Risk of Potential Drug-Drug Interactions among Brazilian Elderly A Population-Based, Cross-Sectional Study

Background: Drug-drug interactions (DDIs) are one of the main causes of adverse reactions related to medications, being responsible for up to 23% of hospital admissions. However, only a few studies have evaluated this problem in elderly Brazilians. Objectives: To determine the prevalence of potential DDIs (PDDIs) in community-dwelling elderly people in Brazil, analyse these interactions with regard to severity and clinical implications, and identify associated factors. Methods: A population-based cross-sectional study was carried out involving 2143 elderly (aged 60 years) residents of the metropolitan area of Sao Paulo, Brazil. Data were obtained from the SABE (Saude, Bem estar e Envelhecimento [Health, Well-Being, and Aging]) survey, which is a multicentre study carried out in seven countries of Latin America and the Caribbean, coordinated by the Pan-American Health Organization. PDDIs were analysed using a computerized program and categorized according to level of severity, onset, mechanism and documentation in the literature. The STATA software statistical package was used for data analysis, and logistic regression was conducted to determine whether variables were associated with PDDIs. Results: Analysis revealed that 568 (26.5%) of the elderly population included in the study were taking medications that could lead to a DDI. Almost two-thirds (64.4%) of the elderly population exposed to PDDIs were women, 50.7% were aged >= 75 years, 71.7% reported having fair or poor health and 65.8% took 2-5 medications. A total of 125 different PDDIs were identified; the treatment combination of an ACE inhibitor with a thiazide or loop diuretic (associated with hypotension) was the most frequent cause of PDDIs (n=322 patients; 56.7% of individuals with PDDIs). Analysis of the PDDIs revealed that 70.4% were of moderate severity, 64.8% were supported by good quality evidence and 56.8% were considered of delayed onset. The multivariate analysis showed that the risk of a PDDI was significantly increased among elderly individuals using six or more medications (odds ratio [OR] 3.37) and in patients with hypertension (OR 2.56), diabetes mellitus (OR 1.73) or heart problems (OR 3.36). Conclusions: Approximately one-quarter of the elderly population living in Sao Paulo could be taking two or more potentially interacting medicines. Polypharmacy predisposes elderly individuals to PDDIs. More than half of these drug combinations (57.6%, n = 72) were part of commonly employed treatment regimens and may be responsible for adverse reactions that compromise the safety of elderly individuals, especially at home. Educational initiatives are needed to avoid unnecessary risks.

Effect of image analysis software on neurofunctional activation during processing of emotional human faces

Functional brain imaging techniques such as functional MRI (fMRI) that allow the in vivo investigation of the human brain have been exponentially employed to address the neurophysiological substrates of emotional processing. Despite the growing number of fMRI studies in the field, when taken separately these individual imaging studies demonstrate contrasting findings and variable pictures, and are unable to definitively characterize the neural networks underlying each specific emotional condition. Different imaging packages, as well as the statistical approaches for image processing and analysis, probably have a detrimental role by increasing the heterogeneity of findings. In particular, it is unclear to what extent the observed neurofunctional response of the brain cortex during emotional processing depends on the fMRI package used in the analysis. In this pilot study, we performed a double analysis of an fMRI dataset using emotional faces. The Statistical Parametric Mapping (SPM) version 2.6 (Wellcome Department of Cognitive Neurology, London, UK) and the XBAM 3.4 (Brain Imaging Analysis Unit, Institute of Psychiatry, Kings College London, UK) programs, which use parametric and non-parametric analysis, respectively, were used to assess our results. Both packages revealed that processing of emotional faces was associated with an increased activation in the brain`s visual areas (occipital, fusiform and lingual gyri), in the cerebellum, in the parietal cortex, in the cingulate cortex (anterior and posterior cingulate), and in the dorsolateral and ventrolateral prefrontal cortex. However, blood oxygenation level-dependent (BOLD) response in the temporal regions, insula and putamen was evident in the XBAM analysis but not in the SPM analysis. Overall, SPM and XBAM analyses revealed comparable whole-group brain responses. Further Studies are needed to explore the between-group compatibility of the different imaging packages in other cognitive and emotional processing domains. (C) 2009 Elsevier Ltd. All rights reserved.

A new candidate locus for bilateral perisylvian polymicrogyria mapped on chromosome Xq27

Polymicrogyria (PMG) is characterized by an excessive number of small and prominent brain gyri, separated by shallow sulci. Bilateral perisylvian polymicrogyria (BPP) is the most common form of PMG. Clinical signs include pseudobulbar paresis, mental retardation, and epilepsy. Familial forms of BPP have been described and a candidate locus was previously mapped to chromosome Xq28, distal do marker DXS8103. The objective of this study was to perform linkage analysis in one family segregating BPP. A total of 15 individuals, including 8 affected patients with BPP were evaluated. Family members were examined by a neurologist and subjected to magnetic resonance imaging scans. Individuals were genotyped for 18 microsatellite markers, flanking a 42.3 cM interval on ch Xq27-q28. Two-point and multipoint linkage analysis was performed using the LINKAGE package and haplotype reconstruction was performed by GENEHUNTER software. Our results showed a wide spectrum of clinical manifestations in affected individuals with BPP, ranging from normal to mild neurological abnormalities. Two-point linkage analysis yield a Zmax=2.06 at theta=0.00 for markers DXS1205 and DXS1227. Multipoint lod-scores indicate a candidate interval of 13 cM between markers DSXS1205 and DXS8043, on ch Xq27.2-Xq27.3. These results point to a new locus for BPP in a more centromeric location than previously reported. (C) 2008 Wiley-Liss, Inc.

Using a cartographic modeling language to manipulate spectral satellite imagery

Land related information about the Earth's surface is commonIJ found in two forms: (1) map infornlation and (2) satellite image da ta. Satellite imagery provides a good visual picture of what is on the ground but complex image processing is required to interpret features in an image scene. Increasingly, methods are being sought to integrate the knowledge embodied in mop information into the interpretation task, or, alternatively, to bypass interpretation and perform biophysical modeling directly on derived data sources. A cartographic modeling language, as a generic map analysis package, is suggested as a means to integrate geographical knowledge and imagery in a process-oriented view of the Earth. Specialized cartographic models may be developed by users, which incorporate mapping information in performing land classification. In addition, a cartographic modeling language may be enhanced with operators suited to processing remotely sensed imagery. We demonstrate the usefulness of a cartographic modeling language for pre-processing satellite imagery, and define two nerv cartographic operators that evaluate image neighborhoods as post-processing operations to interpret thematic map values. The language and operators are demonstrated with an example image classification task.

Facies architecture of the CRP-3 drillhole, Victoria Land Basin, Antarctica

The Cenozoic Victoria Land Basin (VLB) stratigraphic section penetrated by CRP-3 is mostly of Early Oligocene age. It contains an array of lithofacies comprising fine-grained mudrocks, interlaminated and interbedded mudrocks/sandstones, mud-rich and mud-poor sandstones, conglomerates and diametites that are together interpreted as the products of shallow marine to possibly non-marine environments of deposition, affected by the periodic advance and retreat of tidewater glaciers. This lithofacies assemblage can be readily rationalised using the facies scheme designed originally for CRP-2/2A, and published previously. The uppermost 330 metres below sea floor (mbsf) shows a cyclical arrangement of lithofacies also similar to that recognised throughout CRP-2/2A, and interpreted to reflect cyclical variations in relative sea-level driven by ice volume fluctuations ("Motif A"). Between 330 and 480 mbsf, a series of less clearly cyclical units, generally fining-upward but nonetheless incorporating a significant subset of the facies assemblage, has been identified and noted in the Initial Report as "Motif B. Below 480 mbsf, the section is arranged into a repetitive succession of fining-upward units, each of which comprises dolerite clast conglomerate at the base passing upward into relatively thick intervals of sandstones. The cycles present down 480 mbsf are defined as sequences, each interpreted to record cyclical variation of relative sea-level. The thickness distribution of sequences in CRP-3 provides some insights into the geological variables controlling sediment accumulation in the Early Oligocene section. The uppermost part of the section in CRP-3 comprises two or three thick, complete sequences that show a broadly symmetrical arrangement of lithofacies (similar to Sequences 9-11 in CRP-2/2A). This suggests a period of relatively rapid tectonic subsidence, which allowed preservation of the complete facies cycle. Below Sequence 3, however, is a considerable interval of thin, incomplete and erosionally truncated sequences (4-23), which incorporates both the remainder of Motif A sequences and all Motif B sequences recognised. The thinner and more truncated sequences suggest sediment accumulation under conditions of reduced accommodation, and given the lack of evidence for glacial conditions (see Powell et al., this volume) tends to argue for a period of reduced tectonic subsidence. The section below 480 mbsf consists of a series of fining-upward, conglomerate to sandstone intervals which cannot be readily interpreted in terms of relative sea-level change. A relatively mudrock-rich interval above the basal conglomerate/breccia (782-762 mbsf) may record initial flooding of the basin during early rift subsidence. The lithostratigraphy summarised above has been linked to seismic reflection data using depth conversion techniques (Henrys et al., this volume). The three uppermost reflectors ("o", "p" and "q") correlate to the package of thick sequences 1-3, and several deeper reflectors can also be correlated to sequence boundaries. The package of thick Sequences 1-3 shows a sheet-like cross-sectional geometry on seismic reflection lines, unlike the similar package recognised in CRP-2/2A.

Use of the web to provide learning support for a large metabolism and nutrition class

To support student learning in a large Metabolism and Nutrition class, we have introduced a web-based package, using a commercially available program, WebCT. The package was developed at a minimal cost and with limited resources. In addition to downloadable (PDF) versions of lecture Powerpoint presentations, tutorial outlines and a practical class exercise, web-based self-directed learning exercises were included to reinforce and extend lecture material in an active learning environment. The web-site also contained a variety of formative and summative assessment tasks that examined both factual recall and higher order thinking Detailed course information, timetables and a bulletin board were also readily accessible. Student usage of the site was generally high, but varied widely between individual students. Students who achieved a high overall score for the course completed on average three times as many formative assessment items and achieved a higher score for all tests than students who did poorly. Student feedback about the site was very positive with the majority of students reporting that the course material and assessment items that were available were useful to their learning. Administration of the course was also facilitated. (C) 2001 IUBMB. Published by Elsevier Science Ltd. All rights reserved.

Replacing prelinguistic behaviors with functional communication

This study evaluated the effectiveness of a teacher-implemented intervention package designed to replace prelinguistic behaviors with functional communication. Four young children with autism participated in a multiple-probe design across three communicative functions. Initially, three existing communication functions were selected for each child. Next, the existing prelinguistic behaviors that the children used to achieve these functions were identified. Replacement forms that were considered more recognizable and symbolic were defined to achieve these same functions. After a baseline phase, teachers received inservice training, consultation, and feedback on how to encourage, acknowledge, and respond to the replacement forms. During intervention, the replacement forms increased and prelinguistic behaviors decreased in most cases. The results suggested that the teacher-implemented intervention was effective in replacing prelinguistic behaviors with alternative forms of functional communication.

Multi-threading and message communication in Qu-Prolog

This paper presents the multi-threading and internet message communication capabilities of Qu-Prolog. Message addresses are symbolic and the communications package provides high-level support that completely hides details of IP addresses and port numbers as well as the underlying TCP/IP transport layer. The combination of the multi-threads and the high level inter-thread message communications provide simple, powerful support for implementing internet distributed intelligent applications.

Probabilistic modelling of CO2 corrosion laboratory data using neural networks

The present paper addresses two major concerns that were identified when developing neural network based prediction models and which can limit their wider applicability in the industry. The first problem is that it appears neural network models are not readily available to a corrosion engineer. Therefore the first part of this paper describes a neural network model of CO2 corrosion which was created using a standard commercial software package and simple modelling strategies. It was found that such a model was able to capture practically all of the trends noticed in the experimental data with acceptable accuracy. This exercise has proven that a corrosion engineer could readily develop a neural network model such as the one described below for any problem at hand, given that sufficient experimental data exist. This applies even in the cases when the understanding of the underlying processes is poor. The second problem arises from cases when all the required inputs for a model are not known or can be estimated with a limited degree of accuracy. It seems advantageous to have models that can take as input a range rather than a single value. One such model, based on the so-called Monte Carlo approach, is presented. A number of comparisons are shown which have illustrated how a corrosion engineer might use this approach to rapidly test the sensitivity of a model to the uncertainities associated with the input parameters. (C) 2001 Elsevier Science Ltd. All rights reserved.

Xmds: eXtensible multi-dimensional simulator

A software package that efficiently solves a comprehensive range of problems based on coupled complex nonlinear stochastic ODEs and PDEs is outlined. Its input and output syntax is formulated as a subset of XML, thus making a step towards a standard for specifying numerical simulations.

Development and characterisation of recombinant hepatitis delta virus-like particles

Injection of particulate hepatitis B virus surface antigen (HBsAg) in mice leads to the induction of a HBsAg-specific class-I-restricted cytotoxic T lymphocyte (CTL) response. It is proposed that any protein internal to HBsAg will also be able to elicit a specific CTL response. In this study, several carboxy-terminal truncations of hepatitis C virus (HCV) core protein were fused to varying lengths of amino-terminal truncated large hepatitis delta antigen (L-HDAg). These constructs were analysed for their ability to be expressed and the particles secreted in the presence of HBsAg after transfection into HuH-7 cells. The secretion efficiency of the various HCV core-HDAg chimeric proteins was generally poor. Constructs containing full length HDAg appeared to be more stable than truncated versions and the length of the inserted protein was restricted to around 40 amino acids. Thus, the use of L-HDAg as a chimera to package foreign proteins is limited. Consequently, a polyepitope (polytope) containing a B-cell epitope from human papillomavirus (HPV 16) and multiple T-cell epitopes from the HCV polyprotein was used to create the construct, L-HDAg-polyB. This chimeric protein was shown to be reliant on the co-expression of HBsAg for secretion into the cell culture fluid and was secreted more efficiently than the previous HCV core-HDAg constructs. These L-HDAg-polyB virus-like particles (VLPs) had a buoyant density of similar to 1.2 g/cm(3) in caesium chloride and similar to 1.15 g/cm(3) in sucrose. The VLPs were also immunoprecipitated using an anti-HBs but not an anti-HD antibody. Thus, these recombinant VLPs have similar biophysical properties to L-HDAg VLPs.

Predicting coal ash slag flow characteristics (viscosity model for the Al2O3-CaO-'FeO'-SiO2 system)

A model has been developed which enables the viscosities of coal ash slags to be predicted as a function of composition and temperature under reducing conditions. The model describes both completely liquid and heterogeneous, i.e. partly crystallised, slags in the Al2O3-CaO-'FeO'-SiO2 system in equilibrium with metallic iron. The Urbain formalism has been modified to describe the viscosities of the liquid slag phase over the complete range of compositions and a wide range of temperatures. The computer package F * A * C * T was used to predict the proportions of solids and the compositions of the remaining liquid phases. The Roscoe equation has been used to describe the effect of presence of solid suspension (slurry effect) on the viscosity of partly crystallised slag systems. The model provides a good description of the experimental data of fully liquid, and liquid + solids mixtures, over the complete range of compositions and a wide range of temperatures. This model can now be used for viscosity predictions in industrial slag systems. Examples of the application of the new model to coal ash fluxing and blending are given in the paper. (C) 2001 Elsevier Science Ltd. All rights reserved.