Analysis of clinical isolates of Propionibacterium acnes by optimised RAPD

Random amplification of polymorphic DNA (RAPD) was evaluated as a genotypic method for typing clinical strains of Propionibacterium acnes. RAPD can suffer from problems of reproducibility if parameters are not standardised. In this study the reaction conditions were optimised by adjusting template DNA concentration and buffer constituents. All isolates were typeable using the optimised RAPD protocol which was found to be highly discriminatory (Simpson's diversity index, 0.98) and reproducible. Typing of P. acnes by optimised RAPD is an invaluable tool for the epidemiological investigation of P. acnes for which no other widely accepted method currently exists. © 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

The production of clinical dextran using membrane processes

Clinical dextran is used as a blood volume expander. The British Pharmacopeia (BP) specification for this product requires the amount of dextran below 12,000 MW and above 98,000 MW to be strictly controlled. Dextran is presently fractionated industrially using ethanol precipitation. The aim of this work was to develop an ultrafiltration system which could replace the present industrial process. Initially these molecular weight (MW) bands were removed using batch ultrafiltration. A large number of membranes were tested. The correct BP specification could be achieved using these membranes but there was a significant loss of saleable material. To overcome this problem a four stage ultrafiltration cascade (UFC) was used. This work is the first known example of a UFC being used to remove both the high and low MW dextran. To remove the high MW material it was necessary to remove 90% of the MW distribution and retain the remaining 10%. The UFC significantly reduced the amount of dialysate required. To achieve the correct specification below 12,000 MW, the UFC required only 2.5 - 3.0 diavolumes while the batch system required 6 - 7. The UFC also improved the efficiency of the fractionation process. The UFC could retain up to 96% of the high MW material while the batch system could only retain 82.5% using the same number of diavolumes. On average the UFC efficiency was approximately 10% better than the equivalent batch system. The UFC was found to be more predictable than the industrial process and the specification of the final product was easier to control. The UFC can be used to improve the fractionation of any polymer and also has several other potential uses including enzyme purification. A dextransucrase bioreactor was also developed. This preliminary investigation highlighted the problems involved with the development of a successful bioreactor for this enzyme system.

Topographic, haemodynamic and psychophysical investigation of glaucomatous optic neuropathy

Loss of optic nerve head (ONH) axons in primary open angle glaucoma (POAG) has been attributed to both mechanical and vascular factors. Confocal scanning laser ophthalmoscopy (cSLO) provides a promising tool for the topographic follow-up of the ONH in glaucoma, while scanning laser Doppler flowmetry (SLDF) facilitates the rapid non-invasive assessment of retinal capillary blood flow. The purposes of these investigations were to optimise the techniques and explore their potential to classify and monitor disease. Preliminary investigations explored the reproducibility and validity of cSLO and SLDF and showed that: For cSLO: In a model eye, measurements are accurate over a range of axial lengths. For best reproducibility, seven images per visit are required, with a contour line located on Elschnig's scleral ring and transferred automatically between images. For SLDF: Three perfusion images are required for optimum reproducibility. Physiological changes induced by gas perturbation can be measured. Cross-sectional comparison of groups of normal subjects and early POAG patients showed that: cSLO parameters differentiate the early POAG group. Blood volume measured by SLDF showed group differences in superior nasal retina only. Longitudinal investigation of ONH topography, haemodynamic and visual field indices in normal subjects and POAG patients showed that: cSLO detects topographical change over time more frequently in the POAG group. Important parameters include: C:D area ratio, cup and rim area, mean depth in contour, volumes above and below reference and surface. Factor analysis identified "cup" and "rim" factors that can be used to detect change over time in individual patients. Blood flow changes were most apparent in the inferior nasal peripapillary retina of the POAG group. Perimetry is of clinical value for the identification of glaucoma but is less sensitive than cSLO for monitoring glaucomatous change.

An investigation of the pressaccidic spike potential

A large negative spike potential, which is closely related to the onset of saccadic eyemovements, can be recorded from electrodes adjacent to the orbits. This potential, thepresaccadic spike potential, has often been regarded as an artefact related to eyemovement recordings and little work has been performed to establish its normal waveformand parameters. A positive spike potential, exactly coincident with the frontal negativespike, has also been recorded from electrodes positioned over the posterior scalp andthere has been some debate regarding any possible relationship between the twopotentials. The frontal spike potential has been associated with motor unit activity in theextraocular muscles prior to the saccade. This thesis investigates both the large anteriorand smaller posterior spike potentials and relates these recordings to the saccadic eyemovements associated with them. The anterior spike potential has been recorded from normal subjects to ascertain its normallatency and amplitude parameters for both horizontal and vertical saccades. A relationshipbetween saccade size and spike potential amplitude is described, the spike potentialamplitude reducing with smaller saccades. The potential amplitude also reduces withadvancing age. Studying the topographical distribution of the spike potential across thescalp shows the posterior spike activity may arise from potential spread of the larger frontalspike potential. Spike potential recordings from subjects with anomalous eye movements further implicate the extraocular muscles and their innervation in the generation of the spike potential. These recordings indicate that the spike potential may have some use as a clinical recording from patients with disease conditions affecting either their extraocular muscles or the innervational pathways to these muscles. Further recordings of the potential are necessary, however, to determine the exact nature of the changes which may occur with such conditions.

Investigation into visual defects attributed to Vigabatrin

Vigabatrin (VGB) is a transaminase inhibitor that elicits its anitepileptic effect by increasing GABA concentrations in the brain and retina. - Assess whether certain factors predispose patients to develop severe visual field loss. - Develop a sensitive algorithm for investigating the progression of visual field loss. - Determine the most sensitive clinical regimen for diagnosing VGB-attributed visual field loss. - Investigate whether the reports of central retinal sparing are accurate. The investigations have resulted in a number of significant findings: - The anatomical evidence in combination with the pattern of visual field loss suggests that the damage induced by VGB therapy occurs at retinal level, and is most likely a toxic effect. - The quantitative algorithm, designed within the course of this investigation, provided increased sensitivity in determining the severity of visual field loss. - Maximum VGB dose predisposes patients to develop severe visual field loss. - The SITA Standard algorithm was found to be as sensitive and significantly faster, in diagnosing visual field defects attributed to VGB, when compared to the Full Threshold algorithm. The Full Threshold was found to be the most repeatable between visits. - The normal SWAP 10-2 database provided an effective method of differentiating SWAP defects. - SWAP, FDT and the mfERG have increased sensitivity in detecting visual field loss attributed to VGB. The pattern of visual field loss from these investigations suggests that VGB produces a diffuse effect across the retina including subtle central abnormalities and more severe peripheral defects. - Abnormalities detected using the mfERG have suggested that VGB adversely affects the photoreceptors Müller, amacrine and ganglion cells in the retina. An urgent review of the manufacturers recommended maximum dose for VGB is required.

An investigation into the impact of safety features on the ergonomics of surgical scalpels

In the case of surgical scalpels, blade retraction and disposability have been incorporated into a number of commercial designs to address sharps injury and infection transmission issues. Despite these new designs, the traditional metal reusable scalpel is still extensively used and this paper attempts to determine whether the introduction of safety features has compromised the ergonomics and so potentially the take-up of the newer designs. Examples of scalpels have been analysed to determine the ergonomic impact of these design changes. Trials and questionnaires were carried out using both clinical and non-clinical user groups, with the trials making use of assessment of incision quality, cutting force, electromyography and video monitoring. The results showed that ergonomic performance was altered by the design changes and that while these could be for the worse, the introduction of safety features could act as a catalyst to encourage re-evaluation of the ergonomic demands of a highly traditional product.

A mixed methods investigation of parental factors in non-attendance at general paediatric hospital outpatient appointments

Non-attendance at paediatric outpatient appointments results in delayed diagnosis and treatment, putting children at risk of avoidable ill health, and incurring considerable health service costs. Links between missed appointments and clinical, socio-demographic, and access-related factors have been indicated, but parental cognitions associated with non-attendance have yet to be investigated. The aims of this project were to evaluate the effectiveness and theoretical bases of existing interventions designed to reduce non-attendance; to consider the ways in which missed appointments are managed by healthcare providers; to explore parents’ beliefs and experiences of attending and missing appointments; and to investigate the factors underlying these beliefs. A systematic literature review focusing on non-attendance interventions was conducted Within a mixed methods framework, interviews were conducted with healthcare professionals, subsequent interviews were conducted with parents who had attended or missed a General Paediatric outpatient appointment, and a cross-sectional questionnaire study of parents’ beliefs was implemented. The systematic review revealed that text message appointment reminders are effective at reducing non-attendance rates, but that no interventions have thus far been developed using theories of behaviour. Healthcare professionals recognised both barriers and parents’ beliefs as influences on attendance, but also believed there were ‘types’ of families who miss appointments. Healthcare professionals disagreed somewhat about how non-attendance should best be managed. The parent interview study found six themes. The findings reflect parents’ perceptions about the importance of attending and of their ability to attend. The results of the questionnaire study corroborate this structure of beliefs as the analysis produced two factors, the perceived ‘worth’ of attending and anticipated ‘worry’ when attending. This thesis demonstrates an original approach to investigating non-attendance at children’s outpatient appointments, using mixed methods and adopting a psychological rather than service-use perspective. The findings contribute to Health Psychology theory and offer recommendations for healthcare providers.

Solid oral forms availability in children:a cost saving investigation

AIM: To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. METHOD: Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. RESULTS: Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of 5K and 8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of 238K and 410K (single institution). CONCLUSION: Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules.

The clinical competency of practicing and nonpracticing faculty of associate degree schools of nursing

This study assesses and describes the perception of clinical competency and the relationship to clinical practice of full-time nursing faculty in the associate degree nursing programs in the state of Florida. The study was developed around one major hypothesis and four research questions. The Hygiene-Motivators Theory proposed by Herzberg, Mausner, and Snyderman (1959) provided the conceptual framework to explain factors that would motivate a person to expand workload and maintain job satisfaction.^ Data were collected from the 244 faculty members teaching full-time at the 15 associate degree schools of nursing accredited by the National League for Nursing in the state of Florida. A total of 186 faculty (76%) responded and 175 (72%) cases were used for data analysis.^ Two instruments were modified and combined for the investigation. The instruments were the Faculty Perception of Practice Questionnaire (Parascenzo, 1983) and a three-part Attributes Deemed Necessary for Faculty to Proclaim Clinical Competency (Smith, 1991) scale. Computer analyses employing descriptive and inferential statistics were performed.^ The findings revealed that faculty were closely divided as to practice activities with more faculty nonpracticing than practicing. Factors identified as impediments to increased clinical practice were identified as teaching load and personal/family responsibilities that lead to a lack of time and lack of opportunity. Those faculty who practice did so as moonlighters in positions that would not require advanced training. Both the practicing and nonpracticing faculty reported a high level of satisfaction with their activities as a means of maintaining clinical practice. While both groups reported a high level of expertise, those practicing faculty perceived themselves to be more clinically competent on the attributes of knowledge, skills, and on the total attribute scale. It was further revealed that perception of competency declined with the length of time spent out of practice. There was no difference in the two groups on the attributes of values/attitude. ^

Collimation of a D-D Neutron Generator for Clinical Implementation of Neutron Stimulated Emission Computed Tomography: a Monte Carlo Study

This work is an investigation into collimator designs for a deuterium-deuterium (DD) neutron generator for an inexpensive and compact neutron imaging system that can be implemented in a hospital. The envisioned application is for a spectroscopic imaging technique called neutron stimulated emission computed tomography (NSECT).

Previous NSECT studies have been performed using a Van-de-Graaff accelerator at the Triangle Universities Nuclear Laboratory (TUNL) in Duke University. This facility has provided invaluable research into the development of NSECT. To transition the current imaging method into a clinically feasible system, there is a need for a high-intensity fast neutron source that can produce collimated beams. The DD neutron generator from Adelphi Technologies Inc. is being explored as a possible candidate to provide the uncollimated neutrons. This DD generator is a compact source that produces 2.5 MeV fast neutrons with intensities of 1012 n/s (4π). The neutron energy is sufficient to excite most isotopes of interest in the body with the exception of carbon and oxygen. However, a special collimator is needed to collimate the 4π neutron emission into a narrow beam. This work describes the development and evaluation of a series of collimator designs to collimate the DD generator for narrow beams suitable for NSECT imaging.

A neutron collimator made of high-density polyethylene (HDPE) and lead was modeled and simulated using the GEANT4 toolkit. The collimator was designed as a 52 x 52 x 52 cm3 HDPE block coupled with 1 cm lead shielding. Non-tapering (cylindrical) and tapering (conical) opening designs were modeled into the collimator to permit passage of neutrons. The shape, size, and geometry of the aperture were varied to assess the effects on the collimated neutron beam. Parameters varied were: inlet diameter (1-5 cm), outlet diameter (1-5 cm), aperture diameter (0.5-1.5 cm), and aperture placement (13-39 cm). For each combination of collimator parameters, the spatial and energy distributions of neutrons and gammas were tracked and analyzed to determine three performance parameters: neutron beam-width, primary neutron flux, and the output quality. To evaluate these parameters, the simulated neutron beams are then regenerated for a NSECT breast scan. Scan involved a realistic breast lesion implanted into an anthropomorphic female phantom.

This work indicates potential for collimating and shielding a DD neutron generator for use in a clinical NSECT system. The proposed collimator designs produced a well-collimated neutron beam that can be used for NSECT breast imaging. The aperture diameter showed a strong correlation to the beam-width, where the collimated neutron beam-width was about 10% larger than the physical aperture diameter. In addition, a collimator opening consisting of a tapering inlet and cylindrical outlet allowed greater neutron throughput when compared to a simple cylindrical opening. The tapering inlet design can allow additional neutron throughput when the neck is placed farther from the source. On the other hand, the tapering designs also decrease output quality (i.e. increase in stray neutrons outside the primary collimated beam). All collimators are cataloged in measures of beam-width, neutron flux, and output quality. For a particular NSECT application, an optimal choice should be based on the collimator specifications listed in this work.

Investigation and Management of Erythrocytosis

An absolute erythrocytosis is present when the red cell mass is greater than 125 % of the predicted value for sex and body mass. It can have a primary or secondary and congenital or acquired cause. New causes particularly congenital continue to be discovered and investigated. Investigation for the cause starts with repeat and confirmation of the raised hemoglobin and measurement of an erythropoietin level to indicate whether to pursue primary or secondary causes and then further investigations as appropriate. Management options include low dose aspirin and venesection. Specific management advice is available for certain specific clinical situations.

Bacteriologic investigation of the effects of sodium hypochlorite and chlorhexidine during the endodontic treatment of teeth with apical periodontitis

SIQUEIRA JR. et al. Bacteriologic investigation of the effects of sodium hypochlorite and chlorhexidine during the endodontic treatment of teeth with apical periodontitis. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., v. 104, n. 1, p. 122-130, 2007.

An Investigation into the Implementation of CYP-IAPT Routine Outcome Measures in their First Year of Integration into Child Psychotherapy Practice

This thesis examines the impact on child and adolescent psychotherapists within CAMHS of the introduction of routine outcome measures (ROMs) associated with the Children and Young People’s Improving access to Psychological Therapies programme (CYP-IAPT). All CAMHS therapists working within a particular NHS mental health Trust1 were required to trial CYP-IAPT ROMs as part of their everyday clinical practice from October 2013-September 2014. During this period considerable freedom was allowed as to which of the measures each therapist used and at what frequency. In order to assess the impact of CYP-IAPT ROMs on child psychotherapy, I conducted semi-structured interviews with eight psychotherapists within a particular CAMHS partnership within one NHS Trust. Each statement was coded and grouped according to whether it related to initial (generic) assessment, goal setting / monitoring, monitoring on-going progress, therapeutic alliance, or to issues concerning how data might be used or interpreted by managers and commissioners. Analysis of interviews revealed greatest concern about session-by session ROMs, as these are felt to impact most significantly on psychotherapy; therapists felt that session-by-session ROMs do not take account of negative transference relationships, they are overly repetitive and used to reward / punish the therapist. Measures used at assessment and review were viewed as most compatible with psychotherapy, although often experienced as excessively time consuming. The Goal Based Outcome Measure was generally experienced as compatible with psychotherapy so long as goals are formed collaboratively between therapist and young person. There was considerable anxiety about how data may be (mis)used and (mis)interpreted by managers and commissioners, for example to end treatment prematurely, trigger change of therapist in the face of negative ROMs data, or to damage psychotherapy. Use of ROMs for short term and generic work was experienced as less intrusive and contentious.

Clinical utility of amyloid PET imaging in the differential diagnosis of atypical dementias and its impact on caregivers

La maladie d’Alzheimer (MA) se caractérise pathologiquement par l’accumulation de plaques amyloïde dans le cerveau. La tomographie par émission de positrons (TEP) permet d’imager les plaques amyloïde in vivo. Le but de ce projet est d’évaluer le rôle de la TEP amyloïde dans le processus diagnostique de la MA dans des cas de démences atypiques. Le deuxième but de ce projet est de déterminer l’impact de la révélation d’un diagnostic plus certain chez les proches aidants. 28 patients sans diagnostic malgré une investigation exhaustive ont été sélectionnées et imagées avec le traceur amyloïde 18F-NAV4694 (âge 59,3 ans, é-t. 5,8; MMSE 21.4, é-t 6.0). Les neurologues référents documentaient par la suite tout changement de niveau de certitude, de diagnostic, de traitement et/ou de prise en charge. Les proches aidants consentants ont été rencontrés subséquemment, et un questionnaire avec une échelle de Likert a été utilisé afin de documenter l’impact de l’imagerie leur perception de la maladie. Notre cohorte a été également divisée entre amyloïde positifs (14/28) et négatifs (14/28). Un changement de diagnostic a lieu dans 9/28 cas (32,1% :17.8% ont changé de MA à non-MA, 14,3% de non-MA à MA). Il y avait une augmentation significative (p<0,05) de 44% dans la certitude du neurologue suite à cet examen. Un changement de prise en charge a été obtenu dans 20/28 (71,4%) des cas. Bien que non significatifs statistiquement, un impact favorable sur les proches-aidants a été noté. Cette étude suggère que l’imagerie amyloïde a un rôle bénéfique dans les cas de démences atypiques n’ayant pu être élucidés avec les techniques d’investigations actuellement recommandées. De plus, le processus a été perçu positivement par les proches aidants, notamment en encourageant du temps de qualité avec leurs personnes chères. Ceci illustre un rôle prometteur des biomarqueurs, qui sont de plus en plus explorés.