Strategies against racism: a comparison of a social movement and case studies of anti-racist policy and practice in the local state

The thesis compares two contrasting strategies employed with the aim of combating particular forms of racism within contemporary Britain. Both are assessed as political strategies in their own right and placed within the broader context of reformist and revolutionary political traditions. The sociology of social movements is examined critically, as are Marxist and post-Marxist writings on the role of human agency within social structures and on the nature of social movements. The history of the Anti Nazi League (ANL) in the late 1970s and its opposition to the National Front is considered as an example of anti-racist social movement based on the Trotskyist model of the United Front. The degree to which the Anti Nazi League corresponded to such a model is analysed as are the potential broader applications for such a strategy. The strategy with which the ANL is compared is the development of anti-racist and equal opportunities policies within local government in the 1980s, primarily by Labour-controlled local authorities. The theory of the local state and the political phenomenon of municipal socialism are discussed, specifically the role of various groups operating in and around local authorities in the formation and implementation of anti-racist policy and practice. Following this general discussion, two case studies in each of the areas of local authority housing, education and employment are explored to consider in depth the problems of specific anti-racist policies. In summation the efficacy of the two strategies are considered as parts of wider political currents in tandem with their declared specific objectives.

Innovation in teams : a qualitative and quantitative study of team behaviours

This thesis explores the processes of team innovation. It utilises two studies, an organisationally based pilot and an experimental study, to examine and identify aspects of teams' behaviours that are important for successful innovative outcome. The pilot study, based in two automotive manufacturers, involved the collection of team members' experiences through semi-structured interviews, and identified a number of factors that affected teams' innovative performance. These included: the application of ideative & dissemination processes; the importance of good team relationships, especially those of a more informal nature, in facilitating information and ideative processes; the role of external linkages in enhancing quality and radicality of innovations; and the potential attenuation of innovative ideas by time deadlines. This study revealed a number key team behaviours that may be important in successful innovation outcomes. These included; goal setting, idea generation and development, external contact, task and personal information exchange, leadership, positive feedback and resource deployment. These behaviours formed the basis of a coding system used in the second part of the research. Building on the results from the field based research, an experimental study was undertaken to examine the behavioural differences between three groups of sixteen teams undertaking innovative an task to produce an anti-drugs poster. They were randomly assigned to one of three innovation category conditions suggested by King and Anderson (1990), emergent, imported and imposed. These conditions determined the teams level of access to additional information on previously successful campaigns and the degree of freedom they had with regarding to the design of the poster. In addition, a further experimental condition was imposed on half of the teams per category which involved a formal time deadline for task completion. The teams were video taped for the duration of their innovation and their behaviours analysed and coded in five main aspects including; ideation, external focus, goal setting, interpersonal, directive and resource related activities. A panel of experts, utilising five scales developed from West and Anderson's (1996) innovation outcome measures, assessed the teams' outputs. ANOVAs and repeated measure ANOVAs were deployed to identify whether there were significant differences between the different conditions. The results indicated that there were some behavioural differences between the categories and that over the duration of the task behavioural changes were identified. The results, however, revealed a complex picture and suggested limited support for three distinctive innovation categories. There were many differences in behaviours, but rarely between more than two of the categories. A main finding was the impact that different levels of constraint had in changing teams' focus of attention. For example, emergent teams were found to use both their own team and external resources, whilst those who could import information about other successful campaigns were likely to concentrate outside the team and pay limited attention to the internal resources available within the team. In contrast, those operating under task constraints with aspects of the task imposed onto them were more likely to attend to internal team resources and pay limited attention to the external world. As indicated by the earlier field study, time deadlines did significantly change teams' behaviour, reducing ideative and information exchange behaviours. The model shows an important behavioural progression related to innovate teams. This progression involved the teams' openness initially to external sources, and then to the intra-team environment. Premature closure on the final idea before their mid-point was found to have a detrimental impact on team's innovation. Ideative behaviour per se was not significant for innovation outcome, instead the development of intra-team support and trust emerged as crucial. Analysis of variance revealed some limited differentiation between the behaviours of teams operating under the aforementioned three innovation categories. There were also distinct detrimental differences in the behaviour of those operating under a time deadline. Overall, the study identified the complex interrelationships of team behaviours and outcomes, and between teams and their context.

Disparate effects of non-steroidal anti-inflammatory drugs on apoptosis in guinea-pig gastric mucous cells: inhibition of basal apoptosis by diclofenac

Non-steroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in gastrointestinal cancer cell lines. Similar actions on normal gastric epithelial cells could contribute to NSAID gastropathy. The present work therefore compared the actions of diclofenac, ibuprofen, indomethacin, and the cyclo-oxygenase-2 selective inhibitor, NS-398, on a primary culture of guinea-pig gastric mucous epithelial cells. Cell number was assessed by staining with crystal violet. Apoptotic activity was determined by condensation and fragmentation of nuclei and by assay of caspase-3-like activity. Necrosis was evaluated from release of cellular enzymes. Ibuprofen (250 μM for 24 h) promoted cell loss, and apoptosis, under both basal conditions and when apoptosis was increased by 25 μM N-Hexanoyl-D-sphingosine (C6-ceramide). Diclofenac (250 μM for 24 h) reduced the proportion of apoptotic nuclei from 5.2 to 2.1%, and caused inhibition of caspase-3-like activity, without causing necrosis under basal conditions. No such reduction in apoptotic activity was evident in the presence of 25 μM C6-ceramide. The inhibitory effect of diclofenac on basal caspase-3-like activity was also exhibited by the structurally similar mefenamic and flufenamic acids (1–250 μM), but not by niflumic acid. Inhibition of superoxide production by the cells increased caspase-3-like activity, but the inhibitory action of diclofenac on caspase activity remained. Diclofenac did not affect superoxide production. Diclofenac inhibited caspase-3-like activity in cell homogenates and also inhibited human recombinant caspase-3. In conclusion, NSAIDs vary in their effect on apoptotic activity in a primary culture of guinea-pig gastric mucous epithelial cells, and the inhibitory effect of diclofenac on basal apoptosis could involve an action on caspase activity.

From the outside in:consumer anti-choice and policy implications in the mobile gaming market

Significant growth in mobile media consumption has prompted a call to better understand the socio-cultural and policy dimensions of consumer choices. Contrary to industry and technology led analysis, this study argues that to guide consumer choice and innovation via regulatory policies requires an understanding of both ex-ante as well as in ex-post consumption conditions. This study examines mobile phone gaming to uncover how consumer anti-choice shapes decision-making as a framework for closely interrogating the ways in which policy concerns impact on consumers' behavior. Through eleven focus groups (n=62), the study empirically identifies voluntary, intentional, and positive consumer anti-choice behaviors all of which impact policy initiatives when consumers, both gamers and non-gamers, self-regulate their behaviors. Findings point to four types of policy implication: regulating the self-regulated, understanding anti-choice, boundary-setting and including the self-excluded. © 2012 Elsevier Ltd.

Behavioural and neurochemical correlates of drugs acting at imidazoline and a2-adrenoceptor binding sites

A number of agents with differing selectivity profiles for the non-a2 adrenoceptor binding site (NAIBS), imidazoline preferring receptor (IPR) and a2-adrenoceptor were employed in a series of behavioural and neurochemical experiments to determine a functional role for the former two sites. The highly selective NAIBS ligand RX801 077 produced an increase in rat brain extracellular noradrenaline (NA) levels, as determined by the technique of in vivo microdialysis, which may underlie its ability to produce a discriminable cue in the same species. This increase in NA may be due to a suggested link between the NAIBS and the monoamine oxidase inhibitor (MAOI) activity of RX801 077. For instance, the RX801 077 cue was substituted for by the MAOI drugs pargyline and moclobemide, which themselves down regulate NAIBS when administered chronically. RX811 059 substituted for the RX801 077 cue which may be due its ability to stimulate NA release via its activity as a highly selective a2-adrenoceptor antagonist. An effect upon NA output may also explain the ability of RX801 077 to 'mimic' the anti-immobility effect of the antidepressant drug desmethylimipramine (DMJ) in the forced swimming test. Further studies are therefore required to examine a possible role for the NAIBS in the treatment of depression. Discriminable cues were also produced by RX811 059 and the a2- adrenoceptor agonist clonidine, probably as a consequence of their respective ability to stimulate and inhibit NA output via their opposing activity at a2-adrenoceptors. The IPR has been suggested to play a role in mediating the hypotensive effect of clonidine, although a precise role was unable to be established for this site in the present studies due to the unavailability of highly selective IPA agents.

Formulation of topical non-steroidal anti-inflammatory agents

Reversed-pahse high-performance liquid chromatographic (HPLC) methods were developed for the assay of indomethacin, its decomposition products, ibuprofen and its (tetrahydro-2-furanyl)methyl-, (tetrahydro-2-(2H)pyranyl)methyl- and cyclohexylmethyl esters. The development and application of these HPLC systems were studied. A number of physico-chemical parameters that affect percutaneous absorption were investigated. The pKa values of indomethacin and ibuprofen were determined using the solubility method. Potentiometric titration and the Taft equation were also used for ibuprofen. The incorporation of ethanol or propylene glycol in the solvent resulted in an improvement in the aqueous solubility of these compounds. The partition coefficients were evaluated in order to establish the affinity of these drugs towards the stratum corneum. The stability of indomethacin and of ibuprofen esters were investigated and the effect of temperature and pH on the decomposition rates were studied. The effect of cetyltrimethylammonium bromide on the alkaline degradation of indomethacin was also followed. In the presence of alcohol, indomethacin alcoholysis was observed and the kinetics of decomposition were subjected to non-linear regression analysis and the rate constants for the various pathways were quantified. The non-isothermal, sufactant non-isoconcentration and non-isopH degradation of indomethacin were investigated. The analysis of the data was undertaken using NONISO, a BASIC computer program. The degradation profiles obtained from both non-iso and iso-kinetic studies show that there is close concordance in the results. The metabolic biotransformation of ibuprofen esters was followed using esterases from hog liver and rat skin homogenates. The results showed that the esters were very labile under these conditions. The presence of propylene glycol affected the rates of enzymic hydrolysis of the ester. The hydrolysis is modelled using an equation involving the dielectric constant of the medium. The percutaneous absorption of indomethacin and of ibuprofen and its esters was followed from solutions using an in vitro excised human skin model. The absorption profiles followed first order kinetics. The diffusion process was related to their solubility and to the human skin/solvent partition coefficient. The percutaneous absorption of two ibuprofen esters from suspensions in 20% propylene glycol-water were also followed through rat skin with only ibuprofen being detected in the receiver phase. The sensitivity of ibuprofen esters to enzymic hydrolysis compared to the chemical hydrolysis may prove valuable in the formulation of topical delivery systems.

Studies on the anti-inflammatory effect of S-Adenosyl-L-methionine

1. S-adenosyl-L-methionine (SAMe) had no effect on cytochrome C reduction by superoxide generated from xanthine oxidase except at high concentrations. This was due to direct inhibition of the enzyme. 2. SAMe inhibited the neutrophil respiratory burst , measured by luminol enhanced chemiluminescence, to FMLP and zymosan A but not to PMA. 3. Adenosine and methylthioadenosine (MTA) inhibited the respiratory burst elicited by FMLP. 4. SAMe inhibited the phagocytosis of latex particles by neutrophils at high concentrations but methionine and S-adenosyl L-homocysteine had no effect. 5. Treatment with SAMe had no effect on cell infiltration or PGE2 production in 6-day air pouches. 6. Treatment with SAMe at the optimum dose of 50mg/kg inhibited the early phases of carrageenan induced rat hind paw inflammation but had a lesser effect on the secondary response. The antiinflammatory effect was sustained after inhibiton of polyamine synthesis. 7. SAMe increased liver putrescine levels in the presence and absence of inflammation Spermidine levels were increased in the presence of inflammation but spermine levels were unaffected by any of the treatments. 8. MT A and adenosine increased liver putrescine and spermidine levels 9. Treatment with SAMe had no effect on the polyamine status of blood. lO.Treatment with SAMe had no effect on the levels of glutathione in liver or blood. 11.SAMe and MTA inhibited histamine and platelet-activating factor (PAF) induced hind paw inflammation but had no effect on inflammation induced by dextran, zymosan, compound 48/80, 5-hydroxytryptamine, arachidonic acid or glucose oxidase. MTA was more effective than SAMe. 12. PAP-induced rat hind paw inflammation was inhibited by isoprenaline and verapamil. Combinations of these drugs with SAMe or MT A had no further enhancement of effect. 13. Incubation of rat PMNLs with [14c ] SAMe increased the intracellular levels of S-adenosyl-L-homocysteine in a dose dependent manner, but had no effect on the intracellular levels of SAMe, adenosine or MT A. 14. Pharmacokinetic studies of plasma SAMe following a single dose of the drug (50mg/kg) i.p. demonstrated that SAMe is rapidly absorbed and metabolised

The anti-inflammatory action of tetracyclines

For six decades tetracyclines have been successfully used for their broad spectrum antibiotic effects. However, non-antibiotic effects of tetracyclines have been reported. The anti-inflammatory effects of tetracycline drugs have been investigated in the context of a range of inflammatory diseases including sepsis and a number of neurodegenerative diseases. This thesis investigates the effects of a range of clinically important tetracyclines (oxytetracycline, doxycycline, minocycline and tigecycline) on the ability of the J774.2 cell line to produce nitric oxide when stimulated with the bacterial cell wall component, LPS. The proteome of J774.2 cells was analysed in response to LPS stimulation (1 µg/ml) with and without prior treatment with minocycline (50µg/ml), this allows the unbiased analysis of the cellular proteome in response to minocycline and LPS, protein spots of interest were excised and identified by nano-electrospray ionisation-linear ion trap mass spectroscopy. All of the tetracyclines that were investigated inhibited LPS-induced nitric oxide production in a dose dependent manner and this was due to the inhibition of inducible nitric oxide synthase expression. This is the first report to show that tigecycline inhibits inducible nitric oxide expression and nitric oxide production. Using two-dimensional gel electrophoresis and total protein staining eleven proteins were identified as being modulated by LPS. Of these eleven proteins; expression of some, but not all was modulated when the cells received a prior treatment with minocycline suggesting that minocycline does not completely block LPS-induced macrophage activation but probably specifically acts on particular inflammatory signaling pathways in macrophages. Three protein spots with a similar molecular weight but different pI values identified in this proteomic study were identified as ATP synthase ß chain. These different protein spots probably correspond to different phosphorylation states of the protein, suggesting that minocycline affects the balance of protein kinase and protein phosphatase activity in the immune response.

Computer-aided design, synthesis and screening of potential anti-microbial compounds

The work presented in this thesis falls into three main categories: The design and synthesis of potential anti-tuberculosis drugs targeting a mycobacterial esterase and the enzyme dUTPase; synthesis and anti-microbial SAR studies on a set of carboxamidrazones; synthesis and anti-microbial SAR studies on a set of thiosem icarbazones.

Anti-obesity fixed-dose combinations

The management of hypertension, dyslipidaemia and hyperglycaemia often requires multiple medications that combine two or more agents with different modes of action to give additive efficacy. In some situations lower doses of two agents with different modes of action can achieve greater efficacy than a high dose of one agent. This is achieved by addressing different pathophysiological features of the disease, whilst at the same time producing fewer side effects than a high dose of one agent. Several examples of this have been described for combinations of blood glucose-lowering therapies in type 2 diabetes. However, the pill burden associated with multiple medications can reduce patient adherence and compromise the potential value of the treatments. To reduce the number of daily doses, single-tablet (‘fixed-dose’) combinations have been introduced to offer greater convenience. There are several ant-diabetic FDCs, mostly combining metformin with another type of glucose-lowering agent. The UK has been less enthusiastic about FDCs than many other parts of the world, and does not have most of these combinations available. One of the concerns expressed about FDCs is a reduced flexibility to select desired doses of the two agents for dose titration. However, in practise the variety of dosage strengths for most FDCs matches the dosages available as separate tablets. Another concern has been the preference to add drugs one at a time to be able to attribute any adverse effects. In most cases the FDC is used when a second drug has been added to a monotherapy that is already a component of the FDC, so it is only the same as adding one agent but without increasing the pill burden.

The pharmacology of centrally acting drugs in animals of altered thyroid status

The pharmacological effects of a number of centrally acting drugs have been compared in euthyroid mice and mice made hyperthyroid by pretreatment with sodium-1-thyroxine. The potencies of two barbiturates, pentobarbitone and thiopentone - as indicated by the duration of their hypnotic actions and their acute toxicities - are increased in hyperthyroid mice. An acutely active uncoupler of phosphorylative oxidation is 2, 4-dinitrophenol, an agent which proved to be a potent hypnotic when administered intracerebrally. An attempt has been made to relate the mechanism of action of the barbiturates to the uncoupling effects of thyroxine and 2, 4-dinitrophenol. The pharmacological effects of chlorpromazine, reserpine and amphetamine-like drugs have also been studied in hyperthyroid mice. After pretreatment with thyroxine, mice show a reduced tendency to become hypothermic after chlorpromazine or reserpine; in fact, under suitable laboratory conditions these agents produce a hyperthermic effect. Yet their known depressant effects upon locomotor activity were not substantially altered. Thus it appeared that depression of locomotor activity and hypothermia are not necessarily correlated, an observation at variance with previously held opinion. These results have been discussed in the light of our knowledge of the role of the thyroid gland in thermoregulation. The actions of tremorine and its metabolite, oxotremorine, have also been examined. Hyperthyroid animals are less susceptible to both the hypothermia and tremor produced by these agents. An attempt is made to explain these observations, in view of the known mechanism of action of oxotremorine and the tremorgenic actions that thyroxine may have. A number of experimental methods have been used to study the anti-nociceptive (analgesic) effects of drugs in euthyroid and hyperthyroid mice. The sites and mechanisms of action of these drugs and the known actions of thyroxine have been discussed.

Estimating the efficiency of healthcare facilities providing HIV/AIDS treatment in Zambia:a data envelopment approach

Zambia and many other countries in Sub-Saharan Africa face a key challenge of sustaining high levels of coverage of AIDS treatment under prospects of dwindling global resources for HIV/AIDS treatment. Policy debate in HIV/AIDS is increasingly paying more focus to efficiency in the use of available resources. In this chapter, we apply Data Envelopment Analysis (DEA) to estimate short term technical efficiency of 34 HIV/AIDS treatment facilities in Zambia. The data consists of input variables such as human resources, medical equipment, building space, drugs, medical supplies, and other materials used in providing HIV/AIDS treatment. Two main outputs namely, numbers of ART-years (Anti-Retroviral Therapy-years) and pre-ART-years are included in the model. Results show the mean technical efficiency score to be 83%, with great variability in efficiency scores across the facilities. Scale inefficiency is also shown to be significant. About half of the facilities were on the efficiency frontier. We also construct bootstrap confidence intervals around the efficiency scores.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo

Substantial evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have potential as chemopreventative/therapeutic agents. However, these agents cannot be universally recommended for prevention purposes due to their potential side-effect profiles. Here, we compared the growth inhibitory and mechanistic activity of aspirin to two novel analogues, diaspirin (DiA) and fumaryl diaspirin (F-DiA). We found that the aspirin analogues inhibited cell proliferation and induced apoptosis of colorectal cancer cells at significantly lower doses than aspirin. Similar to aspirin, we found that an early response to the analogues was a reduction in levels of cyclin D1 and stimulation of the NF-κB pathway. This stimulation was associated with a significant reduction in basal levels of NF-κB transcriptional activity, in keeping with previous data for aspirin. However, in contrast to aspirin, DiA and F-DiA activity was not associated with nucleolar accumulation of RelA. For all assays, F-DiA had a more rapid and significant effect than DiA, identifying this agent as particularly active against colorectal cancer. Using a syngeneic colorectal tumour model in mice, we found that, while both agents significantly inhibited tumour growth in vivo, this effect was particularly pronounced for F-DiA. These data identify two compounds that are active against colorectal cancer in vitro and in vivo. They also identify a potential mechanism of action of these agents and shed light on the chemical structures that may be important for the antitumour effects of aspirin.