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.

Logics, thresholds, strategic power, and the promotion of liberalisation by governments: a case study from British Higher Education

Liberalisation has become an increasingly important policy trend, both in the private and public sectors of advanced industrial economies. This article eschews deterministic accounts of liberalisation by considering why government attempts to institute competition may be successful in some cases and not others. It considers the relative strength of explanations focusing on the institutional context, and on the volume and power of sectoral actors supporting liberalisation. These approaches are applied to two attempts to liberalise, one successful and one unsuccessful, within one sector in one nation – higher education in Britain. Each explanation is seen to have some explanatory power, but none is sufficient to explain why competition was generalised in the one case and not the other. The article counsels the need for scholars of liberalisation to be open to multiple explanations which may require the marshalling of multiple sources and types of evidence.

Sensitivity of antioxidant-deficient yeast to hypochlorite and chlorite

Sodium hypochlorite and sodium chlorite are commonly used as disinfectants, and understanding the mechanisms of microbial resistance to these compounds is of considerable importance. In this study, the role of oxidative stress and antioxidant enzymes in the sensitivity of the yeast Saccharomyces cerevisiae to hypochlorite and chlorite was studied. Yeast mutants lacking Cu-Zn superoxide dismutase, but not mutants deficient in cytoplasmic and peroxisomal catalase, were hypersensitive to the action of both hypochlorite and chlorite. Both compounds depleted cellular glutathione, induced the production of reactive oxygen species and decreased the viability of the cells. The toxicity of hypochlorite and chlorite was abolished by hypoxic and anoxic conditions and ameliorated by thiol antioxidants and ascorbate. The results demonstrated that the action of hypochlorite and chlorite involves the formation of superoxide and peroxide and that SOD1 is protective, probably by limiting the formation of hydroxyl radicals and damage to proteins.

Molecular basis for reduced estrone sulfate transport and altered modulator sensitivity of transmembrane helix (TM) 6 and TM17 mutants of multidrug resistance protein 1 (ABCC1)

Multidrug resistance protein 1 (MRP1) confers drug resistance and also mediates cellular efflux of many organic anions. MRP1 also transports glutathione (GSH); furthermore, this tripeptide stimulates transport of several substrates, including estrone 3-sulfate. We have previously shown that mutations of Lys(332) in transmembrane helix (TM) 6 and Trp(1246) in TM17 cause different substrate-selective losses in MRP1 transport activity. Here we have extended our characterization of mutants K332L and W1246C to further define the different roles these two residues play in determining the substrate and inhibitor specificity of MRP1. Thus, we have shown that TM17-Trp(1246) is crucial for conferring drug resistance and for binding and transport of methotrexate, estradiol glucuronide, and estrone 3-sulfate, as well as for binding of the tricyclic isoxazole inhibitor N-[3-(9-chloro-3-methyl-4-oxo-4H-isoxazolo-[4,3-c]quinolin-5-yl)-cyclohexylmethyl]-benzamide (LY465803). In contrast, TM6-Lys(332) is important for enabling GSH and GSH-containing compounds to serve as substrates (e.g., leukotriene C(4)) or modulators (e.g., S-decyl-GSH, GSH disulfide) of MRP1 and, further, for enabling GSH (or S-methyl-GSH) to enhance the transport of estrone 3-sulfate and increase the inhibitory potency of LY465803. On the other hand, both mutants are as sensitive as wild-type MRP1 to the non-GSH-containing inhibitors (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK571), 1-[2-hydroxy-3-propyl-4-[4-(1H-tetrazol-5-yl)butoxy]phenyl]-ethanone (LY171883), and highly potent 6-[4'-carboxyphenylthio]-5[S]-hydroxy-7[E], 11[Z]14[Z]-eicosatetrenoic acid (BAY u9773). Finally, the differing abilities of the cysteinyl leukotriene derivatives leukotriene C(4), D(4), and F(4) to inhibit estradiol glucuronide transport by wild-type and K332L mutant MRP1 provide further evidence that TM6-Lys(332) is involved in the recognition of the gamma-Glu portion of substrates and modulators containing GSH or GSH-like moieties.

Separate influences of acoustic AM and FM sensitivity on the phonological decoding skills of impaired and normal readers

Developmental dyslexia is associated with deficits in the processing of basic auditory stimuli. Yet it is unclear how these sensory impairments might contribute to poor reading skills. This study better characterizes the relationship between phonological decoding skills, the lack of which is generally accepted to comprise the core deficit in reading disabilities, and auditory sensitivity to amplitude modulation (AM) and frequency modulation (FM). Thirty-eight adult subjects, 17 of whom had a history of developmental dyslexia, completed a battery, of psychophysical measures of sensitivity to FM and AM at different modulation rates, along with a measure of pseudoword reading accuracy and standardized assessments of literacy and cognitive skills. The subjects with a history of dyslexia were significantly less sensitive than controls to 2-Hz FM and 20-Hz AM only. The absence of a significant group difference for 2-Hz AM shows that the dyslexics do not have a general deficit in detecting all slow modulations. Thresholds for detecting 2-Hz and 240-Hz FM and 20-Hz AM correlated significantly with pseudoword reading accuracy. After accounting for various cognitive skills, however, multiple regression analyses showed that detection thresholds for both 2-Hz FM and 20-Hz AM were significant and independent predictors of pseudoword reading ability in the entire sample. Thresholds for 2-Hz AM and 240-Hz FM did not explain significant additional variance in pseudoword reading skill, it is therefore possible that certain components of auditory processing of modulations are related to phonological decoding skills, whereas others are not.

Antecedents of strategic flexibility:management cognition, firm resources and strategic options

Purpose: Current conceptualisations of strategic flexibility and its antecedents are theory-driven, which has resulted in a lack of consensus. To summarise this domain the paper aims to develop and present an a priori conceptual model of the antecedents and outcomes of strategic flexibility. Discussion and insights into the conceptual model, and the relationships specified, are made through a novel qualitative empirical approach. The implications for further research and a framework for further theoretical development are presented. Design/methodology/approach: An exploratory qualitative research design is used applying multiple data collection techniques in a branch network of a large regional retailer in the UK. The development of strategic options and the complex relationship to strategic flexibility is investigated. Findings: The number and type of strategic options developed by managers impact on the degree of strategic flexibility and also on the ability of the firm to achieve competitive differentiation. Additionally, the type of strategic option implemented by managers is dependent on the competitive situation faced at a local level. Evidence of managers' limited perception of competition was identified based on their spatial embeddedness. Research limitations/implications: A single, in-depth case study was used. The data gathered is rich and appropriate for the exploratory approach adopted here. However, generalisability of the findings is limited. Practical implications: Strategic flexibility is rooted in the ability of front-line mangers to develop and implement strategic options; this in turn facilitates competitive differentiation. Originality/value: The research presented is unique in this domain on two accounts. First, theory is developed by presenting an a priori conceptual model, and testing through in-depth qualitative data gathering. Second, insights into strategic flexibility are presented through an examination of managerial cognition, resources and strategic option generation using cognitive mapping and laddering technique. © Emerald Group Publishing Limited.

Sensitivity of LPGs in PCFs fabricated by an electric arc to temperature, strain, and external refractive index

Sensing properties of long-period gratings (LPGs) fabricated in photonic crystal fibers by an electric arc are explained and quantified by semianalytical and numerical models. In particular, the grating's insensitivity to temperature and simultaneous sensitivity to strain and refractive index are simulated. The modeling procedure is generalized so that it can be applied to a wide range of LPGs in various fibers. © 2007 IEEE.

How are task reflexivity and intercultural sensitivity related to the academic performance of MBA students?

Higher education in business school environments is increasingly focused on how to best equip students with the skills necessary for leadership in the global workplace. This paper examines the impact of two particularly important cognitive capabilities - task reflexivity and intercultural sensitivity, on academic performance in an MBA programme. It was hypothesised that in an intercultural learning environment, task reflexivity would be associated with higher academic performance, and that this relationship would be mediated via intercultural sensitivity. Questionnaire data from 77 MBA students was analysed alongside academic performance. Results demonstrated that task reflexivity was indirectly related to academic performance through intercultural sensitivity. These findings suggest that engagement in task reflexivity enables students to develop greater levels of intercultural sensitivity, allowing them to reap the positive effects of diversity in their peer group for their own learning and performance. Limitations and practical implications of the research for professional practice are discussed. © 2014 © 2014 Society for Research into Higher Education.

Normative contrast sensitivity values for the back-lit Melbourne Edge Test and the effect of visual impairment

Background: The Melbourne Edge Test (MET) is a portable forced-choice edge detection contrast sensitivity (CS) test. The original externally illuminated paper test has been superseded by a backlit version. The aim of this study was to establish normative values for age and to assess change with visual impairment. Method: The MET was administered to 168 people with normal vision (18-93 years old) and 93 patients with visual impairment (39-97 years old). Distance visual acuity (VA) was measured with a log MAR chart. Results: In those eyes without disease, MET CS was stable until the age of 50 years (23.8 ± .7 dB) after which it decreased at a rate of ≈1.5 dB per decade. Compared with normative values, people with low vision were found to have significantly reduced CS, which could not be totally accounted for by reduced VA. Conclusions: The MET provides a quick and easy measure of CS, which highlights a reduction in visual function that may not be detectable using VA measurements. © 2004 The College of Optometrists.

Strategic development and physicochemical analysis of oral preparations for unstable drugs

Oral liquid formulations are ideal dosage forms for paediatric, geriatric and patient with dysphagia. Dysphagia is prominent among patients suffering from stroke, motor neurone disease, advanced Alzheimer’s and Parkinson’s disease. However oral liquid preparations are particularly difficult to formulate for hydrophobic and unstable drugs. Therefore current methods employed in solving this issue include the use of ‘specials’ or extemporaneous preparations. In order to challenge this, the government has encouraged research into the field of oral liquid formulations, with the EMEA and MHRA publishing list of drugs of interest. The current work investigates strategic formulation development and characterisation of select API’s (captopril, gliclazide, melatonin, L-arginine and lansoprazole), each with unique obstacles to overcome during solubilisation, stabilisation and when developing a palatable dosage from. By preparing a validated calibration protocol for each of the drug candidates, the oral liquid formulations were assessed for stability, according to the ICH guidelines along with thorough physiochemical characterisation. The results showed that pH and polarity of the solvent had the greatest influence on the extent of drug solubilisation, with inclusion of antioxidants and molecular steric hindrance influencing the extent of drug stability. Captopril, a hydrophilic ACE inhibitor (160 mg.mL-1), undergoes dimerisation with another captopril molecule. It was found that with the addition of EDTA and HP-β-CD, the drug molecule was stabilised and prevented from initiating a thiol induced first order free radical oxidation. The cyclodextrin provided further steric hindrance (1:1 molar ratio) resulting in complete reduction of the intensity of sulphur like smell associated with captopril. Palatability is a crucial factor in patient compliance, particularly when developing a dosage form targeted towards paediatrics. L-arginine is extremely bitter in solution (148.7 g.L-1). The addition of tartaric acid into the 100 mg.mL-1 formulation was sufficient to mask the bitterness associated with its guanidium ions. The hydrophobicity of gliclazide (55 mg.L-1) was strategically challenged using a binary system of a co-solvent and surfactant to reduce the polarity of the medium and ultimately increase the solubility of the drug. A second simpler method was developed using pH modification with L-arginine. Melatonin has two major obstacles in formulation: solubility (100 μg.mL-1) and photosensitivity, which were both overcome by lowering the dielectric constant of the medium and by reversibly binding the drug within the cyclodextrin cup (1:1 ratio). The cyclodextrin acts by preventing UV rays from reaching the drug molecule and initiated the degradation pathway. Lansoprazole is an acid labile drug that could only be delivered orally via a delivery vehicle. In oral liquid preparations this involved nanoparticulate vesicles. The extent of drug loading was found to be influenced by the type of polymer, concentration of polymer, and the molecular weight. All of the formulations achieved relatively long shelf-lives with good preservative efficacy.

Numerical and experimental analysis of sensitivity-enhanced RI sensor based on Ex-TFG in thin cladding fiber

We report a highly sensitive refractive index (RI) sensor in the aqueous solution, which is based on an 81°-tilted fiber grating structure inscribed into a thin cladding fiber with 40 μm cladding radius. The numerical analysis has indicated that the RI sensitivity of cladding resonance mode of the grating can be significantly enhanced with reducing cladding size. This has been proved by the experimental results as the RI sensitivities of TM and TE resonance peaks in the index region of 1.345 have been increased to 1180 nm/RIU and 1150 nm/RIU, respectively, from only 200 and 170 nm/RIU for the same grating structure inscribed in standard telecom fiber with 62.5-μm cladding radius. Although the temperature sensitivity has also increased, the change in temperature sensitivity is still insignificant in comparison with RI sensitivity enhancement.

Refractive index and temperature sensitivity characteristics of a micro-slot fiber Bragg grating

Fabrication and characterization of a UVinscribed fiber Bragg grating (FBG) with a micro-slot liquid core is presented. Femtosecond (fs) laser patterning/chemical etching technique was employed to engrave a micro-slot with dimensions of 5.74 μm(h) × 125 μm(w) × 1388.72 μm(l) across the whole grating. The device has been evaluated for refractive index (RI) and temperature sensitivities and exhibited distinctive thermal response and RI sensitivity beyond the detection limit of reported fiber gratings. This structure has not just been RI sensitive, but also maintained the robustness comparing with the bare core FBGs and long-period gratings with the partial cladding etched off. © 2012 Optical Society of America.