1,732 research outputs found

    A randomised study of carboplatin vs sequential ifosfamide/carboplatin for patients with FIGO stage III epithelial ovarian carcinoma

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    In a study designed to compare response rates of patients with stage III epithelial ovarian carcinoma to ifosfamide and carboplatin, 152 patients were randomised to receive either sequential therapy with three cycles of ifosfamide followed by three cycles of carboplatin, or to six cycles of single agent carboplatin. Ifosfamide was given every 3 weeks in a dose of 5 gm m-2 as a 24 h infusion with mesna, 1 gm m-2 by i.v. bolus prior to ifosfamide, 3 gm m-2 with ifosfamide, and 1 gm m-2 as an 8 h infusion after ifosfamide. Carboplatin was given in a dose of 400 mg m-2 by short i.v. infusion every 4 weeks. Sixty-eight evaluable patients were randomised to sequential ifosfamide/carboplatin, and 67 to single agent carboplatin. Median follow-up is 36 months (range 5.5-82.3). After three cycles of treatment two patients in the ifosfamide/carboplatin arm achieved complete remission (CR), and 12 partial remission (PR) for an overall response rate of 29%, whereas in the carboplatin arm ten patients achieved CR, and 23 PR, for an overall response rate of 63% (P = 0.0008). Seven of 15 patients with progressive disease, and nine of 20 patients with stable disease at the initial response evaluation, following three cycles of ifosfamide, subsequently responded to carboplatin therapy so that the final response rate to the complete regimen was 65% for the ifosfamide/carboplatin arm, compared to 71% for the carboplatin arm (NS). For the ifosfamide/carboplatin arm, median recurrence free survival and overall survival were 14.1 months and 18.7 months. Corresponding figures for the carboplatin arm were 14.5 months and 21.5 months (NS). Both treatments were generally well tolerated. However 47% of patients in the ifosfamide/carboplatin arm developed alopecia sufficient to require a wig, compared to only 2% in the carboplatin arm. Ifosfamide is clearly less effective, and more toxic than carboplatin. Ifosfamide failures can however be effectively salvaged by subsequent carboplatin treatment. Ifosfamide cannot be recommended for single agent therapy in ovarian carcinoma, however the combination of carboplatin plus ifosfamide might be a suitable treatment to be tested in a future randomised study against carboplatin alone

    Providing Self-Aware Systems with Reflexivity

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    We propose a new type of self-aware systems inspired by ideas from higher-order theories of consciousness. First, we discussed the crucial distinction between introspection and reflexion. Then, we focus on computational reflexion as a mechanism by which a computer program can inspect its own code at every stage of the computation. Finally, we provide a formal definition and a proof-of-concept implementation of computational reflexion, viewed as an enriched form of program interpretation and a way to dynamically "augment" a computational process.Comment: 12 pages plus bibliography, appendices with code description, code of the proof-of-concept implementation, and examples of executio

    The velocity of the arterial pulse wave: a viscous-fluid shock wave in an elastic tube

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    <p>Abstract</p> <p>Background</p> <p>The arterial pulse is a viscous-fluid shock wave that is initiated by blood ejected from the heart. This wave travels away from the heart at a speed termed the pulse wave velocity (PWV). The PWV increases during the course of a number of diseases, and this increase is often attributed to arterial stiffness. As the pulse wave approaches a point in an artery, the pressure rises as does the pressure gradient. This pressure gradient increases the rate of blood flow ahead of the wave. The rate of blood flow ahead of the wave decreases with distance because the pressure gradient also decreases with distance ahead of the wave. Consequently, the amount of blood per unit length in a segment of an artery increases ahead of the wave, and this increase stretches the wall of the artery. As a result, the tension in the wall increases, and this results in an increase in the pressure of blood in the artery.</p> <p>Methods</p> <p>An expression for the PWV is derived from an equation describing the flow-pressure coupling (FPC) for a pulse wave in an incompressible, viscous fluid in an elastic tube. The initial increase in force of the fluid in the tube is described by an increasing exponential function of time. The relationship between force gradient and fluid flow is approximated by an expression known to hold for a rigid tube.</p> <p>Results</p> <p>For large arteries, the PWV derived by this method agrees with the Korteweg-Moens equation for the PWV in a non-viscous fluid. For small arteries, the PWV is approximately proportional to the Korteweg-Moens velocity divided by the radius of the artery. The PWV in small arteries is also predicted to increase when the specific rate of increase in pressure as a function of time decreases. This rate decreases with increasing myocardial ischemia, suggesting an explanation for the observation that an increase in the PWV is a predictor of future myocardial infarction. The derivation of the equation for the PWV that has been used for more than fifty years is analyzed and shown to yield predictions that do not appear to be correct.</p> <p>Conclusion</p> <p>Contrary to the theory used for more than fifty years to predict the PWV, it speeds up as arteries become smaller and smaller. Furthermore, an increase in the PWV in some cases may be due to decreasing force of myocardial contraction rather than arterial stiffness.</p

    A four-helix bundle stores copper for methane oxidation

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    Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

    Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

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    Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

    Presence of Antibodies Against Coxiella burnetii and Risk of Spontaneous Abortion: A Nested Case-Control Study

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    BACKGROUND AND AIMS: Q fever is a bacterial zoonosis caused by infection with Coxiella burnetii. It is well established that Q fever causes fetal loss in small ruminants. The suspicion has been raised that pregnant women may also experience adverse pregnancy outcome when the infection is acquired or reactivated during pregnancy. The purpose of this study was to assess the potential association between serologic markers of infection with C. burnetii and spontaneous abortion. METHODS: A nested case-control study within the Danish National Birth Cohort, a cohort of 100,418 pregnancies recruited from 1996-2002. Women were recruited in first trimester of pregnancy and followed prospectively. Median gestational age at enrolment was 8 weeks (25 and 75 percentiles: 7 weeks; 10 weeks). During pregnancy, a blood sample was collected at gestational week 6-12 and stored in a bio bank. For this study, a case sample of 218 pregnancies was drawn randomly among the pregnancies in the cohort which ended with a miscarriage before 22 gestational weeks, and a reference group of 482 pregnancies was selected in a random fashion among all pregnancies in the cohort. From these pregnancies, serum samples were screened for antibodies against C. burnetii in a commercial enzyme-linked immunosorbent assay (ELISA). Samples that proved IgG or IgM antibody positive were subsequently confirmatory tested by an immunofluorescence (IFA) test. RESULTS: Among cases, 11 (5%) were C. burnetii positive in ELISA of which one was confirmed in the IFA assay compared to 29 (6%) ELISA positive and 3 IFA confirmed in the random sample. CONCLUSIONS: We found no evidence of a higher prevalence of C. burnetii antibodies in serum samples from women who later miscarried and the present study does not indicate a major association between Q fever infection and spontaneous abortion in humans. Very early first trimester abortions were, however, not included in the study

    Myogenic progenitors contribute to open but not closed fracture repair

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    <p>Abstract</p> <p>Background</p> <p>Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair.</p> <p>Methods</p> <p>We employed a <it>MyoD</it>-Cre<sup>+</sup>:Z/AP<sup>+ </sup>conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a <it>human alkaline phosphatase (hAP) </it>reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing.</p> <p>Results</p> <p>In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP<sup>+ </sup>cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP<sup>+ </sup>cells detected in the open fracture callus. At early stages of repair, many hAP<sup>+ </sup>cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP<sup>+ </sup>cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP<sup>+ </sup>staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors.</p> <p>Conclusions</p> <p>These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery.</p> <p>Please see related article: <url>http://www.biomedcentral.com/1741-7015/9/136</url></p

    Decomposing Neural Synchrony: Toward an Explanation for Near-Zero Phase-Lag in Cortical Oscillatory Networks

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    Background: Synchronized oscillation in cortical networks has been suggested as a mechanism for diverse functions ranging from perceptual binding to memory formation to sensorimotor integration. Concomitant with synchronization is the occurrence of near-zero phase-lag often observed between network components. Recent theories have considered the importance of this phenomenon in establishing an effective communication framework among neuronal ensembles. Methodology/Principal Findings: Two factors, among possibly others, can be hypothesized to contribute to the near-zero phase-lag relationship: (1) positively correlated common input with no significant relative time delay and (2) bidirectional interaction. Thus far, no empirical test of these hypotheses has been possible for lack of means to tease apart the specific causes underlying the observed synchrony. In this work simulation examples were first used to illustrate the ideas. A quantitative method that decomposes the statistical interdependence between two cortical areas into a feed-forward, a feed-back and a common-input component was then introduced and applied to test the hypotheses on multichannel local field potential recordings from two behaving monkeys. Conclusion/Significance: The near-zero phase-lag phenomenon is important in the study of large-scale oscillatory networks. A rigorous mathematical theorem is used for the first time to empirically examine the factors that contribute to this phenomenon. Given the critical role that oscillatory activity is likely to play in the regulation of biological processes at al
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