329 research outputs found

    Increasing Dominance - the Role of Advertising, Pricing and Product Design

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    Despite the empirical relevance of advertising strategies in concentrated markets, the economics literature is largely silent on the effect of persuasive advertising strategies on pricing, market structure and increasing (or decreasing) dominance. In a simple model of persuasive advertising and pricing with differentiated goods, we analyze the interdependencies between ex-ante asymmetries in consumer appeal, advertising and prices. Products with larger initial appeal to consumers will be advertised more heavily but priced at a higher level - that is, advertising and price discounts are strategic substitutes for products with asymmetric initial appeal. We find that the escalating effect of advertising dominates the moderating effect of pricing so that post-competition market shares are more asymmetric than pre-competition differences in consumer appeal. We further find that collusive advertising (but competitive pricing) generates the same market outcomes, and that network effects lead to even more extreme market outcomes, both directly and via the effect on advertising

    Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies

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    MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation, (2) MRI system setup and calibrations, (3) data acquisition and image reconstruction, and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the HP 13C MRI Consensus Group as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods & Equipment study groups. It further aims to provide a comprehensive reference for future consensus building as the field continues to advance human studies with this metabolic imaging modality

    Quality of Reporting and Study Design of CKD Cohort Studies Assessing Mortality in the Elderly Before and After STROBE:A Systematic Review

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    BACKGROUND:The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was published in October 2007 to improve quality of reporting of observational studies. The aim of this review was to assess the impact of the STROBE statement on observational study reporting and study design quality in the nephrology literature. STUDY DESIGN:Systematic literature review. SETTING & POPULATION:European and North American, Pre-dialysis Chronic Kidney Disease (CKD) cohort studies. SELECTION CRITERIA FOR STUDIES:Studies assessing the association between CKD and mortality in the elderly (>65 years) published from 1st January 2002 to 31st December 2013 were included, following systematic searching of MEDLINE & EMBASE. PREDICTOR:Time period before and after the publication of the STROBE statement. OUTCOME:Quality of study reporting using the STROBE statement and quality of study design using the Newcastle Ottawa Scale (NOS), Scottish Intercollegiate Guidelines Network (SIGN) and Critical Appraisal Skills Programme (CASP) tools. RESULTS:37 papers (11 Pre & 26 Post STROBE) were identified from 3621 potential articles. Only four of the 22 STROBE items and their sub-criteria (objectives reporting, choice of quantitative groups and description of and carrying out sensitivity analysis) showed improvements, with the majority of items showing little change between the period before and after publication of the STROBE statement. Pre- and post-period analysis revealed a Manuscript STROBE score increase (median score 77.8% (Inter-quartile range [IQR], 64.7-82.0) vs 83% (IQR, 78.4-84.9, p = 0.05). There was no change in quality of study design with identical median scores in the two periods for NOS (Manuscript NOS score 88.9), SIGN (Manuscript SIGN score 83.3) and CASP (Manuscript CASP score 91.7) tools. LIMITATIONS:Only 37 Studies from Europe and North America were included from one medical specialty. Assessment of study design largely reliant on good reporting. CONCLUSIONS:This study highlights continuing deficiencies in the reporting of STROBE items and their sub-criteria in cohort studies in nephrology. There was weak evidence of improvement in the overall reporting quality, with no improvement in methodological quality of CKD cohort studies between the period before and after publication of the STROBE statement

    Reimagining pheromone signalling in the model nematode Caenorhabditis elegans

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    Caenorhabditis elegans is an important, widely used developmental and genetic model. A pheromone has long been known to cause juvenile developmental arrest in C. elegans, a phenomenon that is common among nematodes more widely. Many novel effects of this pheromone are now being discovered—most recently, that exogenous supply of this pheromone controls adult worms reproduction. Here, we suggest that to properly understand and interpret these phenomena, C. elegans natural ecology must be considered, about which rather little is known. With this perspective, we suggest that C. elegans pheromone signalling evolves very locally, such that there are different dialects of pheromone signalling among ecological communities and among kin groups, and we also argue that pheromone signals may also evolve to be manipulative and dishonest. New approaches must be undertaken to study these phenomena in C. elegans. While model systems have been tremendously important tools in modern biological research, taking account of their natural history is necessary, and key, to properly understand and interpret laboratory-based discoveries.understand and interpret laboratory-based discoveries

    Neural Correlates of True Memory, False Memory, and Deception

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    We used functional magnetic resonance imaging (fMRI) to determine whether neural activity can differentiate between true memory, false memory, and deception. Subjects heard a series of semantically related words and were later asked to make a recognition judgment of old words, semantically related nonstudied words (lures for false recognition), and unrelated new words. They were also asked to make a deceptive response to half of the old and unrelated new words. There were 3 main findings. First, consistent with the notion that executive function supports deception, 2 types of deception (pretending to know and pretending not to know) recruited prefrontal activity. Second, consistent with the sensory reactivation hypothesis, the difference between true recognition and false recognition was found in the left temporoparietal regions probably engaged in the encoding of auditorily presented words. Third, the left prefrontal cortex was activated during pretending to know relative to correct rejection and false recognition, whereas the right anterior hippocampus was activated during false recognition relative to correct rejection and pretending to know. These findings indicate that fMRI can detect the difference in brain activity between deception and false memory despite the fact that subjects respond with “I know” to novel events in both processes

    High Fat Diet Prevents Over-Crowding Induced Decrease of Sex Ratio in Mice

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    Adaptive theory predicts that mothers would be advantaged by adjusting the sex ratio of their offspring in relation to their offspring's future reproductive success. In the present study, we tested the effect of housing mice under crowded condition on the sex ratio and whether the fat content of the diet has any influence on the outcome of pregnancies. Three-week-old mice were placed on the control diet (NFD) for 3 weeks. Thereafter the mice were allotted randomly to two groups of 7 cages each with 4, 6, 8, 10, 12, 14, and 16 mice in every cage to create increasing crowding gradient and fed either NFD or high fat diet (HFD). After 4 weeks, dams were bred and outcomes of pregnancy were analyzed. The average dam body weight (DBW) at conception, litter size (LS) and SR were significantly higher in HFD fed dams. Further, male biased litters declined with increasing crowding in NFD group but not in HFD. The LS and SR in NFD declined significantly with increasing crowding, whereas only LS was reduced in HFD group. We conclude that female mice housed under overcrowding conditions shift offspring SR in favor of daughters in consistent with the TW hypothesis and high fat diet reduces this influence of overcrowding

    Antifascismo: un espacio de encuentro entre el exilio y la política nacional. El caso de Vicente Lombardo Toledano en México (1936-1945)

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    This article puts forward an original interpretation of antifascism, understood as a transatlantic political culture, focusing upon the case of the union leader Vicente Lombardo Toledano. Between the Spanish Civil War and the Second World War, antifascism in Mexico acquired several meanings, centred on the reinvention of the Mexican Revolution’s legacy, while benefiting from the collaboration between European antifascist exiles and local left-wing circles. Making use of novel sources, this article vindicates the key role that Mexico was then able to enjoy internationally due to its ideological commitments.Este artículo propone una lectura original del antifascismo, entendido como una cultura política trasatlántica, a partir del caso del líder sindicalista Vicente Lombardo Toledano. Se discute la evolución del significado del antifascismo en México, centrado en la recreación del legado de la Revolución Mexicana, en el período comprendido entre la Guerra Civil española y la Segunda Guerra Mundial, enfatizando la colaboración entre el exilio antifascista europeo y los círculos izquierdistas locales. A partir de varios documentos inéditos, se reivindica el protagonismo que México ejerció entonces en virtud de su compromiso ideológico

    La expedición minera del barón de Nordenflicht y las autoridades peruanas

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    Traditionally, the failure of Baron Nordenflicht’s mining expedition to Peru has been attributed to the negative attitude towards the mission supposedly displayed by the Peruvian authorities in general and Viceroy Francisco Gil y Lemos (1790-1796) in particular. This article refutes this theory, proving that the failure of the expedition was the result of its own technical shortcomings and not a consequence of a supposed lack of support on the part of the authorities.Tanto los integrantes de la expedición minera del barón de Nordenflicht como la historiografía tradicional han responsabilizado al virrey Francisco Gil y Lemos (1790-1796) y a las autoridades peruanas del fracaso de la misión. Este artículo refuta documentalmente esta versión, demostrando que dicho fracaso se debió a razones técnicas y no a supuestas trabas por parte de las autoridades virreinales

    Apparent Shear Sensitivity of Molecular Rotors in Various Solvents

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    Fluorescent environment-sensitive dyes often change their spectral properties concomitantly with multiple solvent properties, such as polarity, protonation, hydrogen bond formation, or viscosity. Careful consideration of the response is needed when a fluorescent dye is used to report a single property. Recently, we observed an increase of emission intensity of viscosity-sensitive molecular rotors in fluids subject to flow and speculated that either polar-polar interaction or hydrogen bond formation play a role in the apparent flow sensitivity. In this study, we show experimental evidence that photoisomerization to an isomer with a lower quantum yield, first proposed by Rumble et al. (J Phys Chem A 116(44):10786-10792, 2012), plays a key role in the observed phenomenon. We subjected four molecular rotors with different electron acceptor motifs to fluid flow in solvents of different polarity and ability to form hydrogen bonds. We also measured the isomerization dynamics in a custom fluorophotometer with extremely low light exposure. Our results indicate that the photoisomerization rate depends both on the solvent and on the electron acceptor group, as does the recovery of the original isomer in the dark. In most solvents, recovery of the dark isomer is much more rapid than originally reported, and a state of quasi-equilibrium between both isomers is possible. Moreover, the sensitivity (i.e., relative intensity increase at the same flow rate) is also solvent-dependent. The intensity increase can be detected at very low velocities (as low as 0.06 mm/s). Characteristic for fluorescent dyes is the high spatial resolution, and no flow measurement device with comparable sensitivity and spatial resolution exists, although the nature of the solvent needs to be taken into account for quantitative flow measurement

    Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

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    The canonical Wnt/β-catenin signaling pathway governs diverse developmental, homeostatic and pathologic processes. Palmitoylated Wnt ligands engage cell surface Frizzled (Fzd) receptors and Lrp5/6 co-receptors enabling β-catenin nuclear translocation and Tcf/Lef-dependent gene transactivation1–3. Mutations in Wnt downstream signaling components have revealed diverse functions presumptively attributed to Wnt ligands themselves, although direct attribution remains elusive, as complicated by redundancy between 19 mammalian Wnts and 10 Fzds1 and Wnt hydrophobicity2,3. For example, individual Wnt ligand mutations have not revealed homeostatic phenotypes in the intestinal epithelium4, an archetypal canonical Wnt pathway-dependent rapidly self-renewing tissue whose regeneration is fueled by proliferative crypt Lgr5+ intestinal stem cells (ISCs)5–9. R-spondin ligands (Rspo1–4) engage distinct Lgr4-6 and Rnf43/Znrf3 receptor classes10–13, markedly potentiate canonical Wnt/β-catenin signaling and induce intestinal organoid growth in vitro and Lgr5+ ISCs in vivo8,14–17. However, the interchangeability, functional cooperation and relative contributions of Wnt versus Rspo ligands to in vivo canonical Wnt signaling and ISC biology remain unknown. Here, we deconstructed functional roles of Wnt versus Rspo ligands in the intestinal crypt stem cell niche. We demonstrate that the default fate of Lgr5+ ISCs is lineage commitment, escape from which requires both Rspo and Wnt ligands. However, gain-of-function studies using Rspo versus a novel non-lipidated Wnt analog reveal qualitatively distinct, non-interchangeable roles for these ligands in ISCs. Wnts are insufficient to induce Lgr5+ ISC self-renewal, but rather confer a basal competency by maintaining Rspo receptor expression that enables Rspo to actively drive and specify the extent of stem cell expansion. This functionally non-equivalent yet cooperative interplay between Wnt and Rspo ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precision control of tissue regeneration
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