A critical analysis of the 'amyloid cascade hypothesis'

The 'amyloid cascade hypothesis' (ACH) is the most influential model of the pathogenesis of Alzheimer's disease (AD). The hypothesis proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD, leading to the formation of extracellular senile plaques (SP), tau-immunoreactive neurofibrillary tangles (NFT), neuronal loss, and ultimately, clinical dementia. Ever since the formulation of the ACH, however, there have been questions regarding whether it completely describes AD pathogenesis. This review critically examines various aspects of the ACH including its origin and development, the role of amyloid precursor protein (APP), whether SP and NFT are related to the development of clinical dementia, whether Aβ and tau are 'reactive' proteins, and whether there is a pathogenic relationship between SP and NFT. The results of transgenic experiments and treatments for AD designed on the basis of the ACH are also reviewed. It was concluded: (1) Aβ and tau could be the products rather than the cause of neuro-degeneration in AD, (2) it is doubtful whether there is a direct causal link between Aβ and tau, and (3) SP and NFT may not be directly related to the development of dementia, (4) transgenic models involving APP alone do not completely replicate AD pathology, and (5) treatments based on the ACH have been unsuccessful. Hence, a modification of the ACH is proposed which may provide a more complete explanation of the pathogenesis of AD.

New product marketing and consumer innovative behaviour:a study of the Greek market

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY WITH PRIOR ARRANGEMENT

Cost-based pricing in the NHS internal market : accounting choices and the achievement of economic efficiency

Since 1988, quasi-markets have been introduced into many areas of social policy in the UK, the NHS internal market is one example. Markets operate by price signals. The NHS Internal Market, if it is to operate efficiently, requires purchasers and providers to respond to price signals. The research hypothesis is - cost accounting methods can be developed to enable healthcare contracts to be priced on a cost-basis in a manner which will facilitate the achievement of economic efficiency in the NHS internal market. Surveys of hospitals in 1991 and 1994 established the cost methods adopted in deriving the prices for healthcare contracts in the first year of the market and three years on. An in-depth view of the costing for pricing process was gained through case studies. Hospitals had inadequate cost information on which to price healthcare contracts at the inception of the internal market: prices did not reflect the relative performance of healthcare providers sufficiently closely to enable the market's espoused efficiency aims to be achieved. Price variations were often due to differing costing approaches rather than efficiency. Furthermore, price comparisons were often meaningless because of inadequate definition of the services (products). In April 1993, the NHS Executive issued guidance on costing for contracting to all NHS providers in an attempt to improve the validity of price comparisons between alternative providers. The case studies and the 1994 survey show that although price comparison has improved, considerable problems remain. Consistency is not assured, and the problem of adequate product definition is still to be solved. Moreover, the case studies clearly highlight the mismatch of rigid, full-cost pricing rules with both the financial management considerations at local level and the emerging internal market(s). Incentives exist to cost-shift, and healthcare prices can easily be manipulated. In the search for a new health policy paradigm to replace traditional bureaucratic provision, cost-based pricing cannot be used to ensure a more efficient allocation of healthcare resources.

The modelling of energy efficient drying for DSM (BL)

This thesis investigates the modelling of drying processes for the promotion of market-led Demand Side Management (DSM) as applied to the UK Public Electricity Suppliers. A review of DSM in the electricity supply industry is provided, together with a discussion of the relevant drivers supporting market-led DSM and energy services (ES). The potential opportunities for ES in a fully deregulated energy market are outlined. It is suggested that targeted industrial sector energy efficiency schemes offer significant opportunity for long term customer and supplier benefit. On a process level, industrial drying is highlighted as offering significant scope for the application of energy services. Drying is an energy-intensive process used widely throughout industry. The results of an energy survey suggest that 17.7 per cent of total UK industrial energy use derives from drying processes. Comparison with published work indicates that energy use for drying shows an increasing trend against a background of reducing overall industrial energy use. Airless drying is highlighted as offering potential energy saving and production benefits to industry. To this end, a comprehensive review of the novel airless drying technology and its background theory is made. Advantages and disadvantages of airless operation are defined and the limited market penetration of airless drying is identified, as are the key opportunities for energy saving. Limited literature has been found which details the modelling of energy use for airless drying. A review of drying theory and previous modelling work is made in an attempt to model energy consumption for drying processes. The history of drying models is presented as well as a discussion of the different approaches taken and their relative merits. The viability of deriving energy use from empirical drying data is examined. Adaptive neuro fuzzy inference systems (ANFIS) are successfully applied to the modelling of drying rates for 3 drying technologies, namely convective air, heat pump and airless drying. The ANFIS systems are then integrated into a novel energy services model for the prediction of relative drying times, energy cost and atmospheric carbon dioxide emission levels. The author believes that this work constitutes the first to use fuzzy systems for the modelling of drying performance as an energy services approach to DSM. To gain an insight into the 'real world' use of energy for drying, this thesis presents a unique first-order energy audit of every ceramic sanitaryware manufacturing site in the UK. Previously unknown patterns of energy use are highlighted. Supplementary comments on the timing and use of drying systems are also made. The limitations of such large scope energy surveys are discussed.

Unifractality and multifractality in the Italian stock market

Tests for random walk behaviour in the Italian stock market are presented, based on an investigation of the fractal properties of the log return series for the Mibtel index. The random walk hypothesis is evaluated against alternatives accommodating either unifractality or multifractality. Critical values for the test statistics are generated using Monte Carlo simulations of random Gaussian innovations. Evidence is reported of multifractality, and the departure from random walk behaviour is statistically significant on standard criteria. The observed pattern is attributed primarily to fat tails in the return probability distribution, associated with volatility clustering in returns measured over various time scales. © 2009 Elsevier Inc. All rights reserved.