91 research outputs found

    Communication enhancement: a process dividend for the organisation and the HRM department?

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    Quality has become a key issue for organisations seeking competitive advantage and coping with ever changing market demands. Evidence suggests that the human resource implications of such initiatives are frequently underestimated and neglected Powell, 1995). The present study surveyed 133 Irish organisations implementing Quality Initiatives (QIs), focusing particularly on the impact of these initiatives on internal communication processes and the role played by the human resource (HR) function in these changes. Results indicate the overall success of the QIs in enhancing internal communication processes, but highlight two issues: the surprising absence of HR function involvement in the deliverance of these communication enhancements and the perception by most respondents that while the stated tangible QI objectives have been achieved, there is still some distance to be travelled to fulfil employee expectations on the more intangible communication based needs. The implications of these findings are discussed in terms of the changing face of the HR function and the long term success of QIs

    Gaining competitive advantage through a quality culture: the role of human resource management

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    There is a good deal of evidence that, as technological transfer becomes increasingly rapid, the source of competitive advantage for many companies now lies within their workforces (Pfeffer, 1994). However, the issue of how to sustain and promote this type of competitive advantage may be more problematic than one based on keeping up-to-date with changing machinery and techniques. For some companies, investment in people and in the appropriate human resource practices to foster their development and commitment requires a consideration of the ways in which they have usually tackled such matters. For the human resource function this represents the opportunity to become involved in major change initiatives, but it may require a rethinking oftraditional roles. This paper considers the implications for both the human resource function and for human resource practices of the changes wrought within companies involved in the implementation of quality initiatives. Quality has become a key issue for companies seeking competitive advantage and recent research indicates that a focus on the human resource implications of these quality initiatives, although frequently a neglected dimension, may be critical to their long term success (Powell, 1995). The paper begins by considering some of the literature on the impact of quality programmes on the human resource function in particular and on human resource practices in general before reporting on the findings of research in some Irish companies

    Adaphostin toxicity in a sensitive non-small cell lung cancer model is mediated through Nrf2 signaling and heme oxygenase 1

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    <p>Abstract</p> <p>Background</p> <p>Preclinical toxicity of adaphostin has been related to oxidative stress. This study investigated the regulatory mechanism underlying adaphostin induction of heme oxygenase 1 (HMOX1) which plays a significant role in modulation of drug-induced toxicity in the non-small cell lung cancer cell line model, NCI-H522.</p> <p>Methods</p> <p>The transcriptional response of NCI-H522 to adaphostin prominently involved oxidative stress genes, particularly HMOX1. Reactive oxygen species (ROS) involvement was additionally established by generation of ROS prior to modulation of adaphostin-toxicity with antioxidants. To identify up-stream regulatory elements of HMOX1, immunofluorescence was used to evaluate nuclear translocation of the transcription factor, NF-E2-related factor 2 (Nrf2), in the presence of adaphostin. The PI3-kinase inhibitor, wortmannin, was employed as a pharmacological inhibitor of this process.</p> <p>Results</p> <p>Generation of ROS provided a substantial foundation for the sensitivity of NCI-H522 to adaphostin. However, in contrast to leukemia cell lines, transcriptional response to oxidative stress was associated with induction of HMOX1, which was dependent on nuclear translocation of the transcription factor, Nrf2. Pretreatment of cells with wortmannin inhibited translocation of Nrf2 and induction of HMOX1. Wortmannin pretreatment was also able to diminish adaphostin induction of HMOX1, and as a consequence, enhance the toxicity of adaphostin to NCI-H522.</p> <p>Conclusions</p> <p>Adaphostin-induced oxidative stress in NCI-H522 was mediated through nuclear translocation of Nrf2 leading to upregulation of HMOX1. Inhibition of Nrf2 translocation by wortmannin inhibited this cytoprotective response, and enhanced the toxicity of adaphostin, suggesting that inhibitors of the PI3K pathway, such as wortmannin, might augment the antiproliferative effects of adaphostin in solid tumors that depend on the Nrf2/ARE pathway for protection against oxidative stress.</p

    4-Pyridone-3-carboxamide-1-β-D-ribonucleoside Triphosphate (4PyTP), a Novel NAD+ Metabolite Accumulating in Erythrocytes of Uremic Children: A Biomarker for a Toxic NAD+ Analogue in Other Tissues?

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    We have identified a novel nucleotide, 4-pyridone 3/5-carboxamide ribonucleoside triphosphate (4PyTP), which accumulates in human erythrocytes during renal failure. Using plasma and erythrocyte extracts obtained from children with chronic renal failure we show that the concentration of 4PyTP is increased, as well as other soluble NAD+ metabolites (nicotinamide, N1-methylnicotinamide and 4Py-riboside) and the major nicotinamide metabolite N1-methyl-2-pyridone-5-carboxamide (2PY), with increasing degrees of renal failure. We noted that 2PY concentration was highest in the plasma of haemodialysis patients, while 4PyTP was highest in erythrocytes of children undergoing peritoneal dialysis: its concentration correlated closely with 4Py-riboside, an authentic precursor of 4PyTP, in the plasma. In the dialysis patients, GTP concentration was elevated: similar accumulation was noted previously, as a paradoxical effect in erythrocytes during treatment with immunosuppressants such as ribavirin and mycophenolate mofetil, which deplete GTP through inhibition of IMP dehydrogenase in nucleated cells such as lymphocytes. We predict that 4Py-riboside and 4Py-nucleotides bind to this enzyme and alter its activity. The enzymes that regenerate NAD+ from nicotinamide riboside also convert the drugs tiazofurin and benzamide riboside into NAD+ analogues that inhibit IMP dehydrogenase more effectively than the related ribosides: we therefore propose that the accumulation of 4PyTP in erythrocytes during renal failure is a marker for the accumulation of a related toxic NAD+ analogue that inhibits IMP dehydrogenase in other cells

    Conducting Large-Scale Mixed-Method Research on Harm and Abuse Prevention with Children under 12: Learning from a UK feasibility study

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    This paper reports on a feasibility study for an evaluation of a UK primary school-based prevention programme that addresses multiple forms of abuse and neglect, identifying research design and ethical issues and exploring research practice. For this feasibility study, 194 children aged 6–11 years completed a baseline survey and 113 did so following the intervention. Eight focus groups were undertaken with 52 children and nine interviews with school staff. We highlight key considerations for conducting large-scale mixed-method research on sensitive topics with younger children, a focus that is largely absent from the extant research methods literature. The feasibility study showed that younger children can contribute their views on sensitive topics in ways that are measurable, replicable and reliable, contesting ideas that certain topics are too sensitive to explore with younger children

    The N-terminus of CD14 acts to bind apoptotic cells and confers rapid-tethering capabilities on non-myeloid cells:CD14 and rapid tethering of apoptotic cells

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    Cell death and removal of cell corpses in a timely manner is a key event in both physiological and pathological situations including tissue homeostasis and the resolution of inflammation. Phagocytic clearance of cells dying by apoptosis is a complex sequential process comprising attraction, recognition, tethering, signalling and ultimately phagocytosis and degradation of cell corpses. A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within this process. The role of myeloid cell CD14 in mediating apoptotic cell interactions with macrophages has long been known though key molecules and residues involved have not been defined. Here we sought to further dissect the function of CD14 in apoptotic cell clearance. A novel panel of THP-1 cell-derived phagocytes was employed to demonstrate that CD14 mediates effective apoptotic cell interactions with macrophages in the absence of detectable TLR4 whilst binding and responsiveness to LPS requires TLR4. Using a targeted series of CD14 point mutants expressed in non-myeloid cells we reveal CD14 residue 11 as key in the binding of apoptotic cells whilst other residues are reported as key for LPS binding. Importantly we note that expression of CD14 in non-myeloid cells confers the ability to bind rapidly to apoptotic cells. Analysis of a panel of epithelial cells reveals that a number naturally express CD14 and that this is competent to mediate apoptotic cell clearance. Taken together these data suggest that CD14 relies on residue 11 for apoptotic cell tethering and it may be an important tethering molecule on so called 'non-professional' phagocytes thus contributing to apoptotic cell clearance in a non-myeloid setting. Furthermore these data establish CD14 as a rapid-acting tethering molecule, expressed in monocytes, which may thus confer responsiveness of circulating monocytes to apoptotic cell derived material. © 2013 Thomas et al

    A High-Density EEG Investigation into Steady State Binaural Beat Stimulation

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    Binaural beats are an auditory phenomenon that has been suggested to alter physiological and cognitive processes including vigilance and brainwave entrainment. Some personality traits measured by the NEO Five Factor Model have been found to alter entrainment using pulsing light stimuli, but as yet no studies have examined if this occurs using steady state presentation of binaural beats for a relatively short presentation of two minutes. This study aimed to examine if binaural beat stimulation altered vigilance or cortical frequencies and if personality traits were involved. Thirty-one participants were played binaural beat stimuli designed to elicit a response at either the Theta (7 Hz) or Beta (16 Hz) frequency bands while undertaking a zero-back vigilance task. EEG was recorded from a high-density electrode cap. No significant differences were found in vigilance or cortical frequency power during binaural beat stimulation compared to a white noise control period. Furthermore, no significant relationships were detected between the above and the Big Five personality traits. This suggests a short presentation of steady state binaural beats are not sufficient to alter vigilance or entrain cortical frequencies at the two bands examined and that certain personality traits were not more susceptible than others
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