Malnutrition in Parkinson's disease and an individualised approach to its management

It has been reported that poor nutritional status, in the form of weight loss and resulting body mass index (BMI) changes, is an issue in people with Parkinson's disease (PWP). The symptoms resulting from Parkinson's disease (PD) and the side effects of PD medication have been implicated in the aetiology of nutritional decline. However, the evidence on which these claims are based is, on one hand, contradictory, and on the other, restricted primarily to otherwise healthy PWP. Despite the claims that PWP suffer from poor nutritional status, evidence is lacking to inform nutrition-related care for the management of malnutrition in PWP. The aims of this thesis were to better quantify the extent of poor nutritional status in PWP, determine the important factors differentiating the well-nourished from the malnourished and evaluate the effectiveness of an individualised nutrition intervention on nutritional status. Phase DBS: Nutritional status in people with Parkinson's disease scheduled for deep-brain stimulation surgery The pre-operative rate of malnutrition in a convenience sample of people with Parkinson's disease (PWP) scheduled for deep-brain stimulation (DBS) surgery was determined. Poorly controlled PD symptoms may result in a higher risk of malnutrition in this sub-group of PWP. Fifteen patients (11 male, median age 68.0 (42.0 – 78.0) years, median PD duration 6.75 (0.5 – 24.0) years) participated and data were collected during hospital admission for the DBS surgery. The scored PG-SGA was used to assess nutritional status, anthropometric measures (weight, height, mid-arm circumference, waist circumference, body mass index (BMI)) were taken, and body composition was measured using bioelectrical impedance spectroscopy (BIS). Six (40%) of the participants were malnourished (SGA-B) while 53% reported significant weight loss following diagnosis. BMI was significantly different between SGA-A and SGA-B (25.6 vs 23.0kg/m 2, p<.05). There were no differences in any other variables, including PG-SGA score and the presence of non-motor symptoms. The conclusion was that malnutrition in this group is higher than that in other studies reporting malnutrition in PWP, and it is under-recognised. As poorer surgical outcomes are associated with poorer pre-operative nutritional status in other surgeries, it might be beneficial to identify patients at nutritional risk prior to surgery so that appropriate nutrition interventions can be implemented. Phase I: Nutritional status in community-dwelling adults with Parkinson's disease The rate of malnutrition in community-dwelling adults (>18 years) with Parkinson's disease was determined. One hundred twenty-five PWP (74 male, median age 70.0 (35.0 – 92.0) years, median PD duration 6.0 (0.0 – 31.0) years) participated. The scored PG-SGA was used to assess nutritional status, anthropometric measures (weight, height, mid-arm circumference (MAC), calf circumference, waist circumference, body mass index (BMI)) were taken. Nineteen (15%) of the participants were malnourished (SGA-B). All anthropometric indices were significantly different between SGA-A and SGA-B (BMI 25.9 vs 20.0kg/m2; MAC 29.1 – 25.5cm; waist circumference 95.5 vs 82.5cm; calf circumference 36.5 vs 32.5cm; all p<.05). The PG-SGA score was also significantly lower in the malnourished (2 vs 8, p<.05). The nutrition impact symptoms which differentiated between well-nourished and malnourished were no appetite, constipation, diarrhoea, problems swallowing and feel full quickly. This study concluded that malnutrition in community-dwelling PWP is higher than that documented in community-dwelling elderly (2 – 11%), yet is likely to be under-recognised. Nutrition impact symptoms play a role in reduced intake. Appropriate screening and referral processes should be established for early detection of those at risk. Phase I: Nutrition assessment tools in people with Parkinson's disease There are a number of validated and reliable nutrition screening and assessment tools available for use. None of these tools have been evaluated in PWP. In the sample described above, the use of the World Health Organisation (WHO) cut-off (≤18.5kg/m2), age-specific BMI cut-offs (≤18.5kg/m2 for under 65 years, ≤23.5kg/m2 for 65 years and older) and the revised Mini-Nutritional Assessment short form (MNA-SF) were evaluated as nutrition screening tools. The PG-SGA (including the SGA classification) and the MNA full form were evaluated as nutrition assessment tools using the SGA classification as the gold standard. For screening, the MNA-SF performed the best with sensitivity (Sn) of 94.7% and specificity (Sp) of 78.3%. For assessment, the PG-SGA with a cut-off score of 4 (Sn 100%, Sp 69.8%) performed better than the MNA (Sn 84.2%, Sp 87.7%). As the MNA has been recommended more for use as a nutrition screening tool, the MNA-SF might be more appropriate and take less time to complete. The PG-SGA might be useful to inform and monitor nutrition interventions. Phase I: Predictors of poor nutritional status in people with Parkinson's disease A number of assessments were conducted as part of the Phase I research, including those for the severity of PD motor symptoms, cognitive function, depression, anxiety, non-motor symptoms, constipation, freezing of gait and the ability to carry out activities of daily living. A higher score in all of these assessments indicates greater impairment. In addition, information about medical conditions, medications, age, age at PD diagnosis and living situation was collected. These were compared between those classified as SGA-A and as SGA-B. Regression analysis was used to identify which factors were predictive of malnutrition (SGA-B). Differences between the groups included disease severity (4% more severe SGA-A vs 21% SGA-B, p<.05), activities of daily living score (13 SGA-A vs 18 SGA-B, p<.05), depressive symptom score (8 SGA-A vs 14 SGA-B, p<.05) and gastrointestinal symptoms (4 SGA-A vs 6 SGA-B, p<.05). Significant predictors of malnutrition according to SGA were age at diagnosis (OR 1.09, 95% CI 1.01 – 1.18), amount of dopaminergic medication per kg body weight (mg/kg) (OR 1.17, 95% CI 1.04 – 1.31), more severe motor symptoms (OR 1.10, 95% CI 1.02 – 1.19), less anxiety (OR 0.90, 95% CI 0.82 – 0.98) and more depressive symptoms (OR 1.23, 95% CI 1.07 – 1.41). Significant predictors of a higher PG-SGA score included living alone (β=0.14, 95% CI 0.01 – 0.26), more depressive symptoms (β=0.02, 95% CI 0.01 – 0.02) and more severe motor symptoms (OR 0.01, 95% CI 0.01 – 0.02). More severe disease is associated with malnutrition, and this may be compounded by lack of social support. Phase II: Nutrition intervention Nineteen of the people identified in Phase I as requiring nutrition support were included in Phase II, in which a nutrition intervention was conducted. Nine participants were in the standard care group (SC), which received an information sheet only, and the other 10 participants were in the intervention group (INT), which received individualised nutrition information and weekly follow-up. INT gained 2.2% of starting body weight over the 12 week intervention period resulting in significant increases in weight, BMI, mid-arm circumference and waist circumference. The SC group gained 1% of starting weight over the 12 weeks which did not result in any significant changes in anthropometric indices. Energy and protein intake (18.3kJ/kg vs 3.8kJ/kg and 0.3g/kg vs 0.15g/kg) increased in both groups. The increase in protein intake was only significant in the SC group. The changes in intake, when compared between the groups, were no different. There were no significant changes in any motor or non-motor symptoms or in "off" times or dyskinesias in either group. Aspects of quality of life improved over the 12 weeks as well, especially emotional well-being. This thesis makes a significant contribution to the evidence base for the presence of malnutrition in Parkinson's disease as well as for the identification of those who would potentially benefit from nutrition screening and assessment. The nutrition intervention demonstrated that a traditional high protein, high energy approach to the management of malnutrition resulted in improved nutritional status and anthropometric indices with no effect on the presence of Parkinson's disease symptoms and a positive effect on quality of life.

Analysis of nonlinear sequences and streamciphers

Streamciphers are common cryptographic algorithms used to protect the confidentiality of frame-based communications like mobile phone conversations and Internet traffic. Streamciphers are ideal cryptographic algorithms to encrypt these types of traffic as they have the potential to encrypt them quickly and securely, and have low error propagation. The main objective of this thesis is to determine whether structural features of keystream generators affect the security provided by stream ciphers.These structural features pertain to the state-update and output functions used in keystream generators. Using linear sequences as keystream to encrypt messages is known to be insecure. Modern keystream generators use nonlinear sequences as keystream.The nonlinearity can be introduced through a keystream generator's state-update function, output function, or both. The first contribution of this thesis relates to nonlinear sequences produced by the well-known Trivium stream cipher. Trivium is one of the stream ciphers selected in a final portfolio resulting from a multi-year project in Europe called the ecrypt project. Trivium's structural simplicity makes it a popular cipher to cryptanalyse, but to date, there are no attacks in the public literature which are faster than exhaustive keysearch. Algebraic analyses are performed on the Trivium stream cipher, which uses a nonlinear state-update and linear output function to produce keystream. Two algebraic investigations are performed: an examination of the sliding property in the initialisation process and algebraic analyses of Trivium-like streamciphers using a combination of the algebraic techniques previously applied separately by Berbain et al. and Raddum. For certain iterations of Trivium's state-update function, we examine the sets of slid pairs, looking particularly to form chains of slid pairs. No chains exist for a small number of iterations.This has implications for the period of keystreams produced by Trivium. Secondly, using our combination of the methods of Berbain et al. and Raddum, we analysed Trivium-like ciphers and improved on previous on previous analysis with regards to forming systems of equations on these ciphers. Using these new systems of equations, we were able to successfully recover the initial state of Bivium-A.The attack complexity for Bivium-B and Trivium were, however, worse than exhaustive keysearch. We also show that the selection of stages which are used as input to the output function and the size of registers which are used in the construction of the system of equations affect the success of the attack. The second contribution of this thesis is the examination of state convergence. State convergence is an undesirable characteristic in keystream generators for stream ciphers, as it implies that the effective session key size of the stream cipher is smaller than the designers intended. We identify methods which can be used to detect state convergence. As a case study, theMixer streamcipher, which uses nonlinear state-update and output functions to produce keystream, is analysed. Mixer is found to suffer from state convergence as the state-update function used in its initialisation process is not one-to-one. A discussion of several other streamciphers which are known to suffer from state convergence is given. From our analysis of these stream ciphers, three mechanisms which can cause state convergence are identified.The effect state convergence can have on stream cipher cryptanalysis is examined. We show that state convergence can have a positive effect if the goal of the attacker is to recover the initial state of the keystream generator. The third contribution of this thesis is the examination of the distributions of bit patterns in the sequences produced by nonlinear filter generators (NLFGs) and linearly filtered nonlinear feedback shift registers. We show that the selection of stages used as input to a keystream generator's output function can affect the distribution of bit patterns in sequences produced by these keystreamgenerators, and that the effect differs for nonlinear filter generators and linearly filtered nonlinear feedback shift registers. In the case of NLFGs, the keystream sequences produced when the output functions take inputs from consecutive register stages are less uniform than sequences produced by NLFGs whose output functions take inputs from unevenly spaced register stages. The opposite is true for keystream sequences produced by linearly filtered nonlinear feedback shift registers.

Self excitation in equity indices

A "self-exciting" market is one in which the probability of observing a crash increases in response to the occurrence of a crash. It essentially describes cases where the initial crash serves to weaken the system to some extent, making subsequent crashes more likely. This thesis investigates if equity markets possess this property. A self-exciting extension of the well-known jump-based Bates (1996) model is used as the workhorse model for this thesis, and a particle-filtering algorithm is used to facilitate estimation by means of maximum likelihood. The estimation method is developed so that option prices are easily included in the dataset, leading to higher quality estimates. Equilibrium arguments are used to price the risks associated with the time-varying crash probability, and in turn to motivate a risk-neutral system for use in option pricing. The option pricing function for the model is obtained via the application of widely-used Fourier techniques. An application to S&P500 index returns and a panel of S&P500 index option prices reveals evidence of self excitation.

Star performers : task and contextual performance are components, but are they enough?

Identifying outstanding performers or ‘stars’ is a critical component of managing talent. However, organizational effectiveness in this area is limited by the current lack of guidance about the behaviour and characteristics of stars. We address this gap by combining a conceptual analysis with an empirical study involving 174 managers. Conceptually we examine the alignment of managers’ perceptions of outstanding performance with the well established task and contextual performance model and find this framework accounts for a core element in managers’ judgments about outstanding performers. However, a second, more qualitative approach finds that other dimensions including being self-directed, and a willingness to lead are also important. Our findings are consistent with a long-term trend toward identifying work effectiveness with highly discretionary, psychological and behavioural elements, and we consider the implications of this for the study and management of high level, individual effectiveness.

Consistent HMM parameter estimation using Kerridge inaccuracy rates

In this paper, we propose a novel online hidden Markov model (HMM) parameter estimator based on Kerridge inaccuracy rate (KIR) concepts. Under mild identifiability conditions, we prove that our online KIR-based estimator is strongly consistent. In simulation studies, we illustrate the convergence behaviour of our proposed online KIR-based estimator and provide a counter-example illustrating the local convergence properties of the well known recursive maximum likelihood estimator (arguably the best existing solution).

Efficient selective identity-based encryption without random oracles

We construct two efficient Identity-Based Encryption (IBE) systems that admit selective-identity security reductions without random oracles in groups equipped with a bilinear map. Selective-identity secure IBE is a slightly weaker security model than the standard security model for IBE. In this model the adversary must commit ahead of time to the identity that it intends to attack, whereas in an adaptive-identity attack the adversary is allowed to choose this identity adaptively. Our first system—BB1—is based on the well studied decisional bilinear Diffie–Hellman assumption, and extends naturally to systems with hierarchical identities, or HIBE. Our second system—BB2—is based on a stronger assumption which we call the Bilinear Diffie–Hellman Inversion assumption and provides another approach to building IBE systems. Our first system, BB1, is very versatile and well suited for practical applications: the basic hierarchical construction can be efficiently secured against chosen-ciphertext attacks, and further extended to support efficient non-interactive threshold decryption, among others, all without using random oracles. Both systems, BB1 and BB2, can be modified generically to provide “full” IBE security (i.e., against adaptive-identity attacks), either using random oracles, or in the standard model at the expense of a non-polynomial but easy-to-compensate security reduction.

Recursive pathways to marginal likelihood estimation with prior-sensitivity analysis

We investigate the utility to computational Bayesian analyses of a particular family of recursive marginal likelihood estimators characterized by the (equivalent) algorithms known as "biased sampling" or "reverse logistic regression" in the statistics literature and "the density of states" in physics. Through a pair of numerical examples (including mixture modeling of the well-known galaxy dataset) we highlight the remarkable diversity of sampling schemes amenable to such recursive normalization, as well as the notable efficiency of the resulting pseudo-mixture distributions for gauging prior-sensitivity in the Bayesian model selection context. Our key theoretical contributions are to introduce a novel heuristic ("thermodynamic integration via importance sampling") for qualifying the role of the bridging sequence in this procedure, and to reveal various connections between these recursive estimators and the nested sampling technique.

Performance-based structural fire design and testing of structures

Fire incident in buildings is common in Hong Kong and this could lead to heavy casualties due to its high population density, so the fire safety design of the framed structure is an important research topic. This paper describes a computer tool for determination of capacity of structural safety against various fire scenarios and the well-accepted second-order direct plastic analysis is adopted for simulation of material yielding and buckling. A computer method is developed to predict structural behaviour of bare steel framed structures at elevated temperatures but the work can be applied to structures made of other materials. These effects of thermal expansion and material degradation due to heating are required to be considered in order to capture the actual behavior of the structure under fire. Degradation of material strength with increasing temperature is included by a set of temperature-stress-strain curves according to BS5950 Part 8 mainly, which implicitly allows for creep deformation. Several numerical and experimental verifications of framed structures are presented and compared against solutions by other researchers. The proposed method allows us to adopt the truly performance-based structural fire analysis and design with significant saving in cost and time.

pGreen : a versatile and flexible binary Ti vector for Agrobacterium-mediated plant transformation

Binary Ti vectors are the plasmid vectors of choice in Agrobacterium-mediated plant transformation protocols. The pGreen series of binary Ti vectors are configured for ease-of-use and to meet the demands of a wide range of transformation procedures for many plant species. This plasmid system allows any arrangement of selectable marker and reporter gene at the right and left T-DNA borders without compromising the choice of restriction sites for cloning, since the pGreen cloning sites are based on the well-known pBluescript general vector plasmids. Its size and copy number in Escherichia coli offers increased efficiencies in routine in vitro recombination procedures. pGreen can replicate in Agrobacterium only if another plasmid, pSoup, is co-resident in the same strain. pSoup provides replication functions in trans for pGreen. The removal of RepA and Mob functions has enabled the size of pGreen to be kept to a minimum. Versions of pGreen have been used to transform several plant species with the same efficiencies as other binary Ti vectors. Information on the pGreen plasmid system is supplemented by an Internet site (http://www.pgreen.ac.uk) through which comprehensive information, protocols, order forms and lists of different pGreen marker gene permutations can be found.