CORSALL: collaboration in research support by academic libraries in Leicestershire: final report

The CORSALL project involved De Montfort University, Loughborough University, and the University of Leicester. Its purpose was to investigate ways in which the Libraries of the three Universities might collaborate more closely in the services they provide for their researchers (i.e. research-active academic staff and research students). The project was commissioned by the three Libraries in response to interest from researchers and senior management at their respective universities. It ran from March to December 2000, and included DMU’s libraries in Bedford, Milton Keynes and Lincolnshire in its scope.No abstract provide

Inflammation and end-organ damage with obesity and gender

Latest epidemiological data suggests that 1.5 billion adults worldwide are obese or overweight. Excess weight and adipocyte hypertrophy have long been associated with contributing to low-grade systemic inflammation through elevated adipokine secretion. These increased endocrine signals further augment the metabolic dysfunction related to the presence of obesity. A chronic exposure to obesity mediated inflammation is also suggested to be responsible for progression of renal pathology and eventual end-stage organ failure. In human clinical statistics, these factors indicate a gender disparity, as males demonstrate much faster progression rates of obesity-linked renal disease than females. Therefore, the aim of this thesis was to investigate the role of gender in obesity mediated inflammation in the development of renal disease using a large animal model i.e. sheep. Post-natal female and male sheep were exposed to a lean or obesogenic environment by restricting physical activity from ≈3 months to ≈17 months of age. Analysis of body composition and adipose tissue physiology, morphology and deposition identified the development of moderate obesity following chronic exposure to a low physical environment, although no differences were observed with gender. With obesity, both genders demonstrated metabolic irregularities; males showed hyperinsulinaemia and females displayed hypercortisolism. Gene expression analysis identified an up-regulation of inflammatory related genes in perirenal adipose tissue (PAT) and kidney in obese males, a finding not seen in females, although obese females exhibited an up-regulation in glucocorticoid receptor abundance in PAT. Furthermore, the males demonstrated adaptations in renal structure and function with obesity, modifications not observed in females. The main conclusion of my thesis is that after the development of obesity, males appear much more sensitive to the metabolic, inflammatory and renal adaptations associated with an obese condition. Females displayed a down-regulation of inflammatory genes with obesity which I propose acts as a protective mechanism against the progression of renal disease, perhaps mediated by an immunosuppressive glucocorticoid action in adipose tissue. It is also possible that sex hormones play a role in obesity inflammatory renal disease development, postulated to occur through HPA activation and epigenetic alterations

The placenta, maternal diet and adipose tissue development in the newborn

Background: A majority of adipose tissue present in the newborn possess the unique mitochondrial protein, uncoupling protein (UCP1). It is thus highly metabolically active and capable of producing 300 times more heat per unit mass than any other organ in the body. The extent to which maternal obesity and/or an obesogenic diet impacts on placental function thereby resetting the relative distribution of different types of fat in the fetus is unknown. Summary: Developmentally the majority (if not all) fat in the fetus can be considered as classical brown fat, in which UCP1 is highly abundant. In contrast, beige (or recruitable) fat which possess 90% less UCP1 may only appear after birth, as a majority of fat depots undergo a pronounced transformation that is usually accompanied by the loss of UCP1. The extent to which this process can be modulated in a depot-specific manner and/or changes in the maternal metabolic environment remain unknown. Key Messages: An increased understanding of the mechanism by which offspring born to mothers possess excessive adipose tissue could enable sustainable interventions designed to promote the abundance of UCP1 possessing adipocytes. Ultimately, this would increase their energy expenditure and improve glucose homeostasis in these individuals

Effectiveness of nurse delivered endoscopy: findings from randomised multi-institution nurse endoscopy trial (MINuET)

Objective To compare the clinical effectiveness of doctors and nurses in undertaking upper and lower gastrointestinal endoscopy. Design Pragmatic trial with Zelen's randomisation before consent to minimise distortion of existing practice. Setting 23 hospitals in the United Kingdom. In six hospitals, nurses undertook both upper and lower gastrointestinal endoscopy, yielding a total of 29 centres. Participants 67 doctors and 30 nurses. Of 4964 potentially eligible patients, we randomised 4128 (83%) and recruited 1888 (38%) from July 2002 to June 2003. Interventions Diagnostic upper gastrointestinal endoscopy and flexible sigmoidoscopy, undertaken with or without sedation, with the standard preparation, techniques, and protocols of participating hospitals. After referral for either procedure, patients were randomised between doctors and nurses. Main outcome measures Gastrointestinal symptom rating questionnaire (primary outcome), gastrointestinal endoscopy satisfaction questionnaire and state-trait anxiety inventory (all analysed by intention to treat); immediate and delayed complications; quality of examination and corresponding report; patients' preferences for operator; and new diagnoses at one year (all analysed according to who carried out the procedure). Results There was no significant difference between groups in outcome at one day, one month, or one year after endoscopy, except that patients were more satisfied with nurses after one day. Nurses were also more thorough than doctors in examining the stomach and oesophagus. While quality of life scores were slightly better in patients the doctor group, this was not statistically significant. Conclusions Diagnostic endoscopy can be undertaken safely and effectively by nurses. Trial registration International standard RCT 8276570

Inflammation and end-organ damage with obesity and gender

Latest epidemiological data suggests that 1.5 billion adults worldwide are obese or overweight. Excess weight and adipocyte hypertrophy have long been associated with contributing to low-grade systemic inflammation through elevated adipokine secretion. These increased endocrine signals further augment the metabolic dysfunction related to the presence of obesity. A chronic exposure to obesity mediated inflammation is also suggested to be responsible for progression of renal pathology and eventual end-stage organ failure. In human clinical statistics, these factors indicate a gender disparity, as males demonstrate much faster progression rates of obesity-linked renal disease than females. Therefore, the aim of this thesis was to investigate the role of gender in obesity mediated inflammation in the development of renal disease using a large animal model i.e. sheep. Post-natal female and male sheep were exposed to a lean or obesogenic environment by restricting physical activity from ≈3 months to ≈17 months of age. Analysis of body composition and adipose tissue physiology, morphology and deposition identified the development of moderate obesity following chronic exposure to a low physical environment, although no differences were observed with gender. With obesity, both genders demonstrated metabolic irregularities; males showed hyperinsulinaemia and females displayed hypercortisolism. Gene expression analysis identified an up-regulation of inflammatory related genes in perirenal adipose tissue (PAT) and kidney in obese males, a finding not seen in females, although obese females exhibited an up-regulation in glucocorticoid receptor abundance in PAT. Furthermore, the males demonstrated adaptations in renal structure and function with obesity, modifications not observed in females. The main conclusion of my thesis is that after the development of obesity, males appear much more sensitive to the metabolic, inflammatory and renal adaptations associated with an obese condition. Females displayed a down-regulation of inflammatory genes with obesity which I propose acts as a protective mechanism against the progression of renal disease, perhaps mediated by an immunosuppressive glucocorticoid action in adipose tissue. It is also possible that sex hormones play a role in obesity inflammatory renal disease development, postulated to occur through HPA activation and epigenetic alterations

A survey of partial differential equations in geometric design

YesComputer aided geometric design is an area where the improvement of surface generation techniques is an everlasting demand since faster and more accurate geometric models are required. Traditional methods for generating surfaces were initially mainly based upon interpolation algorithms. Recently, partial differential equations (PDE) were introduced as a valuable tool for geometric modelling since they offer a number of features from which these areas can benefit. This work summarises the uses given to PDE surfaces as a surface generation technique togethe

Cold-induced beigeing of stem cell-derived adipocytes is not fully reversible after return to normothermia

Beige adipocytes possess the morphological and biochemical characteristics of brown adipocytes, including the mitochondrial uncoupling protein (UCP)1. Mesenchymal stem cells (MSCs) are somatic multipotent progenitors which differentiate into lipid-laden adipocytes. Induction of MSC adipogenesis under hypothermic culture conditions (i.e. 32°C) promotes the appearance of a beige adipogenic phenotype, but the stability of this phenotypic switch after cells are returned to normothermic conditions of 37°C has not been fully examined. Here, cells transferred from 32°C to 37°C retained their multilocular beige-like morphology and exhibited an intermediate gene expression profile, with both beige-like and white adipocyte characteristics while maintaining UCP1 protein expression. Metabolic profile analysis indicated that the bioenergetic status of cells initially differentiated at 32°C adapted post-transfer to 37°C, showing an increase in mitochondrial respiration and glycolysis. The ability of the transferred cells to respond under stress conditions (e.g. carbonyl cyanide-4- phenylhydrazone (FCCP) treatment) demonstrated higher functional capacity of enzymes involved in the electron transport chain and capability to supply substrate to the mitochondria. Overall, MSC derived adipocytes incubated at 32°C were able to remain metabolically active and retain brown-like features after 3 weeks of acclimatisation at 37°C, indicating these phenotypic characteristics acquired in response to environmental conditions are not fully reversible

Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep

Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity

Caffeine exposure induces browning features in adipose tissue in vitro and in vivo

Brown adipose tissue (BAT) is able to rapidly generate heat and metabolise macronutrients, such as glucose and lipids, through activation of mitochondrial uncoupling protein 1 (UCP1). Diet can modulate UCP1 function but the capacity of individual nutrients to promote the abundance and activity of UCP1 is not well established. Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown. This study examined the effect of caffeine on BAT thermogenesis in vitro and in vivo. Stem cell-derived adipocytes exposed to caffeine (1mM) showed increased UCP1 protein abundance and cell metabolism with enhanced oxygen consumption and proton leak. These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content. Caffeine also increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression and mitochondrial biogenesis, together with a number of BAT selective and beige gene markers. In vivo, drinking coffee (but not water) stimulated the temperature of the supraclavicular region, which co-locates to the main region of BAT in adult humans, and is indicative of thermogenesis. Taken together, these results demonstrate that caffeine can promote BAT function at thermoneutrality and may have the potential to be used therapeutically in adult humans

Can contracts be both plain and precise?

One argument against the use of plain language in legal documents is that it is impossible to convey legal meanings in plain language with the same precision as in specialist legal discourse (Hunt, 2003). We tested this claim by redrafting an extract from a lease agreement into plain English in three stages, producing three versions of the extract in progressively plainer English. We submitted these with the original lease agreement to a senior advocate to elicit his opinion on whether the plain-language versions of the extract are equivalent to the original in legal force. Various differences between the versions are analysed using lexical semantics and Systemic Functional Grammar (as described in Halliday & Matthiessen, 2004). This analysis reveals that the redrafted versions could easily be altered to eliminate the difference between them and the original extract, and that ‘plain language’ as conceived by redrafters of official documents may be easy for non-experts to read, but more difficult for experts. This demonstrates that a ‘one-size-fits-all’ approach to readability is often not tenable, and that plain-language activists can learn much from research (such as Street, 1993) which asserts the existence of a plurality of literacies