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End-stage osteoarthritis is characterised by pain and reduced physical function, for which total knee arthroplasty (TKA) is recognised to be a highly effective procedure. Post-operative outcome and resultant function however is variable. Many factors are thought to influence outcome; in particular quadriceps muscle strength is one of the strongest predictors of the patient’s ability to perform functional tasks. Muscle atrophy has been shown to account for only a third of the variance in muscle power, the remainder is currently unexplained. In this thesis it is hypothesised that physiological and mechanical factors will affect muscle power post TKA. A new design of prosthesis with an axis of rotation of the knee based on new kinematical observations has been suggested to confer a mechanical advantage to the knee extensor mechanism by lengthening its moment arm, and thus reducing the muscular effort required to extend the knee, however this has not as yet been clinically demonstrated. A strong extensor mechanism is recognised as being paramount to the patients return to functional activity following TKA, but there has been no consideration as to the mechanisms how and to what extent the muscle tissue actually recovers. It is known that muscle satellite cells are essential for the regeneration of skeletal muscle and that these cells are activated following damage, but these have not been considered in relation to recovery from orthopaedic procedures. It is hypothesised that the number of satellite cells in the extensor mechanism will vary in the patient population and will influence muscle recovery. A double blind randomised controlled trial of 212 TKA patients was conducted to compare the new implant design with a traditional model. Patient outcome was assessed at four points over a one year period. The new implant was superior in measures of knee flexion, lower limb power output and by patient report questionnaire (Oxford Knee Score) Two-way ANOVA, p = <0.001 in all cases. Extensor mechanism power was significantly increased between all four assessment points in the new implant group, the control group demonstrating change between the second and third assessment only (p= <0.001). Analysis of the outcome assessments used demonstrated a changing relationship between function and patient report of that function. Regression models demonstrated that patient report of function became more consistent with direct functional assessment as the influence of pain diminished post-operatively. A hierarchical model is presented that highlights the limitation of patient report data in isolation. Muscle satellite cells were isolated from biopsies of the quadriceps muscle of 18 patients at the time of surgery and counted by an immunofluorescent staining technique. The number of satellite cells detected accounted for a third of the postoperative variance in power output (R2 = 36.6%). This was confirmed in another cohort of 11 patients with a more sensitive qPCR technique. It was further found that the activated satellite cells accounted for around two thirds of the change in postoperative power output (R2 = 66.7%). In conclusion, both mechanical and physiological factors have a significant effect on muscle power post total knee arthroplasty.

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This study explores the relationship between acute sugar consumption and its effect on executive function (EF). Specifically, this study examines the effect of both acute and chronic sugar consumption on EF. An epidemiological survey was given on an online work distribution platform, where participants finished cognitive tasks of EF after completing questionnaires assessing sugar consumption both in the last year and last 24 hours (n = 273). It was hypothesized that acute and chronic sugar intake would significantly predict scores on measures of aspects of EF. Additionally, it was hypothesized that chronic sugar intake would significantly moderate the relationship between acute sugar intake and EF. Neither acute nor chronic sugar consumption predicted EF. This effect was not changed by including chronic sugar consumption as a moderating variable upon acute sugar consumption and EF. This research provides greater evidence about what effect sugar consumption has on EF.

Since generalized linear model (GLM) with binary response variable is widely used in many disciplines, many efforts have been made to construct a fit model. However, little attention is paid to the link functions, which play a critical role in GLM model. In this article, we compared three link functions and evaluated different model selection methods based on these three link functions. Also, we provided some suggestions on how to choose the proper link function for binary data. / text

The need for improving cost estimation for solid waste management (SWM) is particularly strong in emerging (industrialising) economies where problems of solid waste are severe, expectations for improvements are high, but finances are constrained. Using literature-based evaluation, traditional methods used to estimate costs of SWM in industrialising regions are classified into two categories- the unit cost method and benchmarking techniques. These current approaches are unable to satisfy two important SWM objectives in industrialising regions- 1. provide an understanding of variables affecting costs of SWM in developing countries, which in turn helps in developing a sound financing strategy, and 2. ensure that scarce financial resources are used to best effect while planning for increasing populations, and raising service levels in developing countries The development of cost models using the cost function approach, which are sometimes used as a cost estimation technique for developed countries' waste management case studies, is deemed as an improvement over current cost estimation approaches for SWM used in industrialising regions. The usefulness, applications and limitations of the cost function approach for developing countries is shown in four ways. First, the application of the cost function methodology to a developing country dataset is shown using data from approximately 300 Indian municipalities. Second, future developmental scenario analyses is conducted at the city level to estimate marginal costs to improve solid waste management (SWM) to handle increasing populations and to raise the level of service. Third, the basic intents for conducting cost function analyses are categorised based on the rich experiences from another public service with many similar characteristics, namely the healthcare sector, and translated for easy understanding for future solid waste engineers. Finally, the potential implications of the health care analyses on the developing city case study demonstrates the way forward in terms of the most important data that needs to be collected and future cost analyses that needs to be conducted. The results from this work indicate a strong need for careful selection and management of data, and awareness of the challenges that developing country datasets pose. The thesis is designed to encourage planners in developing countries to ditch heuristic thinking when planning improvements to SWM, and instead adopt modern rational methods to make cost-wise decisions. Specifically, this thesis provides solid waste management analysts the necessary tools to gather, analyse and interpret cost information in a way that facilitates planning of restricted finances in industrialising regions.

Actin is one of the 2 main proteins in muscle, and is also involved in many non-muscle motile processes. When actin is extracted from non-muscle cells, it is often found as a 1:1 complex with profilin which reduces its tendency to polymerise. The control of this interaction is important and necessary for the production of some labile, filamentous actin containing structures, and for some non-muscle motile events. The profilin:actin complex was originally crystallised as an unknown inhibitor of DNase I and, although actin alone will form a tight 1:1 complex with Dnase I, no physiological explanation has been found for these interactions. The profilin:actin crystals crystallise in the orthorhombic space group P2<SUB>1</SUB>2<SUB>1</SUB>2<SUB>1</SUB>, with cell dimensions of a = 3.85 nm, b = 7.23 nm and c &61 18.74 nm, and have one molecule of each protein per asymmetric unit. The crystals diffract to high resolution, but are susceptible to large changes in the cell dimensions; in particular the c-axis will shrink to as little as 16.5 nm. Interaction of heavy metal salts with the crystals is one of the factors which produce large changes in the cell dimensions, so much work had been done to stabilise the crystals to make isomorphous heavy atom derivatives. At the start of this project, 3 fairly isomorphous heavy atom derivatives had already been discovered and data to high resolution collected on 2 of them. However, the data at high resolution contained large errors due to absorption and the derivatives were not totally isomorphous. Thus I set out to discover some new heavy atom derivatives and also to try to improve the use of the existing data so that the structure of the protein complex could be determined at high resolution. Two new derivatives were discovered, one utilising a modified ATP molecule to introduce a reactive group into the complex and both using the mercury salt p-hydroxy mercuribenzoate. Precession film, diffractometer and oscillation film data were collected on these two derivatives as well as recollecting poor data and missing data for the other derivatives. Some of the previously collected data were reprocessed and all the derivatives, at all resolution limits, from all sources were reexamined to find the best possible set of heavy atom solutions and thus produce the best set of phases and the most reliable electron density map. The result of this work was an electron density map which was much more interpretable in terms of protein structure. Previously, very little regular secondary structure could be seen but in the new map α-helices, β-sheets and the ATP molecule could all be found. Once regular secondary structure can be found, modifications can be made to the phases and the results can be observed to improve, or otherwise, the map. The structure of the profilin:actin complex is now being built and even if the complete atomic coordinates can not be found, there exists a rigorous framework on which to base further work.

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