Intraocular concentrations of chemotherapeutic agents after systemic or local administration

OBJECTIVES: To investigate the concentrations of carboplatin and etoposide achieved in the aqueous and vitreous humors after intravenous infusion in nonhuman primates, and to investigate whether local administration of carboplatin might result in higher concentrations in the vitreous humor. METHODS: Macaca fascicularis primates were treated with 1 of 3 regimens: (1) intravenous carboplatin (18.7 mg/kg), etoposide (5 mg/kg), and vincristine sulfate (0.05 mg/kg), (2) peribulbar carboplatin (10 mg/mL), or (3) episcleral balloon carboplatin (10 mg/mL). Concentrations of chemotherapeutic agents were measured in the plasma and in the aqueous and vitreous humors. RESULTS: No measurable amount of etoposide was detected in the aqueous or vitreous humor after intravenous administration. Mean measured peak vitreous concentration of carboplatin after intravenous administration was 0.31 microg/mL, which was 1% of the peak plasma value. Mean measured peak vitreous concentrations of carboplatin after peribulbar or episcleral balloon administration were 2.38 microg/mL and 2.95 microg/mL, respectively, which represent 7.68- and 9.52-fold increases over the concentration achieved after intravenous administration. No serious toxic effect was observed in any animal. CONCLUSIONS: Peribulbar and episcleral balloon administration of carboplatin seemed to be safe and resulted in higher vitreous concentrations than intravenous administration in this model. These results suggest that these alternate routes of delivery should be explored in children with vitreous seeding of retinoblastoma.     

Practical Application of Hybrid Modelling to Naturally Fractured Reservoirs

This article presents application of a hybrid method for modelling discrete fracture network in an actual naturally fractured reservoir (NFRs) (Palm Valley, Australia). The hybrid method integrates features of geological, statistical, artificial intelligence, and conditional hierarchical stochastic simulation techniques. Both discrete and continuum fracture information could be utilized, such as statistical distributions of fracture orientations, spatial distributions of fracture density, and discrete multi-fractal dimensions. The final output is a 3D network model of discrete fractures, with their corresponding details of location, size, and orientation. The results show an improvement of the hybrid method over previous fracture models.     

Reasoning about non-immediate triggers in biological networks

Modeling molecular interactions in signalling networks is important from various perspectives such as predicting side effects of drugs, explaining unusual cellular behavior and drug and therapy design. Various formal languages have been proposed for representing and reasoning about molecular interactions. The interactions are modeled as triggered events in most of the approaches. The triggering of events is assumed to be immediate: once an interaction is triggered, it should occur immediately. Although working well for engineering systems, this assumption poses a serious problem in modeling biological systems. Our knowledge about biological systems is inherently incomplete, thus molecular interactions are constantly elaborated and refined at different granularity of abstraction. The model of immediate triggers can not consistently deal with this refinement. In this paper we propose an action language to address this problem. We show that the language allows for refinements of biological knowledge, although at a higher cost in terms of complexity.      

Low phase noise millimeter-wave frequency sources using InP-basedHBT MMIC technology

A family of millimeter-wave sources based on InP heterojunction bipolar transistor (HBT) monolithic microwave/millimeter-wave integrated circuit (MMIC) technology has been developed. These sources include 40-GHz, 46-GHz, 62-GHz MMIC fundamental mode oscillators, and a 95-GHz frequency source module using a 23.8-GHz InP HBT MMIC dielectric resonator oscillator (DRO) in conjunction with a GaAs-based high electron mobility transistor (HEMT) MMIC frequency quadrupler and W-band output amplifiers. Good phase noise performance was achieved due to the low 1/f noise of the InP-based HBT devices. To our knowledge, this is the first demonstration of millimeter-wave sources using InP-based HBT MMIC's     

Population pharmacokinetics of nitroglycerin and of its two metabolites after a single 24-hour application of a nitroglycerin transdermal matrix delivery system

OBJECTIVES: To determine whether oxytocin exists in the cerebrospinal fluid (CSF) of dogs and whether the amount of oxytocin in the CSF of dogs with neck or back pain caused by spinal cord compression is significantly different than that in the CSF of clinically normal dogs. STUDY DESIGN: Prospective controlled study. ANIMAL POPULATION: A total of 15 purpose-bred beagles and 17 client-owned dogs. METHODS: CSF was collected by needle puncture of the cerebellar medullary cistern after induction of general anesthesia. Oxytocin levels within the samples were determined through radioimmunoassay. RESULTS: Dogs with spinal cord compression had significantly more oxytocin in their CSF than the clinically normal dogs (13.76 +/- 2.0 pg/mL and 3.61 +/- 0.63 pg/mL, respectively; P < .0001). Dogs with chronic signs (>7 days) had significantly more oxytocin in their CSF than dogs with acute signs (<7 days) (21.60 +/- 0.86 pg/mL and 6.80 +/- 0.81 pg/mL, respectively; P < .0001). Both acutely and chronically affected dogs had significantly more oxytocin in their CSF than the controls (P < .005 and P < .0001 respectively). CONCLUSIONS: Dogs with neck and back pain caused by spinal cord compression have significantly more oxytocin in their CSF than clinically normal dogs. Dogs with chronic clinical signs have significantly more oxytocin in their CSF than dogs with acute clinical signs. CLINICAL RELEVANCE: In humans, intrathecal injection of oxytocin is effective in treating low back pain for up to 5 hours. Intrathecal oxytocin may be a logical choice for perioperative analgesia in dogs undergoing myelography because the intrathecal space is accessed for injection of contrast agent.     

Penicillin vs. erythromycin in the treatment of diphtheria

PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.     

An effective hybrid approach of desirability,fuzzy logic,ANFIS and LAPO algorithm for optimizing compliant mechanism

This paper proposes an efficient hybrid approach for solving multi-objective optimization design of a compliant mechanism. The approach is developed by integrating desirability function approach, fuzzy logic system, adaptive neuro-fuzzy inference system, and Lightning attachment procedure optimization. Box–Behnken design is used to form a numerically experimental matrix. First, a refinement of design variables is conducted through analysis of variance and Taguchi approach in terms of considerably eliminating space of design variables and computation efforts. Next, desirability of two objective functions is computed and transferred into the fuzzy logic system. The output of fuzzy logic system is regarded as single combined objective function. Subsequently, a modeling for fuzzy output is developed via adaptive neuro-fuzzy inference system. Then, LAPO algorithm is adopted for solving the optimization problem. By investigating three different numerical examples, performance of the proposed approach is validated. Numerical results revealed that the proposed approach has a computational accuracy better than that of Taguchi-based fuzzy logic reasoning. Finally, case study 1 is chosen as an optimal solution for the mechanism. Furthermore, the effectiveness of proposed approach is greater than that of the Jaya algorithm and TLBO algorithm through Wilcoxon signed rank test and Friedman test. The proposed approach can be used for related engineering fields.

     

CLARO: modeling and processing uncertain data streams

Uncertain data streams, where data are incomplete and imprecise, have been observed in many environments. Feeding such data streams to existing stream systems produces results of unknown quality, which is of paramount concern to monitoring applications. In this paper, we present the claro system that supports stream processing for uncertain data naturally captured using continuous random variables. claro employs a unique data model that is flexible and allows efficient computation. Built on this model, we develop evaluation techniques for relational operators by exploring statistical theory and approximation. We also consider query planning for complex queries given an accuracy requirement. Evaluation results show that our techniques can achieve high performance while satisfying accuracy requirements and outperform state-of-the-art sampling methods.     

Soluble Prokaryotic Overexpression and Purification of Human GM-CSF Using the Protein Disulfide Isomerase b′a′ Domain

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the colony-stimulating factor (CSF) family, which functions to enhance the proliferation and differentiation of hematopoietic stem cells and other hematopoietic lineages such as neutrophils, dendritic cells, or macrophages. These proteins have thus generated considerable interest in clinical therapy research. A current obstacle to the prokaryotic production of human GM-CSF (hGM-CSF) is its low solubility when overexpressed and subsequent complex refolding processes. In our present study, the solubility of hGM-CSF was examined when combined with three N-terminal fusion tags in five E. coli strains at three different expression temperatures. In the five E. coli strains BL21 (DE3), ClearColi BL21 (DE3), LOBSTR, SHuffle T7 and Origami2 (DE3), the hexahistidine-tagged hGM-CSF showed the best expression but was insoluble in all cases at each examined temperature. Tagging with the maltose-binding protein (MBP) and the b′a′ domain of protein disulfide isomerase (PDIb′a′) greatly improved the soluble overexpression of hGM-CSF at 30 °C and 18 °C. The solubility was not improved using the Origami2 (DE3) and SHuffle T7 strains that have been engineered for disulfide bond formation. Two conventional chromatographic steps were used to purify hGM-CSF from the overexpressed PDIb′a′-hGM-CSF produced in ClearColi BL21 (DE3). In the experiment, 0.65 mg of hGM-CSF was isolated from a 0.5 L flask culture of these E. coli and showed a 98% purity by SDS-PAGE analysis and silver staining. The bioactivity of this purified hGM-CSF was measured at an EC₅₀ of 16.4 ± 2 pM by a CCK8 assay in TF-1 human erythroleukemia cells.