Showing papers by "University of Glasgow published in 2003"
TL;DR: The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time, and may have implications for future lipid-lowering guidelines.
3,436 citations
TL;DR: Cedesartan has a moderate impact in preventing admissions for CHF among patients who have heart failure and LVEF higher than 40%.
2,695 citations
TL;DR: The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction.
2,376 citations
University of California, Berkeley1, Goddard Space Flight Center2, Paul Scherrer Institute3, Lawrence Berkeley National Laboratory4, Oak Ridge National Laboratory5, ETH Zurich6, Montana State University7, University of Alabama in Huntsville8, University of Glasgow9, Rice University10, Open University11
TL;DR: RHESSI as discussed by the authors is a Principal Investigator (PI) mission, where the PI is responsible for all aspects of the mission except the launch vehicle, and is designed to investigate particle acceleration and energy release in solar flares, through imaging and spectroscopy of hard X-ray/gamma-ray continua emitted by energetic electrons, and of gamma-ray lines produced by energetic ions.
Abstract: RHESSI is the sixth in the NASA line of Small Explorer (SMEX) missions and the first managed in the Principal Investigator mode, where the PI is responsible for all aspects of the mission except the launch vehicle. RHESSI is designed to investigate particle acceleration and energy release in solar flares, through imaging and spectroscopy of hard X-ray/gamma-ray continua emitted by energetic electrons, and of gamma-ray lines produced by energetic ions. The single instrument consists of an imager, made up of nine bi-grid rotating modulation collimators (RMCs), in front of a spectrometer with nine cryogenically-cooled germanium detectors (GeDs), one behind each RMC. It provides the first high-resolution hard X-ray imaging spectroscopy, the first high-resolution gamma-ray line spectroscopy, and the first imaging above 100 keV including the first imaging of gamma-ray lines. The spatial resolution is as fine as ~ 2.3 arc sec with a full-Sun (≳ 1°) field of view, and the spectral resolution is ~ 1–10 keV FWHM over the energy range from soft X-rays (3 keV) to gamma-rays (17 MeV). An automated shutter system allows a wide dynamic range (> 107) of flare intensities to be handled without instrument saturation. Data for every photon is stored in a solid-state memory and telemetered to the ground, thus allowing for versatile data analysis keyed to specific science objectives. The spin-stabilized (~ 15 rpm) spacecraft is Sun-pointing to within ~ 0.2° and operates autonomously. RHESSI was launched on 5 February 2002, into a nearly circular, 38° inclination, 600-km altitude orbit and began observations a week later. The mission is operated from Berkeley using a dedicated 11-m antenna for telemetry reception and command uplinks. All data and analysis software are made freely and immediately available to the scientific community.
1,991 citations
TL;DR: Codesartan was generally well tolerated and significantly reduced cardiovascular deaths and hospital admissions for heart failure and there was no significant heterogeneity for candesartan results across the component trials.
1,788 citations
TL;DR: In this paper, a systematic review aimed to examine the results of studies of suicide that used a psychological autopsy method, which offers the most direct technique currently available for examining the relationship between particular antecedents and suicide.
Abstract: BACKGROUND: The psychological autopsy method offers the most direct technique currently available for examining the relationship between particular antecedents and suicide. This systematic review aimed to examine the results of studies of suicide that used a psychological autopsy method. METHOD: A computer aided search of MEDLINE, BIDS ISI and PSYCHLIT, supplemented by reports known to the reviewers and reports identified from the reference lists of other retrieved reports. Two investigators systematically and independently examined all reports. Median proportions were determined and population attributable fractions were calculated, where possible, in cases of suicide and controls. RESULTS: One hundred and fifty-four reports were identified, of which 76 met the criteria for inclusion; 54 were case series and 22 were case-control studies. The median proportion of cases with mental disorder was 91% (95 % CI 81-98%) in the case series. In the case-control studies the figure was 90% (88-95%) in the cases and 27% (14-48%) in the controls. Co-morbid mental disorder and substance abuse also preceded suicide in more cases (38%, 19-57%) than controls (6%, 0-13%). The population attributable fraction for mental disorder ranged from 47-74% in the seven studies in which it could be calculated. The effects of particular disorders and sociological variables have been insufficiently studied to draw clear conclusions. CONCLUSIONS: The results indicated that mental disorder was the most strongly associated variable of those that have been studied. Further studies should focus on specific disorders and psychosocial factors. Suicide prevention strategies may be most effective if focused on the treatment of mental disorders. Language: en
1,609 citations
TL;DR: Magnetic nanoparticles have been proposed for use as biomedical purposes to a large extent for several years as discussed by the authors, which has led to various opportunities such as improving the quality of magnetic resonance imaging, hyperthermic treatment for malignant cells, site-specific drug delivery and manipulation of cell membranes.
Abstract: Magnetic nanoparticles have been proposed for use as biomedical purposes to a large extent for several years. In recent years, nanotechnology has developed to a stage that makes it possible to produce, characterize and specifically tailor the functional properties of nanoparticles for clinical applications. This has led to various opportunities such as improving the quality of magnetic resonance imaging, hyperthermic treatment for malignant cells, site-specific drug delivery and the manipulation of cell membranes. To this end a variety of iron oxide particles have been synthesized. A common failure in targeted systems is due to the opsonization of the particles on entry into the bloodstream, rendering the particles recognizable by the body's major defence system, the reticulo-endothelial system. This review discusses each of the above bio-applications of such magnetic nanoparticles and details some of the main recent advances in biological research.
1,473 citations
TL;DR: The potential for using trees for the phytoremediation of heavy metal-contaminated land is reviewed, including metal tolerance in trees, heavy metal uptake by trees grown on contaminated substrates, heavyMetal compartmentalisation within trees, phytOREmediation using trees and thePhytore mediators of willow (Salix spp.)
1,282 citations
TL;DR: Recent studies with mixed biofilms containing Candida and bacterial species suggest that extensive and striking interactions occur between the prokaryotic and eukaryotic cells in these adherent populations.
1,113 citations
TL;DR: It is shown that Cnp1, which encodes 2′,3′-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly, and the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin.
Abstract: Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss.
942 citations
TL;DR: The immunomodulator imiquimod has proved to be an adjunct for CL therapy and the search for new drugs continues, with bisphosphonates, for example, risedronate and pamidronate, and plant derivatives being reported to have activity against experimental animal infections.
TL;DR: Overall effects of fluvastatin were similar to those of statins in other populations, and seemed to be reduced in cardiac deaths and non-fatal MI, but did not generally reduce rates of coronary intervention procedures or mortality.
TL;DR: PDE4 enzymes stand at a crossroads that allows them to integrate various signalling pathways with that of cAMP in spatially distinct compartments, and the recent elucidation of the structure of the PDE4 catalytic unit allows for molecular insight into the mode of catalysis as well as substrate and inhibitor selectivity.
Abstract: cAMP is a second messenger that controls many key cellular functions. The only way to inactivate cAMP is to degrade it through the action of cAMP phosphodiesterases (PDEs). PDEs are thus poised to play a key regulatory role. PDE4 cAMP-specific phosphodiesterases appear to have specific functions with selective inhibitors serving as potent anti-inflammatory agents. The recent elucidation of the structure of the PDE4 catalytic unit allows for molecular insight into the mode of catalysis as well as substrate and inhibitor selectivity. The four PDE4 genes encode over 16 isoforms, each of which is characterized by a unique N-terminal region. PDE4 isoforms play a pivotal role in controlling functionally and spatially distinct pools of cAMP by virtue of their unique intracellular targeting. Targeting occurs by association with proteins, such as arrestins, SRC family tyrosyl kinases, A-kinase anchoring proteins ('AKAPs') and receptor for activated C kinase 1 ('RACK1'), and, in the case of isoform PDE4A1, by a specific interaction (TAPAS-1) with phosphatidic acid. PDE4 isoforms are 'designed' to be regulated by extracellular-signal-related protein kinase (ERK), which binds to anchor sites on the PDE4 catalytic domain that it phosphorylates. The upstream conserved region 1 (UCR1) and 2 (UCR2) modules that abut the PDE4 catalytic unit confer regulatory functions by orchestrating the functional outcome of phosphorylation by cAMP-dependent protein kinase ('PKA') and ERK. PDE4 enzymes stand at a crossroads that allows them to integrate various signalling pathways with that of cAMP in spatially distinct compartments.
TL;DR: In this article, the movement and behaviour of particles suspended in aqueous solutions subjected to non-uniform ac electric fields is examined and the relative influence of each type of force is described.
Abstract: The movement and behaviour of particles suspended in aqueous solutions subjected to non-uniform ac electric fields is examined. The ac electric fields induce movement of polarizable particles, a phenomenon known as dielectrophoresis. The high strength electric fields that are often used in separation systems can give rise to fluid motion, which in turn results in a viscous drag on the particle. The electric field generates heat, leading to volume forces in the liquid. Gradients in conductivity and permittivity give rise to electrothermal forces and gradients in mass density to buoyancy. In addition, non-uniform ac electric fields produce forces on the induced charges in the diffuse double layer on the electrodes. This causes a steady fluid motion termed ac electro-osmosis. The effects of Brownian motion are also discussed in this context. The orders of magnitude of the various forces experienced by a particle in a model microelectrode system are estimated. The results are discussed in relation to experiments and the relative influence of each type of force is described.
TL;DR: The ability of TIMP3 to inhibit vascular endothelial factor (VEGF)–mediated angiogenesis is demonstrated and the potential mechanism by which this occurs is identified, indicating a new function for this molecule.
Abstract: Tissue inhibitor of metalloproteinases-3 (TIMP3) is one of four members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases (MMP). TIMP3, which encodes a potent angiogenesis inhibitor, is mutated in Sorsby fundus dystrophy, a macular degenerative disease with submacular choroidal neovascularization. In this study we demonstrate the ability of TIMP3 to inhibit vascular endothelial factor (VEGF)-mediated angiogenesis and identify the potential mechanism by which this occurs: TIMP3 blocks the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling and angiogenesis. This property seems to be independent of its MMP-inhibitory activity, indicating a new function for this molecule.
TL;DR: It is shown that manipulation of dietary carotenoid supply invokes parallel changes in cell-mediated immune function and sexual attractiveness in male zebra finches (Taeniopygia guttata).
Abstract: One hypothesis for why females in many animal species frequently prefer to mate with the most elaborately ornamented males predicts that availability of carotenoid pigments is a potentially limiting factor for both ornament expression and immune function. An implicit assumption of this hypothesis is that males that can afford to produce more elaborate carotenoid-dependent displays must be healthier individuals with superior immunocompetence. However, whether variation in circulating carotenoid levels causes variation in both immune function and sexual attractiveness has not been determined in any species. In this study, we show that manipulation of dietary carotenoid supply invokes parallel changes in cell-mediated immune function and sexual attractiveness in male zebra finches (Taeniopygia guttata).
TL;DR: In this paper, the impact of the gate line edge roughness (LER) on the intrinsic parameters fluctuations in deep decananometer (sub 50 nm) gate MOSFETs was investigated.
Abstract: In this paper, we use statistical three-dimensional (3-D) simulations to study the impact of the gate line edge roughness (LER) on the intrinsic parameters fluctuations in deep decananometer (sub 50 nm) gate MOSFETs. The line edge roughness is introduced using a Fourier synthesis technique based on the power spectrum of a Gaussian autocorrelation function. In carefully designed simulation experiments, we investigate the impact of the rms amplitude /spl Delta/ and the correlation length /spl Lambda/ on the intrinsic parameter fluctuations in well scaled, but simple devices with fixed geometry as well as the channel length and width dependence of the fluctuations at fixed LER parameters. For the first time, we superimpose in the simulations LER and random discrete dopants and investigate their relative contribution to the intrinsic parameter fluctuations in the investigated devices. For particular MOSFET geometries, we were able to identify the regions where each of these two sources of intrinsic parameter fluctuations dominates.
TL;DR: A break in the crystal structure of the reaction center–light harvesting 1 (RC–LH1) core complex from Rhodopseudomonas palustris may provide a portal through which UQB can transfer electrons to cytochrome b/c1.
Abstract: The crystal structure at 4.8 angstrom resolution of the reaction center–light harvesting 1 (RC–LH1) core complex from Rhodopseudomonas palustris shows the reaction center surrounded by an oval LH1 complex that consists of 15 pairs of transmembrane helical α- and β-apoproteins and their coordinated bacteriochlorophylls. Complete closure of the RC by the LH1 is prevented by a single transmembrane helix, out of register with the array of inner LH1 α-apoproteins. This break, located next to the binding site in the reaction center for the secondary electron acceptor ubiquinone (UQB), may provide a portal through which UQB can transfer electrons to cytochrome b/c1.
TL;DR: In this paper, a review of the analytical and numerical simulation techniques used to study and predict intrinsic parameters fluctuations is presented, and the future challenges that have to be addressed in order to improve the accuracy and the predictive power of the intrinsic fluctuation simulations are also discussed.
Abstract: Intrinsic parameter fluctuations introduced by discreteness of charge and matter will play an increasingly important role when semiconductor devices are scaled to decananometer and nanometer dimensions in next-generation integrated circuits and systems. In this paper, we review the analytical and the numerical simulation techniques used to study and predict such intrinsic parameters fluctuations. We consider random discrete dopants, trapped charges, atomic-scale interface roughness, and line edge roughness as sources of intrinsic parameter fluctuations. The presented theoretical approach based on Green's functions is restricted to the case of random discrete charges. The numerical simulation approaches based on the drift diffusion approximation with density gradient quantum corrections covers all of the listed sources of fluctuations. The results show that the intrinsic fluctuations in conventional MOSFETs, and later in double gate architectures, will reach levels that will affect the yield and the functionality of the next generation analog and digital circuits unless appropriate changes to the design are made. The future challenges that have to be addressed in order to improve the accuracy and the predictive power of the intrinsic fluctuation simulations are also discussed.
TL;DR: It is shown that consumption of plain, dark chocolate results in an increase in both the total antioxidant capacity and the (−)epicatechin content of blood plasma, but that these effects are markedly reduced when the chocolate is consumed with milk or if milk is incorporated as milk chocolate.
Abstract: Dark chocolate may offer its consumers health benefits the milk variety cannot match. There is some speculation that dietary flavonoids from chocolate, in particular (−)epicatechin, may promote cardiovascular health as a result of direct antioxidant effects or through antithrombotic mechanisms1,2,3. Here we show that consumption of plain, dark chocolate (Fig. 1) results in an increase in both the total antioxidant capacity and the (−)epicatechin content of blood plasma, but that these effects are markedly reduced when the chocolate is consumed with milk or if milk is incorporated as milk chocolate. Our findings indicate that milk may interfere with the absorption of antioxidants from chocolate in vivo and may therefore negate the potential health benefits that can be derived from eating moderate amounts of dark chocolate.
TL;DR: The results indicate that the derivatised particles induce alterations in cell behaviour and morphology distinct from the plain particles, suggesting that cell response can be directed via specifically engineered particle surfaces.
TL;DR: In this article, airline cabin crews are depicted as skilled emotion managers who are able to juggle and synthesize different types of emotion work dependent on situational demands and the capacity for cabin crews to resist and modify the demands of management and customers acts to further contradict Hochschild's claim regarding the ''transmutation' of feelings.
Abstract: This article examines emotion in organizations and the emotion management skills organizational actors possess. While Hochschild's (1983) seminal work on emotional labour is perhaps one of the greatest contributions to our understanding of emotion in organizations, this article challenges key tenets of Hochschild's thesis and goes on to offer an evolved analysis of emotional labour and alternative conceptualizations of organizational emotionality. Using comparable data, this article depicts airline cabin crews as skilled emotion managers who are able to juggle and synthesize different types of emotion work dependent on situational demands. In addition, the capacity for cabin crews to resist and modify the demands of management and customers acts to further contradict Hochschild's claim regarding the `transmutation' of feelings.
TL;DR: An emphasis on methodological appropriateness, and on typologies rather than hierarchies of evidence may be helpful in organising and appraising public health evidence.
Abstract: Debate is ongoing about the nature and use of evidence in public health decision making, and there seems to be an emerging consensus that the "hierarchy of evidence" may be difficult to apply in other settings. It may be unhelpful however to simply abandon the hierarchy without having a framework or guide to replace it. One such framework is discussed. This is based around a matrix, and emphasises the need to match research questions to specific types of research. This emphasis on methodological appropriateness, and on typologies rather than hierarchies of evidence may be helpful in organising and appraising public health evidence.
TL;DR: The calculated energy changes indicate that there may be significant contributions to inter-pigment energy interactions from molecular displacements and these may be of importance to photosynthetic energy transfer.
TL;DR: It is concluded that active smoking impairs the efficacy of short-term oral corticosteroid treatment in chronic asthma.
Abstract: The study was designed to assess the effect of cigarette smoking on the therapeutic response to oral corticosteroids in chronic stable asthma. We performed a randomized, placebo-controlled, crossover study with prednisolone (40 mg daily) or placebo for 2 weeks in smokers with asthma, ex-smokers with asthma, and never-smokers with asthma. All subjects had reversibility in FEV1 after nebulized albuterol of 15% or more and a mean postbronchodilator FEV1% predicted of more than 80%. Efficacy was assessed using FEV1, daily PEF, and an asthma control score. There was a significant improvement after oral prednisolone compared with placebo in FEV1, ml (mean difference, 237; 95% confidence intervals, 43, 231; p = 0.019), morning PEF L/m (mean difference, 36.8; 95% confidence intervals (CI), 11, 62; p = 0.006), and asthma control score (mean difference, −0.72; 95% CI, −1.2, −0.3; p = 0.004) in never-smokers with asthma but no change in smokers with asthma (mean differences of 47, 6.5, and −0.05 with p values of 0.6...
TL;DR: It is demonstrated here that c- myc binds to TFIIIB, a pol III-specific general transcription factor, and directly activates pol III transcription, suggesting that activation of pol III may have a role in the ability of c-Myc to stimulate cell growth.
Abstract: The proto-oncogene product c-Myc has a direct role in both metazoan cell growth and division. RNA polymerase III (pol III) is involved in the generation of transfer RNA and 5S ribosomal RNA, and these molecules must be produced in bulk to meet the need for protein synthesis in growing cells. We demonstrate here that c-Myc binds to TFIIIB, a pol III-specific general transcription factor, and directly activates pol III transcription. Chromatin immunoprecipitation reveals that endogenous c-Myc is present at tRNA and 5S rRNA genes in cultured mammalian cells. These results suggest that activation of pol III may have a role in the ability of c-Myc to stimulate cell growth.
TL;DR: It is suggested that certain environmental circumstances may favour a 'grow fast and die young' strategy if this increases overall reproductive success, and a number of experimental approaches are suggested that might allow the true relationships between growth rate and future performance to be elucidated.
TL;DR: Most somatostatin‐ and enkephalin‐containing boutons found in the dorsal horn of the mid‐lumbar spinal cord of the rat formed synapses at which AMPA receptors were present, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic.
Abstract: Two vesicular glutamate transporters, VGLUT1 and VGLUT2, have recently been identified, and it has been reported that they are expressed by largely nonoverlapping populations of glutamatergic neurons in the brain. We have used immunocytochemistry with antibodies against both transporters, together with markers for various populations of spinal neurons, in an attempt to identify glutamatergic interneurons in the dorsal horn of the mid-lumbar spinal cord of the rat. The great majority (94-100%) of nonprimary axonal boutons that contained somatostatin, substance P or neurotensin, as well as 85% of those that contained enkephalin, were VGLUT2-immunoreactive, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic. In support of this, we found that most somatostatin- and enkephalin-containing boutons (including somatostatin-immunoreactive boutons that lacked calcitonin gene-related peptide and were therefore probably derived from local interneurons) formed synapses at which AMPA receptors were present. We also investigated VGLUT expression in central terminals of primary afferents. Myelinated afferents were identified with cholera toxin B subunit; most of those in lamina I were VGLUT2-immunoreactive, whereas all those in deeper laminae were VGLUT1-immunoreactive, and some (in laminae III-VI) appeared to contain both transporters. However, peptidergic primary afferents that contained substance P or somatostatin (most of which are unmyelinated), as well as nonpeptidergic C fibres (identified with Bandeiraea simplicifolia isolectin B4) showed low levels of VGLUT2-immunoreactivity, or were not immunoreactive with either VGLUT antibody. As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter.
TL;DR: In this article, a computer-based version of the self-report Strengths and Difficulties Questionnaire (SDQ) was developed with colourful graphics illustrating each question.
Abstract: A computer-based version of the self-report Strengths and Difficulties Questionnaire (SDQ) was developed with colourful graphics illustrating each question. One hundred and two children referred to child and adolescent mental health services were recruited and randomly allocated to complete either the new computer-based version or the paper original. A further 112 children from local schools were recruited and completed the computer-based version of the scale. All children who took part in the study were aged between 8 and 15 years. The paper version of the SDQ is recommended for use in children aged 11 and over and, in this age group, the computer-based questionnaire was able to discriminate between the clinical and community sample (ROC = 0.761, 95 % CI 0.676-0.846). Comparison of the paper-based SDQ and computer-based SDQ within the clinic sample found trends towards better test-retest reliability, inter-rater reliability and significantly better user satisfaction in the computer version compared to the paper-based version. The computer-based SDQ has the added advantage of results being automatically added to a spreadsheet out of view from the user reducing the chance of operator error in coding and entering the data. These preliminary results suggest that the computer-based version of the SDQ may represent a further improvement on the paper SDQ. All versions of the SDQ, including the computer-based version, can be downloaded from the Strengths and Difficulties website address www.sdqinfo.com.
TL;DR: Polymorphism in p53 may influence individual responsiveness to cancer therapy, and clinical response following cisplatin-based chemo-radiotherapy for advanced head and neck cancer is influenced by this polymorphism, cancers expressing 72R mutants having lower response rates than those expressing 72P mutants.