The Effect of Fructose vs. Glucose Beverages on Low-Grade Systemic Inflammation

Thesis (Ph.D.)--University of Washington, 2016-04

The role of insulin-like growth factor II and its receptor in mouse preimplantation development

Insulin-like growth factor II (IGF-II) and its receptor, the IGF-II/mannose-6-phosphate (IGF-II/M6P) receptor, are first expressed from the zygotic genome at the two-cell stage of mouse development. However, their role is not clearly defined. Insulin-like growth factor II is believed to mediate growth through the heterologous type 1 IGF and insulin receptors, whereas the IGF-II/M6P receptor is believed to act as a negative regulator of somatic growth by limiting the availability of excess levels of IGF-II. These studies demonstrate that IGF-II does have a role in growth regulation in the early embryo through the IGF-II/M6P receptor. Insulin-like growth factor II stimulated cleavage rate in two-cell embryos in vitro. Moreover, this receptor is required for the glycaemic response of two-cell embryos to IGF-II and for normal progression of early embryos to the blastocyst stage. Improved development of embryos in crowded culture supports the concept of an endogenous embryonic paracrine activity that enhances cell proliferation. These responses indicate that the IGF-II/M6P receptor is functional and likely to participate in such a regulatory circuit. The functional role of IGF-II and its receptor is discussed with reference to regulation of early development.

Hypertension, dyslipidemia, body mass index, Diabetes and smoking status in aboriginal australians in a remote community

Objectives: Study objectives were: 1) to describe the differences in the prevalence of CHID risk factors between Aboriginal people in a remote community and the general Australian population; and 2) to compare the predicted risks of CHD events between Aboriginal and non-Aboriginal Australians. Design: A cross-sectional study. Participants: 681 Aboriginal adults aged 25 to 74 years. Results: Aboriginal young adults had substantially higher prevalence of diabetes compared to non-Aboriginal Australians. The prevalence ratios for diabetes were 12.5, 5.6, 3.2, 1.3, and 0.73 for 25-, 35-, 45-, 55-, and 65- to 74-year-old females, respectively, The corresponding values for males were 12.1, 2.7, 2.9, 0.69, and 0.42. Young females had a higher prevalence of obesity, overweight, and abnormal waist circumference, while males and females 45 years and older tended to have a lower prevalence of overweight and ab. normal waist circumference. Compared to the general population, Aboriginal adults had a lower prevalence of abnormal total cholesterol but a higher prevalence of abnormal HDL, triglycerides, hypertension, and smoking. The risk ratios of abnormal total cholesterol for females ages 2534, 35-44, 45-54, 55-64, and 65-75 years were 0.38, 0.53, 0.48, 0.48, and 0.41, respectively. Conclusions: Aboriginal people in the remote community experienced different levels of CHD risk predictors from the general Australian population. They had a lower prevalence of abnormal total cholesterol and a higher prevalence of abnormal HDL, smoking, diabetes, and hypertension.

Normal values of balance tests in women aged 20-80

OBJECTIVES: To determine normal values for four commonly used clinical functional balance tests from community-dwelling women aged 20 to 80 and to identify any significant decline due to aging. DESIGN: A cross-sectional study was undertaken to provide normative values for four clinical balance tests across 6 decade cohorts. SETTING: The Betty Byrne-Henderson Center for Women and Aging, Royal Womens' Hospital, Brisbane, Australia. PARTICIPANTS: Four hundred fifty-six community-dwelling, independently ambulant women with no obvious neurological or musculoskeletal-related disability, aged 20 to 80, were randomly recruited from a large metropolitan region. MEASUREMENTS: The clinical balance measures/tests were the Timed Up and Go test, step test, Functional Reach test, and lateral reach test. Multivariate analysis was used to test the effect for age, height, and activity level. RESULTS: Normal data were produced for each test across each decade cohort. Gradual decline in balance performance was confirmed, with significant effect for age demonstrated. CONCLUSION: New normative data across the adult age decades are available for these clinical tests. Use of clinical balance tests could complement other balance tests and be used to screen women aged 40 to 60 whose performance is outside the normal values for age and to decrease later falls risk.

Prolotherapy injections, saline injections, and exercises for chronic low-back pain: A randomized trial

Objectives. To assess the efficacy of a prolotherapy injection and exercise protocol in the treatment of chronic nonspecific low back pain. Design. Randomized controlled trial with two- by- two factorial design, triple- blinded for injection status, and single- blinded for exercise status. Setting. General practice. Participants. One hundred ten participants with nonspecific low- back pain of average 14 years duration were randomized to have repeated prolotherapy ( 20% glucose/ 0.2% lignocaine) or normal saline injections into tender lumbo- pelvic ligaments and randomized to perform either flexion/ extension exercises or normal activity over 6 months. Main outcome measures: Pain intensity ( VAS) and disability scores ( Roland- Morris) at 2.5, 4, 6, 12, and 24 months. Results. Follow- up was achieved in 96% at 12 months and 80% at 2 years. Ligament injections, with exercises and with normal activity, resulted in significant and sustained reductions in pain and disability throughout the trial, but no attributable effect was found for prolotherapy injections over saline injections or for exercises over normal activity. At 12 months, the proportions achieving more than 50% reduction in pain from baseline by injection group were glucose- lignocaine: 0.46 versus saline: 0.36. By activity group these proportions were exercise: 0.41 versus normal activity: 0.39. Corresponding proportions for > 50% reduction in disability were glucose- lignocaine: 0.42 versus saline 0.36 and exercise: 0.36 versus normal activity: 0.38. There were no between group differences in any of the above measures. Conclusions. In chronic nonspecific low- back pain, significant and sustained reductions in pain and disability occur with ligament injections, irrespective of the solution injected or the concurrent use of exercises.

What is the best size descriptor to use for pharmacokinetic studies in the obese?

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

Strength analysis of steel-concrete composite beams in combined bending and shear

Despite experimental evidences, the contributions of the concrete slab and composite action to the vertical shear strength of simply supported steel-concrete composite beams are not considered in current design codes, which lead to conservative designs. In this paper, the finite element method is used to investigate the flexural and shear strengths of simply supported composite beams under combined bending and shear. A three-dimensional finite element model has been developed to account for geometric and material nonlinear behavior of composite beams, and verified by experimental results. The verified finite element model is than employed to quantify the contributions of the concrete slab and composite action to the moment and shear capacities of composite beams. The effect of the degree of shear connection on the vertical shear strength of deep composite beams loaded in shear is studied. Design models for vertical shear strength including contributions from the concrete slab and composite action and for the ultimate moment-shear interaction ate proposed for the design of simply supported composite beams in combined bending and shear. The proposed design models provide a consistent and economical design procedure for simply supported composite beams.

Optimum inclusion of field peas, faba beans, chick peas and sweet lupins in poultry diets. II. Broiler experiments

1. Three experiments were undertaken to determine the optimum inclusion rates of held peas, faba beans, chick peas and sweet lupins in broiler starter and finisher diets in amounts up to 360 g/kg. 2. In experiment A chickens in cages grown to 21 d on diets with field peas and faba beans gave better growth rate and feed efficiency than those with sweet lupins and chick peas. Growth rate and Food conversion ratio (FCR) improved with increasing amounts of faba beans in the diet while for chick peas growth rate and FCR declined. Digesta viscosity and excreta stickiness scores were much higher on diets with sweet lupins. Steam pelleting improved growth rate and FCR on all diets. 3. In experiment B birds were in cages and grown from 21 to 42 d. There were no differences between grain legumes (when combined for all inclusions) for growth rate, food intake or FCR. Viscosity was again much higher on the sweet lupin-based diets while the pancreas was significantly enlarged on the diets with chick peas, as observed previously in chickens grown to 21 d. Steam pelleting of diets gave a consistent and positive response for weight gain and FCR. 4. Experiment C was carried out in pens each holding 60 birds under semi-commercial conditions and grown to 4 2 d on starter and finisher diets with the same grain legumes as used previously but each at 2 rates of inclusion similar to those in commercial practice. Field peas at 200 to 300 g/kg and chick peas at 150 to 220 g/kg gave inferior growth to faba beans (150 to 180 g/kg) and sweet lupins (120 g/kg). 5. The results of these experiments allowed tentative recommendations to be made to industry for inclusion rates of these cultivars of the 4 grain legumes. These were: field peas 300 g/kg; faba beans 200 g/kg, chick peas 100 g/kg and sweet lupins

2D strain - a new approach to strain and strain rate: the solution to the angle-dependence of tissue Doppler?

Purpose: Tissue Doppler strain rate imaging (SRI) have been validated and applied in various clinical settings, but the clinical use of this modality is still limited due to time-consuming postprocessing, unfavorable signal to noise ratio and major angle dependency of image acquisition. 2D Strain (2DS) measures strain parameters through automated tissue tracking (Lagrangian strain) rather than tissue velocity regression. We sought to compare the accuracy of this technique with SRI and evaluate whether it overcomes the above limitations. Methods: We assessed 26 patients (13 female, age 60±5yrs) at low risk of CAD and with normal DSE at both baseline and peak stress. End systolic strain (ESS), peak systolic strain rate (SR), and timing parameters were measured by two independent observers using SRI and 2D Strain. Myocardial segments were excluded from the analyses if the insonation angle exceeded 30 degrees or if the segments were not visualized; 417 segments were evaluated. Results: Normal ranges for TVI and CEB approaches were comparable for SR (-0.99 ± 0.39 vs -0.88 ± 0.36, p=NS), ESS (-15.1 ± 6.5 vs -14.9 ± 6.3, p=NS), time to end of systole (174 ± 47 vs 174 ± 53, p=NS) and time to peak SR (TTP; 340 ± 34 vs 375 ± 57). The best correlations between the techniques were for time to end systole (rest r=0.6, p

A formal metamodeling approach to a transformation between the UML state machine and object-z

A significant problem with currently suggested approaches for transforming between models in different languages is that the transformation is often described imprecisely, with the result that the overall transformation task may be imprecise, incomplete and inconsistent. This paper presents a formal metamodeling approach for transforming between UML and Object-Z. In the paper, the two languages are defined in terms of their formal metamodels, and a systematic transformation between the models is provided at the meta-level in terms of formal mapping functions. As a consequence, we can provide a precise, consistent and complete transformation between them.

A methodology for the generation and evaluation of biorefinery process chains, in order to identify the most promising biorefineries for the EU

The topic of bioenergy, biofuels and bioproducts remains at the top of the current political and research agenda. Identification of the optimum processing routes for biomass, in terms of efficiency, cost, environment and socio-economics is vital as concern grows over the remaining fossil fuel resources, climate change and energy security. It is known that the only renewable way of producing conventional hydrocarbon fuels and organic chemicals is from biomass, but the problem remains of identifying the best product mix and the most efficient way of processing biomass to products. The aim is to move Europe towards a biobased economy and it is widely accepted that biorefineries are key to this development. A methodology was required for the generation and evaluation of biorefinery process chains for converting biomass into one or more valuable products that properly considers performance, cost, environment, socio-economics and other factors that influence the commercial viability of a process. In this thesis a methodology to achieve this objective is described. The completed methodology includes process chain generation, process modelling and subsequent analysis and comparison of results in order to evaluate alternative process routes. A modular structure was chosen to allow greater flexibility and allowing the user to generate a large number of different biorefinery configurations The significance of the approach is that the methodology is defined and is thus rigorous and consistent and may be readily re-examined if circumstances change. There was the requirement for consistency in structure and use, particularly for multiple analyses. It was important that analyses could be quickly and easily carried out to consider, for example, different scales, configurations and product portfolios and so that previous outcomes could be readily reconsidered. The result of the completed methodology is the identification of the most promising biorefinery chains from those considered as part of the European Biosynergy Project.

An investigation into the nature, determinants, and dynamics of service quality expectations

On the basis of a review of the substantive quality and service marketing literature current knowledge regarding service quality expectations was found either absent or deficient. The phenomenon is of increasing importance to both marketing researchers and management and was therefore judged worthy of scholarly consideration. Because the service quality literature was insufficiently rich when embarking on the thesis three basic research issues were considered namely the nature, determinants, and dynamics of service quality expectations. These issues were first conceptually and then qualitatively explored. This process generated research hypotheses mainly relating to a model which were subsequently tested through a series of empirical investigations using questionnaire data from field studies in a single context. The results were internally consistent and strongly supported the main research hypotheses. It was found that service quality expectations can be meaningfully described in terms of generic/service-specific, intangible/tangible, and process/outcome categories. Service-specific quality expectations were also shown to be determined by generic service quality expectations, demographic variables, personal values, psychological needs, general service sophistication, service-specific sophistication, purchase motives, and service-specific information when treating service class involvement as an exogenous variable. Subjects who had previously not directly experienced a particular service were additionally found to revise their expectations of quality when exposed to the service with change being driven by a sub-set of identified determinants.

Clinical studies of spatial and temporal aspects of vision: an investigation using psychophysical and electrophysiological techniques

Separate physiological mechanisms which respond to spatial and temporal stimulation have been identified in the visual system. Some pathological conditions may selectively affect these mechanisms, offering a unique opportunity to investigate how psychophysical and electrophysiological tests reflect these visual processes, and thus enhance the use of the tests in clinical diagnosis. Amblyopia and optical blur were studied, representing spatial visual defects of neural and optical origin, respectively. Selective defects of the visual pathways were also studied - optic neuritis which affects the optic nerve, and dementia of the Alzheimer type in which the higher association areas are believed to be affected, but the primary projections spared. Seventy control subjects from 10 to 79 years of age were investigated. This provided material for an additional study of the effect of age on the psychophysical and electrophysiological responses. Spatial processing was measured by visual acuity, the contrast sensitivity function, or spatial modulation transfer function (MTF), and the pattern reversal and pattern onset-offset visual evoked potential (VEP). Temporal, or luminance, processing was measured by the de Lange curve, or temporal MTF, and the flash VEP. The pattern VEP was shown to reflect the integrity of the optic nerve, geniculo striate pathway and primary projections, and was related to high temporal frequency processing. The individual components of the flash VEP differed in their characteristics. The results suggested that the P2 component reflects the function of the higher association areas and is related to low temporal frequency processing, while the Pl component reflects the primary projection areas. The combination of a delayed flash P2 component and a normal latency pattern VEP appears to be specific to dementia of the Alzheimer type and represents an important diagnostic test for this condition.

Priority evaluation in transportation policies and programmes

This work is concerned with the development of techniques for the evaluation of large-scale highway schemes with particular reference to the assessment of their costs and benefits in the context of the current transport planning (T.P.P.) process. It has been carried out in close cooperation with West Midlands County Council, although its application and results are applicable elsewhere. The background to highway evaluation and its development in recent years has been described and the emergence of a number of deficiencies in current planning practise noted. One deficiency in particular stood out, that stemming from inadequate methods of scheme generation and the research has concentrated upon improving this stage of appraisal, to ensure that subsequent stages of design, assessment and implementation are based upon a consistent and responsive foundation. Deficiencies of scheme evaluation were found to stem from inadequate development of appraisal methodologies suffering from difficulties of valuation, measurement and aggregation of the disparate variables that characterise highway evaluation. A failure to respond to local policy priorities was also noted. A 'problem' rather than 'goals' based approach to scheme generation was taken, as it represented the current and foreseeable resource allocation context more realistically. A review of techniques with potential for highway problem based scheme generation, which would work within a series of practical and theoretical constraints were assessed and that of multivariate analysis, and classical factor analysis in particular, was selected, because it offerred considerable application to the difficulties of valuation, measurement and aggregation that existed. Computer programs were written to adapt classical factor analysis to the requirements of T.P.P. highway evaluation, using it to derive a limited number of factors which described the extensive quantity of highway problem data. From this, a series of composite problem scores for 1979 were derived for a case study area of south Birmingham, based upon the factorial solutions, and used to assess highway sites in terms of local policy issues. The methodology was assessed in the light of its ability to describe highway problems in both aggregate and disaggregate terms, to guide scheme design, coordinate with current scheme evaluation methods, and in general to improve upon current appraisal. Analysis of the results was both in subjective, 'common-sense' terms and using statistical methods to assess the changes in problem definition, distribution and priorities that emerged. Overall, the technique was found to improve upon current scheme generation methods in all respects and in particular in overcoming the problems of valuation, measurement and aggregation without recourse to unsubstantiated and questionable assumptions. A number of deficiencies which remained have been outlined and a series of research priorities described which need to be reviewed in the light of current and future evaluation needs.

Developing and evaluating a methodology for business process improvement

Purpose – There appears to be an ever-insatiable demand from markets for organisations to improve their products and services. To meet this, there is a need to provide business process improvement (BPI) methodologies that are holistic, structured and procedural. Therefore, this paper describes research that has formed and tested a generic and practical methodology termed model-based and integrated process improvement (MIPI) to support the implementation of BPI; and to validate its effectiveness in organisations. This methodology has been created as an aid for practitioners within organisations. Design/methodology/approach – The research objectives were achieved by: reviewing and analysing current methodologies, and selecting a few frameworks against key performance indicators. Using a refined Delphi approach and semi-structured interview with the “experts” in the field. Intervention, case study and process research approach to evaluating a methodology. Findings – The BPI methodology was successfully formed and applied by the researcher and directly by the companies involved against the criteria of feasibility, usability and usefulness. Research limitations/implications – The paper has demonstrated a new knowledge on how to systematically assess a BPI methodology in practice. Practical implications – Model-based and integrated process improvement methodology (MIPI) methodology offers the practitioner (experienced and novice) a set of step-by-step aids necessary to make informed, consistent and efficient changes to business processes. Originality/value – The novelty of this research work is the creation of a holistic workbook-based methodology with relevant tools and techniques. It extends the capabilities of existing methodologies.