171 research outputs found

    The relationship between national culture and safety culture: implications for international safety culture assessments

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    In this article we examine the relationship between safety culture and national culture, and the implications of this relationship for international safety culture assessments. Focussing on Hofstede’s uncertainty avoidance (UA) index, a survey study of 13,616 Air Traffic Management (ATM) employees in 21 European countries found a negative association between safety culture and national norm data for uncertainty avoidance. This is theorized to reflect the influence of national tendencies for uncertainty avoidance upon attitudes and practices for managing safety (e.g., anxiety on risk; reliance on protocols; concerns over reporting incidents; openness to different perspectives). The relationship between uncertainty avoidance and safety culture is likely to have implications for international safety culture assessments. Specifically, benchmarking exercises will consistently indicate safety management within organizations in high UA countries to be poorer than low UA countries due to the influence of national culture upon safety practices, which may limit opportunities for identifying and sharing best practice. We propose the use of safety culture against international group norms (SIGN) scores to statistically adjust for the influence of uncertainty avoidance upon safety culture data, and to support the identification of safety practices effective and particular to low or high UA cultures

    Safety culture and power: interactions between perceptions of safety culture, organisational hierarchy, and national culture

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    Practices that involve power dynamics are integral to maintaining organisational safety (e.g. speaking-up, challenging poor behaviour, admitting error, communicating on safety), and staff engagement in these is assumed to be shaped by perceptions of safety culture. These perceptions, in-turn, are associated with (1) positions within an organisational hierarchy (which makes power-related acts more or less threatening), and (2) societal values for power distance (e.g. challenging authority). With a sample of 13,573 of air traffic control staff (controllers, engineers, administrative, and management) from 21 national air traffic providers, we reconfirm the observation that managers perceive safety culture more positively than frontline staff (hypothesis 1), and that workers in countries with established values for hierarchy and power report safety culture as less positive than those from countries with low power distance (hypothesis 2). We then, for the first time, examine the interaction between these two factors, and establish that differences in safety culture perceptions between those higher in the hierarchy (management) and those lower in the hierarchy (air traffic controllers and administrative staff) are exacerbated by national contexts for large power distance (hypothesis 3). The study contributes to the literature by theorising the role of power in safety culture theory, and its influence upon safety culture perceptions. Moving forward, safety culture research and interventions may benefit from considering how power exists and manifests at the level of superior-subordinate dynamics

    Safety sans frontières: an international safety culture model

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    The management of safety culture in international and culturally diverse organisations is a concern for many high-risk industries. Yet, research has primarily developed models of safety culture within Western countries, and there is a need to extend investigations of safety culture to global environments. We examined i) whether safety culture can be reliably measured within a single industry operating across different cultural environments, and ii) if there is an association between safety culture and national culture. The psychometric properties of a safety culture model developed for the air traffic management industry (ATM) were examined in 17 European countries from four culturally distinct regions of Europe (North, East, South, West). Participants were ATM operational staff (n = 5176) and management staff (n = 1230). Through employing multi-group confirmatory factor analysis, good psychometric properties of the model were established. This demonstrates, for the first time, that when safety culture models are tailored to a specific industry, they can operate consistently across national boundaries and occupational groups. Additionally, safety culture scores at both regional and national levels were associated with country-level data on Hofstede’s five national culture dimensions (collectivism, power distance, uncertainty avoidance, masculinity, and uncertainty avoidance). MANOVAs indicated safety culture to be most positive in Northern Europe, less so in Western and Eastern Europe, and least positive in Southern Europe. This indicates that national cultural traits may influence the development of organisational safety culture, with significant implications for safety culture theory and practice

    Enantioselective Dynamic Process Reduction of α- and β-Tetralone and Stereoinversion of Resulting Alcohols in a Selected Strain Culture

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    α-Tetralone and β-tetralone were subjected to biotransformation by 14 fungal strains. Enantiomeric purity of the products depended on the reaction time. 3-Day transformation of α-tetralone in Absidia cylindrospora culture gave S-(+)-1,2,3,4-tetrahydro-1-naftol of 92 % ee, whereas longer biotransformation time resulted in decrease of ee value. 3-Day transformation of β-tetralone by the same strain gave predominantly S-(−)-1,2,3,4-tetrahydro-2-naftol, whereas after 9 days of the reaction, the R-enantiomer with 85 % ee was isolated. Transformation of β-tetralone by Chaetomium sp. KCh 6651 gave pure (S)-(−)-1,2,3,4-tetrahydro-2-naftol in high yield at the concentration of 1 g/l. In this process, a non-selective carbonyl reduction was observed, followed by a selective oxidation of the R-alcohol

    A non-myeloablative chimeric mouse model accurately defines microglia and macrophage contribution in glioma.

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    Resident and peripherally-derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion, and attenuating host immune responses. Differentiating these cells' origins is challenging and current pre-clinical models such as irradiation-based adoptive transfer, parabiosis and transgenic mice have limitations. We aimed to develop a novel non-myeloablative transplantation (NMT) mouse model that permits high levels of peripheral chimerism without blood-brain barrier (BBB) damage or brain infiltration prior to tumour implantation.NMT dosing was determined in C57BL/6J or Pep3/CD45.1 mice conditioned with concentrations of busulfan ranging from 25mg/kg to 125mg/kg. Donor haematopoietic cells labelled with eGFP or CD45.2 were injected via tail vein. Donor chimerism was measured in peripheral blood, bone marrow and spleen using flow cytometry. BBB integrity was assessed with anti-IgG and anti-fibrinogen antibodies. Immunocompetent chimerised animals were orthotopically implanted with murine glioma GL-261 cells. Central and peripheral cell contributions were assessed using immunohistochemistry and flow cytometry. GAMM subpopulation analysis of peripheral cells was performed using Ly6C/MHCII/MerTK/CD64.NMT achieves >80% haematopoietic chimerism by 12 weeks without BBB damage and normal life span. Bone marrow derived cells (BMDC) and peripheral macrophages accounted for approximately 45% of the GAMM population in GL-261 implanted tumours. Existing markers such as CD45 high/low proved inaccurate to determine central and peripheral populations while Ly6C/MHCII/MerTK/CD64 reliably differentiated GAMM subpopulations in chimerised and unchimerised mice.NMT is a powerful method for dissecting tumour microglia and macrophage subpopulations and can guide further investigation of BMDC subsets in glioma and neuro-inflammatory diseases. This article is protected by copyright. All rights reserved

    Intra-Operative Assessment of Cancer with X-Ray Phase Contrast Computed Tomography

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    X-ray Phase-Contrast Computed Tomography (PC-CT) increases contrast in weakly attenuating samples, such as soft tissues. In Edge-Illumination (EI) PC-CT, phase effects are accessed from amplitude modulation of the x-ray beam using alternating transmitting and attenuating masks placed prior to the sample and detector. A large field of view PC-CT scanner using this technique was applied to two areas of cancer assessment, namely excised breast and esophageal tissue. For the breast tissue, Wide Local Excisions (WLEs) were studied intra-operatively using PC-CT for the evaluation of tumor removal in breast conservation surgery. Images were acquired in 10 minutes without compromising on image quality, showing this can be used in a clinical setting. Longer, higher resolution PC-CT images were also taken, with analysis showing previously undetected thinning of tumor strands. This would allow a second use of the system for “virtual histopathology”, outside of surgery. For the esophagus samples, tissues were taken from esophagectomy surgery, where the lower part of the esophagus is removed, and the stomach relocated. For the assessment of ongoing therapy, accurate staging of tumors in the removed esophagus is essential, with the current gold standard provided by histopathology. PCCT images were acquired on several samples and compare well with histopathology, with both modalities showing similar features. Examples are shown where staging of tumor penetration is possible with PC-CT images alone, which is hoped will be an important step in performing the imaging and staging intra-operatively

    Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease

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    CLN1 disease is a fatal inherited neurodegenerative lysosomal storage disease of early childhood, caused by mutations in the CLN1 gene, which encodes the enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology in Ppt1-deficient (Ppt1−/−) mice and human CLN1 disease that contributes to clinical outcome and precedes the onset of brain pathology. Here, we quantified this spinal pathology at 3 and 7 months of age revealing significant and progressive glial activation and vulnerability of spinal interneurons. Tandem mass tagged proteomic analysis of the spinal cord of Ppt1−/−and control mice at these timepoints revealed a significant neuroimmune response and changes in mitochondrial function, cell-signalling pathways and developmental processes. Comparing proteomic changes in the spinal cord and cortex at 3 months revealed many similarly affected processes, except the inflammatory response. These proteomic and pathological data from this largely unexplored region of the CNS may help explain the limited success of previous brain-directed therapies. These data also fundamentally change our understanding of the progressive, site-specific nature of CLN1 disease pathogenesis, and highlight the importance of the neuroimmune response. This should greatly impact our approach to the timing and targeting of future therapeutic trials for this and similar disorders

    Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

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    Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo
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