Showing papers by "University of Southampton published in 2007"
TL;DR: The use of nanoscale disorder is demonstrated to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements, which has implications for cell therapies.
Abstract: A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.
2,249 citations
TL;DR: In this paper, a developmental model of the origins of coronary heart disease was proposed and confirmed in longitudinal studies of men and women around the world, showing that undernutrition in utero permanently changes the body's structure, function and metabolism in ways that lead to heart disease in later life.
Abstract: Current orthodoxy states that coronary heart disease results from the unhealthy lifestyles of westernized adults together with a contribution from genetic inheritance. This does not provide a secure basis for prevention of the disease. Geographical studies gave the first clue that the disease originates during intra-uterine development. Variations in mortality from the disease across England and Wales were shown to correlate closely with past differences in death rates among newborn babies. In the past most deaths among newborns were attributed to low birthweight. This led to the hypothesis that undernutrition in utero permanently changes the body's structure, function and metabolism in ways that lead to coronary heart disease in later life. The association between low birthweight and coronary heart disease has been confirmed in longitudinal studies of men and women around the world. The developmental model of the origins of the disease offers a new way forward.
2,104 citations
TL;DR: Stent thrombosis after 1 year was more common with both sirolimus-eluting stents and paclitaxel-eluted stents than with bare-metal stents, and both drug-elution stents were associated with a marked reduction in target-lesion revascularization.
Abstract: A b s t r ac t Results The 4-year rates of stent thrombosis were 1.2% in the sirolimus-stent group versus 0.6% in the bare-metal-stent group (P = 0.20) and 1.3% in the paclitaxel-stent group versus 0.9% in the bare-metal-stent group (P = 0.30). However, after 1 year, there were five episodes of stent thrombosis in patients with sirolimus-eluting stents versus none in patients with bare-metal stents (P = 0.025) and nine episodes in patients with paclitaxel-eluting stents versus two in patients with bare-metal stents (P = 0.028). The 4-year rates of target-lesion revascularization were markedly reduced in both the sirolimus-stent group and the paclitaxel-stent group, as compared with the bare-metal-stent groups. The rates of death or myocardial infarction did not differ significantly between the groups with drug-eluting stents and those with bare-metal stents. Conclusions Stent thrombosis after 1 year was more common with both sirolimus-eluting stents and paclitaxel-eluting stents than with bare-metal stents. Both drug-eluting stents were associated with a marked reduction in target-lesion revascularization. There were no significant differences in the cumulative rates of death or myocardial infarction at 4 years.
1,668 citations
TL;DR: These guidelines (epic3) provide comprehensive recommendations for preventing HCAI in hospital and other acute care settings based on the best currently available evidence, and the synopses of evidence underpinning the guideline recommendations have been updated.
1,381 citations
TL;DR: In this paper, the authors presented a small (component volume 1 cm3, practical volume 1 5 cm3) electromagnetic generator utilizing discrete components and optimized for a low ambient vibration level based upon real application data.
Abstract: Vibration energy harvesting is receiving a considerable amount of interest as a means for powering wireless sensor nodes This paper presents a small (component volume 01 cm3, practical volume 015 cm3) electromagnetic generator utilizing discrete components and optimized for a low ambient vibration level based upon real application data The generator uses four magnets arranged on an etched cantilever with a wound coil located within the moving magnetic field Magnet size and coil properties were optimized, with the final device producing 46 µW in a resistive load of 4 k? from just 059 m s-2 acceleration levels at its resonant frequency of 52 Hz A voltage of 428 mVrms was obtained from the generator with a 2300 turn coil which has proved sufficient for subsequent rectification and voltage step-up circuitry The generator delivers 30% of the power supplied from the environment to useful electrical power in the load This generator compares very favourably with other demonstrated examples in the literature, both in terms of normalized power density and efficiency
1,313 citations
TL;DR: It is reported that a resonance response with a very high quality factor can be achieved in a planar metamaterial by introducing symmetry breaking in the shape of its structural elements, which enables excitation of trapped modes, i.e., modes that are weakly coupled to free space.
Abstract: We report that a resonance response with a very high quality factor can be achieved in a planar metamaterial by introducing symmetry breaking in the shape of its structural elements, which enables excitation of trapped modes, i.e., modes that are weakly coupled to free space.
1,066 citations
TL;DR: In this paper, the authors compared the estimated oral intake with a threshold of toxicological concern derived from chronic oral toxicity data for structurally-related compounds, and showed that the oral TTC values are valid for topical exposures and that relationship between the external topical dose and the internal dose can be taken into account by conservative default adjustment factors.
1,054 citations
TL;DR: Evidence is reviewed to support the hypothesis that in chronic neurodegenerative diseases such as Alzheimer's disease, with an ongoing innate immune response in the brain, systemic infections and inflammation can cause acute exacerbations of symptoms and drive the progression of neurodegenersation.
Abstract: It is well known that systemic infections cause flare-ups of disease in individuals with asthma and rheumatoid arthritis, and that relapses in multiple sclerosis can often be associated with upper respiratory-tract infections. Here we review evidence to support our hypothesis that in chronic neurodegenerative diseases such as Alzheimer's disease, with an ongoing innate immune response in the brain, systemic infections and inflammation can cause acute exacerbations of symptoms and drive the progression of neurodegeneration.
905 citations
TL;DR: Artificial colours or a sodium benzoate preservative in the diet result in increased hyperactivity in 3- year-old and 8/9-year-old children in the general population.
875 citations
TL;DR: It is proposed that the DOHaD phenomenon can be considered as a subset of the broader processes of developmental plasticity by which organisms adapt to their environment during their life course, allowing genotypic variation to be preserved through transient environmental changes.
Abstract: Biomedical science has little considered the relevance of life history theory and evolutionary and ecological developmental biology to clinical medicine. However, the observations that early life influences can alter later disease risk--the "developmental origins of health and disease" (DOHaD) paradigm--have led to a recognition that these perspectives can inform our understanding of human biology. We propose that the DOHaD phenomenon can be considered as a subset of the broader processes of developmental plasticity by which organisms adapt to their environment during their life course. Such adaptive processes allow genotypic variation to be preserved through transient environmental changes. Cues for plasticity operate particularly during early development; they may affect a single organ or system, but generally they induce integrated adjustments in the mature phenotype, a process underpinned by epigenetic mechanisms and influenced by prediction of the mature environment. In mammals, an adverse intrauterine environment results in an integrated suite of responses, suggesting the involvement of a few key regulatory genes, that resets the developmental trajectory in expectation of poor postnatal conditions. Mismatch between the anticipated and the actual mature environment exposes the organism to risk of adverse consequences-the greater the mismatch, the greater the risk. For humans, prediction is inaccurate for many individuals because of changes in the postnatal environment toward energy-dense nutrition and low energy expenditure, contributing to the epidemic of chronic noncommunicable disease. This view of human disease from the perspectives of life history biology and evolutionary theory offers new approaches to prevention, diagnosis and intervention.
869 citations
TL;DR: Angular and spectrally resolved luminescence show that the polariton emission is beamed in the normal direction with an angular width of +/-5 degrees and spatial size around 5 microm.
Abstract: We observe a room-temperature low-threshold transition to a coherent polariton state in bulk GaN microcavities in the strong-coupling regime. Nonresonant pulsed optical pumping produces rapid thermalization and yields a clear emission threshold of 1 mW, corresponding to an absorbed energy density of 29 mu J cm(-2), 1 order of magnitude smaller than the best optically pumped (In,Ga)N quantum-well surface-emitting lasers (VCSELs). Angular and spectrally resolved luminescence show that the polariton emission is beamed in the normal direction with an angular width of +/- 5 degrees and spatial size around 5 mu m.
TL;DR: The Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS) was released in 2005 June and represents the completion of the SDSS-I project as mentioned in this paper, which includes five-band photometric data for 217 million objects selected over 8000 deg 2 and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 deg 2 of imaging data.
Abstract: This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through 2005 June and represents the completion of the SDSS-I project (whose successor, SDSS-II, will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 deg^2 and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 deg^2 of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus Cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.
TL;DR: This paper demonstrates the application of correlated Gaussian process based approximations to optimization where multiple levels of analysis are available, using an extension to the geostatistical method of co-kriging.
Abstract: This paper demonstrates the application of correlated Gaussian process based approximations to optimization where multiple levels of analysis are available, using an extension to the geostatistical method of co-kriging. An exchange algorithm is used to choose which points of the search space to sample within each level of analysis. The derivation of the co-kriging equations is presented in an intuitive manner, along with a new variance estimator to account for varying degrees of computational ‘noise’ in the multiple levels of analysis. A multi-fidelity wing optimization is used to demonstrate the methodology.
TL;DR: An alternative hypothesis is reviewed: that spontaneous patterns of very low frequency (<0.1 Hz) coherence within a specific brain network thought to support a pattern of generalized task-non-specific cognition during rest, can persist or intrude into periods of active task-specific processing, producing periodic fluctuations in attention that compete with goal-directed activity.
TL;DR: No evidence is available on symptom prevalence in ESRD patients managed conservatively (without dialysis), but evidence in patients discontinuing dialysis suggests they too have significant symptom burden.
TL;DR: It is explained how special structure of the weight matrix and the data matrix can be exploited for efficient cost function and first derivative computation that allows to obtain computationally efficient solution methods.
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16 Apr 2007
TL;DR: Benjamins et al. as mentioned in this paper reviewed the Marine Megafauna Interactions with Tidal Stream Environments and found that scale-dependent patterns emerge from very complex effects. But they did not consider the effect of the number of seabirds in the British Isles.
Abstract: Confusion Reigns? A Review of Marine Megafauna Interactions with Tidal-Stream Environments Steven Benjamins, Andrew C. Dale, Gordon Hastie, James J. Waggitt, Mary-Anne Lea, Beth Scott & Ben Wilson Climate-Driven Trophic Cascades Affecting Seabirds around the British Isles Alan MacDonald, Michael R. Heath, Martin Edwards, Robert W. Furness, John K. Pinnegar, Sarah Wanless, Douglas C. Speirs & Simon P.R. Greenstreet Circumglobal Invasion by the Brown Seaweed Sargassum muticum Aschwin H. Engelen, Alexandra Serebryakova, Put Ang, Kevin Britton-Simmons, Frederic Mineur, Morten F. Pedersen, Francisco Arenas, Consolacion Fernandez, Henning Steen, Robin Svenson, Henrik Pavia, Gunilla Toth, Frederique Viard & Rui Santos Simple, Scale-Dependent Patterns Emerge from Very Complex Effects-An Example from the Intertidal Mussels Mytilus galloprovincialis and Perna perna Christopher D. McQuaid, Francesca Porri, Katy R. Nicastro & Gerardo I. Zardi The Contribution of the Genus Littorina to the Field of Evolutionary Ecology Emilio Rolan-Alvarez, Christopher J. Austin & Elizabeth G. Boulding Spatial, Temporal and Taxonomic Variation in Coral Growth-Implications for the Structure and Function of Coral Reef Ecosystems Morgan S. Pratchett, Kristen D. Anderson, Mia O. Hoogenboom, Elizabeth Widman, Andrew H. Baird, John M. Pandolfi, Peter J. Edmunds & Janice M. Lough
TL;DR: It is shown how immune privilege is far from absolute, and how it varies with age and brain region, as a result of the immunoregulatory characteristics of the CNS-resident cells and their microenvironment.
TL;DR: The ELF panel has good diagnostic accuracy in an independent validation cohort of patients with NAFLD and the addition of established simple markers augments the diagnostic performance across different stages of fibrosis, which will potentially allow superior stratification of patients for emerging therapeutic strategies.
TL;DR: In this paper, the authors trace these discourses and perspectives as a backdrop to under-standings of the nature of enterprise and the entrepreneur in the 20th century and present them as a basis for the present article.
Abstract: Throughout the 20th century multiple discourses of the nature of enterprise and the entrepreneur have developed. In this article, we trace these discourses and perspectives as a backdrop to underst...
TL;DR: In this paper, the results of cavitation tunnel and tank tests on an 800 mm diameter model of a marine current turbine (MCT) were presented, and the results provided useful information for the hydrodynamic design of MCTs and detailed data for the validation of numerical models.
TL;DR: In this article, a plasmon-polariton state can be formed at the boundary between a metal and a dielectric Bragg mirror that can have a zero in-plane wave vector and therefore can be produced by direct optical excitation.
Abstract: Conventional surface plasmons have a wave vector exceeding that of light in vacuum, and therefore cannot be directly excited by light that is simply incident on the surface. However, we propose that a plasmon-polariton state can be formed at the boundary between a metal and a dielectric Bragg mirror that can have a zero in-plane wave vector and therefore can be produced by direct optical excitation. In analogy with the electronic states at a crystal surface proposed by Tamm, we call these excitations Tamm plasmons, and predict that they may exist in both the TE and TM polarizations and are characterized by parabolic dispersion relations.
TL;DR: The data demonstrate that electrospun fibers composed of a collagen and PCL blend represent a suitable substrate for supporting cell proliferation, process outgrowth and migration and as such would be a good material for artificial nerve implants.
TL;DR: High specificity estimates suggest that NAAT tests should be the first-line test for ruling in TB meningitis, but that they need to be combined with the result of other tests in order to rule out disease.
Abstract: Objectives To evaluate the effectiveness of available rapid diagnostic tests to identify tuberculosis (TB) infection. Data sources Electronic databases were searched from 1975 to August 2003 for tests for active TB and to March 2004 for tests for latent tuberculosis infection (LTBI). Review methods Studies were selected and evaluated that (1) tested for LTBI, (2) compared tuberculin skin test (TST) and interferon-gamma assays based on ESAT-6 and CFP-10 antigens and (3) provided information on TB exposure or bacille Calmette-Guerin (BCG) vaccination or HIV status. For each test comparison, the sensitivity, specificity and 95% confidence intervals (CIs) were calculated. Sources of heterogeneity were investigated by adding covariates to the standard regression model. The authors examined whether interferon-gamma assays were more strongly associated with high versus low TB exposure than TST. Odds ratios (ORs) were calculated for the association between test results and exposures from each study along with their 95% CIs. Within each study, the OR value for one test was divided by that for another to produce a ratio of OR (ROR). Results A total of 212 studies were included, providing 368 data sets. A further 19 studies assessing fully automated liquid culture were included. Overall, nucleic acid amplification test (NAAT) accuracy was far superior when applied to respiratory samples as opposed to other body fluids. The better quality in-house studies, were, for pulmonary TB, much better at ruling out TB than the commercial tests (higher sensitivity), but were less good at ruling it in (lower specificity), but it is not possible to recommend any one over another owing to a lack of direct test comparisons. The specificity of NAAT tests was high when applied to body fluids, for example for TB meningitis and pleural TB, but sensitivity was poor, indicating that these tests cannot be used reliably to rule out TB. High specificity estimates suggest that NAAT tests should be the first-line test for ruling in TB meningitis, but that they need to be combined with the result of other tests in order to rule out disease. Evidence for NAAT tests in other forms of TB and for phage-based tests is significantly less prolific than for those above and further research is needed to establish accuracy. There is no evidence to support the use of adenosine deaminase (ADA) tests for diagnosis of pulmonary TB; however, there is considerable evidence to support their use for diagnosis of pleural TB and to a slightly lesser extent for TB meningitis. Anti-TB antibody test performance was universally poor, regardless of type of TB. Fully automated liquid culture methods were superior to culture on solid media, in terms of their speed and their precision. In total, 13 studies were included. Assays based on RD1 specific antigens, ESAT-6 or CFP-10, correlate better with intensity of exposure, and therefore are more likely than TST/purified protein derivative (PPD)-based assays to detect LTBI accurately. An additional advantage is that they are more likely to be independent of BCG vaccination status and HIV status. Conclusions The NAAT tests provide a reliable way of increasing the specificity of diagnosis (ruling in disease) but sensitivity is too poor to rule out disease, especially in smear-negative (paucibacillary) disease where clinical diagnosis is equivocal and where the clinical need is greatest. For extra-pulmonary TB, clinical judgement has both poor sensitivity and specificity. For pleural TB and TB meningitis, adenosine deaminase tests have high sensitivity but limited specificity. NAATs have high specificity and could be used alongside ADA (or interferon-gamma) to increase sensitivity for ruling out disease and NAAT for high specificity to rule it in. All studies from low-prevalence countries strongly suggest that the RD1 antigen-based assays are more accurate than TST- and PPD-based assays for diagnosis of LTBI. If their superior diagnostic capability is found to hold up in routine clinical practice, they could confer several advantages on TB control programmes. Further research for active TB needs to establish diagnostic accuracy in a wide spectrum of patients, against an appropriate reference test, and avoiding the major sources of bias. For LTBI, research needs to address different epidemiological and clinical settings, to evaluate the performance of the main existing commercial assays in head-to-head comparison in both developed and developing countries, and to assess the role of adding more TB-specific antigens to try to improve diagnostic sensitivity.
TL;DR: In this paper, the second-order viscous hydrodynamics in conformal field theories at finite temperature was considered and conformal invariance imposes powerful constraints on the form of second-orders corrections.
Abstract: We consider second-order viscous hydrodynamics in conformal field theories at finite temperature. We show that conformal invariance imposes powerful constraints on the form of the second-order corrections. By matching to the AdS/CFT calculations of correlators, and to recent results for Bjorken flow obtained by Heller and Janik, we find three (out of five) second-order transport coefficients in the strongly coupled N=4 supersymmetric Yang-Mills theory. We also discuss how these new coefficents can arise within the kinetic theory of weakly coupled conformal plasmas. We point out that the Mueller-Israel-Stewart theory, often used in numerical simulations, does not contain all allowed second-order terms and, frequently, terms required by conformal invariance.
TL;DR: Promising synergy has been observed in preclinical models using combinations of immunostimulatory antibodies and other immunotherapy strategies or conventional cancer therapies, and mAbs of this type have now entered clinical trials with encouraging initial results.
Abstract: Increasing immune responses with immunostimulatory monoclonal antibodies (mAbs) directed to immune-receptor molecules is a new and exciting strategy in cancer therapy. This expanding class of agents functions on crucial receptors, either antagonizing those that suppress immune responses or activating others that amplify immune responses. Complications such as autoimmunity and systemic inflammation are problematic side effects associated with these agents. However, promising synergy has been observed in preclinical models using combinations of immunostimulatory antibodies and other immunotherapy strategies or conventional cancer therapies. Importantly, mAbs of this type have now entered clinical trials with encouraging initial results.
TL;DR: In this article, a simple system comprising a vertical spring acting in parallel with two oblique springs is studied, and it is shown that there is a unique relationship between the geometry and the stiffness of the springs that yields a system with zero dynamic stiffness at the static equilibrium position.
TL;DR: The coordination and organometallic chemistry of linear, rigid, tridentate ligands, which incorporate at least one N-heterocyclic carbene and other "classical" donors, is reviewed in this paper.
TL;DR: Hypomethylation of the GR110 promoter may result from lower capacity to methylate hemimethylated DNA during mitosis, and hence metabolic phenotype, may be due to reduced Dnmt1 expression.
Abstract: Prenatal nutritional constraint induces an altered metabolic phenotype in the offspring which in humans confers an increased risk of non-communicable disease. Feeding a protein-restricted (PR) diet to pregnant rats causes hypomethylation of specific gene promoters in the offspring and alters the phenotype. We investigated how altered epigenetic regulation of the hepatic glucocorticoid receptor (GR) 110 promoter is induced in the offspring. Rats were fed a control (180 g casein/kg) or a PR (90 g casein/kg) diet throughout pregnancy, and chow during lactation. Offspring were killed at postnatal day 34 (n 5 per maternal dietary group). Methylation-sensitive PCR showed that GR110 promoter methylation was 33 % lower (P < 0·001) and GR expression 84 % higher (P < 0·05) in the PR offspring. Reverse transcription–PCR showed that DNA methyltransferase-1 (Dnmt1) expression was 17 % lower (P < 0·05) in PR offspring, while Dnmt3a/b and methyl binding domain protein-2 expression was not altered. Thus hypomethylation of the GR110 promoter may result from lower capacity to methylate hemimethylated DNA during mitosis. Histone modifications which facilitate transcription were increased at the GR110 promoter (147–921 %, P < 0·001), while those that suppress methylation were decreased (54 %, P < 0·01) or similar to controls. In human umbilical cord (n 15), there was a 2-fold difference between the highest and lowest level of GR1-CTotal promoter methylation. Dnmt1, but not Dnmt3a, expression predicted 49 % (P = 0·003) of the variation in GR1-CTotal promoter methylation. These findings suggest that induction in the offspring of altered epigenetic regulation of the hepatic GR110 promoter, and hence metabolic phenotype, may be due to reduced Dnmt1 expression.
TL;DR: The Short FES-I is a good and feasible measure to assess fear of falling in older persons, however, if researchers or clinicians are particularly interested in the distributions of specificFear of falling-related activities not included in the Short Fes-I, the use of the full FES -I is recommended.
Abstract: BACKGROUND: the 16-item Falls Efficacy Scale-International (FES-I) has been shown to have excellent reliability and construct validity. However, for practical and clinical purposes, a shortened version of the FES-I would be useful. OBJECTIVE: to develop and validate a shortened version of FES-I while preserving good psychometric properties. DESIGN: initial development of a shortened version using data from a UK survey (Short FES-I; n = 704), test of reliability and validity of the Short FES-I using data from a Dutch survey (n = 300). SETTING: community samples. METHODS: comparison of reliability and validity of the Short FES-I and the FES-I in a random sample of 193 people aged between 70 and 92. RESULTS: the internal and 4-week test-retest reliability of the Short FES-I is excellent (Cronbach's alpha 0.92, intra-class coefficient 0.83) and comparable to the FES-I. The correlation between the Short FES-I and the FES-I is 0.97. Patterns in differences with respect to mean scores according to age, sex, falls history, and overall fear of falling are similar for the Short FES-I and the FES-I. The FES-I had slightly better power to discriminate between groups differentiated by age, sex, falls history, and fear falling, but differences are small. CONCLUSIONS: the Short FES-I is a good and feasible measure to assess fear of falling in older persons. However, if researchers or clinicians are particularly interested in the distributions of specific fear of falling-related activities not included in the Short FES-I, the use of the full FES-I is recommended. Language: en