Measuring mobility in frail older people: reliability and validity of the Physical Mobility Scale

Objectives: The study was designed to show the validity and reliability of scoring the Physical Mobility Scale (PMS). PMS was developed by physiotherapists working in residential aged care to specifically show resident functional mobility and to provide information regarding each resident's need for supervision or assistance from one or two staff members and equipment during position changes, transfers, mobilising and personal care. Methods: Nineteen physiotherapists of varying backgrounds and experience scored the performances of nine residents of care facilities from video recordings. The performances were compared to scores on two 'gold standard' assessment tools. Four of the physiotherapists repeated the evaluations. Results: The PAIS showed excellent content validity and reliability. Conclusions: The PAIS provides graded performance of physical mobility, including level of dependency on staff and equipment. This is a major advantage over existing functional assessment tools. There is no need for specific training for physiotherapists to use the tool.

Dispersal and seasonal distributions of black-faced impala in the Etosha National Park, Namibia

Factors affecting the seasonal distribution of the vulnerable black-faced impala at Etosha National Park, Namibia and the spread of the impala in the park since their translocation there in the 1970s were studied in the hot dry season of 2000 and the wet season of 2001 in order to provide information for future translocations of this antelope. In the 30 years since their release in the park, black-faced impala appear to have dispersed a maximum of 31.5 km from their initial release sites, effectively forming five subpopulations based on their five initial release sites. The mean minimum distance that impala had dispersed between water holes since their release was 7.11 +/- 1.47 km. Black-faced impala concentrated strongly around water holes; more than 50% were within 1 km of water holes in both seasons. Changes in population densities in different habitats may have resulted from seasonal movements of impala between adjacent habitats. The role of initial release sites in determining the distribution of threatened species such as the black-faced impala is discussed in light of its importance for future translocations.

Focusing in on structural genomics: The University of Queensland structural biology pipeline

The flood of new genomic sequence information together with technological innovations in protein structure determination have led to worldwide structural genomics (SG) initiatives. The goals of SG initiatives are to accelerate the process of protein structure determination, to fill in protein fold space and to provide information about the function of uncharacterized proteins. In the long-term, these outcomes are likely to impact on medical biotechnology and drug discovery, leading to a better understanding of disease as well as the development of new therapeutics. Here we describe the high throughput pipeline established at the University of Queensland in Australia. In this focused pipeline, the targets for structure determination are proteins that are expressed in mouse macrophage cells and that are inferred to have a role in innate immunity. The aim is to characterize the molecular structure and the biochemical and cellular function of these targets by using a parallel processing pipeline. The pipeline is designed to work with tens to hundreds of target gene products and comprises target selection, cloning, expression, purification, crystallization and structure determination. The structures from this pipeline will provide insights into the function of previously uncharacterized macrophage proteins and could lead to the validation of new drug targets for chronic obstructive pulmonary disease and arthritis. (c) 2006 Elsevier B.V. All rights reserved.

Establishing a zone where technology innovation is supported

Learning technologies are now a ubiquitous force in the higher education sector however we continue to pursue more inventive ways to use them for teaching and learning. Many teaching academics that seek to be innovative do not have access to a supportive technology innovation zone. The aim of this study was to investigate the articulated staff development needs of academics involved in a faculty based technology innovation project and create the conditions that would cultivate innovation. The study sought to find out how academics perceived they might best be assisted through their technology innovation process so that participants’ needs were incorporated into planning. A questionnaire was used to elicit background information about the academics’ experience, skills and self diagnosed skill deficits in this context. Participants were also requested to provide information about how they thought they would best acquire the skills given their time and other resource constraints. A modified Delphi Technique was utilised to achieve some consensus on what academics required to support technology innovation. Complemented by an enabling and empowering team based approach, the academics were provided with an innovation zone to achieve significant goals for the project.

A D-optimal designed population pharmacokinetic study of itraconazole capsules and solution in adults with cystic fibrosis

Background: Oral itraconazole (ITRA) is used for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis (CF) because of its antifungal activity against Aspergillus species. ITRA has an active hydroxy-metabolite (OH-ITRA) which has similar antifungal activity. ITRA is a highly lipophilic drug which is available in two different oral formulations, a capsule and an oral solution. It is reported that the oral solution has a 60% higher relative bioavailability. The influence of altered gastric physiology associated with CF on the pharmacokinetics (PK) of ITRA and its metabolite has not been previously evaluated. Objectives: 1) To estimate the population (pop) PK parameters for ITRA and its active metabolite OH-ITRA including relative bioavailability of the parent after administration of the parent by both capsule and solution and 2) to assess the performance of the optimal design. Methods: The study was a cross-over design in which 30 patients received the capsule on the first occasion and 3 days later the solution formulation. The design was constrained to have a maximum of 4 blood samples per occasion for estimation of the popPK of both ITRA and OH-ITRA. The sampling times for the population model were optimized previously using POPT v.2.0.[1] POPT is a series of applications that run under MATLAB and provide an evaluation of the information matrix for a nonlinear mixed effects model given a particular design. In addition it can be used to optimize the design based on evaluation of the determinant of the information matrix. The model details for the design were based on prior information obtained from the literature, which suggested that ITRA may have either linear or non-linear elimination. The optimal sampling times were evaluated to provide information for both competing models for the parent and metabolite and for both capsule and solution simultaneously. Blood samples were assayed by validated HPLC.[2] PopPK modelling was performed using FOCE with interaction under NONMEM, version 5 (level 1.1; GloboMax LLC, Hanover, MD, USA). The PK of ITRA and OH‑ITRA was modelled simultaneously using ADVAN 5. Subsequently three methods were assessed for modelling concentrations less than the LOD (limit of detection). These methods (corresponding to methods 5, 6 & 4 from Beal[3], respectively) were (a) where all values less than LOD were assigned to half of LOD, (b) where the closest missing value that is less than LOD was assigned to half the LOD and all previous (if during absorption) or subsequent (if during elimination) missing samples were deleted, and (c) where the contribution of the expectation of each missing concentration to the likelihood is estimated. The LOD was 0.04 mg/L. The final model evaluation was performed via bootstrap with re-sampling and a visual predictive check. The optimal design and the sampling windows of the study were evaluated for execution errors and for agreement between the observed and predicted standard errors. Dosing regimens were simulated for the capsules and the oral solution to assess their ability to achieve ITRA target trough concentration (Cmin,ss of 0.5-2 mg/L) or a combined Cmin,ss for ITRA and OH-ITRA above 1.5mg/L. Results and Discussion: A total of 241 blood samples were collected and analysed, 94% of them were taken within the defined optimal sampling windows, of which 31% where taken within 5 min of the exact optimal times. Forty six per cent of the ITRA values and 28% of the OH-ITRA values were below LOD. The entire profile after administration of the capsule for five patients was below LOD and therefore the data from this occasion was omitted from estimation. A 2-compartment model with 1st order absorption and elimination best described ITRA PK, with 1st order metabolism of the parent to OH-ITRA. For ITRA the clearance (ClItra/F) was 31.5 L/h; apparent volumes of central and peripheral compartments were 56.7 L and 2090 L, respectively. Absorption rate constants for capsule (kacap) and solution (kasol) were 0.0315 h-1 and 0.125 h-1, respectively. Comparative bioavailability of the capsule was 0.82. There was no evidence of nonlinearity in the popPK of ITRA. No screened covariate significantly improved the fit to the data. The results of the parameter estimates from the final model were comparable between the different methods for accounting for missing data, (M4,5,6)[3] and provided similar parameter estimates. The prospective application of an optimal design was found to be successful. Due to the sampling windows, most of the samples could be collected within the daily hospital routine, but still at times that were near optimal for estimating the popPK parameters. The final model was one of the potential competing models considered in the original design. The asymptotic standard errors provided by NONMEM for the final model and empirical values from bootstrap were similar in magnitude to those predicted from the Fisher Information matrix associated with the D-optimal design. Simulations from the final model showed that the current dosing regimen of 200 mg twice daily (bd) would provide a target Cmin,ss (0.5-2 mg/L) for only 35% of patients when administered as the solution and 31% when administered as capsules. The optimal dosing schedule was 500mg bd for both formulations. The target success for this dosing regimen was 87% for the solution with an NNT=4 compared to capsules. This means, for every 4 patients treated with the solution one additional patient will achieve a target success compared to capsule but at an additional cost of AUD $220 per day. The therapeutic target however is still doubtful and potential risks of these dosing schedules need to be assessed on an individual basis. Conclusion: A model was developed which described the popPK of ITRA and its main active metabolite OH-ITRA in adult CF after administration of both capsule and solution. The relative bioavailability of ITRA from the capsule was 82% that of the solution, but considerably more variable. To incorporate missing data, using the simple Beal method 5 (using half LOD for all samples below LOD) provided comparable results to the more complex but theoretically better Beal method 4 (integration method). The optimal sparse design performed well for estimation of model parameters and provided a good fit to the data.

Evoluzione di micotossine regolate ed emergenti attraverso i processi alimentari: dal campo alla digestione

Nel presente lavoro di tesi sono stati studiati diversi aspetti riguardanti micotossine regolate ed emergenti al fine di fornire informazioni circa la loro mitigazione dal campo al prodotto finito, focalizzando l’attenzione sul potenziale impatto del processo tecnologico. Successivamente, il loro ruolo tossicologico, ancora in discussione, è stato indagato attraverso l’applicazione di modelli gastrointestinali. In particolare, lo studio è stato rivolto a DON, micotossina più comune nel grano, DON-3-Glc, che rappresenta la sua principale forma modificata, e alla micotossina ENN B, maggiore rappresentante tra il gruppo delle cosiddette micotossine “emergenti”. Questo studio è stato quindi suddiviso in tre sezioni. La prima è stata rivolta allo sviluppo di esperimenti in serra effettuati su diversi genotipi di grano duro al fine di comprendere meglio il meccanismo di detossificazione dal DON e la resistenza delle diverse varietà ad una delle malattie più gravi che colpiscono questa specie (fusariosi della spiga). La seconda sezione ha riguardato lo studio del reale impatto di alcune filiere di produzione strategiche sul contenuto finale in micotossine. Inoltre, una strategia di mitigazione è stata messa a punto tenendo conto del possibile sviluppo di altri contaminanti legati al processo stesso e ottenendo un prodotto finito adeguato per il consumatore. Nell'ultima sezione di questo lavoro sono invece state effettuate delle indagini circa i possibili risvolti tossicologici di questi composti, valutando il loro destino durante la digestione umana.

Diabetes service provision:a qualitative study of newly diagnosed Type 2 diabetes patients' experiences and views

Aims: To explore newly diagnosed Type 2 diabetes patients' views about Scottish diabetes services at a time when these services are undergoing a major reorganization. To provide recommendations to maximize opportunities brought by the devolvement of services from secondary to primary healthcare settings. Methods: Qualitative panel study with 40 patients newly diagnosed with Type 2 diabetes, recruited from hospital clinics and general practices in Lothian, Scotland. Patients were interviewed three times over 1 year. The study was informed by grounded theory, which involves concurrent data collection and analysis. Results: Patients were generally satisfied with diabetes services irrespective of the types of care received. Most wanted their future care/review to be based in general practice for reasons of convenience and accessibility, although they dis-liked it when appointments were scheduled for different days. Many said they lacked the knowledge/confidence to know how to manage their diabetes in particular situations, and needed access to healthcare professionals who could answer their questions promptly. Patients expressed a need for primary care professionals who had diabetes expertise, but who had more time and were more accessible than general practitioners. Patients who had encountered practice lead nurses for diabetes spoke particularly positively of these professionals. Conclusions: Nurses with diabetes training are particularly well placed to provide information and support to patients in primary care. Ideally, practices should run 'one-stop' diabetes clinics to provide structured care, with easily accessible dietetics, podiatry and retinopathy screening. Newly diagnosed patients may benefit from being made more aware of specific services provided by charitable organizations such as Diabetes UK. © 2005 Diabetes UK.

Minimum description length, regularisation and multi-modal data

Conventional feed forward Neural Networks have used the sum-of-squares cost function for training. A new cost function is presented here with a description length interpretation based on Rissanen's Minimum Description Length principle. It is a heuristic that has a rough interpretation as the number of data points fit by the model. Not concerned with finding optimal descriptions, the cost function prefers to form minimum descriptions in a naive way for computational convenience. The cost function is called the Naive Description Length cost function. Finding minimum description models will be shown to be closely related to the identification of clusters in the data. As a consequence the minimum of this cost function approximates the most probable mode of the data rather than the sum-of-squares cost function that approximates the mean. The new cost function is shown to provide information about the structure of the data. This is done by inspecting the dependence of the error to the amount of regularisation. This structure provides a method of selecting regularisation parameters as an alternative or supplement to Bayesian methods. The new cost function is tested on a number of multi-valued problems such as a simple inverse kinematics problem. It is also tested on a number of classification and regression problems. The mode-seeking property of this cost function is shown to improve prediction in time series problems. Description length principles are used in a similar fashion to derive a regulariser to control network complexity.

Studies of molecular interactions using physical techniques

The investigations described in this thesis concern the molecular interactions between polar solute molecules and various aromatic compounds in solution. Three different physical methods were employed. Nuclear magnetic resonance (n.m.r.) spectroscopy was used to determine the nature and strength of the interactions and the geometry of the transient complexes formed. Cryoscopic studies were used to provide information on the stoichiometry of the complexes. Dielectric constant studies were conducted in an attempt to confirm and supplement the spectroscopic investigations. The systems studied were those between nitromethane, chloroform, acetonitrile (solutes) and various methyl substituted benzenes. In the n.m.r. work the dependence of the solute chemical shift upon the compositions of the solutions was determined. From this the equilibrium quotients (K) for the formation of each complex and the shift induced in the solute proton by the aromatic in the complex were evaluated. The thermodynamic parameters for the interactions were obtained from the determination of K at several temperatures. The stoichiometries of the complexes obtained from cryoscopic studies were found to agree with those deduced from spectroscopic investigations. For most systems it is suggested that only one type of complex, of 1:1 stiochiometry, predominates except that for the acetonitrile-benzene system a 1:2 complex is formed. Two sets of dielectric studies were conducted, the first to show that the nature of the interaction is dipole-induced dipole and the second to calculate K. The equilibrium quotients obtained from spectroscopic and dielectric studies are compared. Time-averaged geometries of the complexes are proposed. The orientation of solute, with respect to the aromatic for the 1:1 complexes, appears to be the one in which the solute lies symmetrically about the aromatic six-fold axis whereas for the 1:2 complex, a sandwich structure is proposed. It is suggested that the complexes are formed through a dipole-induced dipole interaction and steric factors play some part in the complex formation.

Application of thermal neutron radiography for the mass transport of moisture through freezing soil

This thesis reports on the development of a technique to evaluate hydraulic conductivities in a soil (Snowcal) subject to freezing conditions. The technique draws on three distinctly different disciplines, Nuclear Physics, Soil Physics and Remote Sensing to provide a non-destructive and reliable evaluation of hydraulic conductivity throughout a freezing test. Thermal neutron radiography is used to provide information on local water/ice contents at anytime throughout the test. The experimental test rig is designed so that the soil matrix can be radiated by a neutron beam, from a nuclear reactor, to obtain radiographs. The radiographs can then be interpreted, following a process of remote sensing image enhancement, to yield information on relative water/ice contents. Interpretation of the radiographs is accommodated using image analysis equipment capable of distinguishing between 256 shades of grey. Remote sensing image enhancing techniques are then employed to develop false colour images which show the movement of water and development of ice lenses in the soil. Instrumentation is incorporated in the soil in the form of psychrometer/thermocouples, to record water potential, electrical resistance probes to enable ice and water to be differentiated on the radiographs and thermocouples to record the temperature gradient. Water content determinations are made from the enhanced images and plotted against potential measurements to provide the moisture characteristic for the soil. With relevant mathematical theory pore water distributions are obtained and combined with water content data to give hydraulic conductivities. The values for hydraulic conductivity in the saturated soil and at the frozen fringe are compared with established values for silts and silty-sands. The values are in general agreement and, with refinement, this non-destructive technique could afford useful information on a whole range of soils. The technique is of value over other methods because ice lenses are actually seen forming in the soil, supporting the accepted theories of frost action. There are economic and experimental restraints to the work which are associated with the use of a nuclear facility, however, the technique is versatile and has been applied to the study of moisture transfer in porous building materials and could be further developed into other research areas.

Managerial job satisfaction:a longitudinal study

The study examines the job satisfaction of supervisors and managers in four organisations over time. It also considers the importance which they attached to different facets of their job. The major objectives were: To examine the constituent dimensions of job satisfaction at intervals over one year. To examine reasons for change inthe level of job satisfaction at intervals over one year. To provide information on job satisfaction for those concerned with job satisfaction policies. The sample consisted of one hundred and eight people. Each was interviewed on at least three occasions over the course of a year. Interviews took place at predetermined time intervals. The study shows that job satisfaction is dynamic over a relatively short period of time. The ratings which supervisors and managers gave to aspects of their job did not, however, all change by equal amounts or in the same direction. Changes in job satisfaction were associated with events experienced but it was the meaning of those events to correspondents which appeared to be particularly important. People tended to adopt a localised frame of reference when considering their work situation. Certain job variables, such as variety, were consistently and positively correlated with job satisfaction. With some other variables, the relationship varied across time. Frequently, age and job level moderated the association between independent variables and job satisfaction. Links were found between the quality of life and job satisfaction. There was a consistent positive association between job satisfaction and life satisfaction. However, the job was rarely considered to be the main factor contributing to a person's quality of life. The research highlights the difficulties and desirability of introducing standardised job satisfaction policies in the light of individual differences. In addition, it demonstrates that merely correlating variables with job satisfaction at one point in time may conceal complex relationships and meanings. A new measure of job satisfaction - whereby facets are assessed and rated relative to each other was also developed as part of this study.

Planning for cycling in the West Midlands

The issues involved in planning for pedal cyclists are examined with reference to the West Midlands County. Working with a local cycling campaign group, the researcher uses action research methods to investigate and influence the campaign. Development of cycle planning is traced through the literature, focusing on bicycle ownership, bicycle use and cycling policy. UK practice is contrasted with the integrated approach of other countries. An extensive bibliography is provided. Local authority cycle planning through the TPP process is systematically assessed over three years. This provides a context for the information regarding cycling in the West Midlands. Existing data is presented from the 1981 Census and local police road accident and bicycle theft records. The developing relationship between the local authority and the cycle campaign group is narrated in detail, explaining the problems that can beset efforts to improve conditions for cyclists. The researcher was closely involved in this interaction, particularly with policy and a major public inquiry. A survey of the Cycle Campaign Network indicates that the local group was not atypical. To provide information relevant to the local campaign and for effective local planning, a survey of 3,500 West Midlands residents was conducted using a novel combination of questionnaires and interviews. It shows that 1) Bicycle ownership and use is considerably higher than indicated by the 1978/9 National Travel Survey 2) Cycling is most import to certain disadvantaged sections of the community, particularly the young, those without access to a car and in the lower SEGs. The broader issues of transport policy are discussed, concluding that cycling is regarded as a marginal activity and that changes in general transport policy, land use planning and fiscal arrangements are necessary conditions for cycle planning to succeed. An integrated package of cycling measures involving engineering, education, enforcement and encouragement is also required. Recommendations are made concerning central government, local authorities and cycle campaign groups. Subjects for further research are identified.

Fibre optics sensors in tear electrolyte analysis:towards a novel point of care potassium sensor

The diagnosis of ocular disease is increasingly important in optometric practice and there is a need for cost effective point of care assays to assist in that. Although tears are a potentially valuable source of diagnostic information difficulties associated with sample collection and limited sample size together with sample storage and transport have proved major limitations. Progressive developments in electronics and fibre optics together with innovation in sensing technology mean that the construction of inexpensive point of care fibre optic sensing devices is now possible. Tear electrolytes are an obvious family of target analytes, not least to complement the availability of devices that make the routine measurement of tear osmolarity possible in the clinic. In this paper we describe the design, fabrication and calibration of a fibre-optic based electrolyte sensor for the quantification of potassium in tears using the ex vivo contact lens as the sample source. The technology is generic and the same principles can be used in the development of calcium and magnesium sensors. An important objective of this sensor technology development is to provide information at the point of routine optometric examination, which would provide supportive evidence of tear abnormality.

Involving the family in higher education:do they really matter?

In an ever-changing higher education (HE) environment, institutions are seeing the involvement of parents in students' education increasing. This may partly be due to tuition fees and the introduction of deferred variable tuition fees ("top-up fees") from 2006, and also because of the increased number of students choosing to remain in the family home for the duration of their studies. Many students see their families as the most important source of motivation and advice right through from school age to when they make decisions about HE. In the light of this increase in involvement, institutions need to provide information about, and access to, university to ensure that families are fully prepared and able to support their children throughout the university experience. In recognition of the vital role parents play, the Involving the Family project focuses on parents or key family members from groups currently under-represented in HE in order to increase their awareness and understanding of HE. This article evaluates research undertaken to investigate the views, perceptions and key concerns held by minority ethnic parents with regards to their children and participation in HE. The article then details how these results were utilised in the development of the Involving the Family project.

Managing supply chain integration:contemporary approaches and scope for further research

The editorial section of the special issue of Production Planning & Control discusses contemporary approaches and scope for further research into the management of supply chain integration. Supply chain integration (SCI) is one of the major challenges in enhancing supply chain performance. Building and sustaining competitive advantage requires strategic collaboration between supply chain partners and synchronized management of intra- and inter-organizational practices and processes. The special issue attempts to address some of the fundamental SCI questions, which include but are not limited to the fields of organizational collaboration, information technology (IT) use, and risk and vulnerability management. The editorial first reviews a few key articles on SCI to provide information about the existing state of knowledge on SCI along with scope for further research.