399 research outputs found

    Spacelike Singularities and Hidden Symmetries of Gravity

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    We review the intimate connection between (super-)gravity close to a spacelike singularity (the "BKL-limit") and the theory of Lorentzian Kac-Moody algebras. We show that in this limit the gravitational theory can be reformulated in terms of billiard motion in a region of hyperbolic space, revealing that the dynamics is completely determined by a (possibly infinite) sequence of reflections, which are elements of a Lorentzian Coxeter group. Such Coxeter groups are the Weyl groups of infinite-dimensional Kac-Moody algebras, suggesting that these algebras yield symmetries of gravitational theories. Our presentation is aimed to be a self-contained and comprehensive treatment of the subject, with all the relevant mathematical background material introduced and explained in detail. We also review attempts at making the infinite-dimensional symmetries manifest, through the construction of a geodesic sigma model based on a Lorentzian Kac-Moody algebra. An explicit example is provided for the case of the hyperbolic algebra E10, which is conjectured to be an underlying symmetry of M-theory. Illustrations of this conjecture are also discussed in the context of cosmological solutions to eleven-dimensional supergravity.Comment: 228 pages. Typos corrected. References added. Subject index added. Published versio

    Extreme rainfall events alter the trophic structure in bromeliad tanks across the Neotropics

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    Changes in global and regional precipitation regimes are among the most pervasive components of climate change. Intensification of rainfall cycles, ranging from frequent downpours to severe droughts, could cause widespread, but largely unknown, alterations to trophic structure and ecosystem function. We conducted multi-site coordinated experiments to show how variation in the quantity and evenness of rainfall modulates trophic structure in 210 natural freshwater microcosms (tank bromeliads) across Central and South America (18°N to 29°S). The biomass of smaller organisms (detritivores) was higher under more stable hydrological conditions. Conversely, the biomass of predators was highest when rainfall was uneven, resulting in top-heavy biomass pyramids. These results illustrate how extremes of precipitation, resulting in localized droughts or flooding, can erode the base of freshwater food webs, with negative implications for the stability of trophic dynamics

    ArteFill® Permanent Injectable for Soft Tissue Augmentation: II. Indications and Applications

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    Patients ask for procedures with long-lasting effects. ArteFill is the first permanent injectable approved in 2006 by the FDA for nasolabial folds. It consists of cleaned microspheres of polymethylmethacrylate (PMMA) suspended in bovine collagen. Over the development period of 20 years most of its side effects have been eliminated to achieve the same safety standard as today’s hyaluronic acid products. A 5-year follow-up study in U.S. clinical trial patients has shown the same wrinkle improvement as seen at 6 months. Long-term follow-up in European Artecoll patients has shown successful wrinkle correction lasting up to 15 years. A wide variety of off-label indications and applications have been developed that help the physician meet the individual needs of his/her patients. Serious complications after ArteFill injections, such as granuloma formation, have not been reported due to the reduction of PMMA microspheres smaller than 20 μm to less than 1% “by the number.” Minor technique-related side effects, however, may occur during the initial learning curve. Patient and physician satisfaction with ArteFill has been shown to be greater than 90%

    Assessment of ePrescription quality: an observational study at three mail-order pharmacies

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    <p>Abstract</p> <p>Background</p> <p>The introduction of electronic transfer of prescriptions (ETP) or ePrescriptions in ambulatory health care has been suggested to have a positive impact on the prescribing and dispensing processes. Thereby, implying that ePrescribing can improve safety, quality, efficiency, and cost-effectiveness. In December 2007, 68% of all new prescriptions were transferred electronically in Sweden. The aim of the present study was to assess the quality of ePrescriptions by comparing the proportions of ePrescriptions and non-electronic prescriptions necessitating a clarification contact (correction, completion or change) with the prescriber at the time of dispensing.</p> <p>Methods</p> <p>A direct observational study was performed at three Swedish mail-order pharmacies which were known to dispense a large proportion of ePrescriptions (38–75%). Data were gathered on all ePrescriptions dispensed at these pharmacies over a three week period in February 2006. All clarification contacts with prescribers were included in the study and were classified and assessed in comparison with all drug prescriptions dispensed at the same pharmacies over the specified period.</p> <p>Results</p> <p>Of the 31225 prescriptions dispensed during the study period, clarification contacts were made for 2.0% (147/7532) of new ePrescriptions and 1.2% (79/6833) of new non-electronic prescriptions. This represented a relative risk (RR) of 1.7 (95% CI 1.3–2.2) for new ePrescriptions compared to new non-electronic prescriptions. The increased RR was mainly due to 'Dosage and directions for use', which had an RR of 7.6 (95% CI 2.8–20.4) when compared to other clarification contacts. In all, 89.5% of the suggested pharmacist interventions were accepted by the prescriber, 77.7% (192/247) as suggested and an additional 11.7% (29/247) after a modification during contact with the prescriber.</p> <p>Conclusion</p> <p>The increased proportion of prescriptions necessitating a clarification contact for new ePrescriptions compared to new non-electronic prescriptions indicates the need for an increased focus on quality aspects in ePrescribing deployment. ETP technology should be developed towards a two-way communication between the prescriber and the pharmacist with automated checks of missing, inaccurate, or ambiguous information. This would enhance safety and quality for the patient and also improve efficiency and cost-effectiveness within the health care system.</p

    Inhalation of β2 agonists impairs the clearance of nontypable Haemophilus influenzae from the murine respiratory tract

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    BACKGROUND: Nontypable Haemophilus influenzae (NTHi) is a common bacterial pathogen causing human respiratory tract infections under permissive conditions such as chronic obstructive pulmonary disease. Inhalation of β2-receptor agonists is a widely used treatment in patients with chronic obstructive pulmonary disease. The aim of this study was to determine the effect of inhalation of β2 agonists on the host immune response to respiratory tract infection with NTHi. METHODS: Mouse alveolar macrophages were stimulated in vitro with NTHi in the presence or absence of the β2 receptor agonists salmeterol or salbutamol. In addition, mice received salmeterol or salbutamol by inhalation and were intranasally infected with NTHi. End points were pulmonary inflammation and bacterial loads. RESULTS: Both salmeterol and salbutamol inhibited NTHi induced tumor necrosis factor-α (TNFα) release by mouse alveolar macrophages in vitro by a β receptor dependent mechanism. In line, inhalation of either salmeterol or salbutamol was associated with a reduced early TNFα production in lungs of mice infected intranasally with NTHi, an effect that was reversed by concurrent treatment with the β blocker propranolol. The clearance of NTHi from the lungs was impaired in mice treated with salmeterol or salbutamol, an adverse effect that was prevented by propranolol and independent of the reduction in TNFα. CONCLUSION: These data suggest that inhalation of salmeterol or salbutamol may negatively influence an effective clearance of NTHi from the airways

    Improving behaviour in self-testing (IBIS): Study on frequency of use, consequences, information needs and use, and quality of currently available consumer information (protocol)

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    <p>Abstract</p> <p>Background</p> <p>Self-tests are available to consumers for more than 25 conditions, ranging from infectious diseases to cardiovascular risk factors. Self-tests are defined as in-vitro tests on body materials such as blood, urine, faeces, or saliva that are initiated by consumers to diagnose a particular disorder or risk factor without involving a medical professional. In 2006, 16% of a sample of Dutch Internet users had ever used at least one self-test and 17% intended to use a self-test in the future. The objectives of this study are to determine (1) the frequency of self-test use, (2) the consumers' reasons for using or not using a self-test, (3) the information that is used by self-testers in the different self-test stages and the consumers' interpretation of the quality of this information, (4) the consumers' response to self-test results in terms of their confidence in the result, reassurance by the test result, and follow-up behaviour, (5) the information consumers report to need in the decision making process of using or not using a self-test, and in further management on the basis of the self-test result, and (6) the quality of the currently available consumer information on a selected set of self-tests.</p> <p>Methods</p> <p>Mixed methods study with (1) a cross-sectional study consisting of a two-phase Internet-questionnaire, (2) semi-structured interviews with self-testers and consumers who intend to use a self-test, and (3) the assessment of the quality of consumer information of self-tests. The Health Belief Model and the Theory of Planned Behaviour will serve as the theoretical basis for the questionnaires and the interview topic guides.</p> <p>Conclusions</p> <p>The self-testing area is still in a state of flux and therefore it is expected that self-test use will increase in the future. To the best of our knowledge, this is the first study which combines quantitative and qualitative research to identify consumers' information needs and use concerning self-testing, and the consumers' actual follow-up behaviour based on the self-test result, and simultaneously investigates the quality of the currently available consumer information. The results of this study will be used as an input in developing consumer information on self-testing.</p

    Bias and Evolution of the Mutationally Accessible Phenotypic Space in a Developmental System

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    Genetic and developmental architecture may bias the mutationally available phenotypic spectrum. Although such asymmetries in the introduction of variation may influence possible evolutionary trajectories, we lack quantitative characterization of biases in mutationally inducible phenotypic variation, their genotype-dependence, and their underlying molecular and developmental causes. Here we quantify the mutationally accessible phenotypic spectrum of the vulval developmental system using mutation accumulation (MA) lines derived from four wild isolates of the nematodes Caenorhabditis elegans and C. briggsae. The results confirm that on average, spontaneous mutations degrade developmental precision, with MA lines showing a low, yet consistently increased, proportion of developmental defects and variants. This result indicates strong purifying selection acting to maintain an invariant vulval phenotype. Both developmental system and genotype significantly bias the spectrum of mutationally inducible phenotypic variants. First, irrespective of genotype, there is a developmental bias, such that certain phenotypic variants are commonly induced by MA, while others are very rarely or never induced. Second, we found that both the degree and spectrum of mutationally accessible phenotypic variation are genotype-dependent. Overall, C. briggsae MA lines exhibited a two-fold higher decline in precision than the C. elegans MA lines. Moreover, the propensity to generate specific developmental variants depended on the genetic background. We show that such genotype-specific developmental biases are likely due to cryptic quantitative variation in activities of underlying molecular cascades. This analysis allowed us to identify the mutationally most sensitive elements of the vulval developmental system, which may indicate axes of potential evolutionary variation. Consistent with this scenario, we found that evolutionary trends in the vulval system concern the phenotypic characters that are most easily affected by mutation. This study provides an empirical assessment of developmental bias and the evolution of mutationally accessible phenotypes and supports the notion that such bias may influence the directions of evolutionary change
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