838 research outputs found

    Uniform payoff security and Nash equilibrium in metric games

    Get PDF
    We introduce a condition, uniform payoff security, for games with separable metric strategy spaces and payoffs bounded and measurable in players' strategies. We show that if any such metric game G is uniformly payoff secure, then its mixed extension G is payoff secure. We also establish that if a uniformly payoff secure metric game G has compact strategy spaces, and if its mixed extension G has reciprocally upper semicontinuous payoffs, then G has a Nash equilibrium in mixed strategies. We provide several economic examples of metric games satisfying uniform payoff security.Uniform payoff security, Nash equilibrium, discontinuous games, mixed extension.

    Riociguat: Mode of action and clinical development in pulmonary hypertension

    Get PDF
    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure and increased pulmonary vascular resistance. If untreated, they can result in death due to right heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. Here we describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH, and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and the pivotal Phase III randomized clinical trials in PAH and CTEPH

    The molecular characterisation of Escherichia coli K1 isolated from neonatal nasogastric feeding tubes

    Get PDF
    Background: The most common cause of Gram-negative bacterial neonatal meningitis is E. coli K1. It has a mortality rate of 10–15%, and neurological sequelae in 30– 50% of cases. Infections can be attributable to nosocomial sources, however the pre-colonisation of enteral feeding tubes has not been considered as a specific risk factor. Methods: Thirty E. coli strains, which had been isolated in an earlier study, from the residual lumen liquid and biofilms of neonatal nasogastric feeding tubes were genotyped using pulsed-field gel electrophoresis, and 7-loci multilocus sequence typing. Potential pathogenicity and biofilm associated traits were determined using specific PCR probes, genome analysis, and in vitro tissue culture assays. Results: The E. coli strains clustered into five pulsotypes, which were genotyped as sequence types (ST) 95, 73, 127, 394 and 2076 (Achman scheme). The extra-intestinal pathogenic E. coli (ExPEC) phylogenetic group B2 ST95 serotype O1:K1:NM strains had been isolated over a 2 week period from 11 neonates who were on different feeding regimes. The E. coli K1 ST95 strains encoded for various virulence traits associated with neonatal meningitis and extracellular matrix formation. These strains attached and invaded intestinal, and both human and rat brain cell lines, and persisted for 48 h in U937 macrophages. E. coli STs 73, 394 and 2076 also persisted in macrophages and invaded Caco-2 and human brain cells, but only ST394 invaded rat brain cells. E. coli ST127 was notable as it did not invade any cell lines. Conclusions: Routes by which E. coli K1 can be disseminated within a neonatal intensive care unit are uncertain, however the colonisation of neonatal enteral feeding tubes may be one reservoir source which could constitute a serious health risk to neonates following ingestion

    An impinging remnant meniscus causing early polyethylene failure in total knee arthroplasty: a case report

    Get PDF
    The management of patients with an apparently normal functional total knee arthroplasty (TKA) suffering from unexplained persistent pain and swelling is a challenging issue. The usual causes of pain after total knee replacement are well known, but there are a small number of patients in whom its aetiology is obscure. Malfunction due to soft tissue impingement has rarely been reported. A patient with an unusual case of posterior soft tissue impingement secondary to a trapped posterior horn of a remnant medial meniscus after TKA and responsible for severe early polyethylene wear, is reported. The diagnosis was confirmed by arthroscopy. Treatment was performed by arthrotomy. The meniscus remnant was removed followed by total synovectomy and isolated exchange of the polyethylene insert. To our knowledge, this is the first well-documented case reporting this association

    Spontaneous and deliberate future thinking: A dual process account

    Get PDF
    © 2019 Springer Nature.This is the final published version of an article published in Psychological Research, licensed under a Creative Commons Attri-bution 4.0 International License. Available online at: https://doi.org/10.1007/s00426-019-01262-7.In this article, we address an apparent paradox in the literature on mental time travel and mind-wandering: How is it possible that future thinking is both constructive, yet often experienced as occurring spontaneously? We identify and describe two ‘routes’ whereby episodic future thoughts are brought to consciousness, with each of the ‘routes’ being associated with separable cognitive processes and functions. Voluntary future thinking relies on controlled, deliberate and slow cognitive processing. The other, termed involuntary or spontaneous future thinking, relies on automatic processes that allows ‘fully-fledged’ episodic future thoughts to freely come to mind, often triggered by internal or external cues. To unravel the paradox, we propose that the majority of spontaneous future thoughts are ‘pre-made’ (i.e., each spontaneous future thought is a re-iteration of a previously constructed future event), and therefore based on simple, well-understood, memory processes. We also propose that the pre-made hypothesis explains why spontaneous future thoughts occur rapidly, are similar to involuntary memories, and predominantly about upcoming tasks and goals. We also raise the possibility that spontaneous future thinking is the default mode of imagining the future. This dual process approach complements and extends standard theoretical approaches that emphasise constructive simulation, and outlines novel opportunities for researchers examining voluntary and spontaneous forms of future thinking.Peer reviewe

    Emerging applications of fluorescence spectroscopy in medical microbiology field

    Get PDF
    There are many diagnostic techniques and methods available for diagnosis of medically important microorganisms like bacteria, viruses, fungi and parasites. But, almost all these techniques and methods have some limitations or inconvenience. Most of these techniques are laborious, time consuming and with chances of false positive or false negative results. It warrants the need of a diagnostic technique which can overcome these limitations and problems. At present, there is emerging trend to use Fluorescence spectroscopy as a diagnostic as well as research tool in many fields of medical sciences. Here, we will critically discuss research studies which propose that Fluorescence spectroscopy may be an excellent diagnostic as well as excellent research tool in medical microbiology field with high sensitivity and specificity

    Arthroscopic evaluation of the ACL double bundle structure

    Get PDF
    In order to describe the arthroscopic presence of the double bundle structure and to evaluate the value of different portals in knee arthroscopy, we assessed the AM and PL bundle anatomy. We prospectively examined the knees of 60 patients undergoing arthroscopic surgery for pathology unrelated to the ACL. Arthroscopy was performed in a two portal technique using an anterolateral (ALP) and an anteromedial (AMP) portal. With the arthroscope in the ALP, we could distinguish an AM and PL bundle in 28%. Switching the arthroscope to the AMP, differentiation of the bundles was possible in 67%. In all remaining cases visualization of the PL bundle was possible after retraction of the AM bundle. Use of AMP increased visualization of the PL bundle. It seems reasonable to perform arthroscopy for ACL reconstruction with the arthroscope in the AMP and to establish an additional medial working portal to increase the visualization of the femoral ACL insertion sites for optimal femoral tunnel placement

    Role of Cellular Heparan Sulfate Proteoglycans in Infection of Human Adenovirus Serotype 3 and 35

    Get PDF
    Species B human adenoviruses (Ads) are increasingly associated with outbreaks of acute respiratory disease in U.S. military personnel and civil population. The initial interaction of Ads with cellular attachment receptors on host cells is via Ad fiber knob protein. Our previous studies showed that one species B Ad receptor is the complement receptor CD46 that is used by serotypes 11, 16, 21, 35, and 50 but not by serotypes 3, 7, and 14. In this study, we attempted to identify yet-unknown species B cellular receptors. For this purpose we used recombinant Ad3 and Ad35 fiber knobs in high-throughput receptor screening methods including mass spectrometry analysis and glycan arrays. Surprisingly, we found that the main interacting surface molecules of Ad3 fiber knob are cellular heparan sulfate proteoglycans (HSPGs). We subsequently found that HSPGs acted as low-affinity co-receptors for Ad3 but did not represent the main receptor of this serotype. Our study also revealed a new CD46-independent infection pathway of Ad35. This Ad35 infection mechanism is mediated by cellular HSPGs. The interaction of Ad35 with HSPGs is not via fiber knob, whereas Ad3 interacts with HSPGs via fiber knob. Both Ad3 and Ad35 interacted specifically with the sulfated regions within HSPGs that have also been implicated in binding physiologic ligands. In conclusion, our findings show that Ad3 and Ad35 directly utilize HSPGs as co-receptors for infection. Our data suggest that adenoviruses evolved to simulate the presence of physiologic HSPG ligands in order to increase infection
    corecore