Refinements in stress echocardiographic techniques improve inter-institutional agreement in interpretation of dobutamine stress echocardiograms

Aims To determine the degree of inter-institutional agreement in the assessment of dobutamine stress echocardiograms using modern stress echo cardiographic technology in combination with standardized data acquisition and assessment criteria. Method and Results Among six experienced institutions, 150 dobutamine stress echocardiograms (dobutamine up to 40 mug.kg(-1) min(-1) and atropine up to I mg) were performed on patients with suspected coronary artery disease using fundamental and harmonic imaging following a consistent digital acquisition protocol. Each dobutamine stress echocardiogram was assessed at every institution regarding endocardial visibility and left ventricular wall motion without knowledge of any other data using standardized reading criteria. No patients were excluded due to poor image quality or inadequate stress level. Coronary angiography was performed within 4 weeks. Coronary angiography demonstrated significant coronary artery disease (less than or equal to50% diameter stenosis) in 87 patients. Using harmonic imaging an average of 5.2+/-0.9 institutions agreed on dobutamine stress echocardiogram results as being normal or abnormal (mean kappa 0.55; 95% CI 0.50-0.60). Agreement was higher in patients with no (equal assessment of dobutamine stress echocardiogram results by 5.5 +/- 0.8 institutions) or three-vessel coronary artery disease (5.4 +/- 0.8 institutions) and lower in one- or two- vessel disease (5.0 +/- 0.9 and 5.2 +/- 1.0 institutions, respectively-, P=0.041). Disagreement on test results was greater in only minor wall motion abnormalities. Agreement on dobutamine stress echocardiogram results was lower using fundamental imaging (mean kappa 0.49; 95% CI 0.44-0.54; P

Using workflow technology to manage flexible e-learning services

Workflow technology provides a suitable platform to define and manage the coordination of business process activities. We introduce a flexible e-learning environment – called Flex-eL – that has been built upon workflow technology. The workflow functionality of Flex-eL manages the coordination of learning and assessment activities of the course process between students and teaching staff. It provides a unique environment for teachers to design and develop process-centric courses and to monitor student progress. It allows students to learn at their own pace while observing the learning guidelines and checkpoints modeled into the course process by teaching staff. We also report on the successful deployment of the concept and system for university courses and our experiences from the implementation.

The multicopper oxidase of Pseudomonas aeruginosa is a ferroxidase with a central role in iron acquisition

Recently it has been observed that multicopper oxidases are present in a number of microbial genomes, raising the question of their function in prokaryotes. Here we describe the analysis of an mco mutant from the opportunistic pathogen Pseudomonas aeruginosa. Unlike wild-type Pseudomonas aeruginosa, the mco mutant was unable to grow aerobically on minimal media with Fe(II) as sole iron source. In contrast, both the wild-type and mutant strain were able to grow either anaerobically via denitrification with Fe(II) or aerobically with Fe(III). Analysis of iron uptake showed that the mco mutant was impaired in Fe(II) uptake but unaffected in Fe(III) uptake. Purification and analysis of the MCO protein confirmed ferroxidase activity. Taken together, these data show that the mco gene encodes a multicopper oxidase that is involved in the oxidation of Fe(II) to Fe(III) subsequent to its acquisition by the cell. In view of the widespread distribution of the mco gene in bacteria, it is suggested that an iron acquisition mechanism involving multicopper oxidases may be an important and hitherto unrecognized feature of bacterial pathogenicity.

Role of peripheral afference during acquisition of a complex coordination task

It has long been supposed that the interference observed in certain patterns of coordination is mediated, at least in part, by peripheral afference from the moving limbs. We manipulated the level of afferent input, arising from movement of the opposite limb, during the acquisition of a complex coordination task. Participants learned to generate flexion and extension movements of the right wrist, of 75degrees amplitude, that were a quarter cycle out of phase with a 1-Hz sinusoidal visual reference signal. On separate trials, the left wrist either was at rest, or was moved passively by a torque motor through 50degrees, 75degrees or 100degrees, in synchrony with the reference signal. Five acquisition sessions were conducted on successive days. A retention session was conducted I week later. Performance was initially superior when the opposite limb was moved passively than when it was static. The amplitude and frequency of active movement were lower in the static condition than in the driven conditions and the variation in the relative phase relation across trials was greater than in the driven conditions. In addition, the variability of amplitude, frequency and the relative phase relation during each trial was greater when the opposite limb was static than when driven. Similar effects were expressed in electromyograms. The most marked and consistent differences in the accuracy and consistency of performance (defined in terms of relative phase) were between the static condition and the condition in which the left wrist was moved through 50degrees. These outcomes were exhibited most prominently during initial exposure to the task. Increases in task performance during the acquisition period, as assessed by a number of kinematic variables, were generally well described by power functions. In addition, the recruitment of extensor carpi radialis (ECR), and the degree of co-contraction of flexor carpi radialis and ECR, decreased during acquisition. Our results indicate that, in an appropriate task context, afferent feedback from the opposite limb, even when out of phase with the focal movement, may have a positive influence upon the stability of coordination.

Applications of motion study in developmental disabilities: A review

Motion study is an engineering technology that analyzes human body motions. During the past decade (1990-1999) a series of studies investigated the role of motion study in developmental disabilities. This article reviews the literature on the applications of motion study in the field. A historical and conceptual review of motion study leading to the current status of studies is presented followed by a review of the research literature. Two main eras of research focus were identified. The first era (1990-1995) of studies established the superior effectiveness and efficiency of tasks designed with motion study or motion study-related principles over traditional site-based task designs. The second era (1995-1999) of studies examined the interaction between motion study-based task designs and other variables such as choice, preference, and functionally equivalent and competing task designs and communicative alternatives. Our review found that applying motion study principles as an antecedent guide and practice to eliminating or reducing ineffective motions and simplifying effective motions resulted in positive task outcomes with most of the participants.

Implications of missed opportunities for learning and assessment in design and technology education

Supporting student learning can be difficult, especially within open-ended or loosely structured activities, often seen as valuable for promoting student autonomy in many curriculum areas and contexts. This paper reports an investigation into the experiences of three teachers who implemented design and technology education ideas in their primary school classrooms for the first time. The teachers did not capitalise upon many of the opportunities for scaffolding their students' learning within the open-ended activities they implemented. Limitations of the teachers' conceptual and procedural knowledge of design and technology were elements that influenced their early experiences. The study has implications for professional developers planning programs in newly introduced areas of the curriculum to support teachers in supporting learning within open-ended and loosely structured problem solving activities. (C) 2001 Elsevier Science Ltd. All rights reserved.

Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical group A streptococcal peptide vaccine candidate from the M protein using lipid-core peptide technology

A conserved helical peptide vaccine candidate from the M protein of group A streptococci, p145, has been described. Minimal epitopes within p145 have been defined and an epitope recognized by protective antibodies, but not by autoreactive T cells, has been identified. When administered to mice, p145 has low immunogenicity. Many boosts of peptide are required to achieve a high antibody titre (> 12 800). To attempt to overcome this low immunogenicity, lipid-core peptide technology was employed. Lipid-core peptides (LCP) consist of an oligomeric polylysine core, with multiple copies of the peptide of choice, conjugated to a series of lipoamino acids, which acts as an anchor for the antigen. Seven different LCP constructs based on the p145 peptide sequence were synthesized (LCP1-->LCP7) and the immunogenicity of the compounds examined. The most immunogenic constructs contained the longest alkyl side-chains. The number of lipoamino acids in the constructs affected the immunogenicity and spacing between the alkyl side-chains increased immunogenicity. An increase in immunogenicity (enzyme-linked immunosorbent assay (ELISA) titres) of up to 100-fold was demonstrated using this technology and some constructs without adjuvant were more immunogenic than p145 administered with complete Freund's adjuvant (CFA). The fine specificity of the induced antibody response differed for the different constructs but one construct, LCP4, induced antibodies of identical fine specificity to those found in endemic human serum. Opsonic activity of LCP4 antisera was more than double that of p145 antisera. These data show the potential for LCP technology to both enhance immunogenicity of complex peptides and to focus the immune response towards or away from critical epitopes.

Aerosolization of protein solutions using thermal inkjet technology

Vapotronics Inc. is developing the thermal inkjet (TIJ) technology used extensively in the printer industry to create a digital aerosol inhaler for the inhalation of therapeutics for local and systemic delivery. The operation of thermal inkjet printers requires generation of high temperatures and vaporization of the liquid formulation to effect droplet ejection. A study was conducted to develop formulations that would permit the generation of aerosols of therapeutic proteins without damage to the inkjet system or degradation of the proteins. Two proteins, human growth hormone and insulin, were formulated and aerosolized. The aerosol was collected and subjected to assays to compare the physicochemical and biological activities of these proteins before and after aerosolization. In each case, there was no significant changes to the proteins as a result of the aerosolization, providing evidence that TIJ can be used for aerosolizing solutions of protein therapeutics.

Acquisition and loss of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia over a 5-year period: effect of a triclosan/copolymer dentifrice

Objectives: The present study describes the natural history of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia over a 5-year period and the effect of a triclosan/copolymer dentifrice on these organisms in a normal adult population. Material and Methods: Subgingival plaque samples were collected from 504 adult volunteers. Probing pocket depths (PPD) and relative attachment levels were measured using an automated probe. Participants were matched for disease status (CPI), plaque index, age and gender, and allocated to receive either a triclosan/copolymer or placebo dentifrice. Re-examination and subgingival plaque sampling was repeated after 1, 2, 3, 4 and 5 years. P. gingivalis, A. actinomycetemcomitans and P. intermedia were detected and quantitated using an enzyme linked immunosorbent assay. Logistic regression and generalised linear modelling were used to analyse the data. Results: This 5-year longitudinal study showed considerable volatility in acquisition and loss (below the level of detection) of all three organisms in this population. Relatively few subjects had these organisms on multiple occasions. While P. gingivalis was related to loss of attachment and to PPD greater than or equal to3.5 mm, there was no relationship between A. actinomycetemcomitans or P. intermedia and disease progression over the 5 years of the study. Smokers with P. gingivalis had more PPD greater than or equal to3.5 mm than smokers without this organism. There was no significant effect of the triclosan dentifrice on P. gingivalis or A. actinomycetemcomitans . Subjects using triclosan were more likely to have P. intermedia than those not using the dentifrice; however this did not translate into these subjects having higher levels of P. intermedia and its presence was uniform showing no signs of increasing over the course of the study. Conclusion: The present 5-year longitudinal study has shown the transient nature of colonisation with P. gingivalis , A. actinomycetemcomitans and P. intermedia in a normal adult population. The use of a triclosan-containing dentifrice did not lead to an overgrowth of these organisms. The clinical effect of the dentifrice would appear to be independent of its antimicrobial properties.

Valuing of firm's prior knowledge: A measure of knowledge distance

Knowledge, especially scientific and technological knowledge, grows according to knowledge trajectories and guideposts that make up the prior knowledge of an organization. We argue that these knowledge structures and their specific components lead to successful innovation. A firm's prior knowledge facilitates the absorption of new knowledge, thereby renewing a firm's systematic search, transfer and acquisition of knowledge and capabilities. In particular, the exponential growth in biotechnology is characterized by the convergence of disparate scientific and technological knowledge resources. This paper examines the shift from protein-based to DNA-based diagnostic technologies as an example, to quantify the value of a firm's prior knowledge using relative values of knowledge distance. The distance between core prior knowledge and the rate of transition from one knowledge system to another has been identified as a proxy for the value a firm's prior knowledge. The overall difficulty of transition from one technology paradigm to another is discussed. We argue this transition is possible when the knowledge distance is minimal and the transition process has a correspondingly high value of absorptive capacities. Our findings show knowledge distance is a determinant of the feasibility, continuity and capture of scientific and technological knowledge. Copyright © 2003 John Wiley & Sons, Ltd.