Theoretical foundations of neural networks

Neural networks have often been motivated by superficial analogy with biological nervous systems. Recently, however, it has become widely recognised that the effective application of neural networks requires instead a deeper understanding of the theoretical foundations of these models. Insight into neural networks comes from a number of fields including statistical pattern recognition, computational learning theory, statistics, information geometry and statistical mechanics. As an illustration of the importance of understanding the theoretical basis for neural network models, we consider their application to the solution of multi-valued inverse problems. We show how a naive application of the standard least-squares approach can lead to very poor results, and how an appreciation of the underlying statistical goals of the modelling process allows the development of a more general and more powerful formalism which can tackle the problem of multi-modality.

Growth, sporulation and spore properties of bacillus stearothemophilus produced in chemically defined media

The nutritional requirements for the vegetative growth of B. stearothermophilus strains NCIB 8919, NCTC lO,OO3 (wild) were found to be DL-methionine, biotin, nicotinic acid, thiamin, glucose and mineral salts. Strains NCIB 8920 required in addition L-tryptophan. B. stearothermophilus NCTC lO,OO3 (mutant) grew in a medium containing only glucose and mineral salts. Separate chemically defined media for the growth of Bacillus stearothermophilus strains NCIB 8919, 8920, NCTC lO,OO3 (wild) and NCTC lO,OO3 (mutant) were developed. Optimally aerated culture of B. stearothermonhilus NCTC lO,OO3(mutant) required 1.0 x 10-4 M. Mn2+ and 2.4 x 10-3 M. glutamic acid for optimal sporulation. Specific nutrient depletion of growth affected percentage sporulation. Spore suspensions of B. stearothermophilus NCTC 10,003 (mutant) were prepared from media in which sulphate (SO4-), nitrogen (N-),phosphate (Po4-), carbon (C-), magnesium-carbon simultaneously (Ng-C-) depleted growth. The heat resistance, dormancy and chemistry of these spores varied considerably. B. stearothermophilus NCTC 10,003 10,00310,00(mutant) spores prepared from carbon depleted cultures containing high and low concentrations of calcium, iron or manganese showed variations in heat resistance,dormancy and chemical composition. Progressive increase in the concentration of medium calciumfrom 1.0 X 10-5  M to 1.4 X 10-4 M. progressively increased theheat resistance of B. stearothermophilus NCTC 10,003 (mutant) spores prepared from nitrogen depleted cultures (N-). The thermodynamic functions for germination rate, magnesium and manganese release of N- and SO4- spores were within the range expected of enzymic reactions. The thermodynamic functions for the breaking of dormancy in SO4- spores and that for the release of D.P.A. were identical. Sublethal heating of SO4- spores (96.5°C and below) induced dormancy in these spores, whereas heating above 96.5°C gave rise to heat activation. Pooled results of the chemical analyses of all spore types studied showed that the concentration of D.P.A. and calcium were positively related to heat resistance whereas magnesium concentration and Mg/Ca molar ratio were inversely proportional to heat resistance.

The development of an in vivo model of drug-induced terminal differentiation of Leukaemic cells

The technique of growing human leukaemic cells in diffusion chambers was developed to enable chemicals to be assessed for their ability to induce terminal differentiation. HL-60 promyelocytic leukaemia cell growth, in a lucite chamber with a Millipore filter, was optimised by use of a lateral incision site. Chambers were constructed using 0.45um filters and contained 150ul of serum-free HL-60 cells at a density of 1x106 cells/ml. The chambers were implanted into CBA/Ca mice and spontaneous terminal differentiation of the cells to granulocytes was prevented by the use of serum-free medium. Under these conditions there was an initial growth lag of 72 hours and a logarithmic phase of growth for 96 hours; the cell number reached a plateau after 168 hours of culture in vivo. The amount of drug in the plasma of the animal and in chambers that had been implanted for 5 days, was determined after a single ip injection of equitoxic doses of N-methylformamide, N-ethylformamide, tetramethylurea, N-dibutylformamide, N-tetramethylbutylformamide and hexamethylenebisacetamide. Concentrations of both TMU and HMBA were obtained in the plasma and in the chamber which were pharmacologically effective for the induction of differentiation of HL-60 cells in vitro, that is 12mM TMU and 5mM HMBA. A 4 day regime of treatment of animals implanted with chambers demonstrated that TMU and HMBA induced terminal differentiation of 50% and 35%, respectively, of the implanted HL-60 cells to granulocyte-like cells, assessed by measurement of functional and biochemical markers of maturity. None of the other agents attained concentrations in the plasma that were pharmacologically effective for the induction of differentiation of the cells in vitro and were unable to induce the terminal differentiation of the cells in vivo.

Changing treaty and changing economic context:the dynamic relationship of the legislature and the judiciary in the pursuit of capital liberalisation

Introduction For a significant period of time (the late 1950s--1980s), a lack of capital freedom was a major obstacle to the progress of the internal market project. The free movements of goods, persons and services were achieved, and developed, primarily through the case law of the Court of Justice of the European Union (CJEU). On the other hand, the Court played a (self-imposed) limited role in the development of the free movement of capital. It was through a progressive series of legislation that the freedom was finally achieved. John Usher has noted that the consequence of this is that ‘free movement of capital thus became the only Treaty “freedom” to be achieved in the manner envisaged in the Treaty’. For this reason, the relationship of the Court and legislature in this area is of particular importance in the broader context of the internal market. The rest of this chapter is split into four sections and will attempt to describe (and account for) the differing relationships between the legislature and the judiciary during the different stages of capital liberalisation. Section 2 will deal with the situation under the original Treaty of Rome. Section 3 will examine a single legislative intervention: Directive 88/361. It was this intervention that contained the obligation for Member States to fully liberalise capital movements. It is therefore the most important contribution to the completion of the internal market in the capital sphere. An examination will be made of whether the interpretation of the Directive demonstrates a changed (or changing attitude) of the Court towards the EU legislature. Section 4 will examine the changes brought about by the Treaty on European Union in 1993. It was at Maastricht that the Member States finally introduced into the Treaty framework an absolute obligation to liberalise capital movements. Finally, Section 5 will consider the Treaty of Lisbon and the possibility of future interventions by the legislature. By looking at the patterns that run through the different parts, this chapter will attempt to engage with the question of whether the approaches were products of their historical context, or whether they can be applied to other areas within the capital movement sphere.

Diagnosis of central venous catheter related infection in adult patients

Intravascular catheters are one of the main causes of bacteraemia and septicaemia in hospitalised patients and continue to be associated with a significant morbidity and mortality. Two main types of infections occur, they can be either localised at the catheter insertion site of systemic with a septicaemia. The clinical parameters related to these infections are presented. The laboratory diagnosis of these infections is also extensively reviewed and recommendations are made as to the most appropriate diagnostic method to be used. © 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Is measurement of blood pressure worthwhile in the diabetic eye clinic?

Purpose - The UK Prospective Diabetic Study has confirmed the importance of blood pressure (BP) as a major risk factor for diabetic retinopathy (DR). We wanted to investigate whether measuring the BP in the diabetic eye clinic could identify new hypertensive patients and monitor control in existing ones. Patients and methods - We compared BP in patients attending the diabetic eye clinic with home blood pressure measurement (HBPM) and ambulatory BP measurement (ABPM). In all, 106 patients attending a diabetic eye clinic were selected at random from clinic attendees. BP measurement (on an Omron 705 CP) was performed in the eye clinic and also compared to HBPM three times per day with an Omron 705 CP machine, and was compared to diabetic clinic measurements. In addition, 11 randomly chosen patients had 24 h ABPM to validate the above techniques. Results - In all, 106 patients (70 male and 36 female) were recruited for the study, of which 71 were known to be hypertensive on antihypertensive medication. Of the total, 75 patients (70.8%) had BP>140/85 in the eye clinic, of which 51 (68%) were known to be hypertensive on treatment and this was confirmed in 46 (90%) on HBPM. A total of, 24 patients (22.6%) were newly diagnosed as hypertensive in the eye clinic, which was confirmed by HBPM in 22 patients (92%). The mean BP of the measurements performed in the eye clinic was significantly higher than that carried out in the diabetic clinic (P<0.01). Tropicamide 1% and phenylephrine 2.5% eye drop instillation had no effect on BP. In 11 randomly chosen patients, 24 h ABPM validated both diabetic eye clinic and home BP measurements. Conclusion - Attendance at the diabetic eye clinic is an important chance to detect both new patients with systemic hypertension and those with inadequate BP control. Ophthalmologists should be encouraged to measure BP in their diabetic patients attending diabetic eye clinics, as it is an important risk factor for DR. On the basis of our findings, good BP control is a goal yet to be achieved in diabetic patients with retinopathy.

Anisotropic surface chemistry of aspirin crystals

The wettability of the (001), (100), and (011) crystallographic facets of macroscopic aspirin crystals has been experimentally investigated using a sessile drop contact angle (θ) method. θ for a nonpolar liquid was very similar for all three facets, though significant θ differences were observed for three polar probe liquids. The observed hydrophobicity of the (001) and (100) facets is ascribed to a reduced hydrogen bonding potential at these surfaces, whilst the observed hydrophilicity of facet (011) may be attributed to presence of surface carboxylic functionalities as confirmed by X-ray photoelectron spectroscopy (XPS). The dispersive component of the surface free energy (γ) was similar for all three facets (35 ± 2 mJ/m). The total surface energy, γs varied between 46 and 60 mJ/m due to significant variations in the polar/acid-base components of γ for all facets. Surface polarity as determined by γ measurements and XPS data were in good agreement, linking the variations in wettability to the concentration of oxygen containing surface functional groups. In conclusion, the wettability and the surface energy of a crystalline organic solid, such as aspirin, was found to be anisotropic and facet dependant, and in this case, related to the presence of surface carboxylic functionalities. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association.