3 resultados para Tragedy at Pike River Mine : How and why 29 men died

em Cambridge University Engineering Department Publications Database


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Purpose - As traditional manufacturing, previously vital to the UK economy, is increasingly outsourced to lower-cost locations, policy makers seek leadership in emerging industries by encouraging innovative start-up firms to pursue competitive opportunities. Emerging industries can either be those where a technology exists but the corresponding downstream value chain is unclear, or a new technology may subvert the existing value chain to satisfy existing customer needs. Hence, this area shows evidence of both technology-push and market-pull forces. The purpose of this paper is to focus on market-pull and technology-push orientations in manufacturing ventures, specifically examining how and why this orientation shifts during the firm's formative years. Design/methodology/approach - A multiple case study approach of 25 UK start-ups in emerging industries is used to examine this seldom explored area. The authors offer two models of dynamic business-orientation in start-ups and explain the common reasons for shifts in orientation and why these two orientations do not generally co-exist during early firm development. Findings - Separate evolution paths were found for strategic orientation in manufacturing start-ups and separate reasons for them to shift in their early development. Technology-push start-ups often changed to a market-pull orientation because of new partners, new market information or shift in management priorities. In contrast, many of the start-ups beginning with a market-pull orientation shifted to a technology-push orientation because early market experiences necessitated a focus on improving processes in order to increase productivity or meet partner specifications, or meet a demand for complementary products. Originality/value - While a significant body of work exists regarding manufacturing strategy in established firms, little work has been found that investigates how manufacturing strategy emerges in start-up companies, particularly those in emerging industries. © Emerald Group Publishing Limited.

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BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

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Understanding how and why changes propagate during engineering design is critical because most products and systems emerge from predecessors and not through clean sheet design. This paper applies change propagation analysis methods and extends prior reasoning through examination of a large data set from industry including 41,500 change requests, spanning 8 years during the design of a complex sensor system. Different methods are used to analyze the data and the results are compared to each other and evaluated in the context of previous findings. In particular the networks of connected parent, child and sibling changes are resolved over time and mapped to 46 subsystem areas. A normalized change propagation index (CPI) is then developed, showing the relative strength of each area on the absorber-multiplier spectrum between -1 and +1. Multipliers send out more changes than they receive and are good candidates for more focused change management. Another interesting finding is the quantitative confirmation of the "ripple" change pattern. Unlike the earlier prediction, however, it was found that the peak of cyclical change activity occurred late in the program driven by systems integration and functional testing. Patterns emerged from the data and offer clear implications for technical change management approaches in system design. Copyright © 2007 by ASME.