71 research outputs found

    Do Sticky Prices Make Sense?

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    Dynamic stochastic general equilibrium models with sticky prices are prominent in recent research on macroeconomic ‡uctuations. A main argument for these models is that they have solid microfoundations. But staggered prices and wages are imposed exogenously. How plausible are sticky prices and wages in these models? We show that, in a standard model, staggered wage and price setting implies implausibly large reshu ing of production and labor supply on the microeconomic level. Furthermore, rationality is violated because households sometimes end up with negative markups. Substantial “menu costs ” are needed in order to rationalize the assumed behavior. We present an alternative model with deep habits, e ¢ ciency wages, and ranking, which can generate a high degree of persistence without the above mentioned problems.

    Modelling of Mouse Experimental Colitis by Global Property Screens: A Holistic Approach to Assess Drug Effects in Inflammatory Bowel Disease

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    Preclinical disease models play an important role in the establishment of new treatment paradigms, identification of biomarkers and assessment of drug efficacy and safety. However, the accuracy of these models in context of the human disease are sometimes questioned, e.g. due to trials failing to confirm efficacy in humans. We suggest that one reason behind this gap in predictability may relate to how the preclinical data is analyzed and interpreted. In the present paper, we introduce a holistic approach to analyze and illustrate data in context of one of the most commonly used colitis models, i.e. the mouse dextran sulphate sodium (DSS) colitis model. Diseased mice were followed over time along disease progression and by use of tool pharmacological compounds activating nuclear hormone receptors, respectively. A new multivariate statistics approach was applied including principal component analysis (PCA) with treatment prediction subsequent to establishing the principal component analysis model. Thus, several studies could be overlaid and compared to each other in a new, comprehensive and holistic way. This method, named mouse colitis global property screening, appears applicable not only to any animal modelling series of studies but also to human clinical studies. The prerequisites for the study set up and calculations are delineated and examples of new learnings from the global property screening will be presented

    Metabolic, health and lifestyle profiling of breast cancer radiotherapy patients and the risk of developing fatigue

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    Background: Fatigue is commonly reported by cancer patients. In some instances it can persist after treatment is com-pleted. In order to develop effective treatment strategies it is important to understand the mechanisms underlying the development of fatigue and to be able to predict those that may be at greatest risk of experiencing fatigue during and following treatment. The current paper examines predisposing factors for fatigue including altered fatty acid homeosta-sis in a cohort of breast cancer radiotherapy patients. Methodology: Patients had undergone breast-conserving surgery and adjuvant breast irradiation. Prior to radiotherapy the patients were free from significant fatigue. Levels of fatigue were determined prior to and following radiotherapy using the Functional Assessment of Cancer Therapy fatigue sub-scale. Plasma fatty acid levels, urinary and plasma amino acid levels, blood biochemistry factors and general health and lifestyle characteristics were assessed. Results: Following radiotherapy, significant fatigue affected approximately one third of the 26 patients and these subjects were then assigned to the fatigued cohort. Univariate analysis revealed that higher levels of the fatty acids myristic acid and eicosadienoic acid were present for the fatigued cohort prior to radio-therapy. Multivariate analysis also revealed that fatty acid homeostasis was altered between the fatigued and non-fatigued groups at baseline. Orthogonal partial least squares discriminant analysis of the general health, lifestyle and metabolic data revealed that the fatigued and non-fatigued patients could be clustered into two clearly separate groups. Conclusions: The results supported the proposition that the fatigued patients had an underlying metabolic ho-meostasis which may predispose them to the development of fatigue. Biochemical and general health profiling of breast cancer patients has the potential to identify those at most risk of developing significant fatigue following radiotherapy

    Effect of Low Temperature on Growth and Ultra-Structure of Staphylococcus spp

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    The effect of temperature fluctuation is an important factor in bacterial growth especially for pathogens such as the staphylococci that have to remain viable during potentially harsh and prolonged transfer conditions between hosts. The aim of this study was to investigate the response of S. aureus, S. epidermidis, and S. lugdunensis when exposed to low temperature (4°C) for prolonged periods, and how this factor affected their subsequent growth, colony morphology, cellular ultra-structure, and amino acid composition in the non-cytoplasmic hydrolysate fraction. Clinical isolates were grown under optimal conditions and then subjected to 4°C conditions for a period of 8 wks. Cold-stressed and reference control samples were assessed under transmission electron microscopy (TEM) to identify potential ultra-structural changes. To determine changes in amino acid composition, cells were fractured to remove the lipid and cytoplasmic components and the remaining structural components were hydrolysed. Amino acid profiles for the hydrolysis fraction were then analysed for changes by using principal component analysis (PCA). Exposure of the three staphylococci to prolonged low temperature stress resulted in the formation of increasing proportions of small colony variant (SCV) phenotypes. TEM revealed that SCV cells had significantly thicker and more diffuse cell-walls than their corresponding WT samples for both S. aureus and S. epidermidis, but the changes were not significant for S. lugdunensis. Substantial species-specific alterations in the amino acid composition of the structural hydrolysate fraction were also observed in the cold-treated cells. The data indicated that the staphylococci responded over prolonged periods of cold-stress treatment by transforming into SCV populations. The observed ultra-structural and amino acid changes were proposed to represent response mechanisms for staphylococcal survival amidst hostile conditions, thus maintaining the viability of the species until favourable conditions arise again

    Murine Gammaretrovirus Group G3 Was Not Found in Swedish Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia

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    BACKGROUND: The recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans. RESULTS: Three major groups of murine endogenous gammaretroviruses were identified. The third group encompassed both exogenous and endogenous Murine Leukemia Viruses (MLVs), and most XMRV/HMRV sequences reported from patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Two sensitive real-time PCRs for this group were developed. The predicted and observed amplification range for these and three published XMRV/HMRV PCRs demonstrated conspicuous differences between some of them, partly explainable by a recombinatorial origin of XMRV. Three reverse transcription real-time PCRs (RTQPCRs), directed against conserved and not overlapping stretches of env, gag and integrase (INT) sequences of XMRV/HMRV were used on human samples. White blood cells from 78 patients suffering from ME/CFS, of which 30 patients also fulfilled the diagnostic criteria for fibromyalgia (ME/CFS/FM) and in 7 patients with fibromyalgia (FM) only, all from the Gothenburg area of Sweden. As controls we analyzed 168 sera from Uppsala blood donors. We controlled for presence and amplifiability of nucleic acid and for mouse DNA contamination. To score as positive, a sample had to react with several of the XMRV/HMRV PCRs. None of the samples gave PCR reactions which fulfilled the positivity criteria. CONCLUSIONS: XMRV/HMRV like proviruses occur in the third murine gammaretrovirus group, characterized here. PCRs developed by us, and others, approximately cover this group, except for the INT RTQPCR, which is rather strictly XMRV specific. Using such PCRs, XMRV/HMRV could not be detected in PBMC and plasma samples from Swedish patients suffering from ME/CFS/FM, and in sera from Swedish blood donors

    Chemography:  The Art of Navigating in Chemical Space

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    Identification of Novel Biomarkers in Seasonal Allergic Rhinitis by Combining Proteomic, Multivariate and Pathway Analysis

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    Background: Glucocorticoids (GCs) play a key role in the treatment of seasonal allergic rhinitis (SAR). However, some patients show a low response to GC treatment. We hypothesized that proteins that correlated to discrimination between symptomatic high and low responders (HR and LR) to GC treatment might be regulated by GCs and therefore suitable as biomarkers for GC treatment. Methodology/Principal Findings: We identified 953 nasal fluid proteins in symptomatic HR and LR with a LC MS/MS based-quantitative proteomics analysis and performed multivariate analysis to identify a combination of proteins that best separated symptomatic HR and LR. Pathway analysis showed that those proteins were most enriched in the acute phase response pathway. We prioritized candidate biomarkers for GC treatment based on the multivariate and pathway analysis. Next, we tested if those candidate biomarkers differed before and after GC treatment in nasal fluids from 40 patients with SAR using ELISA. Several proteins including ORM (P&lt;0.0001), APOH (P&lt;0.0001), FGA (P&lt;0.01), CTSD (P&lt;0.05) and SERPINB3 (P&lt;0.05) differed significantly before and after GC treatment. Particularly, ORM (P&lt;0.01), FGA (P&lt;0.05) and APOH (P&lt;0.01) that belonged to the acute phase response pathway decreased significantly in HR but not LR before and after GC treatment. Conclusions/Significance: We identified several novel biomarkers for GC treatment response in SAR with combined proteomics, multivariate and pathway analysis. The analytical principles may be generally applicable to identify biomarkers in clinical studies of complex diseases.Funding Agencies|European Commission|223367|MultiMod||Swedish Medical Research Council||</p
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