1,537 research outputs found

    Effect of human rotavirus vaccine on severe diarrhea in African infants.

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    BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. METHODS: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. RESULTS: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. CONCLUSIONS: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.

    A role for glycosaminoglycans in the development of collagen fibrils

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    AbstractExtensive data on the glycosaminoglycan (GAG) composition and the collagen fibril diameter distribution have been collected for a diverse range of connective tissues. It is shown that tissues with the smallest diameter collagen fibrils (mass-average diameter < 60 nm) have high concentrations of hyaluronic acid and that tissues with the largest diameter collagen fibrils (mass-average diameter ∌200 nm) have high concentrations of dermatan sulphate. It is suggested that the lateral growth of fibrils beyond a diameter of about 60 nm is inhibited by the presence of an excess of hyaluronic acid but that this inhibitory effect may be removed by an increasing concentration of chondroitin sulphate and/or dermatan sulphate. It is also postulated that high concentrations of chondroitin sulphate will inhibit fibril growth beyond a mass-average diameter of ∌150 nm. Such an inhibition may in turn be removed by an increasing concentration of dermatan sulphate such that it becomes the dominant GAG present in the tissue

    In vivo MRI-based simulation of fatigue process: a possible trigger for human carotid atherosclerotic plaque rupture.

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    BACKGROUND: Atherosclerotic plaque is subjected to a repetitive deformation due to arterial pulsatility during each cardiac cycle and damage may be accumulated over a time period causing fibrous cap (FC) fatigue, which may ultimately lead to rupture. In this study, we investigate the fatigue process in human carotid plaques using in vivo carotid magnetic resonance (MR) imaging. METHOD: Twenty seven patients with atherosclerotic carotid artery disease were included in this study. Multi-sequence, high-resolution MR imaging was performed to depict the plaque structure. Twenty patients were found with ruptured FC or ulceration and 7 without. Modified Paris law was used to govern crack propagation and the propagation direction was perpendicular to the maximum principal stress at the element node located at the vulnerable site. RESULTS: The predicted crack initiations from 20 patients with FC defect all matched with the locations of the in vivo observed FC defect. Crack length increased rapidly with numerical steps. The natural logarithm of fatigue life decreased linearly with the local FC thickness (R(2) = 0.67). Plaques (n=7) without FC defect had a longer fatigue life compared with those with FC defect (p = 0.03). CONCLUSION: Fatigue process seems to explain the development of cracks in FC, which ultimately lead to plaque rupture.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    MRI-based biomechanical parameters for carotid artery plaque vulnerability assessment.

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    Carotid atherosclerotic plaques are a major cause of ischaemic stroke. The biomechanical environment to which the arterial wall and plaque is subjected to plays an important role in the initiation, progression and rupture of carotid plaques. MRI is frequently used to characterize the morphology of a carotid plaque, but new developments in MRI enable more functional assessment of carotid plaques. In this review, MRI based biomechanical parameters are evaluated on their current status, clinical applicability, and future developments. Blood flow related biomechanical parameters, including endothelial wall shear stress and oscillatory shear index, have been shown to be related to plaque formation. Deriving these parameters directly from MRI flow measurements is feasible and has great potential for future carotid plaque development prediction. Blood pressure induced stresses in a plaque may exceed the tissue strength, potentially leading to plaque rupture. Multi-contrast MRI based stress calculations in combination with tissue strength assessment based on MRI inflammation imaging may provide a plaque stress-strength balance that can be used to assess the plaque rupture risk potential. Direct plaque strain analysis based on dynamic MRI is already able to identify local plaque displacement during the cardiac cycle. However, clinical evidence linking MRI strain to plaque vulnerability is still lacking. MRI based biomechanical parameters may lead to improved assessment of carotid plaque development and rupture risk. However, better MRI systems and faster sequences are required to improve the spatial and temporal resolution, as well as increase the image contrast and signal-to-noise ratio.This is the author accepted manuscript. The final version is available from Schattauer via http://dx.doi.org/10.1160/TH15-09-071

    Local blood pressure associates with the degree of luminal stenosis in patients with atherosclerotic disease in the middle cerebral artery.

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    The mechanism underlying atherosclerotic ischemic events within the middle cerebral artery (MCA) is unclear. High structural stress induced by blood pressure might be a potential aetiology as plaque rupture occurs when such mechanical loading exceeds its material strength. To perform reliable analyses quantifying the mechanical loading within a plaque, the local blood pressure is needed. However, data on MCA blood pressure is currently lacking. In this study, the arterial pressure proximal to the stenotic site in the MCA was measured in 15 patients scheduled for intervention. The relationships between these local measurements and pre-intervention and intra-intervention non-invasive arm measurements were assessed. The impact of luminal stenosis on the local blood pressure was quantified. Compared with the pre-intervention arm measurement, the intra-intervention arm pressure decreased significantly by 23.9 ± 11.8 and 9.3 ± 14.7 % at diastole and systole, respectively. The pressure proximal to the stenosis was much lower than the pre-intervention arm measurement (diastole: 65.3 ± 15.7 vs 82.0 ± 9.7, p < 0.01; systole: 81.1 ± 15.9 vs 133.9 ± 18.7, p < 0.01; unit: mmHg). The systolic pressure in the MCA in patients with stenosis <70 % (n = 6) was significantly higher than the value in patients with stenosis ≄70 % (n = 9) (92.0 ± 7.3 vs 73.9 ± 16.1, p = 0.02; unit: mmHg), as was pulse pressure (22.8 ± 6.4 vs 11.1 ± 8.3, p = 0.01; unit: mmHg). However, diastolic pressure remained unaffected (69.2 ± 9.3 vs 62.8 ± 19.0, p = 0.58; unit: mmHg). In conclusion, the obtained results are helpful in understanding the local hemodynamic environment modulated by the presence of atherosclerosis. The local pressure measurements can be used for computational analysis to quantify the critical mechanical condition within an MCA lesion.Emerging Frontier Technology Joint Research Program of Shanghai Municipal Hospital, China (Grant ID: SHDC12013110), National Natural Science Foundation of China (Grant ID: 31470910), National Institute for Health Research Cambridge Biomedical Research CentreThis is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12938-016-0202-

    Vanishing Preons in the Fifth Dimension

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    We examine supersymmetric solutions of N=2, D=5 gauged supergravity coupled to an arbitrary number of abelian vector multiplets using the spinorial geometry method. By making use of methods developed in hep-th/0606049 to analyse preons in type IIB supergravity, we show that there are no solutions preserving exactly 3/4 of the supersymmetry.Comment: 19 pages, latex. Reference added, and further modification to the introductio

    Solutions of Minimal Four Dimensional de Sitter Supergravity

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    Pseudo-supersymmetric solutions of minimal N=2N=2, D=4D=4 de Sitter supergravity are classified using spinorial geometry techniques. We find three classes of solutions. The first class of solution consists of geometries which are fibrations over a 3-dimensional manifold equipped with a Gauduchon-Tod structure. The second class of solution is the cosmological Majumdar-Papapetrou solution of Kastor and Traschen, and the third corresponds to gravitational waves propagating in the Nariai cosmology.Comment: 17 Pages. Minor correction to section 4; equation (4.21) corrected and (old) equation (4.26) deleted; the final result is unchange
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