159 research outputs found

    Hamiltonian ABC

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    Approximate Bayesian computation (ABC) is a powerful and elegant framework for performing inference in simulation-based models. However, due to the difficulty in scaling likelihood estimates, ABC remains useful for relatively low-dimensional problems. We introduce Hamiltonian ABC (HABC), a set of likelihood-free algorithms that apply recent advances in scaling Bayesian learning using Hamiltonian Monte Carlo (HMC) and stochastic gradients. We find that a small number forward simulations can effectively approximate the ABC gradient, allowing Hamiltonian dynamics to efficiently traverse parameter spaces. We also describe a new simple yet general approach of incorporating random seeds into the state of the Markov chain, further reducing the random walk behavior of HABC. We demonstrate HABC on several typical ABC problems, and show that HABC samples comparably to regular Bayesian inference using true gradients on a high-dimensional problem from machine learning.Comment: Submission to UAI 201

    Speech dysprosody but no music ‘dysprosody’ in Parkinson’s disease

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    AbstractParkinson’s disease is characterized not only by bradykinesia, rigidity, and tremor, but also by impairments of expressive and receptive linguistic prosody. The facilitating effect of music with a salient beat on patients’ gait suggests that it might have a similar effect on vocal behavior, however it is currently unknown whether singing is affected by the disease. In the present study, fifteen Parkinson patients were compared with fifteen healthy controls during the singing of familiar melodies and improvised melodic continuations. While patients’ speech could reliably be distinguished from that of healthy controls matched for age and gender, purely on the basis of aural perception, no significant differences in singing were observed, either in pitch, pitch range, pitch variability, and tempo, or in scale tone distribution, interval size or interval variability. The apparent dissociation of speech and singing in Parkinson’s disease suggests that music could be used to facilitate expressive linguistic prosody

    Selection of planned supply initiatives: the role of senior management expertise

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    Purpose – The purpose of this paper is to assess the selection of planned supply initiatives and the role of senior management expertise. The drivers that influence the selection of particular supply initiatives by firms are of major interest to both practitioners and academics, as choices indicate priorities for resources, potential performance gaps and needs for future research. Moreover, theory indicates that senior management expertise and firm‐level resources might influence the likelihood of selecting particular initiatives. Design/methodology/approach – A synthesis of the literature supported the development of a five‐dimensional framework of major supply initiatives. Logistic regression was conducted with data from a survey of chief purchasing officers at large North American firms. The impact of firm‐level resources and senior management expertise, including background and experience, was assessed for the selection of supply initiatives. Findings – After controlling for general industry‐level factors, both firm resources and senior management expertise were found to systematically affect the likelihood of a firm planning to pursue particular initiatives. First, hiring senior management from outside the firm decreased the likelihood that network‐based initiatives were planned, while senior management who last worked in supply were found to be negatively related to planned supply strategy initiatives. Second, firms with greater use of e‐business technologies favored additional investment in supply networks. Research limitations/implications – This research focused on large firms in developed countries, and additional research is needed to explore the generalizability to small and medium‐sized enterprises and less‐developed countries. Moreover, additional work is needed to explore trade‐offs between planned and emergent initiatives, as only the former were empirically assessed. Originality/value – Senior management expertise has received relatively little attention in prior research, yet was found to be a significant factor influencing strategic, process and network‐related supply initiatives. Moreover, the framework of supply initiatives provides a basis for assessing and benchmarking firm‐level supply chain strategy and investment patterns. Finally, empirical evidence emerged that both firm and individual‐level factors influenced the probability of selecting particular initiatives

    Utilizing e-business technologies in supply chains: The impact of firm characteristics and teams

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    This paper presents findings from an exploratory study that analyzes the drivers and outcomes of e-business technology use in the supply chain. Using a combination of case studies and survey data from a diverse sample of industries, the research examines how industry context, firm characteristics and firm-level strategic resources, such as purchasing teams, influence the exploitation of e-business technologies and the relationship between e-business technology use and firm performance. Based on a synthesis of related literatures from transaction cost economics and the relational view of the supply chain, a two-dimensional framework for e-business technology is proposed with transactional and relational dimensions. However, empirical analysis indicated that transactional technologies can be further subdivided into two factors: dyadic cooperation and price determination. Significant differences were found between the two dimensions in terms of their overall levels of adoption, with dyadic coordination being the most widely adopted. In addition, the development of strategic resources expanded, in particular internal and customer teams, the use of e-business technologies expanded. Purchasing organizational structure and firm size also were positively related to the adoption of transactional e-business technologies. Finally, of particular importance to practitioners, e-business technologies targeted at reducing dyadic coordination costs lead to improved financial performance

    Hypoxic oligodendrocyte precursor cell-derived VEGFA is associated with blood–brain barrier impairment

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    Abstract Cerebral small vessel disease is characterised by decreased cerebral blood flow and blood–brain barrier impairments which play a key role in the development of white matter lesions. We hypothesised that cerebral hypoperfusion causes local hypoxia, affecting oligodendrocyte precursor cell—endothelial cell signalling leading to blood–brain barrier dysfunction as an early mechanism for the development of white matter lesions. Bilateral carotid artery stenosis was used as a mouse model for cerebral hypoperfusion. Pimonidazole, a hypoxic cell marker, was injected prior to humane sacrifice at day 7. Myelin content, vascular density, blood–brain barrier leakages, and hypoxic cell density were quantified. Primary mouse oligodendrocyte precursor cells were exposed to hypoxia and RNA sequencing was performed. Vegfa gene expression and protein secretion was examined in an oligodendrocyte precursor cell line exposed to hypoxia. Additionally, human blood plasma VEGFA levels were measured and correlated to blood–brain barrier permeability in normal-appearing white matter and white matter lesions of cerebral small vessel disease patients and controls. Cerebral blood flow was reduced in the stenosis mice, with an increase in hypoxic cell number and blood–brain barrier leakages in the cortical areas but no changes in myelin content or vascular density. Vegfa upregulation was identified in hypoxic oligodendrocyte precursor cells, which was mediated via Hif1α and Epas1. In humans, VEGFA plasma levels were increased in patients versus controls. VEGFA plasma levels were associated with increased blood–brain barrier permeability in normal appearing white matter of patients. Cerebral hypoperfusion mediates hypoxia induced VEGFA expression in oligodendrocyte precursor cells through Hif1α/Epas1 signalling. VEGFA could in turn increase BBB permeability. In humans, increased VEGFA plasma levels in cerebral small vessel disease patients were associated with increased blood–brain barrier permeability in the normal appearing white matter. Our results support a role of VEGFA expression in cerebral hypoperfusion as seen in cerebral small vessel disease

    Colouration in amphibians as a reflection of nutritional status : the case of tree frogs in Costa Rica

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    Colouration has been considered a cue for mating success in many species; ornaments in males often are related to carotenoid mobilization towards feathers and/or skin and can signal general health and nutrition status. However, there are several factors that can also link with status, such as physiological blood parameters and body condition, but there is not substantial evidence which supports the existence of these relationships and interactions in anurans. This study evaluated how body score and blood values interact with colouration in free-range Agalychnis callidryas and Agalychnis annae males. We found significant associations between body condition and plasmatic proteins and haematocrit, as well as between body condition and colour values from the chromaticity diagram. We also demonstrated that there is a significant relation between the glucose and plasmatic protein values that were reflected in the ventral colours of the animals, and haematocrit inversely affected most of those colour values. Significant differences were found between species as well as between populations of A. callidryas, suggesting that despite colour variation, there are also biochemical differences within animals from the same species located in different regions. These data provide information on underlying factors for colouration of male tree frogs in nature, provide insights about the dynamics of several nutrients in the amphibian model and how this could affect the reproductive output of the animals

    Effectiveness of computer-navigated minimally invasive total hip surgery compared to conventional total hip arthroplasty: design of a randomized controlled trial

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    BACKGROUND: Moderate to severe osteoarthrosis is the most common indication for Total Hip Arthroplasty (THA). Minimally Invasive Total Hip Surgery (MIS) and computer-navigated surgery were introduced several years ago. However, the literature lacks well-designed studies that provide evidence of superiority of computer-navigated MIS over a conventional THA technique. Hence, the purpose of this study is to compare (cost)effectiveness of computer-navigated MIS with a conventional technique for THA. It is our hypothesis that computer-navigated MIS will lead to a quicker recovery during the early postoperative period (3 months), and to an outcome at least as good 6 months postoperatively. We also hypothesize that computer-navigated MIS leads to fewer perioperative complications and better prosthesis positioning. Furthermore, cost advantages of computer-navigated MIS over conventional THA technique are expected. METHODS/DESIGN: A cluster randomized controlled trial will be executed. Patients between the ages of 18 and 75 admitted for primary cementless unilateral THA will be included. Patients will be stratified using the Charnley classification. They will be randomly allocated to have computer-navigated MIS or conventional THA technique. Measurements take place preoperatively, perioperatively, and 6 weeks and 3 and 6 months postoperatively. Degree of limping (gait analysis), self-reported functional status and health-related quality of life (questionnaires) will be assessed preoperatively as well as postoperatively. Perioperative complications will be registered. Radiographic evaluation of prosthesis positioning will take place 6 weeks postoperatively. An evaluation of costs within and outside the healthcare sector will focus on differences in costs between computer-navigated MIS and conventional THA technique. DISCUSSION: Based on studies performed so far, few objective data quantifying the risks and benefits of computer-navigated MIS are available. Therefore, this study has been designed to compare (cost) effectiveness of computer-navigated MIS with a conventional technique for THA. The results of this trial will be presented as soon as they become available
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