445 research outputs found

    Factor Market Rivalry, Factor Market Myopia, and Strategic Blind Spots: The Case Of The Truck Driver Labor Market

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    This article explores the relationships among factor market rivalry, factor market myopia, and strategic blind spots in the context of the labor market for truck drivers. Levitt (1960) developed the concept of market myopia to explain how managers often overlooked key competitors in product markets. Trucking managers might do the same thing in looking at competition for truck drivers. Factor market myopia and strategic blind spots help to explain how this happens, and how it becomes more severe in the context of factor market rivalry. In the trucking industry, factor market myopia and strategic blind spots may mean that managers overlook competition for workers who not only can drive trucks, but can also do many other jobs. We find that the labor market for truck drivers offers important lessons on the practical and theoretical ways in which these ideas interact

    Nerve injury induces robust allodynia and ectopic discharges in Na(v)1.3 null mutant mice

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    Changes in sodium channel activity and neuronal hyperexcitability contribute to neuropathic pain, a major clinical problem. There is strong evidence that the re-expression of the embryonic voltage-gated sodium channel subunit Na(v)1.3 underlies neuronal hyperexcitability and neuropathic pain. Here we show that acute and inflammatory pain behaviour is unchanged in global Na(v)1.3 mutant mice. Surprisingly, neuropathic pain also developed normally in the Na(v)1.3 mutant mouse. To rule out any genetic compensation mechanisms that may have masked the phenotype, we investigated neuropathic pain in two conditional Na(v)1.3 mutant mouse lines. We used Na(v)1.8-Cre mice to delete Nav1.3 in nociceptors at E14 and NFH-Cre mice to delete Na(v)1.3 throughout the nervous system postnatally. Again normal levels of neuropathic pain developed after nerve injury in both lines. Furthermore, ectopic discharges from damaged nerves were unaffected by the absence of Na(v)1.3 in global knock-out mice. Our data demonstrate that Na(v)1.3 is neither necessary nor sufficient for the development of nerve-injury related pain

    Freeform three-mirror anastigmatic large-aperture telescope and receiver optics for CMB-S4

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    CMB-S4, the next-generation ground-based cosmic microwave background (CMB) observatory, will provide detailed maps of the CMB at millimeter wavelengths to dramatically advance our understanding of the origin and evolution of the universe. CMB-S4 will deploy large and small aperture telescopes with hundreds of thousands of detectors to observe the CMB at arcminute and degree resolutions at millimeter wavelengths. Inflationary science benefits from a deep delensing survey at arcminute resolutions capable of observing a large field of view at millimeter wavelengths. This kind of survey acts as a complement to a degree angular resolution survey. The delensing survey requires a nearly uniform distribution of cameras per frequency band across the focal plane. We present a large-throughput, large-aperture (5-meter diameter) freeform three-mirror anastigmatic telescope and an array of 85 cameras for CMB observations at arcminute resolutions, which meets the needs of the delensing survey of CMB-S4. A detailed prescription of this three-mirror telescope and cameras is provided, with a series of numerical calculations that indicate expected optical performance and mechanical tolerance

    Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance

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    The ardA gene, found in many prokaryotes including important pathogenic species, allows associated mobile genetic elements to evade the ubiquitous Type I DNA restriction systems and thereby assist the spread of resistance genes in bacterial populations. As such, ardA contributes to a major healthcare problem. We have solved the structure of the ArdA protein from the conjugative transposon Tn916 and find that it has a novel extremely elongated curved cylindrical structure with defined helical grooves. The high density of aspartate and glutamate residues on the surface follow a helical pattern and the whole protein mimics a 42-base pair stretch of B-form DNA making ArdA by far the largest DNA mimic known. Each monomer of this dimeric structure comprises three alphaā€“beta domains, each with a different fold. These domains have the same fold as previously determined proteins possessing entirely different functions. This DNA mimicry explains how ArdA can bind and inhibit the Type I restriction enzymes and we demonstrate that 6 different ardA from pathogenic bacteria can function in Escherichia coli hosting a range of different Type I restriction systems

    Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability

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    Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resultedĀ in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2 ) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmissionĀ within the dorsal horn were increased in Cntnap2 mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability

    Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study.

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    OBJECTIVE: To compare four haemoglobin measurement methods in whole blood donors. BACKGROUND: To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold). METHODS: We compared the following four methods in 21ā€‰840 blood donors (aged ā‰„18ā€‰years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) "post donation" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) "portable haemoglobinometry" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation ("deferred") incorrectly; and test preference. RESULTS: Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry. CONCLUSION: In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry

    Elicitation of expert prior opinion: application to the MYPAN trial in childhood polyarteritis nodosa.

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    OBJECTIVES: Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa). METHODS: A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis. RESULTS: A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available. CONCLUSIONS: We suggest that the methodological template we propose could be applied to trial design for other rare diseases
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