975 research outputs found

    Mergers with Quality Differentiated Products

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    We consider the impact of merger on the equilibrium price and quality of products. Consumer demand for both products depends not only on own price and quality, but also on the price and quality of the other product. We consider both the case in which the merging firms produce gross complements, and the case in which the firms produce gross substitutes. In both cases, merger may lower or increase both product price and quality. In the case in which firms produce complementary products, it may happen that firms both lower price and increase product quality when merged. This happens when the cross quality elasticities of demand and the cross price elasticities of demand are equal in magnitude. Surprisingly, we also find that there are situations under which merger between firms producing substitutes increases welfare. For example, it is possible that merger between firms producing gross complements may result in higher product quality but lower social welfare, and merger between firms producing substitute products may result in lower product quality but higher social welfare.

    Detection of terminal complement components in experimental immune glomerular injury

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    Detection of terminal complement components in experimental immune glomerular injury. Complement mediates glomerulonephritis by inflammatory cell-dependent and non-inflammatory cell-independent effects on glomerular permeability. The latter may involve terminal components of the complement system. We examined several models of immunologic renal injury in the rat by immunofluorescence (IF) for terminal complement components C5, C6, C7, and C8 in glomeruli using antisera to human C5-8, which cross-react with the analogous rat complement components. Rats with the heterologous and autologous phases of passive Heymann nephritis (PHN) had proteinuria and 1 to 2+ capillary wall deposits of heterologous or rat IgG, rat C3, and C5-8. Complement depletion with cobra venom factor (CVF) significantly decreased proteinuria in both models and prevented deposition of all complement components. Rats with active Heymann nephritis had similar deposits of rat IgG and C5-8. Rats with anti-GBM nephritis and aminonucleoside nephrosis had severe proteinuria which was not affected by CVF treatment and deposits of C5-8 were absent. The presence of terminal complement components in immune deposits in experimental glomerular disease correlates with a functional role for complement in mediating glomerular injury. These data support the hypothesis that the terminal complement pathway may be a major mediator of some types of immune glomerular injury.DĂ©tection des constituants terminaux du complĂ©ment au cours de lĂ©sions immunes glomĂ©rulaires expĂ©rimentales. Le complĂ©ment est le mĂ©diateur d'une glomĂ©rulonĂ©phrite par des effets inflammatoires cellule-dĂ©pendants, et non inflammatoires cellule-indĂ©pendants sur la permĂ©abilitĂ© glomĂ©rulaire. Ces derniers pourraient mettre en jeu les constituants terminaux du systĂšme complĂ©mentaire. Nous avons examinĂ© plusieurs modĂšles de lĂ©sions rĂ©nales immunologiques chez le rat par la immunofluorescence (IF) en ce qui concerne les constituants complĂ©mentaires terminaux C5, C6, C7, et C8 dans les glomĂ©rules en utilisant des antisĂ©rums contre C5-8 humain qui croisent avec les constituants complĂ©mentaires analogues du rat. Des rats dans les phases hĂ©tĂ©rologue et autologue d'une nĂ©phrite passive de Heymann (PHN) avaient une prolĂ©inurie et des dĂ©pĂŽts sur les parois capillaires 1 Ă  2 + d'IgG hĂ©tĂ©rologue ou de rat, de C3 et de C5-8 de rat. Une dĂ©plĂ©tion complĂ©mentaire avec du facteur de venin de cobra (CVF) a diminuĂ© significativement la protĂ©inurie dans les deux modĂšles et a prĂ©venu le dĂ©pĂŽt de tous les constituants complĂ©mentaires. Des rats atteints d'une nephrite active de Heymann avaient des dĂ©pĂŽts identiques d'IgG et de C5-8 de rat. Des rats atteints de nĂ©phrite anti-GBM et de nĂ©phrose aux aminoglucosides avaient une protĂ©inurie sĂ©vĂšre non affectĂ©e par le traitement au CVF et les dĂ©pĂŽts de C5-8 Ă©taient absents. La prĂ©sence des constituants terminaux de complĂ©ment dans les dĂ©pĂŽts immuns lors des glomĂ©rulopathies expĂ©rimentales est corrĂ©lĂ©e avec un rĂŽle fonctionnel du complĂ©ment dans la mĂ©diation des lĂ©sions glomĂ©rulaires. Ces donnĂ©es sont en faveur de l'hypothĂšse que la voie terminale du complĂ©ment peut ĂȘtre un mĂ©diateur majeur de certains types de lĂ©sions glomĂ©rulaires immunes

    B Cell IgD Deletion Prevents Alveolar Bone Loss Following Murine Oral Infection

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    Periodontal disease is one of the most common infectious diseases of humans. Immune responses to infection trigger loss of alveolar bone from the jaw and eventual tooth loss. We investigated the contribution of B cell IgD to alveolar bone loss by comparing the response of B cell normal BALB/cJ mice and IgD deficient BALB/c-Igh-5−/−J mice to oral infection with Porphyromonas gingivalis, a gram-negative periodontopathic bacterium from humans. P. gingivalis-infected normal mice lost bone. Specific antibody to P. gingivalis was lower and oral colonization was higher in IgD deficient mice; yet bone loss was completely absent. Infection increased the proportion of CD69+ activated B cells and CD4+ T cells in immune normal mice compared to IgD deficient mice. These data suggest that IgD is an important mediator of alveolar bone resorption, possibly through antigen-specific coactivation of B cells and CD4+ T cells

    A Culturally and Linguistically Responsive Framework for Improving Academic and Postsecondary Outcomes of Students with Moderate or Severe Intellectual Disability

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    The needs of culturally and linguistically diverse (CLD) students with moderate or severe intellectual disability (ID) are quite unique and complex. CLD students with moderate or severe ID face many of the same issues as their non-disabled CLD peers; however, due to the nature of their disability this may lead to even less access to the general curriculum, appropriate services, materials, and meaningful collaboration between families and educators. The purpose of this article is to provide a culturally responsive framework for facilitating academic instruction for CLD students with moderate or severe ID that also includes appropriate supports in an effort to increase access to postsecondary outcomes for this population. Suggestions for accessing the general curriculum and a discussion about increasing parental involvement and accessing appropriate adult agencies to further enhance these outcomes are provided

    Utilization of an Electrochemiluminescence Sensor for Atropine Determination in Complex Matrices

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    A major challenge within forensic science is the development of accurate and robust methodologies that can be utilized on-site for detection at crime scenes and can be used for analyzing multiple sample types. The recent expansion of electrochemical sensors to tackle this hurdle requires sensors that can undergo analysis without any pretreatment. Given the vast array of samples that are submitted for forensic analysis, this can pose a major challenge for all electrochemical sensors, including electrochemiluminescent (ECL)-based sensors. Within this contribution, we demonstrate the capacity for an ECL-based sensor to address this challenge and it is potential to detect and quantify atropine from a wide range of samples directly from herbal material to spiked solutions. This portable platform demonstrates satisfactory analytical parameters with linearity across a concentration range of 0.75 to 100 ÎŒM, reproducibility of 3.0%, repeatability of 9.2%, and a detection limit of ∌0.75 ÎŒM. The sensor displays good selectivity toward alkaloid species and, in particular, the hallucinogenic tropane alkaloid functionality within complex matrices. This portable sensor provides rapid detection alongside low cost and operational simplicity, thus, providing a basis for the exploitation of ECL-based sensors within the forensic arena

    Global status of groundfish stocks

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    We review the status of groundfish stocks using published scientific assessments for 349 individual stocks constituting 90% of global groundfish catch. Overall, average stock abundance is increasing and is currently above the level that would produce maximum sustainable yield (MSY). Fishing pressure for cod-like fishes (Gadiformes) and flatfishes (Pleuronectiformes) was, for several decades, on average well above levels associated with MSY, but is now at or below the level expected to produce MSY. In contrast, fishing pressure for rockfishes (Scorpaeniformes) decreased from near MSY-related levels in the mid-1990s, and since the mid-2000s has remained on average at only one third of MSY-related levels. Regions with the most depressed groundfish stocks are the Northwest Atlantic and the Pacific coast of South America, while stocks from the Northeast and Eastern Central Pacific, Northeast Atlantic, Southeast Atlantic and Southwest Pacific tend to have greatest average abundance relative to MSY-based reference points. In the most recent year available for each stock, the catch was only 61% of MSY. Equilibrium yield curves indicate that 76% of global potential groundfish yield could be achieved using current estimates of fishing pressure. 15% of this is lost by excess fishing pressure, 67% results from lower than optimal fishing pressure on healthy stocks and 18% is lost from stocks currently overfished but rebuilding. Thus, there is modest opportunity to increase catch of global groundfish fisheries by reducing overfishing on some stocks, but more by increasing harvest on others. However, there may be other reasons not to fully exploit these stocks.Fil: Hilborn, Ray. University of Washington; Estados UnidosFil: Hively, Daniel J.. University of Washington; Estados UnidosFil: Baker Loke, Nicole. University of Washington; Estados UnidosFil: de Moor, Carryn L.. University Of Cape Town; SudĂĄfricaFil: Kurota, Hiroyuki. Japan Fisheries Research and Education Agency; JapĂłnFil: Kathena, Johannes N.. Ministry of Fisheries and Marine Resources; NamibiaFil: Mace, Pamela M.. Ministry for Primary Industries; Nueva ZelandaFil: Minto, CĂłilĂ­n. Galway-Mayo Institute of Technology; IrlandaFil: Parma, Ana MarĂ­a. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Centro Nacional PatagĂłnico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Quiroz, Juan-Carlos. Instituto de Fomento Pesquero; ChileFil: Melnychuk, Michael C.. University of Washington; Estados Unido

    Pro- and anti-tumour activities of CD146/MCAM in breast cancer result from its heterogeneous expression and association with epithelial to mesenchymal transition

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    CD146, also known as melanoma cell adhesion molecule (MCAM), is expressed in numerous cancers and has been implicated in the regulation of metastasis. We show that CD146 negatively regulates transendothelial migration (TEM) in breast cancer. This inhibitory activity is reflected by a reduction in MCAM gene expression and increased promoter methylation in tumour tissue compared to normal breast tissue. However, increased CD146/MCAM expression is associated with poor prognosis in breast cancer, a characteristic that is difficult to reconcile with inhibition of TEM by CD146 and its epigenetic silencing. Single cell transcriptome data revealed MCAM expression in multiple cell types, including the malignant cells, tumour vasculature and normal epithelium. MCAM expressing malignant cells were in the minority and expression was associated with epithelial to mesenchymal transition (EMT). Furthermore, gene expression signatures defining invasiveness and a stem cell-like phenotype were most strongly associated with mesenchymal-like tumour cells with low levels of MCAM mRNA, likely to represent a hybrid epithelial/mesenchymal (E/M) state. Our results show that high levels of MCAM gene expression are associated with poor prognosis in breast cancer because they reflect tumour vascularisation and high levels of EMT. We suggest that high levels of mesenchymal-like malignant cells reflect large populations of hybrid E/M cells and that low CD146 expression on these hybrid cells is permissive for TEM, aiding metastasis

    Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study

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    Background & AimsIn acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure.MethodsPigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure.ResultsThe Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen.ConclusionsThe survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients

    A Novel Stable Isotope Approach for Determining the Impact of Thickening Agents on Water Absorption

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    Research on the bioavailability of water from thickened fluids has recently been published and it concluded that the addition of certain thickening agents (namely, modified maize starch, guar gum, and xanthan gum) does not significantly alter the absorption of water from the healthy, mature human gut. Using xanthan gum as an example, our “proof of concept” study describes a simple, accurate, and noninvasive alternative to the methodology used in that first study, and involves the measurement and comparison of the dilution space ratios of the isotopes 2H and 18O and subsequent calculation of total body water. Our method involves the ingestion of a thickening agent labeled with 2H 1 day after ingestion of 18O. Analyses are based on the isotopic enrichment of urine samples collected prior to the administration of each isotope, and daily urine samples collected for 15 days postdosing. We urge that further research is needed to evaluate the impact of various thickening agents on the bioavailability of water from the developing gut and in cases of gut pathology and recommend our methodology

    Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

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    Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)
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