Organisational slack resources, the definitions and consequences for business flexibility and performance : an empirical investigation

Slack resources are recognised to be those spare capabilities and assets of the organisation that are variable reclaimable for re-deployment. They represent under utilised and hidden spare energies within a company that may be recaptured and employed for a variety of tasks. However their positive contribution to organisational success has been a contentious claim that has provoked the intuitive argument that slack resources are inefficiency and are to be eradicated. The counter argument has been that very efficient organisations are inflexible and therefore incapable of being responsive to an increasingly dynamic environment. Therefore this work compares and contrasts three distinctive industries in a holistic manner and maps the impact of environmental flux on the firm, its subsequent disruptive ripples through the organisation and its absorption by slack resources. Through this process it is demonstrated that slack resources do positively contribute to organisational performance and subsequently the ability of slack to promote sustained competitive advantage is also identified. The major findings of this work are listed. 1. This work has developed and perfected a new research model that aids the investigation of the internal behaviours and consequences of Slack Resources. 2. Supported by argument a new variable of Soft Slack was developed. Its validity was demonstrated in its ability to capture the contribution of intangible assets, such as education, experience, spare management time and further training, to the extant levels of Organisational Hard Slack resources. 3. The validity of Soft Slack was further supported when its contribution to organisational Flexibility was also established. 4. The original argument that Slack Resources enhance organisational Performance has been further developed. It is now evidenced that Slack Resources facilitate Organisational Flexibility and by this process enhances Organisational Performance.

Phenotypic and genotypic analysis of intestinal spirochacies

Pulsed field gel electrophoresis of 82 intestinal spirochaete isolates showed specific differentiation of Serpulina pilosicoli and Serpulina hyodysenteriae although considerable heterogeneity was observed, especially amongst S. pilosicoli isolates. In several cases genotypically similar isolates originated from different animals suggesting that cross-species transmission may have occurred. The Caco-2 and Caco-21HT29 cell models have been proposed as potentially realistic models of intestinal infection. Quantitation of adhesion to the cells showed isolate 3 82/91 (from a bacteraemia) to adhere at significantly greater numbers than any other isolate tested. This isolate produced a PFGE profile which differed from other S. pilosicoli isolates and so would be of interest for further study. Comparison of bacteraemic and other S. pilosicoli isolates suggested that bacteraemic isolates were not more specifically adapted for adhesion to, or invasion of the epithelial cell layer than other S. pilosicoli isolates. Genotypically similar isolates from differing animal origins adhered to the Caco-2 model at similar levels. Generation of a random genomic library of S. pilosicoli and screening with species specific monoclonal antibody has enabled the identification of a gene sequence encoding a protein which showed significant homology with an ancestral form of the enzyme pyruvate oxidoreductase. Immunoscreening with polyclonal serum identified the sequences of two gene clusters and a probable arylsulphatase. One gene cluster represented a ribosomal gene cluster which has a similar molecular arrangement to Borrelia burgdorjeri, Treponema pallidum and Thermatoga maritima. The other gene cluster contained an ABC transporter protein, sorbitol dehydrogenase and phosphomannose isomerase. An ELISA type assay was used to demonstrate that isolates of S. pilosicoli could adhere to components of the extracellular matrix such as collagen (type 1), fibronectin, laminin, and porcine gastric mucin.

Meta-analysis of the population and phenotypic expression of CYP2C9/2C19 polymorphism on drug metabolism in different ethnicities

The term "pharmacogenetics" has been defined as the scientific study of inherited factors that affect the human drug response. Many pharmacogenetie studies have been published since 1995 and have focussed on the principal enzyme family involved in drug metabolism, the cytochrome P450 family, particularly cytochrome P4502C9 and 2C19. In order to investigate the pharmacogenetic aspect of pharmacotherapy, the relevant studies describing the association of pharmacogenetic factor(s) in drug responses must be retrieved from existing literature using a systematic review approach. In addition, the estimation of variant allele prevalence for the gene under study between different ethnic populations is important for pharmacogenetic studies. In this thesis, the prevalence of CYP2C9/2C19 alleles between different ethnicities has been estimated through meta-analysis and the population genetic principle. The clinical outcome of CYP2C9/2C19 allelic variation on the pharmacotherapy of epilepsy has been investigated; although many new antiepileptic drugs have been launched into the market, carbamazepine, phenobarbital and phenytoin are still the major agents in the pharmacotherapy of epilepsy. Therefore, phenytoin was chosen as a model AED and the effect of CYP2C9/2C19 genetic polymorphism on phenytoin metabolism was further examined.An estimation of the allele prevalence was undertaken for three CYP2C9/2C19 alleles respectively using a meta-analysis of studies that fit the Hardy-Weinberg equilibrium. The prevalence of CYP2C9*1 is approximately 81%, 96%, 97% and 94% in Caucasian, Chinese, Japanese, African populations respectively; the pooled prevalence of CYP2C19*1 is about 86%, 57%, 58% and 85% in these ethnic populations respectively. However, the studies of association between CYP2C9/2C19 polymorphism and phenytoin metabolism failed to achieve any qualitative or quantitative conclusion. Therefore, mephenytoin metabolism was examined as a probe drug for association between CYP2C19 polymorphism and mephenytoin metabolic ratio. Similarly, analysis of association between CYP2C9 polymorphism and warfarin dose requirement was undertaken.It was confirmed that subjects carrying two mutated CYP2C19 alleles have higher S/R mephenytoin ratio due to deficient CYP2C19 enzyme activity. The studies of warfarin and CYP2C9 polymorphism did not provide a conclusive result due to poor comparability between studies.The genetic polymorphism of drug metabolism enzymes has been studied extensively, however other genetic factors, such as multiple drug resistance genes (MDR) and genes encoding ion channels, which may contribute to variability in function of drug transporters and targets, require more attention in future pharmacogenetic studies of antiepileptic drugs.

Public sector investment appraisal:the place of flexibility in the decision making process

This thesis reviews the main methodological developments in public sector investment appraisal and finds growing evidence that appraisal techniques are not fulfilling their earlier promise. It is suggested that an important reason for this failure lies in the inability of these techniques to handle uncertainty except in a highly circumscribed fashion. It is argued that a more fruitful approach is to strive for flexibility. Investment projects should be formulated with a view to making them responsive to a wide range of possible future events, rather than embodying a solution which is optimal for one configuration of circumstances only. The distinction drawn in economics between the short and the long run is used to examine the nature of flexibility. The concept of long run flexibility is applied to the pre-investment range of choice open to the decisionmaker. It is demonstrated that flexibility is reduced at a very early stage of decisionmaking by the conventional system of appraisal which evaluates only a small number of options. The pre-appraisal filtering process is considered further in relation to decisionmaking models. It is argued that for public sector projects the narrowing down of options is best understood in relation to an amended mixed scanning model which places importance on the process by which the 'national interest ' is determined. Short run flexibility deals with operational characteristics, the degree to which particular projects may respond to changing demands when the basic investment is already in place. The tension between flexibility and cost is noted. A short case study on the choice of electricity generating plant is presented. The thesis concludes with a brief examination of the approaches used by successive British governments to public sector investment, particularly in relation to the nationalised industries

"Marketing and flexibility":debates past present and future

Special issue editorial: Purpose – The purpose of this paper is to outline the articles presented in the Special Issue on the topic of “Marketing and flexibility”, and to discuss key issues associated with major debates relating to flexibility in order to position the articles within a wider context and highlight some key issues for further research. Design/methodology/approach – Themes in prior research relating to “Marketing and flexibility” are documented and the growth of research interest into strategic flexibility is tabulated. The contributions of each article are briefly discussed. Findings – There has been a steady growth of research interest into flexibility. To provide an example of this growth, the increase in the number of articles published on the topic of strategic flexibility in scholarly journals is highlighted over a 20-year period. Key issues in prior research such as alternative definitions and the different postulated relationships between market orientation and strategic flexibility are revealed, as are issues for future research. Originality/value – Key issues relating to research into flexibility for marketing scholars are revealed.

Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

Antecedents of strategic flexibility:management cognition, firm resources and strategic options

Purpose: Current conceptualisations of strategic flexibility and its antecedents are theory-driven, which has resulted in a lack of consensus. To summarise this domain the paper aims to develop and present an a priori conceptual model of the antecedents and outcomes of strategic flexibility. Discussion and insights into the conceptual model, and the relationships specified, are made through a novel qualitative empirical approach. The implications for further research and a framework for further theoretical development are presented. Design/methodology/approach: An exploratory qualitative research design is used applying multiple data collection techniques in a branch network of a large regional retailer in the UK. The development of strategic options and the complex relationship to strategic flexibility is investigated. Findings: The number and type of strategic options developed by managers impact on the degree of strategic flexibility and also on the ability of the firm to achieve competitive differentiation. Additionally, the type of strategic option implemented by managers is dependent on the competitive situation faced at a local level. Evidence of managers' limited perception of competition was identified based on their spatial embeddedness. Research limitations/implications: A single, in-depth case study was used. The data gathered is rich and appropriate for the exploratory approach adopted here. However, generalisability of the findings is limited. Practical implications: Strategic flexibility is rooted in the ability of front-line mangers to develop and implement strategic options; this in turn facilitates competitive differentiation. Originality/value: The research presented is unique in this domain on two accounts. First, theory is developed by presenting an a priori conceptual model, and testing through in-depth qualitative data gathering. Second, insights into strategic flexibility are presented through an examination of managerial cognition, resources and strategic option generation using cognitive mapping and laddering technique. © Emerald Group Publishing Limited.

Local delivery of the KCa3.1 blocker, TRAM-34, prevents acute angioplasty-induced coronary smooth muscle phenotypic modulation and limits stenosis

Objective-We previously demonstrated that upregulation of intermediate-conductance Ca2+ -activated K+ channels (KCa 3.1) is necessary for mitogen-induced phenotypic modulation in isolated porcine coronary smooth muscle cells (SMCs). The objective of the present study was to determine the role of KCa3.1 in the regulation of coronary SMC phenotypic modulation in vivo using a swine model of postangioplasty restenosis. Methods and Results-Balloon angioplasty was performed on coronary arteries of swine using either noncoated or balloons coated with the specific KCa3.1 blocker TRAM-34. Expression of KCa3.1, c-jun, c-fos, repressor element-1 silencing transcription factor (REST), smooth muscle myosin heavy chain (SMMHC), and myocardin was measured using qRT-PCR in isolated medial cells 2 hours and 2 days postangioplasty. KCa3.1, c-jun, and c-fos mRNA levels were increased 2 hours postangioplasty, whereas REST expression decreased. SMMHC expression was unchanged at 2 hours, but decreased 2 days postangioplasty. Use of TRAM-34 coated balloons prevented KCa3.1 upregulation and REST downregulation at 2 hours, SMMHC and myocardin downregulation at 2 days, and attenuated subsequent restenosis 14 and 28 days postangioplasty. Immunohistochemical analysis demonstrated corresponding changes at the protein level. Conclusion-Blockade of KCa3.1 by delivery of TRAM-34 via balloon catheter prevented smooth muscle phenotypic modulation and limited subsequent restenosis. © 2008 American Heart Association, Inc.

Phenotypic effect of mutations in evolving populations of RNA molecules

Background. The secondary structure of folded RNA sequences is a good model to map phenotype onto genotype, as represented by the RNA sequence. Computational studies of the evolution of ensembles of RNA molecules towards target secondary structures yield valuable clues to the mechanisms behind adaptation of complex populations. The relationship between the space of sequences and structures, the organization of RNA ensembles at mutation-selection equilibrium, the time of adaptation as a function of the population parameters, the presence of collective effects in quasispecies, or the optimal mutation rates to promote adaptation all are issues that can be explored within this framework. Results. We investigate the effect of microscopic mutations on the phenotype of RNA molecules during their in silico evolution and adaptation. We calculate the distribution of the effects of mutations on fitness, the relative fractions of beneficial and deleterious mutations and the corresponding selection coefficients for populations evolving under different mutation rates. Three different situations are explored: the mutation-selection equilibrium (optimized population) in three different fitness landscapes, the dynamics during adaptation towards a goal structure (adapting population), and the behavior under periodic population bottlenecks (perturbed population). Conclusions. The ratio between the number of beneficial and deleterious mutations experienced by a population of RNA sequences increases with the value of the mutation rate µ at which evolution proceeds. In contrast, the selective value of mutations remains almost constant, independent of µ, indicating that adaptation occurs through an increase in the amount of beneficial mutations, with little variations in the average effect they have on fitness. Statistical analyses of the distribution of fitness effects reveal that small effects, either beneficial or deleterious, are well described by a Pareto distribution. These results are robust under changes in the fitness landscape, remarkably when, in addition to selecting a target secondary structure, specific subsequences or low-energy folds are required. A population perturbed by bottlenecks behaves similarly to an adapting population, struggling to return to the optimized state. Whether it can survive in the long run or whether it goes extinct depends critically on the length of the time interval between bottlenecks. © 2010 Stich et al; licensee BioMed Central Ltd.

Flexibility in large scale projects

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Strategic decision making in small businesses:implications for strategic flexibility and strategic adaptation

Strategic decision making (SDM) in a small business is an informal, highly personalised cognitive process which is emergent in nature. SDM determines the extent to which decision makers generate innovative decision-making options, and is therefore critical in order for small businesses to achieve strategic flexibility to enable strategic adaptation to turbulent environments. By examining SDM in small businesses, this research has the potential to address a major criticism of the extant literature in that it has been pre-occupied with measuring the formality of strategic planning and has neglected the informal, highly personalised and cognitive nature of strategic decision making in a small businesses.