9,685 research outputs found

    Prodromal symptoms in knee osteoarthritis: a nested case-control study using data from the Osteoarthritis Initiative.

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    OBJECTIVE: In order to gain a better understanding of the timing of emergent symptoms of osteoarthritis, we sought to investigate the existence, duration and nature of a prodromal symptomatic phase preceding incident radiographic knee osteoarthritis (ROA). DESIGN: Data were from the incidence cohort of the Osteoarthritis Initiative (OAI) public use datasets. Imposing a nested case-control design, ten control knees were selected for each case of incident tibiofemoral ROA between 2004 and 2010 from participants aged 45-79 years. Candidate prodromal symptoms were Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) and Knee injury and Osteoarthritis Outcome Score (KOOS) subscale scores and individual items, available up to 4 years prior to the time of incident ROA. Multi-level models were used to estimate the length of the prodromal phases. RESULTS: The prodromal phase for subscale scores ranged from 29 months (KOOS Other Symptoms) to 37 months (WOMAC Pain). Pain and difficulty on activities associated with higher dynamic knee loading were associated with longer prodromal phases (e.g., pain on twisting/pivoting (39 months, 95% confidence interval: 13, 64) vs pain on standing (25 months: 7, 42)). CONCLUSIONS: Our analysis found that incident ROA is preceded by prodromal symptoms lasting at least 2-3 years. This has potential implications for understanding phasic development and progression of osteoarthritis and for early recognition and management

    How many independent bets are there?

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    The benefits of portfolio diversification is a central tenet implicit to modern financial theory and practice. Linked to diversification is the notion of breadth. Breadth is correctly thought of as the number of in- dependent bets available to an investor. Conventionally applications us- ing breadth frequently assume only the number of separate bets. There may be a large discrepancy between these two interpretations. We uti- lize a simple singular-value decomposition (SVD) and the Keiser-Gutman stopping criterion to select the integer-valued effective dimensionality of the correlation matrix of returns. In an emerging market such as South African we document an estimated breadth that is considerably lower than anticipated. This lack of diversification may be because of market concentration, exposure to the global commodity cycle and local currency volatility. We discuss some practical extensions to a more statistically correct interpretation of market breadth, and its theoretical implications for both global and domestic investors.Comment: Less technical rewrite. 12 Pages, 6 Figures (.eps

    Multiplayer Cost Games with Simple Nash Equilibria

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    Multiplayer games with selfish agents naturally occur in the design of distributed and embedded systems. As the goals of selfish agents are usually neither equivalent nor antagonistic to each other, such games are non zero-sum games. We study such games and show that a large class of these games, including games where the individual objectives are mean- or discounted-payoff, or quantitative reachability, and show that they do not only have a solution, but a simple solution. We establish the existence of Nash equilibria that are composed of k memoryless strategies for each agent in a setting with k agents, one main and k-1 minor strategies. The main strategy describes what happens when all agents comply, whereas the minor strategies ensure that all other agents immediately start to co-operate against the agent who first deviates from the plan. This simplicity is important, as rational agents are an idealisation. Realistically, agents have to decide on their moves with very limited resources, and complicated strategies that require exponential--or even non-elementary--implementations cannot realistically be implemented. The existence of simple strategies that we prove in this paper therefore holds a promise of implementability.Comment: 23 page

    MDS_IES_DB: a database of macronuclear and micronuclear genes in spirotrichous ciliates

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    Ciliated protozoa have two kinds of nuclei: Macronuclei (MAC) and Micronuclei (MIC). In some ciliate classes, such as spirotrichs, most genes undergo several layers of DNA rearrangement during macronuclear development. Because of such processes, these organisms provide ideal systems for studying mechanisms of recombination and gene rearrangement. Here, we describe a database that contains all spirotrich genes for which both MAC and MIC versions are sequenced, with consistent annotation and easy access to all the features. An interface to query the database is available at http://oxytricha.princeton.edu/dimorphism/database.htm

    No dose-response effect of carbohydrate mouth rinse concentration on 5 km running performance in recreational athletes

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    Oral carbohydrate rinsing has been demonstrated to provide beneficial effects on exercise performance of durations of up to one hour, albeit predominately in a laboratory setting. The aim of the present study was to investigate the effects of different concentrations of carbohydrate solution mouth-rinse on 5 km running performance. Fifteen healthy men (n=9; mean±SD age: 42±10 years; height: 177.6±6.1 cm; body mass: 73.9±8.9 kg) and women (n=6; mean±SD age: 43±9 years; height: 166.5±4.1 cm; body mass: 65.7±6.8 kg) performed a 5 km running time trial on a track on four separate occasions. Immediately before starting the time trial and then after each 1 km, subjects rinsed 25 mL of either 0, 3, 6, or 12% maltodextrin for 10 s. Mouth-rinsing with 0, 3, 6 or 12% maltodextrin did not have a significant effect on the time to complete the time trial (0%: 26:34±4:07 min:sec; 3%: 27:17±4:33 min:sec; 6%: 27:05±3:52 min:sec; 12%: 26:47±4.31 min:sec; P=0.071;2 =0.15), heart rate (P=0.095; 2 =0.16), rating of perceived exertion (RPE) (P=0.195; P =0.11), blood glucose (P=0.920; P =0.01) and blood lactate concentration (P=0.831; 2 =0.02), with only non-significant trivial to small differences between concentrations. Results of this study suggest that carbohydrate mouth-rinsing provides no ergogenic advantage over that of an acaloric placebo (0%), and that there is no dose-response relationship between carbohydrate solution concentration and 5 km track running performance

    Effects of Wnt3A and mechanical load on cartilage chondrocyte homeostasis

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    Introduction Articular cartilage functions in withstanding mechanical loads and provides a lubricating surface for frictionless movement of joints. Osteoarthritis, characterised by cartilage degeneration, develops due to the progressive erosion of structural integrity and eventual loss of functional performance. Osteoarthritis is a multi-factorial disorder; two important risk factors are abnormal mechanical load and genetic predisposition. A single nucleotide polymorphism analysis demonstrated an association of hip osteoarthritis with an Arg324Gly substitution mutation in FrzB, a Wnt antagonist. The purpose of this study was two-fold: to assess whether mechanical stimulation modulates β-catenin signalling and catabolic gene expression in articular chondrocytes, and further to investigate whether there is an interplay of mechanical load and Wnt signalling in mediating a catabolic response. Methods Chondrocytes were pre-stimulated with recombinant Wnt3A for 24 hours prior to the application of tensile strain (7.5%, 1 Hz) for 30 minutes. Activation of Wnt signalling, via β-catenin nuclear translocation and downstream effects including the transcriptional activation of c-jun, c-fos and Lef1, markers of chondrocyte phenotype (type II collagen (col2a1), aggrecan (acan), SOX9) and catabolic genes (MMP3, MMP13, ADAMTS-4, ADAMTS-5) were assessed. Results Physiological tensile strain induced col2a1, acan and SOX9 transcription. Load-induced acan and SOX9 expression were repressed in the presence of Wnt3A. Load induced partial β-catenin nuclear translocation; there was an additive effect of load and Wnt3A on β-catenin distribution, with both extensive localisation in the nucleus and cytoplasm. Immediate early response (c-jun) and catabolic genes (MMP3, ADAMTS-4) were up-regulated in Wnt3A stimulated chondrocytes. With load and Wnt3A there was an additive up-regulation of c-fos, MMP3 and ADAMTS-4 transcription, whereas there was a synergistic interplay on c-jun, Lef1 and ADAMTS-5 transcription. Conclusion Our data suggest that load and Wnt, in combination, can repress transcription of chondrocyte matrix genes, whilst enhancing expression of catabolic mediators. Future studies will investigate the respective roles of abnormal loading and genetic predisposition in mediating cartilage degeneration

    Verifying Temporal Regular Properties of Abstractions of Term Rewriting Systems

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    The tree automaton completion is an algorithm used for proving safety properties of systems that can be modeled by a term rewriting system. This representation and verification technique works well for proving properties of infinite systems like cryptographic protocols or more recently on Java Bytecode programs. This algorithm computes a tree automaton which represents a (regular) over approximation of the set of reachable terms by rewriting initial terms. This approach is limited by the lack of information about rewriting relation between terms. Actually, terms in relation by rewriting are in the same equivalence class: there are recognized by the same state in the tree automaton. Our objective is to produce an automaton embedding an abstraction of the rewriting relation sufficient to prove temporal properties of the term rewriting system. We propose to extend the algorithm to produce an automaton having more equivalence classes to distinguish a term or a subterm from its successors w.r.t. rewriting. While ground transitions are used to recognize equivalence classes of terms, epsilon-transitions represent the rewriting relation between terms. From the completed automaton, it is possible to automatically build a Kripke structure abstracting the rewriting sequence. States of the Kripke structure are states of the tree automaton and the transition relation is given by the set of epsilon-transitions. States of the Kripke structure are labelled by the set of terms recognized using ground transitions. On this Kripke structure, we define the Regular Linear Temporal Logic (R-LTL) for expressing properties. Such properties can then be checked using standard model checking algorithms. The only difference between LTL and R-LTL is that predicates are replaced by regular sets of acceptable terms

    Commensal Bacteroidetes protect against Klebsiella pneumoniae colonization and transmission through IL-36 signalling

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    The microbiota primes immune defences but the identity of specific commensal microorganisms that protect against infection is unclear. Conversely, how pathogens compete with the microbiota to establish their host niche is also poorly understood. In the present study, we investigate the antagonism between the microbiota and Klebsiella pneumoniae during colonization and transmission. We discover that maturation of the microbiota drives the development of distinct immune defence programmes in the upper airways and intestine to limit K. pneumoniae colonization within these niches. Immune protection in the intestine depends on the development of Bacteroidetes, interleukin (IL)-36 signalling and macrophages. This effect of Bacteroidetes requires the polysaccharide utilization locus of their conserved commensal colonization factor. Conversely, in the upper airways, Proteobacteria prime immunity through IL-17A, but K. pneumoniae overcomes these defences through encapsulation to effectively colonize this site. Ultimately, we find that host-to-host spread of K. pneumoniae occurs principally from its intestinal reservoir, and that commensal-colonization-factor-producing Bacteroidetes are sufficient to prevent transmission between hosts through IL-36. Thus, our study provides mechanistic insight into when, where and how commensal Bacteroidetes protect against K. pneumoniae colonization and contagion, providing insight into how these protective microorganisms could be harnessed to confer population-level protection against K. pneumoniae infection
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