3,560 research outputs found

    Structure of the Vertex Function

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    An integral representation as a function of invariants is found for the Fourier transform of the matrix element between the vacuum and a one-particle state of the retarded commutator of two currents. A special case is a spectral representation for the vertex as a function of momentum transfer. The threshold in this representation is lower than that found in the usual perturbation theory

    Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients.

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    BACKGROUND: Prostate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood. METHODS: A systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression. RESULTS: Five hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain. CONCLUSIONS: Currently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed

    Structure of the Vertex Function

    Get PDF
    An integral representation as a function of invariants is found for the Fourier transform of the matrix element between the vacuum and a one-particle state of the retarded commutator of two currents. A special case is a spectral representation for the vertex as a function of momentum transfer. The threshold in this representation is lower than that found in the usual perturbation theory

    The Panchromatic Hubble Andromeda Treasury I: Bright UV Stars in the Bulge of M31

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    As part of the Panchromatic Hubble Andromeda Treasury (PHAT) multi-cycle program, we observed a 12' \times 6.5' area of the bulge of M31 with the WFC3/UVIS filters F275W and F336W. From these data we have assembled a sample of \sim4000 UV-bright, old stars, vastly larger than previously available. We use updated Padova stellar evolutionary tracks to classify these hot stars into three classes: Post-AGB stars (P-AGB), Post-Early AGB (PE-AGB) stars and AGB-manqu\'e stars. P-AGB stars are the end result of the asymptotic giant branch (AGB) phase and are expected in a wide range of stellar populations, whereas PE-AGB and AGB-manqu\'e (together referred to as the hot post-horizontal branch; HP-HB) stars are the result of insufficient envelope masses to allow a full AGB phase, and are expected to be particularly prominent at high helium or {\alpha} abundances when the mass loss on the RGB is high. Our data support previous claims that most UV-bright sources in the bulge are likely hot (extreme) horizontal branch stars (EHB) and their progeny. We construct the first radial profiles of these stellar populations, and show that they are highly centrally concentrated, even more so than the integrated UV or optical light. However, we find that this UV-bright population does not dominate the total UV luminosity at any radius, as we are detecting only the progeny of the EHB stars that are the likely source of the UVX. We calculate that only a few percent of MS stars in the central bulge can have gone through the HP-HB phase and that this percentage decreases strongly with distance from the center. We also find that the surface density of hot UV-bright stars has the same radial variation as that of low-mass X-ray binaries. We discuss age, metallicity, and abundance variations as possible explanations for the observed radial variation in the UV-bright population.Comment: Accepted for publication in Ap

    Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

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    This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

    Changes in labial capillary density on ascent to and descent from high altitude

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    Present knowledge of how the microcirculation is altered by prolonged exposure to hypoxia at high altitude is incomplete and modification of existing analytical techniques may improve our knowledge considerably. We set out to use a novel simplified method of measuring in vivo capillary density during an expedition to high altitude using a CytoCam incident dark field imaging video-microscope. The simplified method of data capture involved recording one-second images of the mucosal surface of the inner lip to reveal data about microvasculature density in ten individuals. This was done on ascent to, and descent from, high altitude. Analysis was conducted offline by two independent investigators blinded to the participant identity, testing conditions and the imaging site. Additionally we monitored haemoglobin concentration and haematocrit data to see if we could support or refute mechanisms of altered density relating to vessel recruitment. Repeated sets of paired values were compared using Kruskall Wallis Analysis of Variance tests, whilst comparisons of values between sites was by related samples Wilcoxon Signed Rank Test. Correlation between different variables was performed using Spearman’s rank correlation coefficient, and concordance between analysing investigators using intra-class correlation coefficient. There was a significant increase in capillary density from London on ascent to high altitude; median capillaries per field of view area increased from 22.8 to 25.3 (p=0.021). There was a further increase in vessel density during the six weeks spent at altitude (25.3 to 32.5, p=0.017). Moreover, vessel density remained high on descent to Kathmandu (31.0 capillaries per field of view area), despite a significant decrease in haemoglobin concentration and haematocrit. Using a simplified technique, we have demonstrated an increase in capillary density on early and sustained exposure to hypobaric hypoxia at thigh altitude, and that this remains elevated on descent to normoxia. The technique is simple, reliable and reproducible
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