47 research outputs found

    Mixed Strategies in Discriminatory Divisible-good Auctions

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    Author: Edward J. Anderson, Pär Holmberg and Andrew B. Philpott Keywords: Pay-as-bid Auction; Divisible Good Auction; Mixed Strategy Equilibria; Wholesale Electricity Markets Pages: 71 Published: November 24, 2009 JEL-codes: D43; D44; C72 Download Wp814.pdf (756 kB) Abstract Using the concept of market-distribution functions, we derive general optimality conditions for discriminatory divisible-good auctions, which are also applicable to Bertrand games and non-linear pricing. We introduce the concept of offer distribution function to analyze randomized offer curves, and characterize mixed-strategy Nash equilibria for pay-as-bid auctions where demand is uncertain and costs are common knowledge; a setting for which pure-strategy supply function equilibria typically do not exist. We generalize previous results on mixtures over horizontal offers as in Bertrand-Edgeworth games, but more importantly we characterize novel mixtures over partly increasing supply functions.Pay-as-bid Auction; Divisible Good Auction; Mixed Strategy Equilibria; Wholesale Electricity Markets

    Paediatric tonsillectomy in england a cohort study of clinical practice and outcomes using Hospital Episode Statistics data (2008‐2019)

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    Objectives: To assess the safety of paediatric tonsillectomy procedures conducted in NHS hospitals in England between 2008 and 2019. Design: Retrospective observational cohort study using Hospital Episode Statistics (HES) data. Setting: Acute NHS trusts in England conducting paediatric tonsillectomy procedures Participants: Children (≤16 years old) undergoing bilateral tonsillectomy Main outcome measures: Number of tonsillectomies performed per year by procedural method. In‐hospital complications including return to theatre for arrest of haemorrhage. Readmission within 28 days, including those for pain, haemorrhage and surgical arrest of haemorrhage. Long‐term outcomes: all‐cause mortality, revision tonsillectomy. Results: A total of 318,453 paediatric tonsillectomies were performed from 2008 to 2019: 278,772 dissection (87.5%), 39,681 coblation (12.5%). The proportion of tonsillectomy performed using coblation increased from 7% in 2008/9 to 27% in 2018/9. Five patients died in hospital (including 4 due to respiratory complications). In‐hospital complications occurred in 4,202 children (1.3%), with the most frequent being haemorrhage. Within 28 days of tonsillectomy, 28,170 patients (8.8%) were readmitted and 7 deaths occurred. Readmission rates for haemorrhage and pain have increased since 2008. The proportion of children undergoing revision tonsillectomy procedures within 5 years following coblation tonsillectomy (1.4%) was approximately double that of dissection (0.6%). Conclusions: Clinical practice of paediatric tonsillectomy has changed in England over the past 11 years. The overall mortality rate associated with the procedure is 0.0037%. Differences in outcomes have been identified for different procedural methods. However, routine administrative data is limited in differentiating procedural detail (e.g. we are unable to differentiate intra or extra‐capsular techniques from current clinical coding of tonsillectomy procedures). Therefore prospective national data collection or more granular clinical coding is essential to capture relative outcomes of the different tonsillectomy methods and techniques being used in the NHS

    The impact of digital start-up founders’ higher education on reaching equity investment milestones

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    This paper builds on human capital theory to assess the importance of formal education among graduate entrepreneurs. Using a sample of 4.953 digital start-ups the paper evaluates the impact of start-up founding teams’ higher education on the probability of securing equity investment and subsequent exit for investors. The main findings are: (1), teams with a founder that has a technical education are less likely to remain self-financed and are more likely to secure equity investment and to exit, but the impact of technical education declines with higher level degrees, (2) teams with a founder that has doctoral level business education are less likely to remain self-financed and have a higher probability of securing equity investment, while undergraduate and postgraduate business education have no significant effect, and (3) teams with a founder that has an undergraduate general education (arts and humanities) are less likely to remain self-financed and are more likely to secure equity investment and exit while postgraduate and doctoral general education have no significant effect on securing equity investment and exit. The findings enhance our understanding of factors that influence digital start-ups achieving equity milestones by showing the heterogeneous influence of different types of higher education, and therefore human capital, on new ventures achieving equity milestones. The results suggest that researchers and policy-makers should extend their consideration of universities entrepreneurial activity to include the development of human capital

    Pneumolysin Activates the NLRP3 Inflammasome and Promotes Proinflammatory Cytokines Independently of TLR4

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    Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play a key role in the initiation and instruction of adaptive immunity, but the effects of PLY on DC have not been widely investigated. Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not induce cytokine secretion. These effects have functional significance as adoptive transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T cell proliferation than transfer of DC exposed to antigen alone. PLY synergized with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL-23, IL-6, IL-1β, IL-1α and TNF-α by DC and enhanced cytokines including IL-17A and IFN-γ by splenocytes. PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and IFN-γ are required for protective immunity to pneumococcal infection and intranasal infection of mice with PLY-deficient pneumococci induced significantly less IFN-γ and IL-17A in the lungs compared to infection with wild-type bacteria. IL-1β plays a key role in promoting IL-17A and was previously shown to mediate protection against pneumococcal infection. The enhancement of IL-1β secretion by whole live S. pneumoniae and by PLY in DC required NLRP3, identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was required for protective immunity against respiratory infection with S. pneumoniae. These results add significantly to our understanding of the interactions between PLY and the immune system

    Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases

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    HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals

    Impact of inactivity and exercise on the vasculature in humans

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    The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk

    Fundulus as the premier teleost model in environmental biology : opportunities for new insights using genomics

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    Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology Part D: Genomics and Proteomics 2 (2007): 257-286, doi:10.1016/j.cbd.2007.09.001.A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms.This material is based on work supported by grants from the National Science Foundation DBI-0420504 (LJB), OCE 0308777 (DLC, RNW, BBR), BES-0553523 (AW), IBN 0236494 (BBR), IOB-0519579 (DHE), IOB-0543860 (DWT), FSML-0533189 (SC); National Institute of Health NIEHS P42-ES007381(GVC, MEH), P42-ES10356 (RTD), ES011588 (MFO); and NCRR P20 RR-016463 (DWT); Natural Sciences and Engineering Research Council of Canada Discovery (DLM, TDS, WSM) and Collaborative Research and Development Programs (DLM); NOAA/National Sea Grant NA86RG0052 (LJB), NA16RG2273 (SIK, MEH,GVC, JJS); Environmental Protection Agency U91620701 (WSB), R82902201(SC) and EPA’s Office of Research and Development (DEN)

    Development of FIDO- A Network Design Tool for Fibre Cable Layout

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    There are currently a number of new fibre optic cable networks being laid through New Zealand's major cities. This paper discusses a design tool, termed FIDO (Fibre Diversity Optimiser), that has been developed for a network operator to assist them in their network planning. FIDO combines a specialised visualisation GUI with a mix of optimisation and heuristic procedures to create a customised decision support tool for fibre cable layout. FIDO is currently being used by the operator's design team.
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