A distributed adverse drug reaction detection system using intelligent agents with a fuzzy recognition‐primed decision model

Discovering unknown adverse drug reactions (ADRs) in postmarketing surveillance as early as possible is highly desirable. Nevertheless, current postmarketing surveillance methods largely rely on spontaneous reports that suffer from serious underreporting, latency, and inconsistent reporting. Thus these methods are not ideal for rapidly identifying rare ADRs. The multiagent systems paradigm is an emerging and effective approach to tackling distributed problems, especially when data sources and knowledge are geographically located in different places and coordination and collaboration are necessary for decision making. In this article, we propose an active, multiagent framework for early detection of ADRs by utilizing electronic patient data distributed across many different sources and locations. In this framework, intelligent agents assist a team of experts based on the well‐known human decision‐making model called Recognition‐Primed Decision (RPD). We generalize the RPD model to a fuzzy RPD model and utilize fuzzy logic technology to not only represent, interpret, and compute imprecise and subjective cues that are commonly encountered in the ADR problem but also to retrieve prior experiences by evaluating the extent of matching between the current situation and a past experience. We describe our preliminary multiagent system design and illustrate its potential benefits for assisting expert teams in early detection of previously unknown ADRs. © 2007 Wiley Periodicals, Inc. Int J Int Syst 22: 827–845, 2007.     

Ionization of Acetylacetone in Me2SO—Water Mixtures. Reactivity—Selectivity Principle or Principle of Imperfect Synchronization?

Rate constants for the reversible deprotonation of acetylacetone were measured in carboxylate and amine buffers in water and in 50%, 90% and 95% Me₂SO at 20°C. The Brønsted plot for the carboxylate ions is curved in the Me₂SO—water mixtures, but straight in water. The curvature is in the direction predicted by the Reactivity—Selectivity Principle (RSP). However, the Brønsted plot for the reaction with primary amines is straight in all solvents. This suggests that the curvature observerd with the carboxylate ions is caused by loss of solvation of the base; this loss of solvation is ahead of bond formation in the transition state rather than being a manifestation of the RSP. (Note that all Brønsted plots are based on pK_a values measured in the respective solvents.) The intrinsic rate constant (k₀) for proton transfer increases with the addition of Me₂SO, and more so with the carboxylate buffers than with the amines. This increase in k₀ is attributed to delayed solvation of the developing enolate ion in the transition state; with the carboxylate buffers, an additional factor is the early loss of solvation of the base. The various solvation effects observed in this study can all be understood in the context of the Principle of Imperfect Synchronization (PIS).     

The binding of substrates and inhibitors to the metal center of myoinositol monophosphatase

The synthetic substrate anthraniloyl-beta-glycerol-P binds to myoinositol monophosphatase with a Kd = 5 microM at pH 7.5. The anthraniloyl chromophore, excited at 330 nm, sensitizes the long lived luminescence of bound Tb(III) at 490, 545, 585 and 620 nm. Assuming a mechanism of radiationless energy transfer, the actual distance of separation between the donor-acceptor pair was calculated to be R = 10 A. Tb(III) binds to the monophosphatase with a Kd = 2 microM, whereas Ca-(II) displaces the lanthanide at concentrations above 0.1 mM. The binding studies support the notion that Tb(III), Ca(II) and Mg(II) interact with a common binding site on the protein. Phosphate ion, a strong competitive inhibitor, perturbs the luminescence of bound Tb(III), whereas the substrate beta-glycero-P has no effect on the luminescence yield and long-lived emission of bound Tb(III). It is suggested that the phosphate group of the substrate is not in direct contact with the metal ion coordinated to several amino acid residues of the enzyme.     

Residual stresses and transformation toughening in MoSi2 composites reinforced with partially stabilized zirconia

The results of study of the effects of yttria stabilization (0–6 mol.%) on the room-temperature fracture behavior and toughening mechanisms in zirconia-reinforced MoSi₂ are presented in this paper. Transformation toughening is shown to occur only in composites reinforced with zirconia particles stabilized with 2 mol.% yttria. However, the fracture toughness levels are comparable in the other composites with yttria levels between 0 and 6 mol.%. Toughening in the other composites is attributed to the combined effects of residual stress, microcrack shielding/anti-shielding and/or crack deflection. A rigorous micromechanics-based model is presented for the estimation of residual stress levels in brittle materials reinforced with phases that can transform during cooling or under stress. The model is applied successfully to the rationalization of the observed fracture and toughening phenomena.     

线卡通信系统的基本构件

如今高性能通信系统有多种形式，在企业网络中，它也许是路由器，或是将以太局域网(LAN)的数据转发至OC-48 SONET光网络的多业务转换装置；在蜂窝网络中，它可能是第三代宽带无线网络控制器(RNC)，将基站(BTS)的移动蜂窝电话呼叫发送至公共交换电话网(PSTN)；在存储网络中，它可以是将服务器的数据备份至廉价磁盘冗余阵列(RAID)的光纤通道存储转换器。无论何种特殊类型的网络，这些系统的共同用途是接收来自信息源的数据，决定它需要发至何处，并有效地将它传送至目的地。为了支持这些关键功能，需要有一套通用通信元件或“基本构…     

Development of the bi-directional ultrasound system for base of tongue imaging

The use of conventional ultrasound systems to image the upper airway has been limited because ultrasound energy is attenuated by the air column. In an attempt to study upper airway geometry, we developed a computer controlled bi-directional ultrasound system which combines two conventional ultrasound devices with computer image processing to yield images of upper airway structures. Human studies and cadaver studies were performed to evaluate the system. Images acquired by the bi-directional ultrasound system were comparable to images from 3D volume rendered CT scans. This system may provide valuable data in the study of upper airway physiology and pathology.     

Dye coupling between rat striatal neurons recorded in vivo: compartmental organization and modulation by dopamine

1. The presence of dye coupling between striatal neurons was investigated using in vivo intracellular recording and dye injection in adult rats. In 17% of the cases in which a single striatal neuron was injected with Lucifer yellow, more than one labeled neuron was recovered. In control rats, this dye coupling was observed only between single pairs of medium spiny neurons and only when the neuron injected exhibited the Type II response profile as defined by paired-pulse stimulation of corticostriatal afferents. 2. After intravenous administration of the D1/D2 agonist apomorphine at a behaviorally effective dose (i.e., 0.1-0.3 mg/kg), an increase in the incidence (from 17% to 82% of injected cells) and extent (from 2 cells to 3-7 cells labeled per injection) of dye coupling was observed. This effect was mediated by D2 receptor stimulation because administration of the D2 agonist quinpirole caused similar alterations in the incidence and extent of dye coupling (66% coupled). In contrast, administration of the D1 agonist SKF 38393 or the D1 antagonist SCH 23390 did not result in any significant alteration in dye coupling. 3. In control rats, the entire somatodendritic regions of dye-coupled neurons were found to be localized within single matrix compartments of the striatum. However, after intravenous administration of apomorphine or quinpirole, clusters of dye-coupled neurons were found to extend across the patch/matrix boundary. Moreover, dye coupling was observed after injecting cells exhibiting either the Type I or the Type II response profile. 4. In response to D2 receptor stimulation, both the extent and the pattern of coupling between striatal neurons is altered, resulting in direct coupling between neurons that are otherwise functionally and anatomically segregated in the control animal.