Public sector investment appraisal:the place of flexibility in the decision making process

This thesis reviews the main methodological developments in public sector investment appraisal and finds growing evidence that appraisal techniques are not fulfilling their earlier promise. It is suggested that an important reason for this failure lies in the inability of these techniques to handle uncertainty except in a highly circumscribed fashion. It is argued that a more fruitful approach is to strive for flexibility. Investment projects should be formulated with a view to making them responsive to a wide range of possible future events, rather than embodying a solution which is optimal for one configuration of circumstances only. The distinction drawn in economics between the short and the long run is used to examine the nature of flexibility. The concept of long run flexibility is applied to the pre-investment range of choice open to the decisionmaker. It is demonstrated that flexibility is reduced at a very early stage of decisionmaking by the conventional system of appraisal which evaluates only a small number of options. The pre-appraisal filtering process is considered further in relation to decisionmaking models. It is argued that for public sector projects the narrowing down of options is best understood in relation to an amended mixed scanning model which places importance on the process by which the 'national interest ' is determined. Short run flexibility deals with operational characteristics, the degree to which particular projects may respond to changing demands when the basic investment is already in place. The tension between flexibility and cost is noted. A short case study on the choice of electricity generating plant is presented. The thesis concludes with a brief examination of the approaches used by successive British governments to public sector investment, particularly in relation to the nationalised industries

The pre-treatment and pyrolysis of biomass for the production of liquids for fuels and speciality chemicals

Fast pyrolysis of biomass is a significant technology for producing pyrolysis liquids [also known as bio-oil], which contain a number of chemicals. The pyrolysis liquid can be used as a fuel, can be produced solely as a source of chemicals or can have some of the chemicals extracted and the residue used as a fuel. There were two primary objectives of this work. The first was to determine the fast pyrolysis conditions required to maximise the pyrolysis liquid yield from a number of biomass feedstocks. The second objective was to selectively increase the yield of certain chemicals in the pyrolysis liquid by pre-treatment of the feedstock prior to pyrolysis. For a particular biomass feedstock the pyrolysis liquid yield is affected by the reactor process parameters. It has been found that, providing the other process parameters are restricted to the values shown below, reactor temperature is the controlling parameter. The maximum pyrolysis liquid yield and the temperature at which it occurs has been found by a series of pyrolysis experiments over the temperature range 400-600°C. high heating rates > 1000°C/s; pyrolysis vapour residence times <2 seconds; pyrolysis vapour temperatures >400 but <500°C; rapid quenching of the product vapours. Pre-treatment techniques have been devised to modify the chemical composition and/or structure of the biomass in such a way as to influence the chemical composition of the pyrolysis liquid product. The pre-treatments were divided into two groups, those that remove material from the biomass and those which add material to the biomass. Component removal techniques have selectively increased the yield of levoglucosan from 2.45 to 18.58 mf wt.% [dry feedstock basis]. Additive techniques have selectively increased the yield of hydroxyacetaldehyde from 7.26 to 11.63 mf w.% [dry feedstock basis]. Techno-economic assessment has been carried out on an integrated levoglucosan production process [incorporating pre-treatment, pyrolysis and chemical extraction stages] to assess which method of chemical production is the more cost effective. It has been found that it is better to pre-treat the biomass in order to increase the yield of specific chemicals in the pyrolysis liquid and hence improve subsequent chemicals extraction.

Pre-conception care : current practice and methods of provision

This thesis examines the present provisions for pre-conception care and the views of the providers of services. Pre-conception care is seen by some clinicians and health educators as a means of making any necessary changes in life style, corrections to imbalances in the nutritional status of the prospective mother (and father) and the assessment of any medical problems, thus maximizing the likelihood of the normal development of the baby. Pre-conception care may be described as a service to bridge the gap between the family planning clinic and the first ante-natal booking appointment. There were three separate foci for the empirical research - the Foresight organisation (a charity which has pioneered pre-conception care in Britain); the pre-conception care clinic at the West London Hospital, Hammersmith; and the West Midlands Regional Health Authority. The six main sources of data were: twenty five clinicians operating Foresight pre-conception clinics, couples attending pre-conception clinics, committee members of the Foresight organisation, staff of the West London Hospital pre-conception clinic, Hammersmith, District Health Education Officers working in the West Midlands Regional Health Authority and the members of the Ante-Natal Care Action Group, a sub-group of the Regional Health Advisory Group on Health Promotion and Preventive Medicine. A range of research methods were adopted. These were as follows: questionnaires and report forms used in co-operation with the Foresight clinicians, interviews, participant observation discussions and informal meetings and, finally, literature and official documentation. The research findings illustrated that pre-conception care services provided at the predominantly private Foresight clinics were of a rather `ad hoc' nature. The type of provision varied considerably and clearly reflected the views held by its providers. The protocol which had been developed to assist in the standardization of results was not followed by the clinicians. The pre-conception service provided at the West London Hospital shared some similarities in its approach with the Foresight provision; a major difference was that it did not advocate the use of routine hair trace metal analysis. Interviews with District Health Education Officers and with members of the Ante Natal Care Action Group revealed a tentative and cautious approach to pre-conception care generally and to the Foresight approach in particular. The thesis concludes with a consideration of the future of pre-conception care and the prospects for the establishment of a comprehensive pre-conception care service.

Is randomisation necessary for measuring defocus curves in pre-presbyopes?

Purpose: Defocus curves are used to evaluate the subjective range of clear vision of presbyopic corrections such as in eyes implanted with accommodating intraocular lenses (IOLs). This study determines whether letter sequences and/or lens presentation order ought to be randomised when measuring defocus curves. Methods: Defocus curves (range +2.00DS to -2.00DS) were measured on 18 pre-presbyopic subjects (mean age 24.1 ± 4.2 years) for six combinations of sequential or randomised positive or negative lens progression and non-randomised or randomised letter sequences. The letters were presented on a computerised logMAR chart at 6 m. Results: Overall there was a statistically significant difference between the six combinations (ANOVA, p < 0.05) attributable to the combination of non-randomised letters with non-randomised lens progression from negative to positive defocus (p < 0.01). There was no statistically significant difference in defocus curve measurements if both letters and lens order were randomised compared to if only one of these variables was randomised (p > 0.05). Non-randomised letters, with a sequential lens progression from negative to positive, was significantly different to all other combinations when compared individually (Student's T-test, p < 0.003 on all comparisons), and was confirmed as the sole source of the overall significant difference. There was no statistically significant difference if both lens presentation order and letter sequences were randomised compared to if only one or the other of these variables was randomised. Conclusion: Non-randomised letters and non-randomised lens progression on their own did not affect the subjective amplitude of accommodation as measured by defocus curves, although their combination should be avoided. © 2007 British Contact Lens Association.

Functional recombinant protein is present in the pre-induction phases of Pichia pastoris cultures when grown in bioreactors, but not shake-flasks

Background - Pichia pastoris is a widely-used host for recombinant protein production; expression is typically driven by methanol-inducible alcohol oxidase (AOX) promoters. Recently this system has become an important source of recombinant G protein-coupled receptors (GPCRs) for structural biology and drug discovery. The influence of diverse culture parameters (such as pH, dissolved oxygen concentration, medium composition, antifoam concentration and culture temperature) on productivity has been investigated for a wide range of recombinant proteins in P. pastoris. In contrast, the impact of the pre-induction phases on yield has not been as closely studied. In this study, we examined the pre-induction phases of P. pastoris bioreactor cultivations producing three different recombinant proteins: the GPCR, human A2a adenosine receptor (hA2aR), green fluorescent protein (GFP) and human calcitonin gene-related peptide receptor component protein (as a GFP fusion protein; hCGRP-RCP-GFP). Results - Functional hA2aR was detected in the pre-induction phases of a 1 L bioreactor cultivation of glycerol-grown P. pastoris. In a separate experiment, a glycerol-grown P. pastoris strain secreted soluble GFP prior to methanol addition. When glucose, which has been shown to repress AOX expression, was the pre-induction carbon source, hA2aR and GFP were still produced in the pre-induction phases. Both hA2aR and GFP were also produced in methanol-free cultivations; functional protein yields were maintained or increased after depletion of the carbon source. Analysis of the pre-induction phases of 10 L pilot scale cultivations also demonstrated that pre-induction yields were at least maintained after methanol induction, even in the presence of cytotoxic concentrations of methanol. Additional bioreactor data for hCGRP-RCP-GFP and shake-flask data for GFP, horseradish peroxidase (HRP), the human tetraspanins hCD81 and CD82, and the tight-junction protein human claudin-1, demonstrated that bioreactor but not shake flask cultivations exhibit recombinant protein production in the pre-induction phases of P. pastoris cultures. Conclusions - The production of recombinant hA2aR, GFP and hCGRP-RCP-GFP can be detected in bioreactor cultivations prior to methanol induction, while this is not the case for shake-flask cultivations of GFP, HRP, hCD81, hCD82 and human claudin-1. This confirms earlier suggestions of leaky expression from AOX promoters, which we report here for both glycerol- and glucose-grown cells in bioreactor cultivations. These findings suggest that the productivity of AOX-dependent bioprocesses is not solely dependent on induction by methanol. We conclude that in order to maximize total yields, pre-induction phase cultivation conditions should be optimized, and that increased specific productivity may result in decreased biomass yields.

Linear dispersive pre-defined peak amplitude modulation of spectrally modulated airy-based pulses

Spectrally modulated Airy-based pulses peak amplitude modulation (PAM) in linear dispersive media is investigated, designed, and numerically simulated. As it is shown here, it is possible to design the spectral modulation of the initial Airy-based pulses to obtain a pre-defined PAM profile as the pulse propagates. Although optical pulses self-amplitude modulation is a well-known effect under non-linear propagation, the designed Airy-based pulses exhibit PAM under linear dispersive propagation. This extraordinary linear propagation property can be applied in many kinds of dispersive media, enabling its use in a broad range of experiments and applications. © 2013 Optical Society of America.

Light scattering study of human serum albumin in pre-denaturation:relation to dynamic transition in water at 42°C

Protein functional motions are ultimately connected to water dynamics. The goal of this study is to link the conformational dynamics of albumin to a dynamic transition taking place at ∼ 42°C in water. We report the results of dynamic light scattering measurements of albumin aqueous solution in the temperature interval 20-65°C. The processing of the experimental data produced the temperature dependence of the macromolecular hydrodynamic radius. We demonstrate that the growth of the macromolecular size in this temperature range can be divided into two stages that are connected to the dynamical properties of water. © 2012 Elsevier B.V. All rights reserved.

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy:effects of genetic, demographic and neuropathological variables

Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64). Familial and sporadic cases exhibited similar survival, including progranulin (GRN) gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND) but increased with Alzheimer's disease (AD) or hippocampal sclerosis (HS) co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI) while increased survival was associated with greater densities of enlarged neurons (EN) in the frontal and temporal lobes. The data suggest that: (1) survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA), (2) MND co-morbidity predicts poor survival, and (3) NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.