Quality improvement in professional local government services : a longitudinal study

This sustained longitudinal study, carried out in a single local authority, investigates the implementation of a Total Quality Management (TQM) philosophy in professional local government services. At the start of this research, a large majority of what was written about TQM was polemical and based on limited empirical evidence. This thesis seeks to provide a significant and important piece of work, making a considerable contribution to the current state of knowledge in this area. Teams from four professional services within a single local authority participated in this research, providing the main evidence on how the quality management agenda in a local authority can be successfully implemented. To supplement this rich source of data, various other sources and methods of data collection have been used: 1) Interviews were carried out with senior managers from within the authority; 2) Customer focus groups and questionnaires were used; 3) Interviews were carried out with other organisations, all of which were proponents of a TQM philosophy. A number of tools have been developed to assist in gathering data: 1) The CSFs (critical success factors) benchmarking tool; 2) Five Stages of Quality Improvement Model. A Best Practice Quality Improvement Model, arising from an analysis of the literature and the researcher's own experience is proposed and tested. From the results a number of significant conclusions have been drawn relating to: 1) Triggers for change; 2) Resistance of local government professionals to change 3) Critical success factors and barriers to quality improvement in professional local government services; 4) The problems associated with participant observation and other methodological issues used.

Understanding change in the public sector:a local authority case study

Increasingly managers in the public sector are being required to manage change, but many of the models of change which are available to them have been developed from private sector experience. There is a need to understand more about how the change process unfolds in the public sector. A case study of change in one local authority over the period 1974-87 is provided. The events surrounding housing decentralisation and the introduction of community development are considered in detail. To understand these events a twofold model of change is proposed: a short wave model which explains a change project or event; and a long wave model which considers how these projects or events might be linked together to provide a picture of an organisation over a longer period. The short wave model identifies multiple triggers of change and signals the importance of mediators in recognising these triggers. The extent to which new ideas are implemented and the pace of their adoption is influenced by the balance of power within the organisation and the political tactics which are used. Broad phases in the change process can be identified, but there is not a simple linear passage through these. The long wave model considers the way in which continuity and change feed off one another. It suggests that periods of relative stability may be interspersed with more radical transformations as the dominant paradigm guiding the organisation shifts. However, such paradigmatic shifts in local government may be less obvious than in the private sector due to the diverse nature of the former.

Effects of oxidative stress and neuroprotection in apoptosis in neuronal cell models

The PC12 and SH-SY5Y cell models have been proposed as potentially realistic models to investigate neuronal cell toxicity. The effects of oxidative stress (OS) caused by both H2O2 and Aβ on both cell models were assessed by several methods. Cell toxicity was quantitated by measuring cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) viability assay, an indicator of the integrity of the electron transfer chain (ETC), and cell morphology by fluorescence and video microscopy, both of which showed OS to cause decreased viability and changes in morphology. Levels of intracellular peroxide production, and changes in glutathione and carbonyl levels were also assessed, which showed OS to cause increases in intracellular peroxide production, glutathione and carbonyl levels. Differentiated SH-SY5y cells were also employed and observed to exhibit the greatest sensitivity to toxicity. The neurotrophic factor, nerve growth factor (NGF) was shown to cause protection against OS. Cells pre-treated with NGF showed higher viability after OS, generally less apoptotic morphology, recorded less apoptotic nucleiods, generally lower levels of intracellular peroxides and changes in gene expression. The neutrophic factor, brain derived growth factor (BDNF) and ascorbic acid (AA) were also investigated. BDNF showed no specific neuroprotection, however the preliminary data does warrant further investigation. AA showed a 'janus face' showing either anti-oxidant action and neuroprotection or pro-oxidant action depending on the situation. Results showed that the toxic effects of compounds such as Aβ and H2O2 are cell type dependent, and that OS alters glutathione metabolism in neuronal cells. Following toxic insult, glutathione levels are depleted to low levels. It is herein suggested that this lowering triggers an adaptive response causing alterations in glutathione metabolism as assessed by evaluation of glutathione mRNA biosynthetic enzyme expression and the subsequent increase in glutathione peroxidase (GPX) levels.

Development and validaton of an indicator to compare antibiotic usage in secondary care in England

The use of antibiotics was investigated in twelve acute hospitals in England. Data was collected electronically and by questionnaire for the financial years 2001/2, 2002/3 and 2003/4. Hospitals were selected on the basis of their Medicines Management Self-Assessment Scores (MMAS) and included a cohort of three hospitals with integrated electronic prescribing systems. The total sample size was 6.65% of English NHS activity for 2001/2 based on Finished Consultant Episode (FCE) numbers. Data collected included all antibiotics dispensed (ATC category J01), hospital activity FCE's and beddays, Medicines Management Self-assessment scores, Antibiotic Medicines Management scores (AMS), Primary Care Trust (PCT) of origin of referral populations, PCT antibiotic prescribing rates, Index of Multiple Deprivation for each PCT. The DDD/FCE (Defined Daily Dose/FCE) was found to correlate with the DDD 100beddays (r = 0.74 ptriggers for further investigation including a proportion of 0.24 for the ratio of third generation to first/second generation cephalosporin use, and five percent as the limit for parenteral quinolone DOD of total quinolone DOD usage. It was possible to demonstrate a correlation between the IMD 2000 and primary care antibiotic prescribing rates but not between primary and secondary care antibiotic prescribing rates for the same referral population or between the weighted mean IMD 2000 for each hospital's referral population and the hospital antibiotic prescribing rate.

A cybernetic methodology to study and design human activities

This thesis offers a methodology to study and design effective communication mechanisms in human activities. The methodology is focused in the management of complexity. It is argued that complexity is not something objective that can be worked out analytically, but something subjective that depends on the viewpoint. Also it is argued that while certain social contexts may inhibit, others may enhance the viewpoint's capabilities to deal with complexity. Certain organisation structures are more likely than others to allow individuals to release their potentials. Thus, the relevance of studying and designing effective organisations. The first part of the thesis offers a `cybernetic methodology' for problem solving in human activities, the second offers a `method' to study and design organisations. The cybernetics methodology discussed in this work is rooted in second order cybernetics, or the cybernetics of the observing systems (Von Foester 1979, Maturana and Varela 1980). Its main tenet is that the known properties of the real world reside in the individual and not in the world itself. This view, which puts emphasis in a, by nature, one sided and unilateral appreciation of reality, triggers the need for dialogue and conversations to construct it. The `method' to study and design organisations, it based on Beer's Viable System Model (Beer 1979, 1981, 1985). This model permits us to assess how successful is an organisation in coping with its environmental complexity, and, moreover, permits us to establish how to make more effective the responses to this complexity. These features of the model are of great significance in a world where complexity is perceived to be growing at an unthinkable pace. But, `seeing' these features of the model assumes an effective appreciation of organisational complexity; hence the need for the methodological discussions offered by the first part of the thesis.

On the mechanisms of cerebellar synaptic plasticity

Changes in the strength of signalling between neurones are thought to provide a cellular substrate for learning and memory. In the cerebellar cortex, raising the frequency and the strength of parallel fibre (PF) stimulation leads to a long-term depression (LTD) of the strength of signalling at the synapse between PFs and Purkinje cells (PCs), which spreads to distant synapses to the same cell via a nitric oxide (NO) dependent mechanism. At the same synapse, but under conditions of reduced post-synaptic calcium activity, raised frequency stimulation (RFS) of PFs triggers a long-term potentiation of synaptic transmission. The aims of the work described in this thesis were to investigate the conditions necessary for LTD and LTP at this synapse following RFS and to identify the origins and second messenger cascades involved in the induction and spread of LTP and LTD. In thin, parasagittal cerebellar slices whole cell patch clamp recordings were made from PCs and the effects of RFS of one of two, independent PF inputs to the same PC were examined under a range of experimental conditions. Under conditions designed to reduce post-synaptic calcium activity, RFS to a single PF input led to LTP and a decreases in paired pulse facilitation (PPF) in both pathways. This heterosynaptic potentiation was prevented by inhibition of protein kinase A (PKA) or by inhibition of NO synthase with either 7-nitroindazole (7-NI) or NG Nitro-L-argenine methyl ester. Inhibition of guanylate cyclase (GC) or protein kinase G (PKG) had no effect. A similar potentiation was observed upon application of the adenylyl cyclase (AC) activator forskolin or the NO donor spermine NONOate. Both of these treatments also resulted in an increase in the frequency of mEPSCs, which provides further evidence for a presynaptic origin of LTP. Forskolin induced potentiation and the increase in mEPSC frequency were blocked by 7-NI. The styryl dye FM1-43, a fluorescent reporter of endo- and exocytosis, was also used to further examine the possible pre-synaptic origins of LTP. RFS or forskolin application enhanced FM1-43 de-staining and NOS inhibitors blocked this effect. Application of NONOate also enhanced FM1-43 de-staining. When post-synaptic calcium activity was less strictly buffered, RFS to a single PF input led to a transient potentiation that was succeeded by LTD in both pathways. This LTD, which resembled previously described forms, was prevented by inhibition of the NO/cGMP/PKG cascade. Modification of the AC/cAMP/PKA cascade had no effect. In summary, the direction of synaptic plasticity at the PF-PC synapse in response to RFS depends largely on the level of post-synaptic calcium activity. LTP and LTD were non-input specific and both forms of plasticity were dependent on NOS activity. Induction of LTP was mediated by a presynaptic mechanism and depended on NO and cAMP production. LTD on the other hand was a post-synaptic process and required activity of the NO/cGMP/PKG signalling cascade.

Modulation of certain 5-HT-related behaviours by serotonergic and noradrenergic systems

The modulation of 5-hydroxytryptamine (5-HT)-related head-twitchbehaviour by antimigraine drugs and migraine triggers was examined inmice. The antimigraine drugs examined produced either inhibition or noeffect on 5-HT-related head-twitching. On the basis of these resultsit is suggested that 5-HT-related head-twitching is unlikely to beuseful in the preclinical screening and discovery of systemically-activeantimigraine agents. The migraine triggers examined, tyramineand beta-PEA initially produced a repeatable complex time-relatedeffect on 5-HT-related head-twitching, with both inhibition andpotentiation of this behaviour being observed, however, when furtherexamination of the effect of the migraine triggers on 5-HT-relatedhead-twitching was attempted some time later the effects seeninitially were no longer produced. The effect of (±)-1-<2, 5-dimethoxy-4-iodophenyl)-2-aminopropane,((±)DOl), on on-going behaviour of mice and rats was examined. Shakingbehaviour was observed in both species. In mice, excessive scratchingbehaviour was also present. (±)DOl-induced scratching and shakingbehaviour were found to be differentially modulated by noradrenergicand serotonergic agents, however, the fact that both behaviours wereblocked by ritanserin (5-HT2/5-HT1c receptor antagonist) and inhibitedby FLA-63 (a dopamine-beta-oxidase inhibitor which depletesnoradrenaline), suggests the pathways mediating these behaviours mustbe convergent in some manner, and that both behaviours require intact5-HT receptors, probably 5-HT2 receptors, for their production. Ingeneral, the behavioural profile of (±)DOI was as expected for anagent which exhibits high affinity binding to 5-HT2/5-HT1c receptors.Little sign of the 5-HTl-related '5-HT syndrome' was seen in eithermice or rats. The effect of a variety of noradrenergic agents on head-twitchinginduced by a variety of shake-inducing agents was examined. A patternof modulatory effect was seen whereby the modulatory effect of thenoradrenergic agents on 5-hydroxytryptophan <5-HTP) (and in some cases, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)) was found to be the opposite of that observed with quipazine and (±)DOI. The relationship between these effects, and their implications for understanding the pharmacology of centrally acting drugs is discussed.

Gingipains from Porphyromonas gingivalis increase the chemotactic and respiratory burst-priming properties of the 77-amino-acid interleukin-8 variant

Porphyromonas gingivalis, a gram-negative anaerobe which is implicated in the etiology of active periodontitis, secretes degradative enzymes (gingipains) and sheds proinflammatory mediators (e.g., lipopolysaccharides [LPS]). LPS triggers the secretion of interleukin-8 (IL-8) from immune (72-amino-acid [aa] variant [IL-8(72aa)]) and nonimmune (IL-8(77aa)) cells. IL-8(77aa) has low chemotactic and respiratory burst-inducing activity but is susceptible to cleavage by gingipains. This study shows that both R- and K-gingipain treatments of IL-8(77aa) significantly enhance burst activation by fMLP and chemotactic activity (P < 0.05) but decrease burst activation and chemotactic activity of IL-8(72aa) toward neutrophil-like HL60 cells and primary neutrophils (P < 0.05). Using tandem mass spectrometry, we have demonstrated that R-gingipain cleaves 5- and 11-aa peptides from the N-terminal portion of IL-8(77aa) and the resultant peptides are biologically active, while K-gingipain removes an 8-aa N-terminal peptide yielding a 69-aa isoform of IL-8 that shows enhanced biological activity. During periodontitis, secreted gingipains may differentially affect neutrophil chemotaxis and activation in response to IL-8 according to the cellular source of the chemokine.

New business formation in a rapidly growing economy: The Irish experience

The extraordinary growth of the Irish economy since the mid-1990s - the 'Celtic Tiger' - has attracted a great deal of interest, commentary and research. Indeed, many countries look to Ireland as an economic development role model, and it has been suggested that Ireland might provide key lessons for other EU members as they seek to achieve the objectives set out in the Lisbon Agenda. Much of the discussion of Ireland's growth has focused on its possible triggers: the long term consequences of the late 1980s fiscal stabilisation; EU structural funds; education; wage moderation; and devaluation of the Irish punt. The industrial policy perspective has highlighted the importance of inflows of foreign direct investment, but a notable absence from the discourse on the 'Celtic Tiger' has been any mention of the role of new business venture creation and entrepreneurship. In this paper we use unpublished Irish VAT data for the years 1988 to 2004 to provide the first detailed look at national trends in business birth and death rates in Ireland over the 'take-off' period. We also use sub-national VAT data to shed light on spatial trends in new venture creation. Our overall conclusions are that new business formation made no detectable contribution to the acceleration of Ireland's growth in the late 1990s, although we do find evidence of spatial convergence in per capita business stocks.

Role of Ca2+ in proteolysis-inducing factor (PIF)-induced atrophy of skeletal muscle

Proteolysis-inducing factor (PIF) induces muscle loss in cancer cachexia through a high affinity membrane bound receptor. This study investigates the mechanism by which the PIF receptor communicates to intracellular signalling pathways. C2C12 murine myoblasts were used as a model using PIF purified from MAC16 tumours. Calcium imaging was determined using fura-4-acetoxymethyl ester (Fura-4-AM). PIF induced a rapid rise in Ca2 +i, which was completely attenuated by a anti-receptor antibody, or peptides representing 20 mers of the N-terminus of the PIF receptor. Other agents catabolic for skeletal muscle including angiotensin II (AngII) tumour necrosis factor-a (TNF-a) and lipopolysaccharide (LPS) also induced a rise in Ca2 +i, but this was not attenuated by anti-PIF-receptor antibody. The rise in Ca2 +i induced by PIF and AngII was completely attenuated by the Zn2 + chelator D-myo-inositol-1,2,6-triphosphate, and this was reversed by administration of exogenous Zn2 +. The Ca2 +i rise induced by PIF was independent of the presence of extracellular Ca2 +, and attenuated by the Ca2 + pump inhibitor thapsigargin, suggesting that the Ca2 +i rise was due to release from intracellular stores. This rise in Ca2 +i induced by PIF was attenuated by both the phospholipase C inhibitor U73122 and 2-APB, an inhibitor of the inositol 1,4,5-triphosphate receptor, suggesting the involvement of a G-protein. Binding of the PIF to its receptor in skeletal muscle triggers a rise in Ca2 +i, which initiates a signalling cascade leading to a depression in protein synthesis, and an increase in protein degradation.

Biomedical events extraction using the hidden vector state model

Objective: Biomedical events extraction concerns about events describing changes on the state of bio-molecules from literature. Comparing to the protein-protein interactions (PPIs) extraction task which often only involves the extraction of binary relations between two proteins, biomedical events extraction is much harder since it needs to deal with complex events consisting of embedded or hierarchical relations among proteins, events, and their textual triggers. In this paper, we propose an information extraction system based on the hidden vector state (HVS) model, called HVS-BioEvent, for biomedical events extraction, and investigate its capability in extracting complex events. Methods and material: HVS has been previously employed for extracting PPIs. In HVS-BioEvent, we propose an automated way to generate abstract annotations for HVS training and further propose novel machine learning approaches for event trigger words identification, and for biomedical events extraction from the HVS parse results. Results: Our proposed system achieves an F-score of 49.57% on the corpus used in the BioNLP'09 shared task, which is only 2.38% lower than the best performing system by UTurku in the BioNLP'09 shared task. Nevertheless, HVS-BioEvent outperforms UTurku's system on complex events extraction with 36.57% vs. 30.52% being achieved for extracting regulation events, and 40.61% vs. 38.99% for negative regulation events. Conclusions: The results suggest that the HVS model with the hierarchical hidden state structure is indeed more suitable for complex event extraction since it could naturally model embedded structural context in sentences.

New business formation in a rapidly growing economy:the Irish experience

The extraordinary growth of the Irish economy since the mid-1990s—the ‘Celtic Tiger’—has attracted a great deal of interest, commentary and research. Indeed, many countries look to Ireland as an economic development role model, and it has been suggested that Ireland might provide key lessons for other EU members as they seek to achieve the objectives set out in the Lisbon Agenda. Much of the discussion of Ireland’s growth has focused on its possible triggers: the long-term consequences of the late 1980s fiscal stabilisation, EU structural funds, education, wage moderation and devaluation of the Irish punt. The industrial policy perspective has highlighted the importance of inflows of foreign direct investment, but a notable absence from the discourse on the ‘Celtic Tiger’ has been any mention of the role of new business venture creation and entrepreneurship. In this paper we use unpublished Irish VAT data for the years 1988–2004 to provide the first detailed look at national trends in business birth and death rates in Ireland over the ‘take-off’ period. We also use sub-national VAT data to shed light on spatial trends in new venture creation. Our overall conclusions are that new business formation made no detectable contribution to the acceleration of Ireland’s growth in the late 1990s, although we do find evidence of spatial convergence in per capita business stocks.

Functional astrocyte-neuron lactate shuttle in a human stem cell-derived neuronal network

The NT2.D1 cell line is one of the most well-documented embryocarcinoma cell lines, and can be differentiated into neurons and astrocytes. Great focus has also been placed on defining the electrophysiological properties of the neuronal cells, and more recently we have investigated the functional properties of their associated astrocytes. We now show for the first time that human stem cell-derived astrocytes produce glycogen and that co-cultures of these cells demonstrate a functional astrocyte-neuron lactate shuttle (ANLS). The ANLS hypothesis proposes that during neuronal activity, glutamate released into the synaptic cleft is taken up by astrocytes and triggers glucose uptake, which is converted into lactate and released via monocarboxylate transporters for neuronal use. Using mixed cultures of NT2-derived neurons and astrocytes, we have shown that these cells modulate their glucose uptake in response to glutamate. Additionally, we demonstrate that in response to increased neuronal activity and under hypoglycaemic conditions, co-cultures modulate glycogen turnover and increase lactate production. Similar results were also shown after treatment with glutamate, potassium, isoproterenol, and dbcAMP. Together, these results demonstrate for the first time a functional ANLS in a human stem cell-derived co-culture. © 2013 ISCBFM.

System of integration of modularised assembly FMS

The modularised assembly FMS (Flexible Manufacturing System) cascade is a form of system design which, the authors feel, could be viable in a variety of organisational and operational settings where high product mix manufacture and unitary batch sizing are common features. The philosophy behind the concept is that production facilities are market-driven and customers' orders place a direct demand pull on final assembly which, in turn, triggers all preceeding activities. Greater flexibility~is recognized as a necessary feature in modern manufacture and the implementation of modularised FMS in conjunction with state-of-the-art hardware and computer software systems enable conditions under which more flexible processing can take place.

How does personality affect trust in B2C e-commerce?

Trust is a critical component of successful e-Commerce. Given the impersonality, anonymity, and automation of transactions, online vendor trustworthiness cannot be assessed by means of body language and other environmental cues that consumers typically use when deciding to trust offline retailers. It is therefore essential that the design of e-Commerce websites compensate by incorporating circumstantial cues in the form of appropriate trust triggers. This paper presents and discusses the results of a study which took an initial look at whether consumers with different personality types (a) are generally more trusting and (b) rely on different trust cues during their assessment of first impression vendor trustworthiness in B2C e-Commerce.