Innovation, networking and globalisation:the role of regional innovation systems in the global innovation process

In the global economy, innovation is one of the most important competitive assets for companies willing to compete in international markets. As competition moves from standardised products to customised ones, depending on each specific market needs, economies of scale are not anymore the only winning strategy. Innovation requires firms to establish processes to acquire and absorb new knowledge, leading to the recent theory of Open Innovation. Knowledge sharing and acquisition happens when firms are embedded in networks with other firms, university, institutions and many other economic actors. Several typologies of innovation and firm networks have been identified, with various geographical spans. One of the first being modelled was the Industrial Cluster (or in Italian Distretto Industriale) which was for long considered the benchmark for innovation and economic development. Other kind of networks have been modelled since the late 1970s; Regional Innovation Systems represent one of the latest and more diffuse model of innovation networks, specifically introduced to combine local networks and the global economy. This model was qualitatively exploited since its introduction, but, together with National Innovation Systems, is among the most inspiring for policy makers and is often cited by them, not always properly. The aim of this research is to setup an econometric model describing Regional Innovation Systems, becoming one the first attempts to test and enhance this theory with a quantitative approach. A dataset of 104 secondary and primary data from European regions was built in order to run a multiple linear regression, testing if Regional Innovation Systems are really correlated to regional innovation and regional innovation in cooperation with foreign partners. Furthermore, an exploratory multiple linear regression was performed to verify which variables, among those describing a Regional Innovation Systems, are the most significant for innovating, alone or with foreign partners. Furthermore, the effectiveness of present innovation policies has been tested based on the findings of the econometric model. The developed model confirmed the role of Regional Innovation Systems for creating innovation even in cooperation with international partners: this represents one of the firsts quantitative confirmation of a theory previously based on qualitative models only. Furthermore the results of this model confirmed a minor influence of National Innovation Systems: comparing the analysis of existing innovation policies, both at regional and national level, to our findings, emerged the need for potential a pivotal change in the direction currently followed by policy makers. Last, while confirming the role of the presence a learning environment in a region and the catalyst role of regional administration, this research offers a potential new perspective for the whole private sector in creating a Regional Innovation System.

The Greater London Authority:problems of strategy integration

The Act that established the Greater London Authority (GLA) incorporated many of New Labour's aspirations for modern governance. Among those aspirations was the notion of policy integration, or 'joining up'. The Mayor of Greater London was required to develop a number of strategies, broadly in the planning and environmental policy domains, and to ensure that those strategies meshed into a coherent overall strategy for promoting London's economic, social and environmental well-being. How would this work in practice, given the need for coordination between the GLA and a number of related functional bodies, and given the political imperative for the GLA to make an impact quickly? Through our analysis of the strategy development and integration efforts of the GLA in its first nine months, we have gleaned new insights into the highly complex and difficult process of policy integration. We argue that the high aspirations of the Act for policy integration have not been met, policy integration instead being narrowly interpreted as the coordination of strategies to the Mayor's political agenda. Finally,we reflect on the likelihood of the GLA, as currently constituted, evolving to meet the functional requirement of policy integration.

Pharmaceutical process optimisation of bulk lyophilisates:implications of powder handling

Lyophilisation or freeze drying is the preferred dehydrating method for pharmaceuticals liable to thermal degradation. Most biologics are unstable in aqueous solution and may use freeze drying to prolong their shelf life. Lyophilisation is however expensive and has seen lots of work aimed at reducing cost. This thesis is motivated by the potential cost savings foreseen with the adoption of a cost efficient bulk drying approach for large and small molecules. Initial studies identified ideal formulations that adapted well to bulk drying and further powder handling requirements downstream in production. Low cost techniques were used to disrupt large dried cakes into powder while the effects of carrier agent concentration were investigated for powder flowability using standard pharmacopoeia methods. This revealed superiority of crystalline mannitol over amorphous sucrose matrices and established that the cohesive and very poor flow nature of freeze dried powders were potential barriers to success. Studies from powder characterisation showed increased powder densification was mainly responsible for significant improvements in flow behaviour and an initial bulking agent concentration of 10-15 %w/v was recommended. Further optimisation studies evaluated the effects of freezing rates and thermal treatment on powder flow behaviour. Slow cooling (0.2 °C/min) with a -25°C annealing hold (2hrs) provided adequate mechanical strength and densification at 0.5-1 M mannitol concentrations. Stable bulk powders require powder transfer into either final vials or intermediate storage closures. The targeted dosing of powder formulations using volumetric and gravimetric powder dispensing systems where evaluated using Immunoglobulin G (IgG), Lactate Dehydrogenase (LDH) and Beta Galactosidase models. Final protein content uniformity in dosed vials was assessed using activity and protein recovery assays to draw conclusions from deviations and pharmacopeia acceptance values. A correlation between very poor flowability (p<0.05), solute concentration, dosing time and accuracy was revealed. LDH and IgG lyophilised in 0.5 M and 1 M mannitol passed Pharmacopeia acceptance values criteria with 0.1-4 while formulations with micro collapse showed the best dose accuracy (0.32-0.4% deviation). Bulk mannitol content above 0.5 M provided no additional benefits to dosing accuracy or content uniformity of dosed units. This study identified considerations which included the type of protein, annealing, cake disruption process, physical form of the phases present, humidity control and recommended gravimetric transfer as optimal for dispensing powder. Dosing lyophilised powders from bulk was demonstrated as practical, time efficient, economical and met regulatory requirements in cases. Finally the use of a new non-destructive technique, X-ray microcomputer tomography (MCT), was explored for cake and particle characterisation. Studies demonstrated good correlation with traditional gas porosimetry (R2 = 0.93) and morphology studies using microscopy. Flow characterisation from sample sizes of less than 1 mL was demonstrated using three dimensional X-ray quantitative image analyses. A platinum-mannitol dispersion model used revealed a relationship between freezing rate, ice nucleation sites and variations in homogeneity within the top to bottom segments of a formulation.

‘Death talk’, ‘loss talk’ and identification in the process of ageing

In this paper, we examine the injunction issued by the prominent politician, broadcaster and older people's advocate, Baroness Joan Bakewell, to engage in ‘death talk’. We see positive ethical potential in this injunction, insofar as it serves as a call to confront more directly the prospects of death and dying, thereby releasing creative energies with which to change our outlook on life and ageing more generally. However, when set against a culture that valorises choice, independence and control, the positive ethical potential of such injunctions is invariably thwarted. We illustrate this with reference to one of Bakewell's interventions in a debate on scientific innovation and population ageing. In examining the context of her intervention, we affirm her intuition about its positive ethical potential, but we also point to an ambivalence that accompanies the formulation of the injunction – one that ultimately blunts the force and significance of her intuition. We suggest that Gilleard and Higgs' idea of the third age/fourth age dialectic, combined with the psycho-analytic concepts of fantasy and mourning, allow us to express this intuition better. In particular, we argue that the expression ‘loss talk’ (rather than ‘death talk’) better captures the ethical negotiations that should ultimately underpin the transformation processes associated with ageing, and that our theoretical contextualisation of her remarks can help us see this more clearly. In this view, deteriorations in our physical and mental capacities are best understood as involving changes in how we see ourselves, i.e. in our identifications, and so what is at stake are losses of identity and the conditions under which we can engage in new processes of identification.

Excipient characterization and particle engineering to develop directly compressed orally disintegrating tablets

ODTs have emerged as a novel oral dosage form with a potential to deliver a wide range of drug candidates to paediatric and geriatric patients. Compression of excipients offers a costeffective and translatable methodology for the manufacture of ODTs. Though, technical challenges prevail such as difficulty to achieve suitable tablet mechanical strength while ensuring rapid disintegration in the mouth, poor compressibility of preferred ODT diluent Dmannitol, and limited use for modified drug-release. The work investigates excipients’ functionality in ODTs and proposes new methodologies for enhancing material characteristics via process and particle engineering. It also aims to expand ODT applications for modified drug-release. Preformulation and formulation studies employed a plethora of techniques/tests including AFM, SEM, DSC, XRD, TGA, HSM, FTIR, hardness, disintegration time, friability, stress/strain and Heckel analysis. Tableting of D-mannitol and cellulosic excipients utilised various compression forces, material concentrations and grades. Engineered D-mannitol particles were made by spray drying mannitol with pore former NH4HCO3. Coated microparticles of model API omeprazole were prepared using water-based film forming polymers. The results of nanoscopic investigations elucidated the compression profiles of ODT excipients. Strong densification of MCC (Py is 625 MPa) occurs due to conglomeration of physicomechanical factors whereas D-mannitol fragments under pressure leading to poor compacts. Addition of cellulosic excipients (L-HPC and HPMC) and granular mannitol to powder mannitol was required to mechanically strengthen the dosage form (hardness >60 N, friability <1%) and to maintain rapid disintegration (<30 sec). Similarly, functionality was integrated into D-mannitol by fabrication of porous, yet, resilient particles which resulted in upto 150% increase in the hardness of compacts. The formulated particles provided resistance to fracture under pressure due to inherent elasticity while promoted tablet disintegration (50-77% reduction in disintegration time) due to porous nature. Additionally, coated microparticles provided an ODT-appropriate modified-release coating strategy by preventing drug (omeprazole) release.

Freezing process optimisation of pharmaceutical formulations for freeze drying

The body of work presented in this thesis are in three main parts: [1] the effect of ultrasound on freezing events of ionic systems, [2] the importance of formulation osmolality in freeze drying, and [3] a novel system for increasing primary freeze drying rate. Chapter 4 briefly presents the work on method optimisation, which is still very much in its infancy. Aspects of freezing such as nucleation and ice crystal growth are strongly related with ice crystal morphology; however, the ice nucleation process typically occurs in a random, non-deterministic and spontaneous manner. In view of this, ultrasound, an emerging application in pharmaceutical sciences, has been applied to aid in the acceleration of nucleation and shorten the freezing process. The research presented in this thesis aimed to study the effect of sonication on nucleation events in ionic solutions, and more importantly how sonication impacts on the freezing process. This work confirmed that nucleation does occur in a random manner. It also showed that ultrasonication aids acceleration of the ice nucleation process and increases the freezing rate of a solution. Cryopreservation of animal sperm is an important aspect of breeding in animal science especially for endangered species. In order for sperm cryopreservation to be successful, cryoprotectants as well as semen extenders are used. One of the factors allowing semen preservation media to be optimum is the osmolality of the semen extenders used. Although preservation of animal sperm has no relation with freeze drying of pharmaceuticals, it was used in this thesis to make a case for considering the osmolality of a formulation (prepared for freeze drying) as a factor for conferring protein protection against the stresses of freeze drying. The osmolalities of some common solutes (mostly sugars) used in freeze drying were determined (molal concentration from 0.1m to 1.2m). Preliminary investigation on the osmolality and osmotic coefficients of common solutes were carried out. It was observed that the osmotic coefficient trend for the sugars analysed could be grouped based on the types of sugar they are. The trends observed show the need for further studies to be carried out with osmolality and to determine how it may be of importance to protein or API protection during freeze drying processes. Primary drying is usually the longest part of the freeze drying process, and primary drying times lasting days or even weeks are not uncommon; however, longer primary drying times lead to longer freeze drying cycles, and consequently increased production costs. Much work has been done previously by others using different processes (such as annealing) in order to improve primary drying times; however, these do not come without drawbacks. A novel system involving the formation of a frozen vial system which results in the creation of a void between the formulation and the inside wall of a vial has been devised to increase the primary freeze drying rate of formulations without product damage. Although the work is not nearly complete, it has been shown that it is possible to improve and increase the primary drying rate of formulations without making any modifications to existing formulations, changing storage vials, or increasing the surface area of freeze dryer shelves.

Electronic information sharing in local government authorities:factors influencing the decision-making process

Local Government Authorities (LGAs) are mainly characterised as information-intensive organisations. To satisfy their information requirements, effective information sharing within and among LGAs is necessary. Nevertheless, the dilemma of Inter-Organisational Information Sharing (IOIS) has been regarded as an inevitable issue for the public sector. Despite a decade of active research and practice, the field lacks a comprehensive framework to examine the factors influencing Electronic Information Sharing (EIS) among LGAs. The research presented in this paper contributes towards resolving this problem by developing a conceptual framework of factors influencing EIS in Government-to-Government (G2G) collaboration. By presenting this model, we attempt to clarify that EIS in LGAs is affected by a combination of environmental, organisational, business process, and technological factors and that it should not be scrutinised merely from a technical perspective. To validate the conceptual rationale, multiple case study based research strategy was selected. From an analysis of the empirical data from two case organisations, this paper exemplifies the importance (i.e. prioritisation) of these factors in influencing EIS by utilising the Analytical Hierarchy Process (AHP) technique. The intent herein is to offer LGA decision-makers with a systematic decision-making process in realising the importance (i.e. from most important to least important) of EIS influential factors. This systematic process will also assist LGA decision-makers in better interpreting EIS and its underlying problems. The research reported herein should be of interest to both academics and practitioners who are involved in IOIS, in general, and collaborative e-Government, in particular. © 2013 Elsevier Ltd. All rights reserved.

Practice based learning approaches in collaborative design and engineering education:a case study investigation into the benefits of a crossdisciplinary practice based learning strategy

This study explores the ongoing pedagogical development of a number of undergraduate design and engineering programmes in the United Kingdom. Observations and data have been collected over several cohorts to bring a valuable perspective to the approaches piloted across two similar university departments while trialling a number of innovative learning strategies. In addition to the concurrent institutional studies the work explores curriculum design that applies the principles of Co-Design, multidisciplinary and trans disciplinary learning, with both engineering and product design students working alongside each other through a practical problem solving learning approach known as the CDIO learning initiative (Conceive, Design Implement and Operate) [1]. The study builds on previous work presented at the 2010 EPDE conference: The Effect of Personality on the Design Team: Lessons from Industry for Design Education [2]. The subsequent work presented in this paper applies the findings to mixed design and engineering team based learning, building on the insight gained through a number of industrial process case studies carried out in current design practice. Developments in delivery also aligning the CDIO principles of learning through doing into a practice based, collaborative learning experience and include elements of the TRIZ creative problem solving technique [3]. The paper will outline case studies involving a number of mixed engineering and design student projects that highlight the CDIO principles, combined with an external industrial design brief. It will compare and contrast the learning experience with that of a KTP derived student project, to examine an industry based model for student projects. In addition key areas of best practice will be presented, and student work from each mode will be discussed at the conference.

Understanding and improving the manufacturing and changeover process in Saudi Arabian business - a multiple case study approach

The importance of the changeover process in the manufacturing industry is becoming widely recognised. Changeover is a complete process of changing between the manufacture of one product to manufacture of an alternative product until specified production and quality rates are reached. The initiatives to improve changeover exist in industry, as better changeover process typically contribute to improved quality performance. A high-quality and reliable changeover process can be achieved through implementation of continuous or radical improvements. This research examines the changeover process of Saudi Arabian manufacturing firms because Saudi Arabia’s government is focused on the expansion of GDP and increasing the number of export manufacturing firms. Furthermore, it is encouraging foreign manufacturing firms to invest within Saudi Arabia. These initiatives, therefore, require that Saudi manufacturing businesses develop the changeover practice in order to compete in the market and achieve the government’s objectives. Therefore, the aim of this research is to discover the current status of changeover process implementation in Saudi Arabian manufacturing businesses. To achieve this aim, the main objective of this research is to develop a conceptual model to understand and examine the effectiveness of the changeover process within Saudi Arabian manufacturing firms, facilitating identification of those activities that affect the reliability and high-quality of the process. In order to provide a comprehensive understanding of this area, this research first explores the concept of quality management and its relationship to firm performance and the performance of manufacturing changeover. An extensive body of literature was reviewed on the subject of lean manufacturing and changeover practice. A research conceptual model was identified based on this review, and focus was on providing high-quality and reliable manufacturing changeover processes during set-up in a dynamic environment. Exploratory research was conducted in sample Saudi manufacturing firms to understand the features of the changeover process within the manufacturing sector, and as a basis for modifying the proposed conceptual model. Qualitative research was employed in the study with semi-structured interviews, direct observations and documentation in order to understand the real situation such as actual daily practice and current status of changeover process in the field. The research instrument, the Changeover Effectiveness Assessment Tool (CEAT) was developed to evaluate changeover practices. A pilot study was conducted by examining the CEAT, proposed for the main research. Consequently, the conceptual model was modified and CEAT was improved in response to the pilot study findings. Case studies have been conducted within eight Saudi manufacturing businesses. These case studies assessed the implementation of manufacturing changeover practice in the lighting and medical products sectors. These two sectors were selected based on their operation strategy which was batch production as well as the fact that they fulfilled the research sampling strategy. The outcomes of the research improved the conceptual model, ultimately to facilitate the firms’ adoption and rapid implementation of a high-quality and reliability changeover during the set-up process. The main finding of this research is that Quality’s factors were considering the lowest levels comparing to the other factors which are People, Process and Infrastructure. This research contributes to enable Saudi businesses to implement the changeover process by adopting the conceptual model. In addition, the guidelines for facilitating implementation were provided in this thesis. Therefore, this research provides insight to enable the Saudi manufacturing industry to be more responsive to rapidly changing customer demands.

Nanotechnology and microfluidics:formulation design and on-chip manufacture of nanoparticles

Nanoparticles offer an ideal platform for the delivery of small molecule drugs, subunit vaccines and genetic constructs. Besides the necessity of a homogenous size distribution, defined loading efficiencies and reasonable production and development costs, one of the major bottlenecks in translating nanoparticles into clinical application is the need for rapid, robust and reproducible development techniques. Within this thesis, microfluidic methods were investigated for the manufacturing, drug or protein loading and purification of pharmaceutically relevant nanoparticles. Initially, methods to prepare small liposomes were evaluated and compared to a microfluidics-directed nanoprecipitation method. To support the implementation of statistical process control, design of experiment models aided the process robustness and validation for the methods investigated and gave an initial overview of the size ranges obtainable in each method whilst evaluating advantages and disadvantages of each method. The lab-on-a-chip system resulted in a high-throughput vesicle manufacturing, enabling a rapid process and a high degree of process control. To further investigate this method, cationic low transition temperature lipids, cationic bola-amphiphiles with delocalized charge centers, neutral lipids and polymers were used in the microfluidics-directed nanoprecipitation method to formulate vesicles. Whereas the total flow rate (TFR) and the ratio of solvent to aqueous stream (flow rate ratio, FRR) was shown to be influential for controlling the vesicle size in high transition temperature lipids, the factor FRR was found the most influential factor controlling the size of vesicles consisting of low transition temperature lipids and polymer-based nanoparticles. The biological activity of the resulting constructs was confirmed by an invitro transfection of pDNA constructs using cationic nanoprecipitated vesicles. Design of experiments and multivariate data analysis revealed the mathematical relationship and significance of the factors TFR and FRR in the microfluidics process to the liposome size, polydispersity and transfection efficiency. Multivariate tools were used to cluster and predict specific in-vivo immune responses dependent on key liposome adjuvant characteristics upon delivery a tuberculosis antigen in a vaccine candidate. The addition of a low solubility model drug (propofol) in the nanoprecipitation method resulted in a significantly higher solubilisation of the drug within the liposomal bilayer, compared to the control method. The microfluidics method underwent scale-up work by increasing the channel diameter and parallelisation of the mixers in a planar way, resulting in an overall 40-fold increase in throughput. Furthermore, microfluidic tools were developed based on a microfluidics-directed tangential flow filtration, which allowed for a continuous manufacturing, purification and concentration of liposomal drug products.

Variable mutation rates as an adaptive strategy in replicator populations

For evolving populations of replicators, there is much evidence that the effect of mutations on fitness depends on the degree of adaptation to the selective pressures at play. In optimized populations, most mutations have deleterious effects, such that low mutation rates are favoured. In contrast to this, in populations thriving in changing environments a larger fraction of mutations have beneficial effects, providing the diversity necessary to adapt to new conditions. What is more, non-adapted populations occasionally benefit from an increase in the mutation rate. Therefore, there is no optimal universal value of the mutation rate and species attempt to adjust it to their momentary adaptive needs. In this work we have used stationary populations of RNA molecules evolving in silico to investigate the relationship between the degree of adaptation of an optimized population and the value of the mutation rate promoting maximal adaptation in a short time to a new selective pressure. Our results show that this value can significantly differ from the optimal value at mutation-selection equilibrium, being strongly influenced by the structure of the population when the adaptive process begins. In the short-term, highly optimized populations containing little variability respond better to environmental changes upon an increase of the mutation rate, whereas populations with a lower degree of optimization but higher variability benefit from reducing the mutation rate to adapt rapidly. These findings show a good agreement with the behaviour exhibited by actual organisms that replicate their genomes under broadly different mutation rates. © 2010 Stich et al.