693 research outputs found

    Expectation adjustment in the housing market: insights from the Scottish auction system

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    This paper examines price expectation adjustment of house buyers and sellers to rapid changes in the housing market using data from Scotland where houses are sold through 'first-price sealed-bid' auctions. These auctions provide more information on market signals, incentives and the behaviour of market participants than private treaty sales. This paper therefore provides a theoretical framework for analysing revealed preference data generated from these auctions. We specifically focus on the analysis of the selling to asking price difference, the 'bid-premium'. The bid-premium is shown to be affected by expectations of future price movements, market duration and high bidding frequency. The bid-premium reflects consumers' expectations, adapting to market conditions more promptly than asking price setting behaviour and final sale prices. The volatile conditions of the recent housing market bubble are fully reflected in the bid-premium, whereas the asking and sale prices are much less prone to rapid movements

    Acute reperfusion intramyocardial hemorrhage leads to regional chronic iron deposition in the heart

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    Intramyocardial hemorrhage commonly occurs in large reperfused myocardial infarctions. However, its long-term fate remains unexplored. We hypothesized that acute reperfusion intramyocardial hemorrhage leads to chronic iron deposition

    High-frequency oscillation and tracheal gas insufflation in patients with severe acute respiratory distress syndrome and traumatic brain injury: an interventional physiological study

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    In acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves gas exchange compared with conventional mechanical ventilation (CMV). We evaluated the effect of HFO-TGI on PaO2/fractional inspired O2 (FiO2) and PaCO2, systemic hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) in patients with traumatic brain injury (TBI) and concurrent severe ARDS

    The effect of high frequency oscillatory ventilation combined with tracheal gas insufflation on extravascular lung water in patients with acute respiratory distress syndrome: a randomized, crossover, physiological study.

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    Purpose: High frequency oscillation combined with tracheal gas insufflation (HFO-TGI) improves oxygenation in patients with Acute Respiratory Distress Syndrome (ARDS). There is limited physiologic data regarding the effects of HFO-TGI on hemodynamics and pulmonary edema during ARDS. The aim of this study was to investigate the effect of HFO-TGI on extravascular lung water (EVLW). Materials and Methods: We conducted a prospective, randomized, crossover study. Consecutive eligible patients with ARDS received sessions of conventional mechanical ventilation (CMV) with recruitment maneuvers (RMs), followed by HFO-TGI with RMs, or vice versa. Each ventilatory technique was administered for 8 hours. The order of administration was randomly assigned. Arterial/central venous blood gas analysis and measurement of hemodynamic parameters and EVLW were performed at baseline and after each 8-hour period using the single-indicator thermodilution technique. Results: Twelve patients received 32 sessions. PaO2/FiO2 and respiratory system compliance were higher (p<0.001 for both), while EVLW indexed to predicted body weight (EVLWI) and oxygenation index were lower (p=0.021 and 0.029, respectively) in HFO-TGI compared with CMV. There was a significant correlation between PaO2/FiO2 improvement and EVLWI drop during HFO-TGI (Rs=-0.452, p= 0.009). Conclusions: HFO-TGI improves gas exchange and lung mechanics in ARDS, and potentially attenuates EVLW accumulation

    Subject-Specific Calculation of Left Atrial Appendage Blood-Borne Particle Residence Time Distribution in Atrial Fibrillation

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    Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology, and the clinically accepted LAA morphology-based classification is highly subjective. The aim of this study was to determine whether LAA blood-borne particle residence time distribution and the proposed quantitative index of LAA 3D geometry can add independent information to the CHA2DS2-VASc score. Data were collected from 16 AF subjects. Subject-specific measurements included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, cardiac output, and heart rate.We quantified 3D LAA appearance in terms of a novel LAA appearance complexity index (LAA-ACI). We employed computational fluid dynamics analysis and a systems-based approach to quantify residence time distribution and associated calculated variable (LAA mean residence time, tm) in each subject. The LAA-ACI captured the subject-specific LAA 3D geometry in terms of a single number. LAA tm varied significantly within a given LAA morphology as defined by the current subjectivemethod and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and LAA tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects’ clinical status. We conclude that LAA-ACI and LAA tm add independent information to the CHA2DS2-VASc score about stasis risk and thereby can potentially enhance its ability to stratify stroke risk in AF patients

    IL-33/ST2 Axis in Organ Fibrosis

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    Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis. The role of the axis in tissue remodeling is better understood considering its crucial role reported in organ development and regeneration. Generally, the IL-33/ST2 signaling pathway has mainly anti-inflammatory/anti-proliferative effects; however, chronic tissue injury is responsible for pro-fibrogenetic responses. Regarding pulmonary fibrosis mature IL-33 enhances pro-fibrogenic type 2 cytokine production in an ST2- and macrophage-dependent manner, while full-length IL-33 is also implicated in the pulmonary fibrotic process in an ST2-independent, Th2-independent fashion. In liver fibrosis, evidence indicate that when acute and massive liver damage occurs, the release of IL-33 might act as an activator of tissue-protective mechanisms, while in cases of chronic injury IL-33 plays the role of a hepatic fibrotic factor. IL-33 signaling has also been involved in the pathogenesis of acute and chronic pancreatitis. Moreover, IL-33 could be used as an early marker for ulcer-associated activated fibroblasts and myofibroblast trans-differentiation; thus one cannot rule out its potential role in inflammatory bowel disease-associated fibrosis. Similarly, the upregulation of the IL-33/ST2 axismay contribute to tubular cell injury and fibrosis via epithelial to mesenchymal transition (EMT) of various cell types in the kidneys. Of note, IL-33 exerts a cardioprotective role via ST2 signaling, while soluble ST2 has been demonstrated as a marker of myocardial fibrosis. Finally, IL-33 is a crucial cytokine in skin pathology responsible for abnormal fibroblast proliferation, leukocyte infiltration and morphologic differentiation of human endothelial cells. Overall, emerging data support a novel contribution of the IL-33/ST2 pathway in tissue fibrosis and highlight the significant role of the Th2 pattern of immune response in the pathophysiology of organ fibrosis

    Selective activation of TNFR1 and NF-κB inhibition by a novel biyouyanagin analogue promotes apoptosis in acute leukemia cells

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    Background: Acquired resistance towards apoptosis is a hallmark of cancer. Elimination of cells bearing activated oncogenes or stimulation of tumor suppressor mediators may provide a selection pressure to overcome resistance. KC-53 is a novel biyouyanagin analogue known to elicit strong anti-inflammatory and anti-viral activity. The current study was designed to evaluate the anticancer efficacy and molecular mechanisms of KC-53 against human cancer cells. Methods: Using the MTT assay we examined initially how KC-53 affects the proliferation rates of thirteen representative human cancer cell lines in comparison to normal peripheral blood mononuclear cells (PBMCs) and immortalized cell lines. To decipher the key molecular events underlying its mode of action we selected the human promyelocytic leukemia HL-60 and the acute lymphocytic leukemia CCRF/CEM cell lines that were found to be the most sensitive to the antiproliferative effects of KC-53. Results: KC-53 promoted rapidly and irreversibly apoptosis in both leukemia cell lines at relatively low concentrations. Apoptosis was characterized by an increase in membrane-associated TNFR1, activation of Caspase-8 and proteolytic inactivation of the death domain kinase RIP1 indicating that KC-53 induced mainly the extrinsic/death receptor apoptotic pathway. Regardless, induction of the intrinsic/mitochondrial pathway was also achieved by Caspase-8 processing of Bid, activation of Caspase-9 and increased translocation of AIF to the nucleus. FADD protein knockdown restored HL-60 and CCRF/CEM cell viability and completely blocked KC-53-induced apoptosis. Furthermore, KC-53 administration dramatically inhibited TNFα-induced serine phosphorylation on TRAF2 and on IκBα hindering therefore p65/NF-κΒ translocation to nucleus. Reduced transcriptional expression of pro-inflammatory and pro-survival p65 target genes, confirmed that the agent functionally inhibited the transcriptional activity of p65. Conclusions: Our findings demonstrate, for the first time, the selective anticancer properties of KC-53 towards leukemic cell lines and provide a detailed understanding of the molecular events underlying its dual anti-proliferative and pro-apoptotic properties. These results provide new insights into the development of innovative and targeted therapies for the treatment of some forms of leukemia

    Brief of Amici Curiae Michael L. Rosin, David G. Post, David F. Forte, Michael Stokes Paulsen, and Sotirios Barber in Support of Presidential Electors

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    The Framers of the Constitution crafted the Electoral College to be an independent institution with the responsibility of selecting the President and Vice-President. Therefore, they intended each elector to exercise independent judgment in deciding whom to vote for. A state cannot revise the Constitution unilaterally by reducing the elector to a ministerial agent who must vote in a particular way or face a sanction. The question of each elector’s moral or political obligation is not before the Court. Nor is the desirability of the current electoral system. Rather, this case turns on what the Constitution allows, and what it prohibits. The historical record strongly supports the notion that the Constitution allows an elector to exercise independent judgment and prohibits a State from interfering with an elector’s ability to do so—a position Congress has consistently reaffirmed. This robust historical record supports only one conclusion: Our constitutional framework allows each elector to vote as he or she chooses
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