On social knowledge, ideology and the nuclear power debate

Many of the issues and problems concerning the role of our frameworks and structures of reasoning in the guidance of the process of social and technological development are encapsulated in the debate about nuclear energy. This thesis takes that debate as a context for analysing the rationality of scientific knowledge of society and the role and influence of such knowledge in debate and decision-making about appropriate forms of social and technological development. After an introductory review of the historical, political and economic context of the issues and of the development of UK energy policy over the last 25 years, the body of the thesis is structured into two parts. In the first part, a critical examination of orthodox conceptions of scientific objectivity is followed by an attempt to elaborate an alternative conception of the nature of the rationality of social scientific knowledge founded upon the notions of 'value-contingency' and 'ideology'. This conception is developed through discussions of the role of social problem-solving in providing a basis for the process of knowledge development and of the role of the state in structuring the problem-solving process and the development of social knowledge to provide a complex 'technical' legitimatory framework. The concept of a dominant 'technocratic ideology' is then elaborated and an attempt made to identify and outline the major cognitive and normative components of this ideology. In particular it is conceived of as presenting interrelated ideological accounts of the appropriate form of knowledge development, of the content of the social world and of the appropriate form of knowledge utilisation, which are underpinned by 'materialistic', 'liberalist' and 'rationalist' normative traditions. The second part of the thesis analyses certain aspects of the debate about nuclear energy in order to attempt to identify the role and influence of the 'technocratic ideology' and its normative commitments as elaborated in the first part, with a view to assessing the validity and implications of such a conception. After a review of the major issues of controversy in the debate, covering the economic, safety, environmental, social and political implications of nuclear energy, an attempt is made to clarify and categorise the main dimensions of the dispute in terms of the perception and valuation of economic benefits and 'social costs'. Arguments in support of nuclear power are then examined, themes of 'technocratic rationality' identified and the implications for the conduct of the debate discussed. Two particular aspects of the debate are then examined in detail to identify the influence of normative, ideological themes. Firstly, pro-nuclear perceptions and interpretations of the energy problem are analysed and liberalist and materialist themes identified; in particular tendencies towards the establishment of 'materialist ethical imperatives' are highlighted. Secondly, aspects of the process of consideration of alternative means to the 'solution' of the energy problem are examined including illustrations of the value-contingent nature of the relevant social knowledge, an analysis of the treatment of the issue of demand-side solutions in pro-nuclear arguments, and a brief discussion of the implications of technocratic rationality for the evaluation of the costs and benefits of nuclear power. Finally, conclusions are drawn on the evidence for the influence of technocratic rationality and the normative themes identified, on the political implications of such dominant ideological themes and on limitations of the analysis and further research directions

Intestinal antimicrobial gene expression: impact of micronutrients in malnourished adults during a randomized trial.

BACKGROUND: Because both micronutrients and antimicrobial peptides protect against diarrhea, we looked for an effect on intestinal antimicrobial peptide gene expression during a randomized controlled trial of multiple micronutrient (MM) supplementation. METHODS: Consenting adults (n=287) in Lusaka, Zambia, were randomized to receive a daily MM supplement or placebo and were followed up for 3.3 years, with a crossover after 2 years. Intestinal biopsy samples were obtained at annual intervals, and messenger RNA of the intestinal antimicrobial peptides human alpha defensin (HD) 5, HD6, human beta-defensin (hBD) 1, hBD2, and LL-37 were quantified by real-time reverse-transcriptase polymerase chain reaction. Samples were also obtained during diarrhea episodes and after convalescence. RESULTS: There was no effect overall of treatment allocation. However, in malnourished adults (body mass index < or =18.5), HD5 mRNA was increased by 0.8 log transcripts/microg total RNA in MM recipients, compared with HD5 mRNA in placebo recipients (P=.007). During diarrhea, HD5 expression was reduced by 0.8 log transcripts in placebo recipients (P=.02) but was not reduced in MM recipients, nor was it reduced after the crossover. Correlations between HD5 and nutritional status were found that were sex-specific but not explained by serum leptin or adiponectin concentrations. CONCLUSIONS: Micronutrient supplementation was associated with up-regulation of HD5 only in malnourished adults. Interactions between antimicrobial gene expression and nutritional status may help to explain the increased risk of infection in individuals with malnutrition

Paediatric inflammatory bowel disease and its relationship with the microbiome

Paediatric inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract, comprising of Crohn's disease (CD), ulcerative colitis (UC), and, where classification is undetermined, inflammatory bowel disease unclassified (IBDU). Paediatric IBD incidence is increasing globally, with prevalence highest in the developed world. Though no specific causative agent has been identified for paediatric IBD, it is believed that a number of factors may contribute to the development of the disease, including genetics and the environment. Another potential component in the development of IBD is the microbiota in the digestive tract, particularly the gut. While the exact role that the microbiome plays in IBD is unclear, many studies acknowledge the complex relationship between the gut bacteria and pathogenesis of IBD. In this review, we look at the increasing number of studies investigating the role the microbiome and other biomes play in paediatric patients with IBD, particularly changes associated with IBD, varying disease states, and therapeutics. The paediatric IBD microbiome is significantly different to that of healthy children, with decreased diversity and differences in bacterial composition (such as a decrease in Firmicutes). Changes in the microbiome relating to various treatments of IBD and disease severity have also been observed in multiple studies. Changes in diversity and composition may also extend to other biomes in paediatric IBD, such as the virome and the mycobiome. Research into biome differences in IBD paediatric patients may help progress our understanding of the aetiology of the disease

Stability, fatty acid composition and sensory properties of the <i>M. Longissimus </i>muscle from beef steers grazing either chicory / ryegrass or ryegrass

Research has shown both production and health benefits for the use of chicory (Cichorium intybus) within ruminant diets. Despite this, little was known about the the effects of this forage, containing differing fatty acid profiles and secondary plant compounds compared to ryegrass, on beef stability, fatty acid composition or sensory properties. An experiment was conducted to investigate whether the inclusion of chicory in the diet of grazing beef steers would alter the meat stability, fatty acid composition and sensory properties of the M. Longissimus muscle compared to beef steers grazing perennial ryegrass (Lolium perenne). Triplicate 2 ha plots were established with a chicory (cv. Puna II) / perennial ryegrass (cv. Premium) mix or a perennial ryegrass (cv. Premium) control. A core group of 36 Belgian Blue - cross steers were used within a two-year beef finishing experiment (n=6 per replicate plot). In the second grazing year, steers were slaughtered as they reached a target fat class of 3. After dressing, half carcass sides were hung for 48 h and then then quartered between the junction of the 10th and 11th rib. Muscle pH was checked at 2 and 48 h post-slaughter. A 250 mm-long section of the hindloin joint containing the M. Longissimus lumborum muscle was removed from the left side of the carcass, posterior to the 10th rib. A 20 mm-thick steak was cut and a muscle sample was vacuum packed and frozen at -20? C for subsequent analysis of vitamin E, a further steak being retained for fatty acid analysis. The remaining section of the loin was vacuum-packed in modified atmosphere packs and subjected to simulated retail display. The remaining section of the conditioned loin was used for sensory analysis. Data on pH, vitamin E concentration and colour stability in a simulated retail display showed there were no effects of including chicory in the diet of grazing beef steers on meat stability. There were also no differences found in the fatty acid composition or the overall eating quality of the steaks from the two treatments. In conclusion, there were no substantive effects of including chicory in the swards of grazing beef cattle on meat stability, fatty acid composition or sensory properties when compared with beef steers grazing ryegrass-only swards.publishersversionPeer reviewe

Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease

Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epitheliu

The impact of mergers on relaxed X-ray clusters - III. Effects on compact cool cores

(Abridged) We use the simulations presented in Poole et al. 2006 to examine the effects of mergers on compact cool cores in X-ray clusters. We propose a scheme for classifying the morphology of clusters based on their surface brightness and entropy profiles. Three dominant morphologies emerge: two hosting compact cores and central temperatures which are cool (CCC systems) or warm (CWC systems) and one hosting extended cores which are warm (EWC systems). We find that CCC states are disrupted only after direct collisions between cluster cores in head-on collisions or during second pericentric passage in off-axis mergers. By the time they relax, our remnant cores have generally been heated to warm core (CWC or EWC) states but subsequently recover CCC states. The only case resulting in a long-lived EWC state is a slightly off-axis 3:1 merger for which the majority of shock heating occurs during the accretion of a low-entropy stream formed from the disruption of the secondary's core. Compression prevents core temperatures from falling until after relaxation thus explaining the observed population of relaxed CWC systems with no need to invoke AGN feedback. The morphological segregation observed in the L_x-T_x and beta-r_c scaling relations is reflected in our simulations as well. However, none of the cases we have studied produce sufficiently high remnant central entropies to account for the most under-luminous EWC systems observed. Lastly, systems which initially host central metallicity gradients do not yield merger remnants with flat metallicity profiles. Taken together, these results suggest that once formed, compact core systems are remarkably stable against disruption from mergers. It remains to be demonstrated exactly how the sizable observed population of extended core systems was formed.Comment: 19 pages, 8 figures, submitted for publication in MNRA

Association between exposure to environmental tobacco smoke and biomarkers of oxidative stress among patients hospitalised with acute myocardial infarction

Objective To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.&lt;p&gt;&lt;/p&gt; Design An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.&lt;p&gt;&lt;/p&gt; Setting Nine acute hospitals in Scotland.&lt;p&gt;&lt;/p&gt; Participants Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).&lt;p&gt;&lt;/p&gt; Intervention None.&lt;p&gt;&lt;/p&gt; Main outcome measures Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.&lt;p&gt;&lt;/p&gt; Results After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).&lt;p&gt;&lt;/p&gt; Conclusions Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.&lt;p&gt;&lt;/p&gt

The XMM Cluster Survey: The interplay between the brightest cluster galaxy and the intra-cluster medium via AGN feedback

Using a sample of 123 X-ray clusters and groups drawn from the XMM-Cluster Survey first data release, we investigate the interplay between the brightest cluster galaxy (BCG), its black hole, and the intra-cluster/group medium (ICM). It appears that for groups and clusters with a BCG likely to host significant AGN feedback, gas cooling dominates in those with Tx > 2 keV while AGN feedback dominates below. This may be understood through the sub-unity exponent found in the scaling relation we derive between the BCG mass and cluster mass over the halo mass range 10^13 < M500 < 10^15Msol and the lack of correlation between radio luminosity and cluster mass, such that BCG AGN in groups can have relatively more energetic influence on the ICM. The Lx - Tx relation for systems with the most massive BCGs, or those with BCGs co-located with the peak of the ICM emission, is steeper than that for those with the least massive and most offset, which instead follows self-similarity. This is evidence that a combination of central gas cooling and powerful, well fuelled AGN causes the departure of the ICM from pure gravitational heating, with the steepened relation crossing self-similarity at Tx = 2 keV. Importantly, regardless of their black hole mass, BCGs are more likely to host radio-loud AGN if they are in a massive cluster (Tx > 2 keV) and again co-located with an effective fuel supply of dense, cooling gas. This demonstrates that the most massive black holes appear to know more about their host cluster than they do about their host galaxy. The results lead us to propose a physically motivated, empirical definition of 'cluster' and 'group', delineated at 2 keV.Comment: Accepted for publication in MNRAS - replaced to match corrected proo

Lead optimization of a pyrazole sulfonamide series of trypanosoma brucei N -myristoyltransferase inhibitors:Identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human african trypanosomiasis

[Image: see text] Trypanosoma bruceiN-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood–brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT