The Research and Implementation of Maintenance Excellence on Clean Utility Systems in the Pharmaceutical Indusry

Maintenance Excellence is the implementation of best maintenance practices within industry; it is the balance of performance, risk, and cost to achieve an optimal solution. This thesis has been structured around the 5 main areas of maintenance excellence; it has documented all the important functions of the maintenance department that contributes towards maintenance excellence. Demonstrating maintenance excellence is a big achievement however demonstrating it on pharmaceutical clean utility systems with strict regulatory controls is a major challenge. Pharmaceutical production is one of the most heavily regulated industries. With such an emphasis on product quality in the pharmaceutical industry, and with such economical and health consequences of machine failure, the maintenance team plays a critical role in the success of the product. It is the maintenance department‟s responsibility to ensure the equipment is kept to a maximum operating condition. It must predict and prevent failures and repair any problems, which may already have led to a failure, while adhering to the rules and procedures set out by their respective regulatory bodies This thesis has explored the regulatory aspects of the business in-dept and presented a number of practical approaches to building in a world-class maintenance program whilst still ensuring the utmost of safety and quality to the patient

Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations

Objectives: After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time. Methods: The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates. Results: Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08). Conclusion: Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes

Under pressure : biomechanics of buoyancy in Bull Kelp (Nereocystis leutkeana)

Maintaining buoyancy with pneumatocysts is essential for subtidal seaweeds with long flexible thalli, such as Nereocystis luetkeana (Nereocystis), to achieve an upright stature and compete for light. However, as Nereocystis grows, pneumatocysts are exposed to significant changes in hydrostatic pressure. Exposure to changing hydrostatic pressure could cause complications since the pneumatocyst is filled with gases that may expand or contract, potentially causing pneumatocysts to break, flood, and no longer be buoyant. This study explored how Nereocystis pneumatocysts resist biomechanical stress and keep the developing sporophyte upright in the water. Throughout development, pneumatocysts had an internal pressure consistently less than atmospheric pressure (3 – 100 kPa), indicating pneumatocysts always experience compressional loads. The structural integrity and design of the pneumatocyst to resist buckling was assessed by measuring compressional modulus (material stiffness), calculating material stress, analyzing critical geometry, and estimating critical buckling pressure. Small pneumatocysts found at depth (inner radius = 0.8 - 0.9 cm; wall thickness = 0.2 cm) were demonstrated to have reached a critical size in development and are at greatest risk of buckling. Pneumatocysts do not adjust material properties or geometry to reduce wall stress, but they are naturally resistant to hydrostatic loads. Critically small pneumatocysts are estimated to buckle at 35 m depth, which was observed to be sporophytes’ lower limit in the field. Data suggest that hydrostatic pressure, not just light limitation, might explain the maximum depth to which Nereocystis is capable of growing. Pneumatocyst gas composition did not change throughout development, and contrary to previous studies, internal gas concentrations were different from the atmosphere with O₂, N₂, CO, and CO₂ concentrations of 59%, 40%, 1.6%, and 0.6% respectively. Furthermore, pneumatocyst surface area to volume ratio did not correlate with the exchange of gases produced from photosynthesis and respiration. As sporophytes grow, total buoyant force is steadily outpaced by the weight of growing thalli, and the risk of the pneumatocyst sinking increases. Adult sporophytes are estimated to sink when pneumatocysts volume reaches 1.3 L, close to the maximum observed size in the field.Science, Faculty ofBotany, Department ofGraduat

ESTIMATION OF THE CORRELATED COMPONENT OF RESPONSE VARIANCE FOR CATEGORICAL VARIABLE

This series contains research reports, written by or in cooperation with staff members of the Statistical Research Division, whose content may be of interest to the general statistical research community. The views reflected in these reports are not necessarily those of the Census Bureau nor do they necessarily represent Census Bureau statistical policy or practice. Inquiries may be addressed to the author(s) or the SRD Report Serie

Indicated benefits of bed epilepsy sensors to users of a telecare service in the Republic of Ireland

This paper examines, by reference to a telecare service evaluation in the Republic of Ireland, the role and potential of bed epilepsy sensors. It points to benefits for both users and carers that arise from the sensors both enabling speedy responses in the event of a seizure, and in their providing reassurance and a better quality of life for both parties