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"Dyke, P. P. G"
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Modeling coastal and marine processes
\"Modeling is now an accepted part in the understanding, prediction and planning of environmental strategies. Perfect for undergraduate students and non-specialist readers, Modeling Coastal and Marine Processes (2nd Edition) offers an introduction into how coastal and marine models are constructed and used. The mathematics, statistics and numerical techniques used are explained in the first few chapters, making this book accessible to those without a high-level maths background. Later chapters cover modeling sea bed friction, tides, shallow sea dynamics, and ecosystem dynamics. Importantly, there is also a chapter on modeling the impact of climate change on coastal and near shore processes. New to this revised edition is a chapter on tides, tsunamis and the prediction of sea level, and additional material on the new application of the numerical techniques: flux corrected transport, finite volumes and adaptive grids to coastal and marine modeling\"-- Provided by publisher.
Book
Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery
In a trial involving nearly 1100 patients undergoing cardiac surgery, there were no significant differences in outcomes among patients receiving transfusions of red cells stored for 10 days or less as compared with outcomes in those receiving red cells stored for 21 days or more.
The objective of red-cell transfusion is to increase oxygen delivery and improve clinical outcomes. However, in the United States, storage systems are licensed for up to 42 days on the basis of the estimated in vivo recovery of transfused red cells rather than on the basis of the clinical effectiveness of the transfusion.
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During storage, red cells undergo numerous changes.
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,
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Some laboratory data suggest that red cells stored for longer periods may not traverse the microcirculation or deliver oxygen as effectively as those stored for shorter periods.
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,
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Several observational studies have assessed the association between the duration of . . .
Journal Article
Long-Term Effectiveness of Highly Active Antiretroviral Therapy on the Survival of Children and Adolescents with HIV Infection: A 10-Year Follow-Up Study
Background. Previous observational studies found highly active antiretroviral therapy (HAART) to be associated with improved survival among human immunodeficiency virus (HIV)– infected children and adolescents. However, these studies had limited follow-up of HIV-infected children undergoing HAART. Given that HIV infection is chronic and that exposure to HAART is likely to be life-long, there is a need to evaluate the long-term effect of HAART on survival in this population. Methods. The study included 1236 children and adolescents who were perinatally infected with HIV, who were on study or enrolled after January 1996 in a United States-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C), and who were not receiving HAART at baseline; subjects were observed for a maximum of 10 years through June 2006. A weighted Cox regression model was used to estimate the effect of HAART on survival, appropriately adjusted for time-varying confounding by severity. Results. At the end of the 10-year follow-up period (median duration of follow-up, 6.3 years; interquartile range, 4.3– 9.8 years), 70% of participants had initiated HAART. Lower CD4 cell percentages, total lymphocyte counts, and albumin levels were associated with an increased probability of initiating HAART. Eighty-five deaths were observed, and the mortality hazard ratio associated with HAART, compared with non-HAART regimens, was 0.24 after adjusting for measured confounding by severity (95% confidence interval, 0.11– 0.51). Conclusions. The use of HAART was highly effective in reducing mortality during the period 1996– 2006 among children and adolescents infected with HIV. With improved long-term survival, continued follow-up is necessary to evaluate the effects of prolonged use of HAART on potential adverse events, immune function, growth, sexual maturation, and quality of life in this population.
Journal Article
G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3
The adhesion G-protein-coupled receptor (GPCR) latrophilin 3 (ADGRL3) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) and substance use in human genetic studies. Knockdown in multiple species leads to hyperlocomotion and altered dopamine signaling. Thus, ADGRL3 is a potential target for treatment of neuropsychiatric disorders that involve dopamine dysfunction, but its basic signaling properties are poorly understood. Identification of adhesion GPCR signaling partners has been limited by a lack of tools to acutely activate these receptors in living cells. Here, we design a novel acute activation strategy to characterize ADGRL3 signaling by engineering a receptor construct in which we could trigger acute activation enzymatically. Using this assay, we found that ADGRL3 signals through G12/G13 and Gq, with G12/13 the most robustly activated. Gα
is a new player in ADGRL3 biology, opening up unexplored roles for ADGRL3 in the brain. Our methodological advancements should be broadly useful in adhesion GPCR research.
Journal Article
Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma
The median survival of glioblastoma multiforme (GBM) is approximately 1 year. Following surgical removal, systemic therapies are limited by the blood-brain barrier. To circumvent this, we developed a method to modify neurons with the genetic sequence for therapeutic monoclonal antibodies using adeno-associated virus (AAV) gene transfer vectors, directing persistent, local expression in the tumor milieu. The human U87MG GBM cell line or patient-derived early passage GBM cells were administered to the striatum of NOD/SCID immunodeficient mice. AAVrh.10BevMab, an AAVrh.10-based vector coding for bevacizumab (Avastin), an anti-human vascular endothelial growth factor (VEGF) monoclonal antibody, was delivered to the area of the GBM xenograft. Localized expression of bevacizumab was demonstrated by quantitative PCR, ELISA and western blotting. Immunohistochemistry showed that bevacizumab was expressed in neurons. Concurrent administration of AAVrh.10BevMab with the U87MG tumor reduced tumor blood vessel density and tumor volume, and increased survival. Administration of AAVrh.10BevMab 1 week after U87MG xenograft reduced growth and increased survival. Studies with patient-derived early passage GBM primary cells showed a reduction in primary tumor burden with an increased survival. These data support the strategy of AAV-mediated central nervous system gene therapy to treat GBM, overcoming the blood-brain barrier through local, persistent delivery of an anti-angiogenesis monoclonal antibody.
Journal Article