Understanding, measuring and treating eating disorders in those with type 1 diabetes

The purpose of this thesis was to explore the nature of Eating Disorders in Type 1 Diabetes. Whether or not Eating Disorders are more prevalent in this demographic is a topic of contention but regardless there is a consensus that those with comorbid Type 1 have considerably worse outcomes and are significantly more difficult to treat. It has been argued that this may be due to a feature unique to this population; insulin omission for weight control. The first aim of this thesis was to systematically review how Eating Disorders have been measured in Type 1 Diabetes, paying particular attention to whether researchers have taken the role of Diabetes regimen and insulin omission into account. Following this a comparison between two Eating Disorder scales, one Diabetes specific the other not, was made in order to compare prevalence rates, to explore which items may be potentially biased and to investigate what the effect of modification may be. The structure of the Diabetes specific scale (the Diabetes Eating Problem Scale Revised) was then explored. The second aim of this thesis was to replicate a pilot study that aimed to explore demographic, psychological and health seeking features of those with Type 1 Diabetes related Eating Disorders. This formed the basis of a structural model whereby psychological and Diabetes specific traits were hypothesised to predict Eating Disorder behaviour and elevated blood glucose levels. A questionnaire built for that study regarding patient attributions was also reanalysed using new data. The final aim was to investigate how Eating Disorders in Type 1 Diabetes have been treated by reviewing literature from the last 2 decades, paying particular attention as to how treatment providers have accommodated the unique needs of those with T1D and whether or not programmes have been successful in relation to both psychological and biological outcomes

HBsAg-vectored DNA vaccines elicit concomitant protective responses to multiple CTL epitopes relevant in human disease.

Vaccines capable of controlling neoplastic and infectious diseases which depend on the cellular immune response for their resolution, have proven difficult to develop. We, and others, have previously demonstrated that the potent immunogenicity of hepatitis B surface antigen (HBsAg), the already- licensed human vaccine for hepatitis B infection, may be exploited to deliver foreign antigens for cytotoxic T-lymphocyte (CTL) induction. In this study we demonstrate that recombinant (r) HBsAg DNA delivering a CTL polyepitope appended at the C' terminus elicits concomitant responses to multiple epitopes restricted through a diversity of MHC class I haplotypes, which are relevant in a number of human diseases. We show that the rHBsAg DNA vaccine elicits concomitant protection against neoplastic and infectious disease. These studies vindicate the use of HBsAg as a powerful vector to deliver CTL responses to foreign antigens, and have implications for a multi-disease vaccine applicable to the HLA-polymorphic human population

Molecularly bonded inherently conductive polymers on substrates and shaped articles thereof

Organic inherently conductive polymers, such as those based on polyaniline, polypyrrole and polythiophene, are formed in-situ onto polymeric surfaces that are chemically activated to bond ionically the conductive polymers to the substrates. The polymeric substrate is preferably a preshaped or preformed thermoplastic film, fabric, or tube, although other forms of thermoplastic and thermoset polymers can be used as the substrates for pretreatment using, most preferably, phosphonylation-based processes followed by exposure to an oxidatively polymerizable compound capable of forming an electrically conductive polymer. The resultant conductive surface imparts unique properties to the substrates and allows their use in antistatic clothing, surface conducting films for electronic components and the like, and electromagnetic interference shielding

Molecularly bonded inherently conductive polymers on substrates and shaped articles thereof

Organic inherently conductive polymers, such as those based on polyaniline, polypyrrole and polythiophene, are formed in-situ onto polymeric surfaces that are chemically activated to bond ionically the conductive polymers to the substrates. The polymeric substrate is preferably a preshaped or preformed thermoplastic film, fabric, or tube, although other forms of thermoplastic and thermoset polymers can be used as the substrates for pretreatment using, most preferably, phosphonylation-based processes followed by exposure to an oxidatively polymerizable compound capable of forming an electrically conductive polymer. The resultant conductive surface imparts unique properties to the substrates and allows their use in antistatic clothing, surface conducting films for electronic components and the like, and electromagnetic interference shielding. In an alternative embodiment, metals such as gold or platinum are bonded to the chemically interactive surface of a preshaped thermoplastic or thermoset article

Large ring 1,3-bridged 2-azetidinones: experimental and theoretical studies

The relationship between angular strain and (re)activity of bicyclic 2-azetidinones is still an open question of major concern in the field of penicillin antibiotics. Our study deals with original 13-membered-ring 1,3-bridged 2-azetidinones related to the carbapenem family, and featuring a "planar amide" instead of the "twisted amide" typical of penam derivatives. The bicycles 11 and 12 were obtained from acetoxy-azetidinone 7, via the key-intermediate 10, by using the RCM (ring closing metathesis) strategy. Theoretical predictions and experimental results of hydrolysis showed that the large bicycle 12, endowed with high conformational flexibility, is more reactive than the bicycle 11, including a C=C bond of E configuration, and the monocyclic 2-azetidinone precursor 10. The processing of 2-azetidinones 10-12 in the active site of serine enzymes has been computed by ab initio methods, considering three models. Due to geometrical parameters of the enzymic cavity (nucleophilic attack from the alpha-face), precursor 10 was predicted more active than 11 and 12 in the acylation step by Ser-OH. Indeed, bicycles 11 and 12 are modest inhibitors of PBP2a, while 10 is a good to excellent inhibitor of PBP2a and R39 bacterial enzymes. (C) 2008 Elsevier Masson SAS. All rights reserved

Understanding, measuring and treating eating disorders in those with type 1 diabetes

The purpose of this thesis was to explore the nature of Eating Disorders in Type 1 Diabetes. Whether or not Eating Disorders are more prevalent in this demographic is a topic of contention but regardless there is a consensus that those with comorbid Type 1 have considerably worse outcomes and are significantly more difficult to treat. It has been argued that this may be due to a feature unique to this population; insulin omission for weight control. The first aim of this thesis was to systematically review how Eating Disorders have been measured in Type 1 Diabetes, paying particular attention to whether researchers have taken the role of Diabetes regimen and insulin omission into account. Following this a comparison between two Eating Disorder scales, one Diabetes specific the other not, was made in order to compare prevalence rates, to explore which items may be potentially biased and to investigate what the effect of modification may be. The structure of the Diabetes specific scale (the Diabetes Eating Problem Scale Revised) was then explored. The second aim of this thesis was to replicate a pilot study that aimed to explore demographic, psychological and health seeking features of those with Type 1 Diabetes related Eating Disorders. This formed the basis of a structural model whereby psychological and Diabetes specific traits were hypothesised to predict Eating Disorder behaviour and elevated blood glucose levels. A questionnaire built for that study regarding patient attributions was also reanalysed using new data. The final aim was to investigate how Eating Disorders in Type 1 Diabetes have been treated by reviewing literature from the last 2 decades, paying particular attention as to how treatment providers have accommodated the unique needs of those with T1D and whether or not programmes have been successful in relation to both psychological and biological outcomes

Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain.

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management

Using virtual reality for science mission planning: A Mars Pathfinder case

NASA's Mars Pathfinder Project requires a Ground Data System (GDS) that supports both engineering and scientific payloads with reduced mission operations staffing, and short planning schedules. Also, successful surface operation of the lander camera requires efficient mission planning and accurate pointing of the camera. To meet these challenges, a new software strategy that integrates virtual reality technology with existing navigational ancillary information and image processing capabilities. The result is an interactive workstation based applications software that provides a high resolution, 3-dimensial, stereo display of Mars as if it were viewed through the lander camera. The design, implementation strategy and parametric specification phases for the development of this software were completed, and the prototype tested. When completed, the software will allow scientists and mission planners to access simulated and actual scenes of Mars' surface. The perspective from the lander camera will enable scientists to plan activities more accurately and completely. The application will also support the sequence and command generation process and will allow testing and verification of camera pointing commands via simulation

The suppression of appetite and food consumption by methylphenidate: the moderating effects of gender and weight status in healthy adults.

Females typically show greater behavioural responses to stimulant drugs than males, including loss of appetite; as seen, for example, in those who use methylphenidate (MP) therapeutically for treatment of attention deficit hyperactivity disorder (ADHD). This is a relevant issue because of the strong link between ADHD and obesity. In a sample (n=132) of normal-weight (BMI25) and obese (BMI30) men and women we assessed appetite, cravings, and snack-food intake in response to MP (0.5 mg/kg) and placebo. Results indicated a significant three-way interaction for the three dependent variables--food-related responding diminishing in all groups from placebo to MP, except in obese males who showed no decreases to the MP challenge. These data show for the first time the existence of gender differences in the appetite response to MP, and are relevant for finding a dopamine pathway to new weight-loss medications, which would be utilized differently in males than in females

Relations of Change in Plasma Levels of LDL‐C, Non‐HDL‐C and apoB With Risk Reduction From Statin Therapy: A Meta‐Analysis of Randomized Trials

Background: Identifying the best markers to judge the adequacy of lipid‐lowering treatment is increasingly important for coronary heart disease (CHD) prevention given that several novel, potent lipid‐lowering therapies are in development. Reductions in LDL‐C, non‐HDL‐C, or apoB can all be used but which most closely relates to benefit, as defined by the reduction in events on statin treatment, is not established. Methods and Results: We performed a random‐effects frequentist and Bayesian meta‐analysis of 7 placebo‐controlled statin trials in which LDL‐C, non‐HDL‐C, and apoB values were available at baseline and at 1‐year follow‐up. Summary level data for change in LDL‐C, non‐HDL‐C, and apoB were related to the relative risk reduction from statin therapy in each trial. In frequentist meta‐analyses, the mean CHD risk reduction (95% CI) per standard deviation decrease in each marker across these 7 trials were 20.1% (15.6%, 24.3%) for LDL‐C; 20.0% (15.2%, 24.7%) for non‐HDL‐C; and 24.4% (19.2%, 29.2%) for apoB. Compared within each trial, risk reduction per change in apoB averaged 21.6% (12.0%, 31.2%) greater than changes in LDL‐C (P<0.001) and 24.3% (22.4%, 26.2%) greater than changes in non‐HDL‐C (P<0.001). Similarly, in Bayesian meta‐analyses using various prior distributions, Bayes factors (BFs) favored reduction in apoB as more closely related to risk reduction from statins compared with LDL‐C or non‐HDL‐C (BFs ranging from 484 to 2380). Conclusions: Using both a frequentist and Bayesian approach, relative risk reduction across 7 major placebo‐controlled statin trials was more closely related to reductions in apoB than to reductions in either non‐HDL‐C or LDL‐C