995 resultados para Graham, James, Sir, 1792-1861


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Includes bibliographical references and index.

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Diabetic peripheral neuropathy (DPN) is one of the most common long-term complications of diabetes. The accurate detection and quantification of DPN are important for defining at-risk patients, anticipating deterioration, and assessing new therapies. Current methods of detecting and quantifying DPN, such as neurophysiology, lack sensitivity, require expert assessment and focus primarily on large nerve fibers. However, the earliest damage to nerve fibers in diabetic neuropathy is to the small nerve fibers. At present, small nerve fiber damage is currently assessed using skin/nerve biopsy; both are invasive technique and are not suitable for repeated investigations.

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This paper develops an improved and accessible framework for modelling time-dependent behaviour of soils using the concepts of elasticity and viscoplasticity. The mathematical description of viscoplastic straining is formulated based on a purely viscoplastic and measurable phenomenon, namely creep. The resulting expression for the viscoplastic strain rates includes a measure of both effective stress and the corresponding volumetric packing of the soil particles. In this way, the model differs from some earlier viscoplastic models and arguably provides a better conceptual description of time-dependent behaviour. Analytical solutions are developed for the simulation of drained and undrained strain-controlled triaxial compression tests. The model is then used to back-analyze the measured response of normally consolidated to moderately overconsolidated specimens of a soft estuarine soil in undrained triaxial compression. The model captures aspects of soil behaviour that cannot be simulated using time-independent elastic–plastic models. Specifically, it can capture the dependence of stress–strain relationships and undrained shear strength on strain rate, the development of irrecoverable plastic strains at constant stress (creep), and the relaxation of stresses at constant strain

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A new elastic–viscoplastic (EVP) soil model has been used to simulate the measured deformation response of a soft estuarine soil loaded by a stage-constructed embankment. The simulation incorporates prefabricated vertical drains installed in the foundation soils and reinforcement installed at the base of the embankment. The numerical simulations closely matched the temporal changes in surface settlement beneath the centerline and shoulder of the embankment. More importantly, the elastic–viscoplastic model simulated the pattern and magnitudes of the lateral deformations beneath the toe of the embankment — a notoriously difficult aspect of modelling the deformation response of soft soils. Simulation of the excess pore-water pressure proved more difficult because of the heterogeneous nature of the estuarine deposit. Excess pore-water pressures were, however, mapped reasonably well at three of the six monitoring locations. The simulations were achieved using a small set of material constants that can easily be obtained from standard laboratory tests. This study validates the use of the EVP model for problems involving soft soil deposits beneath loading from a geotechnical structure.

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Purpose: Antiangiogenic therapies can be an important adjunct to the management of many malignancies. Here we investigated a novel protein, FKBPL, and peptide derivative for their antiangiogenic activity and mechanism of action.

Experimental Design: Recombinant FKBPL (rFKBPL) and its peptide derivative were assessed in a range of human microvascular endothelial cell (HMEC-1) assays in vitro. Their ability to inhibit proliferation, migration, and Matrigel-dependent tubule formation was determined. They were further evaluated in an ex vivo rat model of neovascularization and in two in vivo mouse models of angiogenesis, that is, the sponge implantation and the intravital microscopy models. Antitumor efficacy was determined in two human tumor xenograft models grown in severe compromised immunodeficient (SCID) mice. Finally, the dependence of peptide on CD44 was determined using a CD44-targeted siRNA approach or in cell lines of differing CD44 status.

Results: rFKBPL inhibited endothelial cell migration, tubule formation, and microvessel formation in vitro and in vivo. The region responsible for FKBPL's antiangiogenic activity was identified, and a 24-amino acid peptide (AD-01) spanning this sequence was synthesized. It was potently antiangiogenic and inhibited growth in two human tumor xenograft models (DU145 and MDA-231) when administered systemically, either on its own or in combination with docetaxel. The antiangiogenic activity of FKBPL and AD-01 was dependent on the cell-surface receptor CD44, and signaling downstream of this receptor promoted an antimigratory phenotype.

Conclusion: FKBPL and its peptide derivative AD-01 have potent antiangiogenic activity. Thus, these agents offer the potential of an attractive new approach to antiangiogenic therapy.

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Many factors have been studied as potential correlates in delayed HIV diagnosis and delayed linkage to HIV healthcare. Few studies have analyzed the association of trust as a correlate in HIV diagnosis and HIV medical treatment delays. This study sought to assess the effect of patient trust in physicians and trust in the healthcare system, and whether diminished levels of trust affect delays in HIV diagnosis and/or linking to HIV healthcare, among a cohort of newly diagnosed HIV-infected persons, in Harris County, Texas.^ This study is a secondary data analysis from the Attitude and Beliefs and the Steps of HIV Care Study, also known as the Steps Study, a prospective observational cohort study. From January 2006 to October 2007 patients newly diagnosed with HIV infection and not yet in HIV primary care were recruited from publically funded HIV testing sites in Houston, Texas.^ Two outcomes were assessed in this study. The first outcome sought to determine the influence of trust and whether decreased levels of trust predicted delays in HIV diagnosis. Trust in physicians and trust in the healthcare system were measured via 2 validated trust scales. Trust scores of those with late diagnosis (CD4 counts <200 cells/mm3) were compared statistically with those with early diagnosis (CD4 counts ≥ 200 cells/mm3) in a cross sectional study design. Trust was not found to be predictive of delays in HIV diagnosis. ^ The second outcome utilized the same trust scales and a prospective cohort study design to assess whether there were differences in trust scores between those who successfully linked to HIV healthcare, compared to those who failed to link to HIV healthcare, within 6 months of diagnosis. Patients with higher trust in physicians and trust in the healthcare system were significantly more likely to be linked to HIV healthcare than those with lower trust.^ Overall, this study showed that among low-income persons with undiagnosed HIV infection, low trust is not a barrier to timely diagnosis of HIV infection. Trust may be a factor in promoting a prompt linkage to HIV healthcare among those who are newly diagnosed.^

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pt.15 (1853) [Nomenclature of Diptera.I]

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First published under title: Ante-Nicene Christian library.