Bead compacts. II. Evaluation of rapidly disintegrating nonsegregating compressed bead formulations

In this study, three techniques for the prevention or mitigation of polymer coat fracture on compaction of sustained-release beads into tablets were investigated. All techniques in this paper were evaluated without the addition of any cushioning excipients, but rather by spray coating these excipients to avoid segregation during product manufacturing. First, it was shown that use of swellable polymers such as polyethylene oxide (PEO) serves a unique and effective role in preventing polymer coat rupture. PEO was spray coated between the ethylcellulose (EC) and microcrystalline cellulose (MCC) coats to evaluate its cushioning effect. The compacted PEO layered beads, on dissolution, disintegrated into individual beads with sustained drug release of up to 8 hr. It is postulated that the PEO was hydrated and formed a gel that acts as a sealant for the cracks formed in the ruptured polymer coating (sealant-effect compacts). Second, EC-coated drug-layered beads were also overcoated with cushioning excipients such as polyethylene glycol (PEG) and MCC with an additional coating of a disintegrant. These beads were compressed at pressures of 125, 500, and 1000 pounds into caplets and, on dissolution testing, disintegrated into individual beads when the dissolution medium was switched from simulated gastric to intestinal fluid. The dissolution profiles show that the polymer coat was partly disrupted on compaction, leading to a total drug release in 8-10 hr. Third, EC-coated beads were also granulated with cushioning excipient and compressed. This approach also resulted in a ruptured polymer coat on the beads, but at higher compaction pressure produced a partially disintegrating matrix caplet that showed a nearly zero-order sustained drug release for 24 hr. The effect of bead size and polymer coat thickness was also investigated.     

The Functional Data Model as the Basis for an Enriched Database Query Language

Conventional database languages rely on the user specifying what relations are to be used when evaluating a query. Consequently they preclude queries which involve searching for unspecified connections or associations in the database. In this paper we present Hydra, a functional language with all the facilities to define, update and query a database, which also enables users to carry out associational queries. Hydra uses a graph-based data model in which nodes represent values or entities and arcs the relationships between them. Associational facilities are made possible by the provision of built-in functions which find paths through the database graph. The mappings between sets of nodes in the database graph are represented as functions at the Hydra language level and it is as lists of such functions that associational results are returned. The use of a functional language is important since such languages allow functions to be returned as results; such an approach could not be adopted in a logic-based language which would not permit predicates to be returned as answers. Hydra also allows users to define general computational functions which are not considered to form part of the database. This use of two sets of functions achieves a computationally complete system which extends the query power of previous database systems without compromising their expressive or query power.     

The 1.7 kilogram microchip: energy and material use in the production of semiconductor devices

The scale of environmental impacts associated with the manufacture of microchips is characterized through analysis of material and energy inputs into processes in the production chain. The total weight of secondary fossil fuel and chemical inputs to produce and use a single 2-gram 32MB DRAM chip are estimated at 1600 g and 72 g, respectively. Use of water and elemental gases (mainly N2) in the fabrication stage are 32,000 and 700 g per chip, respectively. The production chain yielding silicon wafers from quartz uses 160 times the energy required for typical silicon, indicating that purification to semiconductor grade materials is energy intensive. Due to its extremely low-entropy, organized structure, the materials intensity of a microchip is orders of magnitude higher than that of "traditional" goods. Future analysis of semiconductor and other low entropy high-tech goods needs to include the use of secondary materials, especially for purification.     

Should hand actions be observed when learning hand motor skills from instructional animations?

This study investigated whether the effectiveness of learning a hand-motor task through an instructional animation required observation of the hands or not. Cognitive load theory was used to predict that both animated conditions (with and without hands) would be equally effective, and that both animations would be superior to an equivalent static graphics presentation. 36 adults were randomly assigned to three groups (With-hands animation, No-hands animation, Statics graphics) and were required to learn how to tie two knots. Test results confirmed that both animations led to superior learning compared to the static presentation. However, the With-hands animation strategy had a further advantage in that it had higher instructional efficiency than the No-hands animation.     

Model Intervals

This paper summarizes the most important results and features of Modal Interval Analysis. The ground idea of Interval mathematics is that ordinary set-theoretical intervals are the consistent context for numerical computing. However, this interval context presents basic structural and semantic rigidity arising from its set-theoretical foundation. To correct this situation, Modal Interval Analysis defines intervals starting from the identification of real numbers with the sets of predicates they accept or reject. A modal interval is defined as a pair formed by a classical interval (i.e. a set of numbers) and a quantifier, following a similar method to that in which real numbers are associated in pairs having the same absolute value but opposite signs. Two different extensions for a continuous function (called semantic extensions, since both will have a meaning thanks to the important semantic theorems) are defined and their properties are established. The definition of the rational extension, and its relationships with the semantic extensions, it make possible to compute the semantic extensions and to give a logical meaning to the interval results of a rational computations.For some functions the semantic extensions are equal, for instance, for the arithmetic operators, which can be obtained through computations with the intervals' bounds, obtaining the definitions of the well-known Kaucher's completed interval arithmetic. It is important to remark that the process of the construction of the Modal Interval Analysis is absolutely different from the process followed by Kaucher.Similarly to the Kaucher's completed interval arithmetic, with modal intervals it is possible to solve the equations A + X = B or A * X = B but with a very important difference. To find the algebraic solution for the equation A + X = B or A * X = B when A, X and B are classical intervals is a single problem: a) to find and interval X which substituted in the corresponding equation, satisfies the equality. Modal Interval Analysis not only solves that problem but also it gives a logical meaning to the solution.As a conclusion, the most important difference between Modal Interval Analysis versus Classical Intervals + Kaucher's Completed Arithmetic is the logical-semantic ground of the modal intervals and the meaning for the interval results in the functional computations or in the solution of a linear equation, provided by the semantic theorems.     

Enhancing OSGi with real‐time Java support

OSGi was designed with embedded systems in mind, its current support is insufficient for coping with one main characteristic of many embedded systems: real‐time performance. This article analyzes different key issues in providing OSGi with real‐time Java performance covering motivational issues, and different integration ways and challenges stemming from the integration. It also contributes a general framework for introducing real‐time performance in OSGi, which is called the real‐time for OSGi framework. The framework uses real‐time Java virtual machines and the real‐time specification for Java. The adoption of this framework allows cyber‐physical systems to experience real‐time Java performance in their applications. The framework introduces several integration levels for OSGi and real‐time specification for Java, and specific real‐time OSGi services. An empirical implementation was carried out using standard software, which was extended with the new defined services. Copyright © 2012 John Wiley & Sons, Ltd.     

Variation in semiochemical-mediated prey-predator interaction:Ips pini (Scolytidae) andThanasimus dubius (Cleridae)

The bark beetleIps pini (Say) displays variation in its response to and production of enantiomeric blends of its pheromone ipsdienol. One of the principal predators ofIps pini isThanasimus dubius (F.), which uses ipsdienol as a kairomone for prey location. During 1988 and 1989, in Wisconsin and Michigan, the response of both species to a range of enantiomeric blends of ipsdienol was investigated. Blends tested had the following ratios of the (S)-(+) to (R)-(–) enantiomers: 3%97%, 25%75%, 50%50%, 75%25%, and 97%3%. Either75% (+) 25% (–) or 50% (+) 50% (–) ipsdienol captured the mostIps pini in both years at both sites. The 25% (+)75% (–) blend also caught moreIps pini than the control during both years at both sites. All blends tested were attractive toThanasimus dubius in both years at both locations. Blend preferences of both species were variable and labile at both sites. Response patterns of both species in Wisconsin were different from those in Michigan each year. Furthermore, response patterns of both species to the ipsdienol blends changed from 1988 to 1989 at both locations. A genetic component to this variation would permit predator-prey coevolution, as well as the development of resistance byIps pini to management strategies based on mass-trapping with single blends.     

Adding clicks to bricks: A study of the consequences on customer loyalty in a service context

With the explosion of the Internet many firms are incorporating technology into their marketing and operations and are adopting a multichannel strategy. The impact of this strategy has been especially high in the services area, which has traditionally relied on close, personal contact between customers and employees. This study explores how overall customer loyalty is built as a consequence of the value provided by each channel (offline and online). It also analyzes the moderating role of complexity of services used and customers’ Internet access in the service value–loyalty link. The model is tested with a sample of 302 multichannel financial services customers who use both the offline (traditional) and the online channel. Results show that offline perceived service value increases online perceived value; offline value has a stronger effect on overall loyalty than online value; and online service complexity and Internet adoption moderate the influence of service value on overall loyalty. Implications for management and theory are discussed.     

Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways

Background

Exposure to fine ambient particulate matter (PM) has consistently been associated with increased morbidity and mortality. The relationship between exposure to ultrafine particles (UFP) and health effects is less firmly established. If UFP cause health effects independently from coarser fractions, this could affect health impact assessment of air pollution, which would possibly lead to alternative policy options to be considered to reduce the disease burden of PM. Therefore, we organized an expert elicitation workshop to assess the evidence for a causal relationship between exposure to UFP and health endpoints.

Methods

An expert elicitation on the health effects of ambient ultrafine particle exposure was carried out, focusing on: 1) the likelihood of causal relationships with key health endpoints, and 2) the likelihood of potential causal pathways for cardiac events. Based on a systematic peer-nomination procedure, fourteen European experts (epidemiologists, toxicologists and clinicians) were selected, of whom twelve attended. They were provided with a briefing book containing key literature. After a group discussion, individual expert judgments in the form of ratings of the likelihood of causal relationships and pathways were obtained using a confidence scheme adapted from the one used by the Intergovernmental Panel on Climate Change.

Results

The likelihood of an independent causal relationship between increased short-term UFP exposure and increased all-cause mortality, hospital admissions for cardiovascular and respiratory diseases, aggravation of asthma symptoms and lung function decrements was rated medium to high by most experts. The likelihood for long-term UFP exposure to be causally related to all cause mortality, cardiovascular and respiratory morbidity and lung cancer was rated slightly lower, mostly medium. The experts rated the likelihood of each of the six identified possible causal pathways separately. Out of these six, the highest likelihood was rated for the pathway involving respiratory inflammation and subsequent thrombotic effects.

Conclusion

The overall medium to high likelihood rating of causality of health effects of UFP exposure and the high likelihood rating of at least one of the proposed causal mechanisms explaining associations between UFP and cardiac events, stresses the importance of considering UFP in future health impact assessments of (transport-related) air pollution, and the need for further research on UFP exposure and health effects.