Copper complexes of new benzodioxotetraaza macrocycles with potential applications in nuclear medicine

Two novel benzodioxotetraaza macrocycles [2,9-dioxo-1,4,7,10-tetraazabicyclo[10.4.0]1,11-hexadeca-1(11),13,15-triene (H(2)L1) and 2,10-dioxo-1,4,8,11-tetraazabicyclo[11.4.0]1,12-heptadeca-1(12),14,16-triene (H(2)L2)] were synthesized by a [1 + 1] crablike cyclization. The protonation constants of both ligands were determined by H-1 NMR titration and by potentiometry at 25.0 degrees C in 0.10 M ionic strength in KNO3. The latter method was also used to ascertain the stability constants of their copper(II) complexes. These studies showed that the CuL1 complex has a much lower thermodynamic stability than the CuL2, and the H(2)L2 displays an excellent affinity for copper(II), due to the good fit of copper(II) into its cavity. The copper complexes of the novel ligands were characterized by electronic spectroscopy in solution and by crystal X-ray diffraction. These studies indicated that the copper center in the CuL1 complex adopts a square-pyramidal geometry with the four nitrogen atoms of the macrocycle forming the equatorial plane and a water molecule at axial position, and the copper in the CuL2 complex is square-planar. Several labeling conditions were tested, and only H(2)L2 could be labeled with Cu-67 efficiently (> 98%) in mild conditions (39 degrees C, 15 min) to provide a slightly hydrophilic radioligand (log D = -0.19 +/- 0.03 at pH 7.4). The in vitro stability was studied in the presence of different buffers or with an excess of diethylenetriamine-pentaethanoic acid. Very high stability was shown under these conditions for over 5 days. The incubation of the radiocopper complex in human serum showed 6% protein binding.

Making sense of supply chain management: acomparative study of aerospace and construction

Current recipes for learning across business sectors too often fail to recognize the embedded and contextual nature of management practice. The existing literature gives little emphasis to the symbiotic relationship between supply chain management and the broader dynamics of context. The aerospace and construction sectors are selected for comparison on the basis that they are so different. The UK aerospace sector has undergone extensive consolidation as a result of the imperatives of global competitive pressures. In contrast, the construction industry has experienced decades of fragmentation and remains highly localized. An increasing proportion of output in the aerospace sector occurs within a small number of large, globally orientated firms. In contrast, construction output is dominated by a plethora of small firms with high levels of subcontracting and a widespread reliance on self-employment. These differences have fundamental implications for the way that supply chain management is understood and implemented in the two sectors. Semi-structured interviews with practitioners from both sectors support the contention that supply chain management is more established in aerospace than construction. The introduction of prime contracting and the increasing use of framework agreements within the construction sector potentially provide a much more supportive climate for supply chain management than has traditionally prevailed. However, progress depends upon an improved continuity of workload under such arrangements.

Learning across business sectors: Knowledge sharing between aerospace and construction

This report addresses the extent that managerial practices can be shared between the aerospace and construction sectors. Current recipes for learning from other industries tend to be oversimplistic and often fail to recognise the embedded and contextual nature of managerial knowledge. Knowledge sharing between business sectors is best understood as an essential source of innovation. The process of comparison challenges assumptions and better equips managers to cope with future change. Comparisons between the aerospace and construction sectors are especially useful because they are so different. The two sectors differ hugely in terms of their institutional context, structure and technological intensity. The aerospace sector has experienced extensive consolidation and is dominated by a small number of global companies. Aerospace companies operate within complex networks of global interdependency such that collaborative working is a commercial imperative. In contrast, the construction sector remains highly fragmented and is characterised by a continued reliance on small firms. The vast majority of construction firms compete within localised markets that are too often characterised by opportunistic behaviour. Comparing construction to aerospace highlights the unique characteristics of both sectors and helps explain how managerial practices are mediated by context. Detailed comparisons between the two sectors are made in a range of areas and guidance is provided for the implementation of knowledge sharing strategies within and across organisations. The commonly accepted notion of ‘best practice’ is exposed as a myth. Indeed, universal models of best practice can be detrimental to performance by deflecting from the need to adapt continuously to changing circumstances. Competitiveness in the construction sector too often rests on efficiency in managing contracts, with a particular emphasis on the allocation of risk. Innovation in construction tends to be problem-driven and is rarely shared from project to project. In aerospace, the dominant model of competitiveness means that firms have little choice other than to invest in continuous innovation, despite difficult trading conditions. Research and development (R&D) expenditure in aerospace continues to rise as a percentage of turnovers. A sustained capacity for innovation within the aerospace sector depends crucially upon stability and continuity of work. In the construction sector, the emergence of the ‘hollowed-out’ firm has undermined the industry’s capacity for innovation. Integrated procurement contexts such as prime contracting in construction potentially provide a more supportive climate for an innovation-based model of competitiveness. However, investment in new ways of working depends upon a shift in thinking not only amongst construction contractors, but also amongst the industry’s major clients.

Learning across business sectors: facets of innovation in aerospace and construction

Innovation is notoriously difficult to define and is invariably intertwined with issues of knowledge creation, continuous improvement and organisational change. An extensive literature classifies numerous types of innovation and militates against any simplistic attempt at definition. It is widely accepted that innovation is at least partly dependent upon the surrounding environment. Industry recipes and institutionally embedded practices shape the environment within which innovation occurs. Recent research directions have addressed the diffusion of innovation and its dependence upon social and institutional structures. In this respect, it is highly pertinent to compare the way that innovation is interpreted and enacted in different industrial sectors. The comparison between UK aerospace and construction is especially revealing because the two sectors are so different and therefore constitute radically different climates for innovation. Empirical research is reported based on semi-structured interviews with practitioners from both sectors. Interpretations of innovation are found to differ dramatically between aerospace and construction. Within the context of an ongoing struggle to define innovation, both industries are striving to become more innovative. The aerospace sector is found to emphasise technical innovation whereas the construction sector emphasises process innovation. An overriding cultural bias in Western economies towards technological innovation results in the common perception that aerospace is much more innovative than construction. The experienced realities of practitioners in the two sectors are much more complex.

Herbal medicine: the science of the art

In the last 50 years science has provided new perspectives on the ancient art of herbal medicine. The present article discusses ways in which the evidence base for the professional use of 'Western' herbal medicine, as therapy to treat disease, known as phytotherapy, can be strengthened and developed. The evidence base for phytotherapy is small and lags behind that for the nutritional sciences, mainly because phytochemicals are ingested as complex mixtures that are incompletely characterised and have only relatively recently been subject to scientific scrutiny. While some methodologies developed for the nutritional sciences can inform phytotherapy research, opportunities for observational studies are more limited, although greater use could be made of patient case notes. Randomised clinical trials of single-herb interventions are relatively easy to undertake and increasing numbers of such studies are being published. Indeed, enough data are available on three herbs (ginkgo (Ginkgo biloba), St John's wort (Hypericum perforatum) and saw palmetto (Serenoa repens)) for meta-analyses to have been undertaken. However, phytotherapy is holistic therapy, using lifestyle advice, nutrition and individually-prescribed mixtures of herbs aimed at reinstating homeostasis. While clinical experience shows that this approach is applicable to a wide range of conditions, including chronic disease, evidence of its efficacy is scarce. Strategies for investigating the full holistic approach of phytotherapy and its main elements are discussed and illustrated through the author's studies at the University of Reading.

The benefits of providing benefit information: examining the effectiveness of provision of simple benefit statements on people's judgements about a medicine

Three experiments examined the effects of adding information about medication benefits to a short written explanation about a medicine. Participants were presented with a fictitious scenario about visiting the doctor, being prescribed an antibiotic and being given information about the medicine. They were asked to make various judgements relating to the information, the medicine and their intention to take it. Experiment 1 found that information about benefits enhanced the judgements, but did not influence the intention to comply. Experiment 2 compared the relative effectiveness of two different forms of the benefit statement, and found that both were effective in improving judgements, but had no effect on intention to comply. Experiment 3 compared the effectiveness of the two forms of benefit information but participants were told that the medicine was associated with four named side effects. Both types of statement improved ratings of the intention to comply, as well as ratings on the other measures. The experiments provide fairly consistent support for the inclusion of benefit information in medicine information leaflets, particularly to balance concerns about side effects.

Expressing medicine side effects: assessing the effectiveness of absolute risk, relative risk, and number needed to harm, and the provision of baseline risk information

Objective: To assess the effectiveness of absolute risk, relative risk, and number needed to harm formats for medicine side effects, with and without the provision of baseline risk information. Methods: A two factor, risk increase format (relative, absolute and NNH) x baseline (present/absent) between participants design was used. A sample of 268 women was given a scenario about increase in side effect risk with third generation oral contraceptives, and were required to answer written questions to assess their understanding, satisfaction, and likelihood of continuing to take the drug. Results: Provision of baseline information significantly improved risk estimates and increased satisfaction, although the estimates were still considerably higher than the actual risk. No differences between presentation formats were observed when baseline information was presented. Without baseline information, absolute risk led to the most accurate performance. Conclusion: The findings support the importance of informing people about baseline level of risk when describing risk increases. In contrast, they offer no support for using number needed to harm. Practice implications: Health professionals should provide baseline risk information when presenting information about risk increases or decreases. More research is needed before numbers needed to harm (or treat) should be given to members of the general populations. (c) 2005 Elsevier Ireland Ltd. All rights reserved.