Pattern and correlates of inpatient admission during the initial acute phase of first-episode psychosis

Objectives: The first aim of this study was to examine the rate, pattern and correlates of inpatient admission during the first 3 months of treatment for first-episode psychosis (FEP). The second aim was to determine whether the pattern of inpatient admission during this period was associated with remission of psychotic symptoms or inpatient service use at 15-month follow-up. Method: One hundred and four consecutive patients with FEP at a specialist treatment service were approached to participate in a follow-up study. Patients were grouped on the basis of the pattern of inpatient admission (none, one, or multiple) during the first 3 months of treatment. Clinical ratings at baseline and 3-month follow-up, and ratings of remission of psychotic symptoms at 3 and 15-month follow-up, were available for two-thirds of the patients. Inpatient data for the 15-month follow-up period were derived from an electronic database for most patients (n = 98). Results: Eighty (76.9%) of the 104 patients were admitted to an inpatient unit during the first 3 months of treatment. Fifty-nine (56.7%) patients had a single admission and 21 (20.2%) had multiple admissions. At baseline, inpatient admission was associated with a diagnosis of affective psychosis and more severe behavioural and functional disturbance but not positive psychotic symptoms. Multiple admissions were associated with risks to self or others at baseline and 3-month follow-up, and lack of remission of positive symptoms at 3 and 15-month follow-up. There was no association between the pattern of inpatient admission during the initial 3-month period and inpatient service use during the following 12-month period. Conclusions: The substantial proportion of young patients with FEP admitted to hospital emphasizes the need for youth-friendly treatment environments and practices. Although patients with multiple admissions during the initial treatment period are less likely to achieve remission, these patients are no more likely to establish a pattern of revolving-door hospitalizations compared with other patients.

Dppa3 is a marker of pluripotency and has a human homologue that is expressed in germ cell tumours

We identified a transcript named 11M2 on the basis of its strong male-specific expression pattern in the developing mouse gonad. 11M2 was found to be expressed by gonad primordial germ cells (PGCs) of both sexes and down-regulated in female PGCs as they enter prophase I of the first meiotic division, similar to the expression of Oct4. Mouse EST analysis revealed expression only in early-stage embryos, embryonic stem cells and pre-meiotic germ cells. 11M2 corresponds to a recently reported gene variously known as PGC7, stella or Dppa3. We have identified the human orthologue of Dppa3 and find by human EST analysis that it is expressed in human testicular germ cell tumours but not in normal human somatic tissues. The expression patterns of mouse and human DPPA3, in undifferentiated embryonic cells, embryonic germ cells and adult germ cell tumours, together suggest a role for this gene in maintaining cell pluripotentiality.

S. cerevisiae as a model for studying mutations in the human gene OPA1 associated with dominant optic atrophy and for drug discovery

L’atrofia ottica dominante (ADOA) è una malattia mitocondriale caratterizzata da difetti visivi, che si manifestano durante l’infanzia, causati da progressiva degenerazione delle cellule gangliari della retina (RGC). ADOA è una malattia genetica associata, nella maggior parte dei casi, a mutazioni nel gene OPA1 che codifica per la GTPasi mitocondriale OPA1, appartenente alla famiglia delle dinamine, principalmente coinvolta nel processo di fusione mitocondriale e nel mantenimento del mtDNA. Finora sono state identificate più di 300 mutazioni patologiche nel gene OPA1. Circa il 50% di queste sono mutazioni missenso, localizzate nel dominio GTPasico, che si pensa agiscano come dominanti negative. Questa classe di mutazioni è associata ad una sindrome più grave nota come “ADOA-plus”. Nel lievito Saccharomyces cerevisiae MGM1 è l’ortologo del gene OPA1: nonostante i due geni abbiano domini funzionali identici le sequenze amminoacidiche sono scarsamente conservate. Questo costituisce una limitazione all’uso del lievito per lo studio e la validazione di mutazioni patologiche nel gene OPA1, infatti solo poche sostituzioni possono essere introdotte e studiate nelle corrispettive posizioni del gene di lievito. Per superare questo ostacolo è stato pertanto costruito un nuovo modello di S. cerevisiae, contenente il gene chimerico MGM1/OPA1, in grado di complementare i difetti OXPHOS del mutante mgm1Δ. Questo gene di fusione contiene una larga parte di sequenza corrispondente al gene OPA1, nella quale è stato inserito un set di nuove mutazioni trovate in pazienti affetti da ADOA e ADOA-plus. La patogenicità di queste mutazioni è stata validata sia caratterizzando i difetti fenotipici associati agli alleli mutati, sia la loro dominanza/recessività nel modello di lievito. A tutt’oggi non è stato identificato alcun trattamento farmacologico per la cura di ADOA e ADOA-plus. Per questa ragione abbiamo utilizzato il nostro modello di lievito per la ricerca di molecole che agiscono come soppressori chimici, ossia composti in grado di ripristinare i difetti fenotipici indotti da mutazioni nel gene OPA1. Attraverso uno screening fenotipico high throughput sono state testate due differenti librerie di composti chimici. Questo approccio, noto con il nome di drug discovery, ha permesso l’identificazione di 23 potenziali molecole attive.

Scale-up in emulsion polymerisation

The procedure for successful scale-up of batchwise emulsion polymerisation has been studied. The relevant literature on liquid-liquid dispersion on scale-up and on emulsion polymerisation has been crit1cally reviewed. Batchwise emulsion polymerisation of styrene in a specially built 3 litre, unbaffled, reactor confirmed that impeller speed had a direct effect on the latex particle size and on the reaction rate. This was noted to be more significant at low soap concentrations and the phenomenon was related to the depletion of micelle forming soap by soap adsorption onto the monomer emulsion surface. The scale-up procedure necessary to maintain constant monomer emulsion surface area in an unbaffled batch reactor was therefore investigated. Three geometrically similar 'vessels of 152, 229 and 305mm internal diameter, and a range of impeller speeds (190 to 960 r.p.m.) were employed. The droplet sizes were measured either through photomicroscopy or via a Coulter Counter. The power input to the impeller was also measured. A scale-up procedure was proposed based on the governing relationship between droplet diameter, impeller speed and impeller diameter. The relationships between impeller speed soap concentration, latex particle size and reaction rate were investigated in a series of polymerisations employing an amended commercial recipe for polystyrene. The particle size was determined via a light transmission technique. Two computer models, based on the Smith and Ewart approach but taking into account the adsorption/desorption of soap at the monomer surface, were successful 1n predicting the particle size and the progress of the reaction up to the end of stage II, i.e. to the end of the period of constant reaction rate.

Estimating additionality and leverage:between public and private sector equity finance in Ireland (2000 – 2002)

This paper aims to contribute to the debate about the role of the public sector in stimulating greater use of private sector equity for business start-up and growth in two ways. First, to examine the extent to which the provision of public sector equity finance enables individual firms to raise additional funds in the private sector market place. Second, to consider the methodological implications for an economic impact assessment of industrial policy interventions (especially those which include an equity component) at the level of the individual firm. We assess the extent to which there may be indirect positive effects (externalities) associated with public sector financial assistance to individual firms and if so how they distort standard evaluation methodologies designed to estimate the level of additionality of that support. The paper draws upon the results of a recent study of the impact of Enterprise Ireland (EI) financial assistance to indigenous Irish industry in the period 2000 to 2002. The paper demonstrates that a process of re-calibration is necessary in estimates of economic impact in order to account for these positive externalities and the result in this study was a ‘boost’ to additionality. In operational and conceptual terms, the study underlines the importance of the relationship between private and public sector sources of equity finance as an important dynamic in the attempt by industrial and regional policy to stimulate the number of firms with viable investment proposals accessing external equity finance.

A genetic algorithm approach to optimising component placement and retrieval sequence for chip shooter machines

A chip shooter machine in printed circuit board (PCB) assembly has three movable mechanisms: an X-Y table carrying a PCB, a feeder carrier with several feeders holding components and a rotary turret with multiple assembly heads to pick up and place components. In order to get the minimal placement or assembly time for a PCB on the machine, all the components on the board should be placed in a perfect sequence, and the components should be set up on a right feeder, or feeders since two feeders can hold the same type of components, and additionally, the assembly head should retrieve or pick up a component from a right feeder. The entire problem is very complicated, and this paper presents a genetic algorithm approach to tackle it.

WASOP, a qualitative methodology for waste minimization: systems thinking, HAZOP principles and nuclear waste

Purpose – The international nuclear community continues to face the challenge of managing both the legacy waste and the new wastes that emerge from ongoing energy production. The UK is in the early stages of proposing a new convention for its nuclear industry, that is: waste minimisation through closely managing the radioactive source which creates the waste. This paper proposes a new technique (called waste and source material operability study (WASOP)) to qualitatively analyse a complex, waste-producing system to minimise avoidable waste and thus increase the protection to the public and the environment. Design/methodology/approach – WASOP critically considers the systemic impact of up and downstream facilities on the minimisation of nuclear waste in a facility. Based on the principles of HAZOP, the technique structures managers' thinking on the impact of mal-operations in interlinking facilities in order to identify preventative actions to reduce the impact on waste production of those mal-operations.' Findings – WASOP was tested with a small group of experienced nuclear regulators and was found to support their qualitative examination of waste minimisation and help them to work towards developing a plan of action. Originality/value – Given the newness of this convention, the wider methodology in which WASOP sits is still in development. However, this paper communicates the latest thinking from nuclear regulators on decision-making methodology for supporting waste minimisation and is hoped to form part of future regulatory guidance. WASOP is believed to have widespread potential application to the minimisation of many other forms of waste, including that from other energy sectors and household/general waste.

Diffuse beta-amyloid (A beta) deposits and neurons: in situ secretion or diffusion of A beta?

The association between diffuse-type beta -amyloid (AP) deposits and neuronal cell bodies in Alzheimer's disease (AD) and Down's syndrome (DS) could result from the secretion of AP from clusters of neurons in situ or the diffusion of A beta from cell processes, glial cells or blood vessels. To decide between these hypotheses, spatial pattern analysis was used to study the relationship between the degree of clustering of neuronal cell bodies and the presence of diffuse deposits in the temporal lobe of patients with DS. Significant clustering of neuronal cell bodies was present in 17/24 (71%) of brain areas studied. in addition, in 23/24 (96%) of brain areas, there was a positive correlation between the presence of diffuse deposits and the density of neurons. Hence, the data support the hypothesis that diffuse deposits develop in situ mainly as a result of the secretion of A beta by local clusters of neurons rather than by significant diffusion. Furthermore, the size of a diffuse deposit is likely to be determined by the number of neurons within a cluster which secrete A beta. The number and density of neurons could also be a factor determining the evolution of a diffuse into a mature amyloid deposit.

Pragmatic approach to the development of robust real-time protocols

This research is concerned with the development of distributed real-time systems, in which software is used for the control of concurrent physical processes. These distributed control systems are required to periodically coordinate the operation of several autonomous physical processes, with the property of an atomic action. The implementation of this coordination must be fault-tolerant if the integrity of the system is to be maintained in the presence of processor or communication failures. Commit protocols have been widely used to provide this type of atomicity and ensure consistency in distributed computer systems. The objective of this research is the development of a class of robust commit protocols, applicable to the coordination of distributed real-time control systems. Extended forms of the standard two phase commit protocol, that provides fault-tolerant and real-time behaviour, were developed. Petri nets are used for the design of the distributed controllers, and to embed the commit protocol models within these controller designs. This composition of controller and protocol model allows the analysis of the complete system in a unified manner. A common problem for Petri net based techniques is that of state space explosion, a modular approach to both the design and analysis would help cope with this problem. Although extensions to Petri nets that allow module construction exist, generally the modularisation is restricted to the specification, and analysis must be performed on the (flat) detailed net. The Petri net designs for the type of distributed systems considered in this research are both large and complex. The top down, bottom up and hybrid synthesis techniques that are used to model large systems in Petri nets are considered. A hybrid approach to Petri net design for a restricted class of communicating processes is developed. Designs produced using this hybrid approach are modular and allow re-use of verified modules. In order to use this form of modular analysis, it is necessary to project an equivalent but reduced behaviour on the modules used. These projections conceal events local to modules that are not essential for the purpose of analysis. To generate the external behaviour, each firing sequence of the subnet is replaced by an atomic transition internal to the module, and the firing of these transitions transforms the input and output markings of the module. Thus local events are concealed through the projection of the external behaviour of modules. This hybrid design approach preserves properties of interest, such as boundedness and liveness, while the systematic concealment of local events allows the management of state space. The approach presented in this research is particularly suited to distributed systems, as the underlying communication model is used as the basis for the interconnection of modules in the design procedure. This hybrid approach is applied to Petri net based design and analysis of distributed controllers for two industrial applications that incorporate the robust, real-time commit protocols developed. Temporal Petri nets, which combine Petri nets and temporal logic, are used to capture and verify causal and temporal aspects of the designs in a unified manner.

The use of flow control devices to improve the flow pattern and throughput of sieve trays

Compared to packings trays are more cost effective column internals because they create a large interfacial area for mass transfer by the interaction of the vapour on the liquid. The tray supports a mass of froth or spray which on most trays (including the most widely used sieve trays) is not in any way controlled. The two important results of the gas/liquid interaction are the tray efficiency and the tray throughput or capacity. After many years of practical experience, both may be predicted by empirical correlations, despite the lack of understanding. It is known that the tray efficiency is in part determined by the liquid flow pattern and the throughput by the liquid froth height which in turn depends on the liquid hold-up and vapour velocity. This thesis describes experimental work on sieve trays in an air-water simulator, 2.44 m in diameter. The liquid flow pattern, for flow rates similar to those used in commercial scale distillation, was observed experimentally by direct observation; by water-cooling, to simulate mass transfer; use of potassium permanganate dye to observe areas of longer residence time; and by height of clear liquid measurements across the tray and in the downcomer using manometers. This work presents experiments designed to evaluate flow control devices proposed to improve the gas liquid interaction and hence improve the tray efficiency and throughput. These are (a) the use of intermediate weirs to redirect liquid to the sides of the tray so as to remove slow moving/stagnant liquid and (b) the use of vapour-directing slots designed to use the vapour to cause liquid to be directed towards the outlet weir thus reducing the liquid hold-up at a given rate i.e. increased throughput. This method also has the advantage of removing slow moving/stagnant liquid. In the experiments using intermediate weirs, which were placed in the centre of the tray. it was found that in general the effect of an intermediate weir depends on the depth of liquid downstream of the weir. If the weir is deeper than the downstream depth it will cause the upstream liquid to be deeper than the downstream liquid. If the weir is not as deep as deep as the downstream depth it may have little or no effect on the upstream depth. An intermediate weir placed at an angle to the direction of flow of liquid increases the liquid towards the sides of the tray without causing an increase in liquid hold-up/ froth height. The maximum proportion of liquid caused to flow sideways by the weir is between 5% and 10%. Experimental work using vapour-directing slots on a rectangular sieve tray has shown that the horizontal momentum that is imparted to the liquid is dependent upon the size of the slot. If too much momentum is transferred to the liquid it causes hydraulic jumps to occur at the mouth of the slot coupled with liquid being entrained, The use of slots also helps to eliminate the hydraulic gradient across sieve trays and provides a more uniform froth height on the tray. By comparing the results obtained of the tray and point efficiencies, it is shown that a slotted tray reduces both values by approximately 10%. This reduction is due to the fact that with a slotted tray the liquid has a reduced residence time Ion the tray coupled also with the fact that large size bubbles are passing through the slots. The effectiveness of using vapour-directing slots on a full circular tray was investigated by using dye to completely colour the biphase. The removal of the dye by clear liquid entering the tray was monitored using an overhead camera. Results obtained show that the slots are successful in their aim of reducing slow moving liquid from the sides of the tray, The net effect of this is an increase in tray efficiency. Measurements of slot vapour-velocity found it to be approximately equal to the hole velocity.

Rolling bearing vibrations: the effects of varying compliance, manufacturing tolerances and wear

In this study some common types of Rolling Bearing vibrations are analysed in depth both theoretically and experimentally. The study is restricted to vibrations in the radial direction of bearings having pure radial load and a positive radial clearance. The general vibrational behaviour of such bearings has been investigated with respect to the effects of varying compliance, manufacturing tolerances and the interaction between the bearing and the machine structure into which it is fitted. The equations of motion for a rotor supported by a bearing in which the stiffness varies with cage position has been set up and examples of solutions,obtained by digital simulation. is given. A method to calculate amplitudes and frequencies of vibration components due to out of roundness of the inner ring and varying roller diameters has been developed. The results from these investigations have been combined with a theory for bearing/machine frame interaction using mechanical impedance technique, thereby facilitating prediction of the vibrational behaviour of the whole set up. Finally. the effects of bearing fatigue and wear have been studied with particular emphasis on the use of vibration analysis for condition monitoring purposes. A number of monitoring methods have been tried and their effectiveness discussed. The experimental investigation was carried out using two purpose built rigs. For the purpose of analysis of the experimental measurements a digital mini computer was adapted for signal processing and a suite of programs was written. The program package performs several of the commonly used signal analysis processes and :include all necessary input and output functions.

Functional near vision assessment in presbyopia

The aim of this thesis was to develop standards of best practice for the subjective assessment of near visual function in presbyopia. Near visual acuity (VA) is a quick and simple measure but an assessment of the maximum reading speed and the smallest print size that can maintain this are equally important, to gain a better reflection of real world visual function. These metrics are dependent on the amplitude of accommodation (AoA) and often this must be evaluated using subjective techniques. Defocus curves are less susceptible than the push-up/push-down test to the influence of blur tolerance but their implementation must be standardised such that letter sequences and the order of lens presentation are randomised, to avoid memory effects, whilst the AoA should be quantified as the range of defocus for which only the best VA is maintained. In addition to such clinical assessments, subjective questionnaire evaluations are also important, to determine whether at least an individual’s needs are met. The Near Activity Visual Questionnaire (NAVQ) developed in this thesis can be used for this. Using these standardised near vision metrics it is shown that visual performance with monovision and multifocal contact lenses is comparable whilst initial outcomes of single optic ‘accommodating’ intraocular lens implantation are unlikely to be sustained in the long-term.

Access to start up finance for ethnic minority graduate entrepreneurs in the West Midlands: a gendered perspective

This aim of this paper, from a study funded by the National Council for Graduate Entrepreneurship (NCGE), is to explore access to finance for ethnic minority graduate entrepreneurs (EMGEs) with a particular focus on comparisons between different ethnic groups, and men and women. The authors interviewed selected individuals based upon a review of literature on finance for ethnic minority enterprise. A number of key results from the survey, in that EMGEs: • use external finance significantly (more so than non graduates) and encounter barriers in accessing finance at start-up, in particular those belonging to poor families. • rely excessively on personal savings and family finance, at the start-up and long after the start-up stage, that has implications for the optimal capital structure. • start up businesses that are, on average, larger than non-graduate enterprises and have the potential to reduce economic inactivity amongst the ethnic population. • have, in contrast to general graduate start-ups, a high level of unemployment, take a longer period of time to enter employment and there is a higher level of dissatisfaction with career progression. These findings raise the question whether the right financial advice is taken and whether this behaviour constrains EMGEs' expansion.

Paediatric 'care closer to home':stake-holder views and barriers to implementation

In this study we explore the views of NHS stakeholders on providing paediatric ‘care closer to home’ (CCTH), in community-based outpatient clinics delivered by consultants. Design: Semi-structured interviews and thematic framework analysis. Setting: UK specialist children's hospital and surrounding primary care trusts. Participants: 37 NHS stakeholders including healthcare professionals, managers, commissioners and executive team members. Results: Participants acknowledged that outreach clinics would involve a change in traditional ways of working and that the physical setting of the clinic would influence aspects of professional practice. Different models of CCTH were discussed, as were alternatives for improving access to specialist care. Participants supported CCTH as a good principle for paediatric outpatient services; however the challenges of setting up and maintaining community clinics meant they questioned how far it could be achieved in practice. Conclusions: The place of service delivery is both an issue of physical location and professional identity. Policy initiatives which ignore assumptions about place, power and identity are likely to meet with limited success.

Pulse oximetry as a screening test for congenital heart defects in newborn infants: a test accuracy study with evaluation of acceptability and cost-effectiveness

Background: Screening for congenital heart defects (CHDs) relies on antenatal ultrasound and postnatal clinical examination; however, life-threatening defects often go undetected. Objective: To determine the accuracy, acceptability and cost-effectiveness of pulse oximetry as a screening test for CHDs in newborn infants. Design: A test accuracy study determined the accuracy of pulse oximetry. Acceptability of testing to parents was evaluated through a questionnaire, and to staff through focus groups. A decision-analytic model was constructed to assess cost-effectiveness. Setting: Six UK maternity units. Participants: These were 20,055 asymptomatic newborns at = 35 weeks’ gestation, their mothers and health-care staff. Interventions: Pulse oximetry was performed prior to discharge from hospital and the results of this index test were compared with a composite reference standard (echocardiography, clinical follow-up and follow-up through interrogation of clinical databases). Main outcome measures: Detection of major CHDs – defined as causing death or requiring invasive intervention up to 12 months of age (subdivided into critical CHDs causing death or intervention before 28 days, and serious CHDs causing death or intervention between 1 and 12 months of age); acceptability of testing to parents and staff; and the cost-effectiveness in terms of cost per timely diagnosis. Results: Fifty-three of the 20,055 babies screened had a major CHD (24 critical and 29 serious), a prevalence of 2.6 per 1000 live births. Pulse oximetry had a sensitivity of 75.0% [95% confidence interval (CI) 53.3% to 90.2%] for critical cases and 49.1% (95% CI 35.1% to 63.2%) for all major CHDs. When 23 cases were excluded, in which a CHD was already suspected following antenatal ultrasound, pulse oximetry had a sensitivity of 58.3% (95% CI 27.7% to 84.8%) for critical cases (12 babies) and 28.6% (95% CI 14.6% to 46.3%) for all major CHDs (35 babies). False-positive (FP) results occurred in 1 in 119 babies (0.84%) without major CHDs (specificity 99.2%, 95% CI 99.0% to 99.3%). However, of the 169 FPs, there were six cases of significant but not major CHDs and 40 cases of respiratory or infective illness requiring medical intervention. The prevalence of major CHDs in babies with normal pulse oximetry was 1.4 (95% CI 0.9 to 2.0) per 1000 live births, as 27 babies with major CHDs (6 critical and 21 serious) were missed. Parent and staff participants were predominantly satisfied with screening, perceiving it as an important test to detect ill babies. There was no evidence that mothers given FP results were more anxious after participating than those given true-negative results, although they were less satisfied with the test. White British/Irish mothers were more likely to participate in the study, and were less anxious and more satisfied than those of other ethnicities. The incremental cost-effectiveness ratio of pulse oximetry plus clinical examination compared with examination alone is approximately £24,900 per timely diagnosis in a population in which antenatal screening for CHDs already exists. Conclusions: Pulse oximetry is a simple, safe, feasible test that is acceptable to parents and staff and adds value to existing screening. It is likely to identify cases of critical CHDs that would otherwise go undetected. It is also likely to be cost-effective given current acceptable thresholds. The detection of other pathologies, such as significant CHDs and respiratory and infective illnesses, is an additional advantage. Other pulse oximetry techniques, such as perfusion index, may enhance detection of aortic obstructive lesions.