Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects

Recombinant glucagon-like peptide-1 (7–36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1 was given for 5d by prandial subcutaneous injections (PSI) (76nmol 30min before meals, four times daily; a total of 302·4nmol/24h) or by continuous subcutaneous infusion (CSI) (12·7nmol/h; a total of 304·8nmol/24h). This was performed in nineteen healthy obese subjects (mean age 44·2 (sem 2·5) years; BMI 39·0 (sem 1·2)kg/m2) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15% reduction in mean food intake per meal (P=0·02) after 5d treatment. A weight loss of 0·55 (sem 0·2) kg (P<0·05) was registered after 5d with PSI of rGLP-1. Gastric emptying rate was reduced during both PSI (P<0·001) and CSI (P<0·05) treatment, but more rapidly and to a greater extent with PSI of rGLP-1. To conclude, a 5d treatment of rGLP-1 at high doses by PSI, but not CSI, promptly slowed gastric emptying as a probable mechanism of action of increased satiety, decreased hunger and, hence, reduced food intake with an ensuing weight loss.

Interaction between disinhibition and restraint: Implications for body weight and eating disturbance

An increase in obesity is usually accompanied by an increase in eating disturbances. Susceptibility to these states may arise from different combinations of underlying traits: Three Factor Eating Questionnaire (TFEQ) Restraint and Disinhibition. Two studies were conducted to examine the interaction between these traits; one on-line study (n=351) and one laboratory-based study (n=120). Participants completed a battery of questionnaires and provided self-report measures of body weight and physical activity. A combination of high Disinhibition and high Restraint was associated with a problematic eating behaviour profile (EAT-26), and a higher rate of smoking and alcohol consumption. A combination of high Disinhibition and low Restraint was associated with a higher susceptibility to weight gain and a higher sedentary behaviour. These data show that different combinations of Disinhibition and Restraint are associated with distinct weight and behaviour outcomes.

Exercise, appetite, and energy balance: The interactions between energy expenditure and intake, and the implications for weight management

This book disseminates current information pertaining to the modulatory effects of foods and other food substances on behavior and neurological pathways and, importantly, vice versa. This ranges from the neuroendocrine control of eating to the effects of life-threatening disease on eating behavior. The importance of this contribution to the scientific literature lies in the fact that food and eating are an essential component of cultural heritage but the effects of perturbations in the food/cognitive axis can be profound. The complex interrelationship between neuropsychological processing, diet, and behavioral outcome is explored within the context of the most contemporary psychobiological research in the area. This comprehensive psychobiology- and pathology-themed text examines the broad spectrum of diet, behavioral, and neuropsychological interactions from normative function to occurrences of severe and enduring psychopathological processes

Acute and long-term effects of exercise on appetite control: Is there any benefit for weight control?

Purpose of review: To examine the relationship between energy intake, appetite control and exercise, with particular reference to longer term exercise studies. This approach is necessary when exploring the benefits of exercise for weight control, as changes in body weight and energy intake are variable and reflect diversity in weight loss. Recent findings: Recent evidence indicates that longer term exercise is characterized by a highly variable response in eating behaviour. Individuals display susceptibility or resistance to exercise-induced weight loss, with changes in energy intake playing a key role in determining the degree of weight loss achieved. Marked differences in hunger and energy intake exist between those who are capable of tolerating periods of exercise-induced energy deficit, and those who are not. Exercise-induced weight loss can increase the orexigenic drive in the fasted state, but for some this is offset by improved postprandial satiety signalling. Summary: The biological and behavioural responses to acute and long-term exercise are highly variable, and these responses interact to determine the propensity for weight change. For some people, long-term exercise stimulates compensatory increases in energy intake that attenuate weight loss. However, favourable changes in body composition and health markers still exist in the absence of weight loss. The physiological mechanisms that confer susceptibility to compensatory overconsumption still need to be determined.

Axisymmetric shell structures for multi-use

Shell structures find use in many fields of engineering, notably structural, mechanical, aerospace and nuclear-reactor disciplines. Axisymmetric shell structures are used as dome type of roofs, hyperbolic cooling towers, silos for storage of grain, oil and industrial chemicals and water tanks. Despite their thin walls, strength is derived due to the curvature. The generally high strength-to-weight ratio of the shell form, combined with its inherent stiffness, has formed the basis of this vast application. With the advent in computation technology, the finite element method and optimisation techniques, structural engineers have extremely versatile tools for the optimum design of such structures. Optimisation of shell structures can result not only in improved designs, but also in a large saving of material. The finite element method being a general numerical procedure that could be used to treat any shell problem to any desired degree of accuracy, requires several runs in order to obtain a complete picture of the effect of one parameter on the shell structure. This redesign I re-analysis cycle has been achieved via structural optimisation in the present research, and MSC/NASTRAN (a commercially available finite element code) has been used in this context for volume optimisation of axisymmetric shell structures under axisymmetric and non-axisymmetric loading conditions. The parametric study of different axisymmetric shell structures has revealed that the hyperbolic shape is the most economical solution of shells of revolution. To establish this, axisymmetric loading; self-weight and hydrostatic pressure, and non-axisymmetric loading; wind pressure and earthquake dynamic forces have been modelled on graphical pre and post processor (PATRAN) and analysis has been performed on two finite element codes (ABAQUS and NASTRAN), numerical model verification studies are performed, and optimum material volume required in the walls of cylindrical, conical, parabolic and hyperbolic forms of axisymmetric shell structures are evaluated and reviewed. Free vibration and transient earthquake analysis of hyperbolic shells have been performed once it was established that hyperbolic shape is the most economical under all possible loading conditions. Effect of important parameters of hyperbolic shell structures; shell wall thickness, height and curvature, have been evaluated and empirical relationships have been developed to estimate an approximate value of the lowest (first) natural frequency of vibration. The outcome of this thesis has been the generation of new research information on performance characteristics of axisymmetric shell structures that will facilitate improved designs of shells with better choice of shapes and enhanced levels of economy and performance. Key words; Axisymmetric shell structures, Finite element analysis, Volume Optimisation_ Free vibration_ Transient response.

Oxygen consumption and muscle activation patterns during constant load exercise

The collective purpose of these two studies was to determine a link between the V02 slow component and the muscle activation patterns that occur during cycling. Six, male subjects performed an incremental cycle ergometer exercise test to determine asub-TvENT (i.e. 80% of TvENT) and supra-TvENT (TvENT + 0.75*(V02 max - TvENT) work load. These two constant work loads were subsequently performed on either three or four occasions for 8 mins each, with V02 captured on a breath-by-breath basis for every test, and EMO of eight major leg muscles collected on one occasion. EMG was collected for the first 10 s of every 30 s period, except for the very first 10 s period. The V02 data was interpolated, time aligned, averaged and smoothed for both intensities. Three models were then fitted to the V02 data to determine the kinetics responses. One of these models was mono-exponential, while the other two were biexponential. A second time delay parameter was the only difference between the two bi-exponential models. An F-test was used to determine significance between the biexponential models using the residual sum of squares term for each model. EMO was integrated to obtain one value for each 10 s period, per muscle. The EMG data was analysed by a two-way repeated measures ANOV A. A correlation was also used to determine significance between V02 and IEMG. The V02 data during the sub-TvENT intensity was best described by a mono-exponential response. In contrast, during supra-TvENT exercise the two bi-exponential models best described the V02 data. The resultant F-test revealed no significant difference between the two models and therefore demonstrated that the slow component was not delayed relative to the onset of the primary component. Furthermore, only two parameters were deemed to be significantly different based upon the two models. This is in contrast to other findings. The EMG data, for most muscles, appeared to follow the same pattern as V02 during both intensities of exercise. On most occasions, the correlation coefficient demonstrated significance. Although some muscles demonstrated the same relative increase in IEMO based upon increases in intensity and duration, it cannot be assumed that these muscles increase their contribution to V02 in a similar fashion. Larger muscles with a higher percentage of type II muscle fibres would have a larger increase in V02 over the same increase in intensity.

Hierarchical models for 2D presence/absence data having ambiguous zeroes: With a biogeographical case study on dingo behaviour

This dissertation is primarily an applied statistical modelling investigation, motivated by a case study comprising real data and real questions. Theoretical questions on modelling and computation of normalization constants arose from pursuit of these data analytic questions. The essence of the thesis can be described as follows. Consider binary data observed on a two-dimensional lattice. A common problem with such data is the ambiguity of zeroes recorded. These may represent zero response given some threshold (presence) or that the threshold has not been triggered (absence). Suppose that the researcher wishes to estimate the effects of covariates on the binary responses, whilst taking into account underlying spatial variation, which is itself of some interest. This situation arises in many contexts and the dingo, cypress and toad case studies described in the motivation chapter are examples of this. Two main approaches to modelling and inference are investigated in this thesis. The first is frequentist and based on generalized linear models, with spatial variation modelled by using a block structure or by smoothing the residuals spatially. The EM algorithm can be used to obtain point estimates, coupled with bootstrapping or asymptotic MLE estimates for standard errors. The second approach is Bayesian and based on a three- or four-tier hierarchical model, comprising a logistic regression with covariates for the data layer, a binary Markov Random field (MRF) for the underlying spatial process, and suitable priors for parameters in these main models. The three-parameter autologistic model is a particular MRF of interest. Markov chain Monte Carlo (MCMC) methods comprising hybrid Metropolis/Gibbs samplers is suitable for computation in this situation. Model performance can be gauged by MCMC diagnostics. Model choice can be assessed by incorporating another tier in the modelling hierarchy. This requires evaluation of a normalization constant, a notoriously difficult problem. Difficulty with estimating the normalization constant for the MRF can be overcome by using a path integral approach, although this is a highly computationally intensive method. Different methods of estimating ratios of normalization constants (N Cs) are investigated, including importance sampling Monte Carlo (ISMC), dependent Monte Carlo based on MCMC simulations (MCMC), and reverse logistic regression (RLR). I develop an idea present though not fully developed in the literature, and propose the Integrated mean canonical statistic (IMCS) method for estimating log NC ratios for binary MRFs. The IMCS method falls within the framework of the newly identified path sampling methods of Gelman & Meng (1998) and outperforms ISMC, MCMC and RLR. It also does not rely on simplifying assumptions, such as ignoring spatio-temporal dependence in the process. A thorough investigation is made of the application of IMCS to the three-parameter Autologistic model. This work introduces background computations required for the full implementation of the four-tier model in Chapter 7. Two different extensions of the three-tier model to a four-tier version are investigated. The first extension incorporates temporal dependence in the underlying spatio-temporal process. The second extensions allows the successes and failures in the data layer to depend on time. The MCMC computational method is extended to incorporate the extra layer. A major contribution of the thesis is the development of a fully Bayesian approach to inference for these hierarchical models for the first time. Note: The author of this thesis has agreed to make it open access but invites people downloading the thesis to send her an email via the 'Contact Author' function.