developed based on the technology acceptance model (TAM) and incorporated some extra important control variables. The model was empirically verified to examine the factors influencing the online banking adoption behaviour of 400 customers. The findings of the study suggests that the quality of the Internet connection, the awareness of online banking and its benefits, the social influence and computer self-efficacy have significant effects on the perceived usefulness (PU) and perceived ease of use (PEOU) of online banking acceptance. Education, trust and resistance to change also have significant impact on the attitude towards the likelihood of adopting online banking. The implications of the findings are discussed and suggestions for future research are presented.

The use of ICT by logistics service providers and implications for training needs:a cross-country perspective

Changes in the international economic scenario in recent years have made it necessary for both industrial and service firms to reformulate their strategies, with a strong focus on the resources required for successful implementation. In this scenario, information and communication technologies (ICT) has a potentially vital role to play both as a key resource for re-engineering business processes within a framework of direct connection between suppliers and customers, and as a source of cost optimisation. There have also been innovations in the logistics and freight transport industry in relation to ICT diffusion. The implementation of such systems by third party logistics providers (3PL) allows the real-time exchange of information between supply chain partners, thereby improving planning capability and customer service. Unlike other industries, the logistics and freight transport industry is lagging somewhat behind other sectors in ICT diffusion. This situation is to be attributed to a series of both industry-specific and other factors, such as: (a) traditional resistance to change on the part of transport and logistics service providers; (b) the small size of firms that places considerable constraints upon investment in ICT; (c) the relative shortage of user-friendly applications; (d) the diffusion of internal standards on the part of the main providers in the industry whose aim is to protect company information, preventing its dissemination among customers and suppliers; (e) the insufficient degree of professional skills for using such technologies on the part of staff in such firms. The latter point is of critical importance insofar as the adoption of ICT is making it increasingly necessary both to develop new technical skills to use different hardware and new software tools, and to be able to plan processes of communication so as to allow the optimal use of ICT. The aim of this paper is to assess the impact of ICT on transport and logistics industry and to highlight how the use of such new technologies is affecting providers' training needs. The first part will provide a conceptual framework of the impact of ICT on the transport and logistics industry. In the second part the state of ICT dissemination in the Italian and Irish third party logistics industry will be outlined. In the third part, the impact of ICT on the training needs of transport and logistics service providers - based on case studies in both countries - are discussed. The implications of the foregoing for the development of appropriate training policies are considered. For the covering abstract see ITRD E126595.

Imagining oneself in a stereotyped role may stifle generalized tendencies to support social change

Imagining oneself in a stereotyped role may not only increase women's endorsement of stereotypes about women and science, but also stifle broader concerns about social change. In the experiment, 81 women imagined themselves on a stereotypical or a counter-stereotypical career path (vs. a control condition). Participants in the stereotypical imagery condition endorsed to a higher extent the stereotypes about women and science, and crucially, were more resistant to social change in general. Stereotype endorsement mediated the relationship between exposure to stereotypes and resistance to social change. Results imply that tackling occupational gender stereotypes is crucial not only because they exclude women from male-dominated careers, but also because of a potentially pervasive negative impact on broader egalitarian concerns.

Technological and organisational change in small- to medium-sized manufacturing companies:a learning organisation perspective

This paper examines the extent to which a learning organisation perspective is attainable in small- to medium-sized manufacturing companies. An audit tool is developed from the literature on organisational learning and recognised processes that lead towards becoming a learning organisation. The paper focuses on the application of the audit tool in three UK automotive component suppliers which are all experiencing pressures for change imposed by the major vehicle manufacturers. The main changes are concerned with tiering of the supply chain and substantial delegation of responsibilities to component suppliers including an increasing emphasis on innovation and continuous improvement. The companies presented in the paper are taken from a research project into the impact of changes in supply chain relationships on the operation of small- and medium-sized manufacturing firms in the West Midlands region of the UK. The ways in which the companies are responding to change are presented together with the results of a self-assessment using the developed audit tool. These results suggest that companies of this type tend to focus on change in those areas that involve least challenge to the established power and authority of management.

Sensitivity of staphylococcus epidermidis to chlorhexidine and associated resistance properties

Staphylococcus epidermidis are common Gram-positive bacteria and are responsible for a number of life-threatening nosocomial infections. Treatment of S. epidermidis infection is problematic because the organism is usually resistant to many antibiotics. The high degree of resistance of this organism to a range of antibiotics and disinfectants is widely known. The aims of this thesis were to investigate and evaluate the susceptibility of isolates of S. epidermidis from various infections to chlorhexidine (CHX) and to other disinfectants such as benzalkonium chloride (BKC), triclosan (TLN) and povidone-iodine (PI). In addition, the mechanisms of resistance of S. epidermidis to chlorhexidine (the original isolates and strains adapted to chlorhexidine by serial passage) were examined and co-resistance to clinically relevant antibiotics investigated. In 3 of the 11 S. epidermidis strains passaged in increasing concentrations of chlorhexidine, resistance to the disinfectant arose (16-fold). These strains were examined further, each showing stable chlorhexidine resistance. Co-resistance to other disinfectants such as BKC, TLN and PI and changes in cell surface hydrophobicity were observed. Increases in resistance were accompanied by an increase in the proportion of neutral lipids and phospholipids in the cell membrane. This increase was most marked in diphosphatidylglycerol. These observations suggest that some strains of S. epidermidis can become resistant to chlorhexidine and related disinfectants/antiseptics by continual exposure. The mechanisms of resistance appear to be related to changes in membrane lipid compositions.

From therapeutic to political education: the centrality of affective sensibility in critical pedagogy

While the need for humanising education is pressing in neoliberal societies, the conditions for its possibility in formal institutions have become particularly cramped. A constellation of factors – the strength of neoliberal ideologies, the corporatisation of universities, the conflation of human freedom with consumer satisfaction, and a wider crisis of hope in the possibility or desirability of social change – make it difficult to apply classical theories of subject-transformation to new work in critical pedagogy. In particular, the growth of interest in pedagogies of comfort (as illustrated in certain forms of ‘therapeutic’ education and concerns about student ‘satisfaction’) and resistance to critical pedagogies suggest that subjectivty has become a primary site of political struggle in education. However, it can no longer be assumed that educators can (or should) liberate students’ repressed desires for ‘humanisation’ by politicising curricula, pedagogy or institutions. Rather, we must work to understand the new meanings and affective conditions of critical subjectivity itself. Bringing critical theories of subject transformation together with new work on ‘pedagogies of discomfort’, I suggest we can create new ways of opening up possibilities for critical education that respond to neoliberal subjectivities without corresponding to or affirming them.

Role of GSH in estrone sulfate binding and translocation by the multidrug resistance protein 1 (MRP1/ABCC1)

Multidrug resistance protein 1 (MRP1/ABCC1) is an ATP-dependent efflux pump that can confer resistance to multiple anticancer drugs and transport conjugated organic anions. Unusually, transport of several MRP1 substrates requires glutathione (GSH). For example, estrone sulfate transport by MRP1 is stimulated by GSH, vincristine is co-transported with GSH, or GSH can be transported alone. In the present study, radioligand binding assays were developed to investigate the mechanistic details of GSH-stimulated transport of estrone sulfate by MRP1. We have established that estrone sulfate binding to MRP1 requires GSH, or its non-reducing analogue S-methyl GSH (S-mGSH), and further that the affinity (Kd) of MRP1 for estrone sulfate is 2.5-fold higher in the presence of S-mGSH than GSH itself. Association kinetics show that GSH binds to MRP1 first, and we propose that GSH binding induces a conformational change, which makes the estrone sulfate binding site accessible. Binding of non-hydrolyzable ATP analogues to MRP1 decreases the affinity for estrone sulfate. However, GSH (or S-mGSH) is still required for estrone sulfate binding, and the affinity for GSH is unchanged. Estrone sulfate affinity remains low following hydrolysis of ATP. The affinity for GSH also appears to decrease in the post-hydrolytic state. Our results indicate ATP binding is sufficient for reconfiguration of the estrone sulfate binding site to lower affinity and argue for the presence of a modulatory GSH binding site not associated with transport of this tripeptide. A model for the mechanism of GSH-stimulated estrone sulfate transport is proposed.