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.     

Multifunctional hydrogels that promote osteogenic hMSC differentiation through stimulation and sequestering of BMP2

The extracellular environment controls many cellular activities thereby linking external material cues to internal cell function. By better understanding these processes, synthetic extracellular material niches can be tailored to present cells with highly regulated physical and/or chemical cues that promote or suppress selected cell functions. Here, poly(ethylene glycol) (PEG) hydrogels were functionalized with fluvastatin-releasing grafts and growth factor binding heparin domains to enable the dynamic exchange of information between the material and cells from the outside-in and inside-out (i.e., bidirectional signaling). By incorporating a fluvastatin-releasing graft and carefully controlling the dose and temporal release, materials were designed to promote bone morphogenic protein (BMP2) and alkaline phosphatase (ALP) production by human mesenchymal stem cells (hMSCs). When the release of fluvastatin was controlled to occur over 2 weeks, BMP2 and ALP production was increased 2.2-fold and 1.7-fold, respectively, at day 28 compared to hMSCs cultured in the absence of fluvastatin. By introducing a heparin functionality into the gel to sequester and localize the hMSC-produced BMP2, the osteogenic differentiation of hMSCs was further augmented over fluvastatin delivery alone. Osteopontin and core binding factor α1 gene expression was 6-fold and 4-fold greater for hMSCs exposed to fluvastatin in the presence of the heparin functionalities, respectively. These results demonstrate how multifunctional gels that interact with cells in a bidirectional manner can efficiently promote selected cell functions, such as the osteogenic differentiation of hMSCs.     

Flow cytometric and microscopic evaluation and effect on fertility of abnormal chromatin condensation in bovine sperm nuclei

The techniques of Feulgen staining, acridine orange staining, and a sperm chromatin structure assay using acridine orange and flow cytometry were compared for selective examination of bovine sperm nuclei. Twenty frozen semen samples were simultaneously analysed by all three methods. The prevalence of abnormally condensed DNA and its relationship to other semen traits were determined in ejaculates from 70 bulbs presented for routine examination for breeding soundness and in frozen semen from 348 bulls evaluated over five years. A breeding trial with 118 beef heifers using semen from six bulls with different degrees of nuclear abnormalities was performed to assess the importance of the defects with respect to fertility. The results indicate that few spermatozoa with abnormal DNA condensation are found in normal semen, but the incidence increases with disturbance of spermatogenesis. However, high numbers of abnormally condensed nuclei were found in the absence of an increase in other defects. This nuclear defect might be at least partially of epididymal origin; it can lower fertility and can be compensated for by increasing the numbers of normal spermatozoa in the insemination dose. The percentage of abnormally condensed sperm nuclei as detected by Feulgen staining was significantly correlated with that detected by microscopy after acridine orange staining and by the sperm chromatin structure assay. We therefore consider the Feulgen technique to be a valuable tool for assessing the nuclear integrity of bovine spermatozoa.     

A review of the effects of water transfers in the La Grande Hydroelectric Complex (Québec,Canada)

Construction of the La Grande Complex in Eastern Canada called for complete or partial diversion of six rivers, the mean annual discharge of which varied from 60 to 1600 m³ s^?1, and the transfer of water from two adjoining watersheds (1586m³ s^?1) into La Grande Rivière. Three of these rivers with reduced flow, Eastmain (from 700 to 95m³ s^?1), Opinaca (from 260 to 35m³ s^?1), and Caniapiscau (from 1708 to 960m³ s^?1) and the waterways with increased flows, Boyd-Sakami (from 1 to 811m³ s^?1) and La Grande Rivière (from 1760 to 3400m³ s^?1) were intensively monitored from 1978 to 1988, while the others were surveyed sporadically. Very few modifications were observed, compared to previous conditions, in banks stability, water quality, and aquatic fauna of the affected rivers: those which appeared can be explained by the water level fluctuations, the water quality of the tributaries of the residual drainage basin, and/or by the direct influence of the reservoirs. In James Bay, the areal extent of the Eastmain River and La Grand Rivière plumes varied with discharge in an exponential relation, mostly under ice cover; resources from the coastal environment had not yet undergone any major changes. Because of the very small population dwelling in the area, less than 3000 inhabitants, modifications in the hydrological regime of these rivers did cause relatively few impacts, the main being greater banks instability in specific locations, reduction of the thickness and ice cover on La Grande Rivière, enhancement of navigation constraints on Eastmain River, and higher mercury levels in fish related to operation of the reservoirs.     

Synthesis and structure-activity study of quaternary ammonium functionalized beta-cyclodextrin-carboxymethylcellulose polymers

Carboxymethylcellulose (CMC) and beta-cyclodextrin (beta-CD)-based polymers functionalized with two types of quaternary ammonium compounds (QACs), the alkaquat DMB-451 (N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride) (DMD-451) named polymer DMB-451, and FMB 1210-8 (a blend of 32 w% N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride and 48 w% of didecyldimethylammonium chloride) named polymer FMB 1210-8, were synthethized and characterized by Fourier transform infrared spectroscopy. The antimicrobial activities of these polymers against Eschericia coli were also evaluated at 25 degrees C in wastewater. The results have indicated that the polymer FMB 1210-8 possesses a high-affinity binding with bacterial cells that induces a rapid disinfection process. Moreover, in the same experimental conditions of disinfection (mixture of 1.0 g of polymer and 100 mL of wastewater), the polymer FMB 1210-8 has a higher antimicrobial efficiency (99.90%) than polymer DMB-451 (92.8%). This phenomenon might be associated to a stronger interaction with bacterial cells due to stronger binding affinity for E. coli cells and greater killing efficiency of the C10 alkyl chains QAC of polymer FMB 1210-8 to disrupt the bacterial cell membrane as compared to N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride. Together, these results suggest that the polymer FMB 1210-8 could constitute a good disinfectant against Escherichia coli, which could be advantageously used in wastewater treatments due to the low toxicity of beta-CD and CMC, and moderated toxicity of FMB 1210-8 to human and environment.