Explicit evidence-based prescribing criteria - an important step in achieving quality therapeutics in nursing homes

Reaction between 5-(4-amino-2-thiabutyl)-5-methyl-3,7-dithianonane-1, 9-diamine (N3S3) and 5- methyl-2,2-bipyridine-5-carbaldehyde and subsequent reduction of the resulting imine with sodium borohydride results in a potentially ditopic ligand (L). Treatment of L with one equivalent of an iron( II) salt led to the monoprotonated complex [Fe(HL)](3+), isolated as the hexafluorophosphate salt. The presence of characteristic bands for the tris( bipyridyl) iron( II) chromophore in the UV/vis spectrum indicated that the iron( II) atom is coordinated octahedrally by the three bipyridyl (bipy) groups. The [Fe( bipy) 3] moiety encloses a cavity composed of the N3S3 portion of the ditopic ligand. The mononuclear and monomeric nature of the complex [Fe(HL)](3+) has been established also by accurate mass analysis. [Fe(HL)](3+) displays reduced stability to base compared with the complex [Fe(bipy)(3)](2+). In aqueous solution [Fe(HL)](3+) exhibits irreversible electrochemical behaviour with an oxidation wave ca. 60 mV to more positive potential than [Fe(bipy)(3)](2+). Investigations of the interaction of [Fe(L)](2+) with copper( II), iron( II), and mercury( II) using mass spectroscopic and potentiometric methods suggested that where complexation occurred, fewer than six of the N3S3 cavity donors were involved. The high affinity of the complex [Fe(L)](2+) for protons is one reason suggested to contribute to the reluctance to coordinate a second metal ion.

Linear ketenimines. Variable structures of C,C-dicyanoketenimines and C,C-bis-sulfonylketenimines

C,C-Dicyanoketenimines 10a-c were generated by flash vacuum thermolysis of ketene NS-acetals 9a-c or by thermal or photochemical decomposition of alpha-azido-,beta-cyanocinnamonitrile 11. In the latter reaction, 3,3-dicyano-2-phenyl-1-azirine 12 is also formed. IR spectroscopy of the keteniminines isolated in Ar matrixes or as neat films, NMR spectroscopy of 10c, and theoretical calculations (B3LYP/6-31G*) demonstrate that these ketenimines have variable geometry, being essentially linear along the CCN-R framework in polar media (neat films and solution), but in the gas phase or Ar matrix they are bent, as is usual for ketenimines. Experiments and calculations agree that a single CN substituent as in 13 is not enough to enforce linearity, and sulfonyl groups are less effective that cyano groups in causing linearity. C,C-Bis(methylsulfonyl)ketenimines 4-5 and a C-cyano-C-(methylsulfonyl)ketenimine 15 are not linear. The compound p-O2NC6H4N=C= C(COOMe)2 previously reported in the literature is probably somewhat linearized along the CCNR moiety. A computational survey (B3LYP/6-31G*) of the inversion barrier at nitrogen indicates that electronegative C-substituents dramatically lower the barrier; this is also true of N-acyl substituents. Increasing polarity causes lower barriers. Although N-alkylbis(methylsulfonyl)ketenimines are not calculated to be linear, the barriers are so low that crystal lattice forces can induce planarity in N-methylbis(methylsulfonyl)ketenimine 3.

Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII

The selection, synthesis and chromatographic evaluation of a synthetic affinity adsorbent for human recombinant factor VIIa is described. The requirement for a metal ion-dependent immunoadsorbent step in the purification of the recombinant human clotting factor, FVIIa, has been obviated by using the X-ray crystallographic structure of the complex of tissue factor (TF) and Factor VIIa and has directed our combinatorial approach to select, synthesise and evaluate a rationally-selected affinity adsorbent from a limited library of putative ligands. The selected and optimised ligand comprises a triazine scaffold bis-substituted with 3-aminobenzoic acid and has been shown to bind selectively to FVIIa in a Ca2+-dependent manner. The adsorbent purifies FVIIa to almost identical purity (>99%), yield (99%), activation/degradation profile and impurity content (∼1000 ppm) as the current immunoadsorption process, while displaying a 10-fold higher static capacity and substantially higher reusability and durability. © 2002 Elsevier Science B.V. All rights reserved.

Early intervention: Narratives of learning, discipline and enculturation

Current understandings about literacy have moved away from the belief that literacy is simply a process that individuals do in their heads. These understandings do not negate the importance of the individual aspects of literacy learning, but they emphasize understandings of literacy as a social practice. In many cases, responses to early literacy intervention seem to be grounded in theories that appear out of step with current literacy research and consequent evidence that literacy is socially and culturally constructed. One such response is the Reading Recovery programme based on Clay’s theory of literacy acquisition. Clay (1992) describes the programme as a second chance to learn. However, others have suggested that programmes like Reading Recovery may in fact work toward the marginalization of particular groups, thereby helping to maintain the status quo along class, gender and ethnic lines. This article allows two professionals to bring their insider’s knowledge of Reading Recovery to an analysis of the construction of the programme. The article interweaves this analysis with the personal narratives of the researchers as they negotiated the borders between different understandings and beliefs about literacy and literacy pedagogy.

Shear stress and sediment transport calculations for swash zone modelling

It is shown that the observed difference in sediment transporting efficiency by the swash uprush, compared with the downrush, could be mainly due to greater bed shear stress for a given velocity in the more abruptly accelerated uprush. The bed shear stress generated by an arbitrary free stream velocity time series is modelled in terms of usual wave boundary layer models plus a phase lead (phi(tau) of the bed shear stress compared with the free stream velocity at the peak frequency. With this approach, the total transport amounts in uprush and downrush can be modelled satisfactorily with the same sediment transport formula, without the need for different uprush and downrush coefficients. While the adaptation of sediment transport formulae from steady flow can thus lead to the right total amounts of sediment moved by this method, the timing of the instantaneous sediment transport rates are probably not accurately modelled due to the highly unsteady nature of the swash and the presence of pre-suspended sediment in the uprush. Nevertheless, the proposed method is a useful intermediate step before we have a complete understanding of sediment transport under very rapid accelerations and of the relative contribution of pre-suspended sediment to the onshore sediment transport in swash zones. (C) 2002 Published by Elsevier Science B.V.

The influence of preparedness on rapid stepping in young and older adults

Objective: To investigate the influence of age and preparation level on postural muscle activation and step completion time during a rapid step task. Design: Postural muscle onset times (EMG) and ground reaction forces were recorded from healthy young (n = 20, age 21 +/- 3 years) and older (n = 25, age 71 +/- 5 years) female adults during a choice reaction-time stepping paradigm. Main outcome measures: Onset times of six trunk and hip muscles, reaction time and components of the step (weight shift time, step time and task time) were recorded. Results: Muscle activation was delayed and movement time was lengthened in both young and older adults when poorly prepared for a stepping task. While reduced preparation did not influence older adults to a greater extent than young adults, the slowest step response and completion time was evident in older adults when poorly prepared to move. Conclusions: A late postural response when poorly prepared to move may be a contributing factor to an increased risk of overbalancing in older adults. Future assessment of and intervention to improve postural stability in older adults should be expanded to incorporate tasks performed at various levels of preparation.

The influence of a concurrent cognitive task on the compensatory stepping response to a perturbation in balance-impaired and healthy elders

This study investigated the influence of a concurrent cognitive task on the compensatory stepping response in balance-impaired elders and the attentional demand of the stepping response. Kinetic, kinematic and neuromuscular measures of a forward recovery step were investigated in 15 young adults, 15 healthy elders and 13 balance-impaired elders in a single task (postural recovery only) and dual task (postural recovery and vocal reaction time task) situation. Results revealed that reaction times were longer in all subjects when performed concurrently with a compensatory step, they were longer for a step than an in-place response and longer for balance-impaired older adults compared with young adults. An interesting finding was that the latter group difference may be related to prioritization between the two tasks rather than attentional demand, as the older adults completed the step before the reaction time, whereas the young adults could perform both concurrently. Few differences in step characteristics were found between tasks, with the most notable being a delayed latency and reduced magnitude of the early automatic postural response in healthy and balance-impaired elders with a concurrent task. (C) 2002 Elsevier Science B.V. All rights reserved.

Adsorption in slit-like pores of activated carbons: Improvement of the Horvath and Kawazoe method

Anew thermodynamic approach has been developed in this paper to analyze adsorption in slitlike pores. The equilibrium is described by two thermodynamic conditions: the Helmholtz free energy must be minimal, and the grand potential functional at that minimum must be negative. This approach has led to local isotherms that describe adsorption in the form of a single layer or two layers near the pore walls. In narrow pores local isotherms have one step that could be either very sharp but continuous or discontinuous benchlike for a definite range of pore width. The latter reflects a so-called 0 --> 1 monolayer transition. In relatively wide pores, local isotherms have two steps, of which the first step corresponds to the appearance of two layers near the pore walls, while the second step corresponds to the filling of the space between these layers. All features of local isotherms are in agreement with the results obtained from the density functional theory and Monte Carlo simulations. The approach is used for determining pore size distributions of carbon materials. We illustrate this with the benzene adsorption data on activated carbon at 20, 50, and 80 degreesC, argon adsorption on activated carbon Norit ROX at 87.3 K, and nitrogen adsorption on activated carbon Norit R1 at 77.3 K.

Simulation of the load-unload response ratio and critical sensitivity in the lattice solid model

The Load-Unload Response Ratio (LURR) method is an intermediate-term earthquake prediction approach that has shown considerable promise. It involves calculating the ratio of a specified energy release measure during loading and unloading where loading and unloading periods are determined from the earth tide induced perturbations in the Coulomb Failure Stress on optimally oriented faults. In the lead-up to large earthquakes, high LURR values are frequently observed a few months or years prior to the event. These signals may have a similar origin to the observed accelerating seismic moment release (AMR) prior to many large earthquakes or may be due to critical sensitivity of the crust when a large earthquake is imminent. As a first step towards studying the underlying physical mechanism for the LURR observations, numerical studies are conducted using the particle based lattice solid model (LSM) to determine whether LURR observations can be reproduced. The model is initialized as a heterogeneous 2-D block made up of random-sized particles bonded by elastic-brittle links. The system is subjected to uniaxial compression from rigid driving plates on the upper and lower edges of the model. Experiments are conducted using both strain and stress control to load the plates. A sinusoidal stress perturbation is added to the gradual compressional loading to simulate loading and unloading cycles and LURR is calculated. The results reproduce signals similar to those observed in earthquake prediction practice with a high LURR value followed by a sudden drop prior to macroscopic failure of the sample. The results suggest that LURR provides a good predictor for catastrophic failure in elastic-brittle systems and motivate further research to study the underlying physical mechanisms and statistical properties of high LURR values. The results provide encouragement for earthquake prediction research and the use of advanced simulation models to probe the physics of earthquakes.

Inhibitors of COP-mediated Transport and Cholera Toxin Action Inhibit Simian Virus 40 Infection

Simian virus 40 (SV40) is a nonenveloped virus that has been shown to pass from surface caveolae to the endoplasmic reticulum in an apparently novel infectious entry pathway. We now show that the initial entry step is blocked by brefeldin A and by incubation at 20degreesC. Subsequent to the entry step, the virus reaches a domain of the rough endoplasmic reticulum by an unknown pathway. This intracellular trafficking pathway is also brefeldin A sensitive. Infection is strongly inhibited by expression of GTP-restricted ADP-ribosylation factor 1 (Arf1) and Sar1 mutants and by microinjection of antibodies to betaCOP. In addition, we demonstrate a potent inhibition of SV40 infection by the dipeptide N-benzoyl-oxycarbonyl-Gly-Phe-amide, which also inhibits late events in cholera toxin action. Our results identify novel inhibitors of SV40 infection and show that SV40 requires COPI- and COPII-dependent transport steps for successful infection.

The role of space as both a conflict trigger and a conflict control mechanism in culturally heterogeneous workgroups

The diversity literature is replete with examples of poor outcomes in Culturally Heterogeneous Workgroups (CHWs) caused by relational difficulties. Although it is widely recognised that culture shapes people's interpretation of behavior and their style of interaction with others in the workplace, what is ill understood is what the specific conflict triggers of these conflicts are. In this paper, we argue that differences in cultural norms and views of physical and psychological space are major triggers of conflict in CHWs. Findings from a field study support the proposition that different viewpoints regarding the use of space, the inability to retreat from exposure to others, decreased interpersonal space, and privacy invasion moderate the relationship between cultural diversity in the workgroup and the type, frequency, and duration of conflict events in CHWs. The paper represents a first step in elucidating the role of space in cross-cultural interactions in the workplace and how space may be a potentially important conflict control mechanism for managers of culturally diverse workgroups.

The JK three-product cyclone - performance and potential applications

In spite of their wide application in comminution circuits, hydrocyclones have at least one significant disadvantage in that their operation inherently tends to return the fine denser liberated minerals to the grinding mill. This results in unnecessary overgrinding which adds to the milling cost and can adversely affect the efficiency of downstream processes. In an attempt to solve this problem, a three-product cyclone has been developed at the Julius Kruttschnitt Mineral Research Centre (JKMRC) to generate a second overflow in which the fine dense liberated minerals can be selectively concentrated for further treatment. In this paper, the design and operation of the three-product cyclone are described. The influence of the length of the second vortex finder on the performance of a 150-mm unit treating a mixture of magnetite and silica is investigated. Conventional cyclone tests were also conducted under similar conditions. Using the operational performance data of the three-product and conventional cyclones, it is shown that by optimising the length of the second vortex finder, the amount of fine dense mineral particles that reports to the three-product cyclone underflow can be reduced. In addition, the three-product cyclone can be used to generate middlings stream that may be more suitable for flash flotation than the conventional cyclone underflow, or alternatively, could be classified with a microscreen to separate the valuables from the gangue. At the same time, a fines stream having similar properties to those of the conventional overflow can be obtained. Hence, if the middlings stream was used as feed for flash flotation or microscreening, the fines stream could be used in lieu of the conventional overflow without compromising the feed requirements for the conventional flotation circuit. Some of the other potential applications of the new cyclone are described. (C) 2003 Elsevier Science B.V. All rights reserved.

Further evidence for the reliance of catalysis by rabbit muscle pyruvate kinase upon isomerization of the ternary complex between enzyme and products

Isothermal calorimetry has been used to examine the effect of thermodynamic non-ideality on the kinetics of catalysis by rabbit muscle pyruvate kinase as the result of molecular crowding by inert cosolutes. The investigation, designed to detect substrate-mediated isomerization of pyruvate kinase, has revealed a 15% enhancement of maximal velocity by supplementation of reaction mixtures with 0.1 M proline, glycine or sorbitol. This effect of thermodynamic non-ideality implicates the existence of a substrate-induced conformational change that is governed by a minor volume decrease and a very small isomerization constant; and hence, substantiates earlier inferences that the rate-determining step in pyruvate kinase kinetics is isomerization of the ternary enzyme product complex rather than the release of products. (C) 2003 Elsevier Science B.V. All rights reserved.