Attenuation of muscle atrophy in a murine model of cachexia by inhibition of the dsRNA-dependent protein kinase

Atrophy of skeletal muscle is due to a depression in protein synthesis and an increase in degradation. Studies in vitro have suggested that activation of the dsRNA-dependent protein kinase (PKR) may be responsible for these changes in protein synthesis and degradation. In order to evaluate whether this is also applicable to cancer cachexia the action of a PKR inhibitor on the development of cachexia has been studied in mice bearing the MAC16 tumour. Treatment of animals with the PKR inhibitor (5 mg kg-1) significantly reduced levels of phospho-PKR in muscle down to that found in non-tumour-bearing mice, and effectively attenuated the depression of body weight, with increased muscle mass, and also inhibited tumour growth. There was an increase in protein synthesis in skeletal muscle, which paralleled a decrease in eukaryotic initiation factor 2α phosphorylation. Protein degradation rates in skeletal muscle were also significantly decreased, as was proteasome activity levels and expression. Myosin levels were increased up to values found in non-tumour-bearing animals. Proteasome expression correlated with a decreased nuclear accumulation of nuclear factor-κB (NF-κB). The PKR inhibitor also significantly inhibited tumour growth, although this appeared to be a separate event from the effect on muscle wasting. These results suggest that inhibition of the autophosphorylation of PKR may represent an appropriate target for the attenuation of muscle atrophy in cancer cachexia. © 2007 Cancer Research UK.

Explaining process and performance in the co-production of knowledge:a comparative analysis of collaborative research projects

Despite considerable and growing interest in the subject of academic researchers and practising managers jointly generating knowledge (which we term ‘co-production’), our searches of management literature revealed few articles based on primary data or multiple cases. Given the increasing commitment to co-production by academics, managers and those funding research, it seems important to strengthen the evidence base about practice and performance in co-production. Literature on collaborative research was reviewed to develop a framework to structure the analysis of this data and relate findings to the limited body of prior research on collaborative research practice and performance. This paper presents empirical data from four completed, large scale co-production projects. Despite major differences between the cases, we find that the key success factors and the indicators of performances are remarkably similar. We demonstrate many, complex influences between factors, between outcomes, and between factors and outcomes, and discuss the features that are distinctive to co-production. Our empirical findings are broadly consonant with prior literature, but go further in trying to understand success factors’ consequences for performance. A second contribution of this paper is the development of a conceptually and methodologically rigorous process for investigating collaborative research, linking process and performance. The paper closes with discussion of the study’s limitations and opportunities for further research.

A conceptual framework for supply chain collaboration:empirical evidence from the agri-food industry

Purpose - The purpose of this paper is to analyse the concept of supply chain collaboration and to provide an overall framework that can be used as a conceptual landmark for further empirical research. In addition, the concept is explored in the context of agri-food industry and particularities are identified. Finally, the paper submits empirical evidence from an exploratory case study in the agri-food industry, at the grower-processor interface, and information regarding the way the concept is actually applied in small medium-sized enterprises (SMEs) is presented. Design/methodology/approach - The paper employed case study research by conducting in-depth interviews in the two companies. Findings - Supply chain collaboration concept is of significant importance for the agri-food industry however, some constraints arise due to the nature of industry's products, and the specific structure of the sector. Subsequently, collaboration in the supply chain is often limited to operational issues and to logistics-related activities. Research limitations/implications - Research is limited to a single case study and further qualitative testing of the conceptual model is needed in order to adjust the model before large scale testing. Practical implications - Case study findings may be transferable to other similar dual relationships at the grower-processor interface. Weaker parts in asymmetric relationships have opportunities to improve their position, altering the dependence balance, by achieving product/process excellence. Originality/value - The paper provides evidence regarding the applicability of the supply chain collaboration concept in the agri-food industry. It takes into consideration not relationships between big multinational companies, but SMEs. © Emerald Group Publishing Limited.

An exploratory study of ICT usage in small logistics service providers

Information and communication technology (ICT) developments have strongly affected supply chain management (SCM) in recent years. ICT has had a great impact on all supply chain processes including planning, purchasing, production management, stock management, physical distribution and related integration management. Technology has become an important dimension of third party logistics (3PL) service supply as competitive advantage increasingly depends on the ability to create value for customers through the effective application of ICT. Within this process, while large 3PLs are gaining substantial benefits from technology usage and implementation, the magnitude of changes spurred by ICT dissemination in small logistics service providers remains unclear. This is reflected by the existing gap in literature where the role and competitive developing processes of small 3PLs are seriously underestimated. This gives rise to the need to develop research and investigation in this particular area. The objective of this paper is to narrow the knowledge gap in the field of ICT adoption in small 3PLs through an empirical investigation. It presents the results of a survey on a sample of small Italian 3PLs.

All change? Managers' experience of organizational change in theory and practice

Purpose - This paper aims to examine the usefulness of organizational change theory for management practice. Design/methodology/approach - The authors present an exploratory, empirical study of managers who were taught organizational change theory as part of a postgraduate degree. Building on the study findings, they analyse managers' subsequent experiences of organizational change; of how they use change theory in practice and the impact on their practice of their earlier formal study. Findings - The paper finds that the complexities of managing change in practice reflect distinctive organizational environments and cultures. The skills and knowledge which managers found most useful were those that enabled them to "make sense" of the organizational change they subsequently experienced. The main impact of their earlier studies was to prompt informative, discursive and reflective approaches to change management. Practical implications - The paper discusses the implications for future teaching of organizational change and the development of organizational change theory. Originality/value - The qualitative findings of the study add to, and help to explain, earlier research findings on the questions of how managers' experience change, how they use organizational change theory and its impact on their practice. © Emerald Group Publishing Limited.

B2B service brand identity and brand performance:an empirical investigation in the UK’s B2B IT services sector

Purpose – This paper aims to apply the business-to-business (B2B) Service Brand Identity (SBI) scale to empirically assess the influence of service brand identity on brand performance for the first time. Design/methodology/approach – Based on data collected from 421 senior marketing executives, this paper applies the B2B SBI and structural equation modeling to fulfill the above purpose. Findings – Brand personality and human resource initiatives have a positive and significant influence on brand performance. Corporate visual identity, in addition to an employee and client focus, has an insignificant impact on performance. Consistent communications have a negative and significant influence on brand performance. Research limitations/implications – Data were only collected from executives in the UK. This research would benefit from replicative studies. Practical implications – This research empirically establishes the brand management activities that drive brand performance. Originality/value – This is the first empirical study to assess the influence service brand identity has on brand performance.

Using the framework method for the analysis of qualitative data in multi-disciplinary health research

Background: The Framework Method is becoming an increasingly popular approach to the management and analysis of qualitative data in health research. However, there is confusion about its potential application and limitations. Discussion. The article discusses when it is appropriate to adopt the Framework Method and explains the procedure for using it in multi-disciplinary health research teams, or those that involve clinicians, patients and lay people. The stages of the method are illustrated using examples from a published study. Summary. Used effectively, with the leadership of an experienced qualitative researcher, the Framework Method is a systematic and flexible approach to analysing qualitative data and is appropriate for use in research teams even where not all members have previous experience of conducting qualitative research. © 2013 Gale et al.; licensee BioMed Central Ltd.

Assessing the impact of management concerns in e-business requirements planning in manufacturing organizations

This paper describes the application of a model, initially developed for determining the e-business requirements of a manufacturing organization, to assess the impact of management concerns on the functions generated. The model has been tested on 13 case studies in small, medium and large organizations. This research shows that the incorporation of concerns for generating the requirements for e-business functions improves the results, because they expose issues that are of relevance to the decision making process relating to e-business. Running the model with both and without concerns, and then presenting the reasons for major variances, can expose the issues and enable them to be studied in detail at the individual function/ reason level. © IFIP International Federation for Information Processing 2013.

Development of a technological innovation capability assessment model:a case study of manufacturing SMEs in Sialkot, Pakistan

Small and Medium Enterprises (SMEs) play an important part in the economy of any country. Initially, a flat management hierarchy, quick response to market changes and cost competitiveness were seen as the competitive characteristics of an SME. Recently, in developed economies, technological capabilities (TCs) management- managing existing and developing or assimilating new technological capabilities for continuous process and product innovations, has become important for both large organisations and SMEs to achieve sustained competitiveness. Therefore, various technological innovation capability (TIC) models have been developed at firm level to assess firms‘ innovation capability level. These models output help policy makers and firm managers to devise policies for deepening a firm‘s technical knowledge generation, acquisition and exploitation capabilities for sustained technological competitive edge. However, in developing countries TCs management is more of TCs upgrading: acquisitions of TCs from abroad, and then assimilating, innovating and exploiting them. Most of the TIC models for developing countries delineate the level of TIC required as firms move from the acquisition to innovative level. However, these models do not provide tools for assessing the existing level of TIC of a firm and various factors affecting TIC, to help practical interventions for TCs upgrading of firms for improved or new processes and products. Recently, the Government of Pakistan (GOP) has realised the importance of TCs upgrading in SMEs-especially export-oriented, for their sustained competitiveness. The GOP has launched various initiatives with local and foreign assistance to identify ways and means of upgrading local SMEs capabilities. This research targets this gap and developed a TICs assessment model for identifying the existing level of TIC of manufacturing SMEs existing in clusters in Sialkot, Pakistan. SME executives in three different export-oriented clusters at Sialkot were interviewed to analyse technological capabilities development initiatives (CDIs) taken by them to develop and upgrade their firms‘ TCs. Data analysed at CDI, firm, cluster and cross-cluster level first helped classify interviewed firms as leader, follower and reactor, with leader firms claiming to introduce mostly new CDIs to their cluster. Second, the data analysis displayed that mostly interviewed leader firms exhibited ‗learning by interacting‘ and ‗learning by training‘ capabilities for expertise acquisition from customers and international consultants. However, these leader firms did not show much evidence of learning by using, reverse engineering and R&D capabilities, which according to the extant literature are necessary for upgrading existing TIC level and thus TCs of firm for better value-added processes and products. The research results are supported by extant literature on Sialkot clusters. Thus, in sum, a TIC assessment model was developed in this research which qualitatively identified interviewed firms‘ TIC levels, the factors affecting them, and is validated by existing literature on interviewed Sialkot clusters. Further, the research gives policy level recommendations for TIC and thus TCs upgrading at firm and cluster level for targeting better value-added markets.

The determinants of R&D investment: A survey of the empirical research

This paper offers an extensive survey and a critical discussion of the empirical literature on the driving factors of R&D. These factors are subsumed under five broad types. The paper first summarises the key predictions from theory regarding each type's R&D effect. It then examines for which factors differences in the theoretical predictions can also be found in empirical studies, and for which factors the empirical evidence is more unanimous. As the focus is on the empirical literature, methodological issues are also highlighted. The major factor types identified in the literature are, individual firm or industry characteristics, particularly internal finance and sales; competition in product markets; R&D tax credits and subsidies; location and resource related factors, such as spillovers from university research within close geographic proximity, membership of a research joint venture and cooperation with research centres, and the human capital embodied in knowledge workers; and spillovers from foreign R&D. Although on balance there is a consensus regarding the R&D effects of most factors, there is also variation in results. Recent work suggests that accounting for non-linearities is one area of research that may explain and encompass contradictory findings.

Contrast and lustre:a model that accounts for eleven different forms of contrast discrimination in binocular vision

Our goal here is a more complete understanding of how information about luminance contrast is encoded and used by the binocular visual system. In two-interval forced-choice experiments we assessed observers' ability to discriminate changes in contrast that could be an increase or decrease of contrast in one or both eyes, or an increase in one eye coupled with a decrease in the other (termed IncDec). The base or pedestal contrasts were either in-phase or out-of-phase in the two eyes. The opposed changes in the IncDec condition did not cancel each other out, implying that along with binocular summation, information is also available from mechanisms that do not sum the two eyes' inputs. These might be monocular mechanisms. With a binocular pedestal, monocular increments of contrast were much easier to see than monocular decrements. These findings suggest that there are separate binocular (B) and monocular (L,R) channels, but only the largest of the three responses, max(L,B,R), is available to perception and decision. Results from contrast discrimination and contrast matching tasks were described very accurately by this model. Stimuli, data, and model responses can all be visualized in a common binocular contrast space, allowing a more direct comparison between models and data. Some results with out-of-phase pedestals were not accounted for by the max model of contrast coding, but were well explained by an extended model in which gratings of opposite polarity create the sensation of lustre. Observers can discriminate changes in lustre alongside changes in contrast.

Centralization of cleft care in the UK. Part 6:a tale of two studies

OBJECTIVES: We summarize and critique the methodology and outcomes from a substantial study which has investigated the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after the UK government started to implement the centralization of cleft care in response to an earlier survey in 1998, the Clinical Standards Advisory Group (CSAG). SETTING AND SAMPLE POPULATION: A UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Data were collected from children born in the UK with a unilateral cleft lip and palate between 1 April 2005 and 31 March 2007. MATERIALS AND METHODS: We discuss and contextualize the outcomes from speech recordings, hearing, photographs, models, oral health and psychosocial factors in the current study. We refer to the earlier survey and other relevant studies. RESULTS: We present arguments for centralization of cleft care in healthcare systems, and we evidence this with improvements seen over a period of 15 years in the UK. We also make recommendations on how future audit and research may configure. CONCLUSIONS: Outcomes for children with a unilateral cleft lip and palate have improved after the introduction of a centralized multidisciplinary service, and other countries may benefit from this model. Predictors of early outcomes are still needed, and repeated cross-sectional studies, larger longitudinal studies and adequately powered trials are required to create a research-led evidence-based (centralized) service.