Analysis of haemochromatosis mutations in the North West population

Background: Hereditary haemochromatosis is a heritable disorder caused by an inborn error in the metabolism of iron. It results in over absorption of iron by the body, which can manifest clinically as fatigue, arthritis, diabetes and cardiovascular problems. The highest prevalence for the genetic mutations that cause hereditary haemochromatosis can be found in the Irish population. Individuals with diabetes may also have haemochromatosis (and vice versa), due to the bi-directional relationship between iron metabolism and glucose metabolism. Objectives: To determine the incidence of the three haemochromatosis mutations C282Y, H63D & S65C, in a population from the North West of Ireland and to investigate whether there is an increased frequency of these three mutations in a diabetic population from the same region. Method: DNA was extracted from 500 whole blood samples (250 diabetic samples and 250 ‘control’ samples) using a Wizard™ kit. PCR was conducted utilising specific primers for each mutation and in accordance with a set protocol. Following amplification, PCR product was subjected to restriction endonuclease digestion, where different restriction enzymes (Rsa I, Nde II & Hinf I) were employed to determine the HFE genotype status of samples. Results: The incidence of C282Y homozygosity (1/83) and C282Y heterozygosity (1/6) in the ‘control’ group was similar to those reported for the general Irish population (1/83 and 1/5, respectively). Incidences of H63D homozygotes and H63D heterozygotes or ‘carriers’ in the diabetic population were greater than that of the ‘control’ population. A significant finding of this study was that of an incidence of 1/32 S65C carriers in the control population. This is, to our knowledge, the highest incidence of the genotype reported to date in the general Irish population. Statistical analysis showed that there was no significant differences between the HFE genotype frequencies in the Diabetic and Control Populations. Conclusion: Results of the study concord with published literature in terms of C282Y homozygosity and C282Y heterozygosity in the general Irish population. An increased frequency of the H63D mutation in diabetic individuals was also found but was not statistically significant. The biochemical effect of the H63D mutation is still unknown. The significance of such a high incidence of S65C carriers in the ‘control’ population warrants further investigation.

Implementation of the I.S. EN 16001:2009 energy management standard into GlaxoSmithKline (GSK) Ltd, Cork

As manufacturers face an increasingly competitive environment, they seek out opportunities to reduce production costs without negatively affecting the yield or the quality of their finished products. The challenge of maintaining high product quality while simultaneously reducing production costs can often be met through investments in energy efficient technologies and energy efficiency practices. Energy management systems can offer both technological and best practice efficiencies in order to achieve substantial savings. A strong energy management system provides a solid foundation for an organisation to reduce production costs and improve site efficiency. The I.S EN16001 energy management standard specifies the requirements for establishing, implementing, maintaining and improving an energy management system and represents the latest best practice for energy management in Ireland. The objective of the energy management system is to establish a systematic approach for improving energy performance continuously. The I.S EN16001 standard specifies the requirements for continuous improvement through using energy more efficiently. The author analysed how GlaxoSmithKline’s (GSK) pharmaceutical manufacturing facility in Cork implemented the I.S. EN16001 energy management system model, and defined how energy saving opportunities where identified and introduced to improve efficiency performance. The author performed an extensive literature research in order to determine the current status of the pharmaceutical industry in Ireland, the processes involved in pharmaceutical manufacturing, the energy users required for pharmaceutical manufacturing and the efficiency measures that can be applied to these energy users in order to reduce energy consumption. The author then analysed how energy management standards are introduced to industry and critically analysed the driving factors for energy management performance in Ireland through case studies. Following an investigation as to how the I.S. EN16001 energy management standard is operated in GSK, a critical analysis of the performance achieved by the GSK energy management system is undertaken in order to determine if implementing the I.S EN16001 standard accelerates achieving energy savings. Since its introduction, the I.S. EN16001 model for energy management has enabled GSK to monitor, target and identify energy efficiency opportunities throughout the site. The model has put in place an energy management system that is continuously reviewed for improvement and to date has reduced GSK’s site operations cost by over 30% through technical improvements and generating energy awareness for smarter energy consumption within the GSK Cork site. Investment in I.S. EN16001 has proved to be a sound business strategy for GSK especially in today's manufacturing environment.

The role of biomass and biorefineries in a sustainable future

Some o f the biggest issues facing humanity in the 21st century include energy security, global warming and resource scarcity. These issues will affect every nation and Ireland is no exception. There is much research underway to uncover technologies that will allow the world to overcome such problems, but none offer the flexibility o f biomass. Unlike other sustainable technologies, which offer a solution to one or at most two o f the above problems, biomass as demonstrated by the author, can play a part in mitigating all o f the above problems. It has been known for some time that biomass can be used in various ways as a form o f renewable energy, but with the development o f biorefineries biomass can be used to produce material as well as fuel products. In this report the author has looked at the viability and benefits o f biomass, bioenergy and biorefining in Ireland. The author has demonstrated that such technologies when implemented correctly are sustainable from an economic, environmental and societal point o f view. The author has shown in this thesis that abundant supplies o f biomass make bio re fineries a viable business opportunity in Ireland and has shown how a number o f biorefinery scenarios have the potential to be extremely profitable. The author has evaluated the profitability o f material product-based bio re fineries as well as fuel productbased configurations. The author demonstrated that value-added co-products help to make bio refineries profitable even when excise-relief is not granted on bio fuels. In this thesis the author has revealed some o f the problems that bioenergy and biorefineries have had to overcome to date and examines challenges that remain for bioenergy and biorefining, and looks at the future opportunities for bio fuels. This report concludes that biomass and biorefining has exciting business potential while offering unique opportunities to mitigate the problems o f the future.

Search for very high energy Gamma radiation from the Starburst Galaxy IC 342

This thesis describes a search for very high energy (VHE) gamma-ray emission from the starburst galaxy IC 342. The analysis was based on data from the 2003 — 2004 observing season recorded using the Whipple 10-metre imaging atmospheric Cherenkov telescope located on Mount Hopkins in southern Arizona. IC 342 may be classed as a non-blazar type galaxy and to date only a few such galaxies (M 87, Cen A, M 82 and NGC 253) have been detected as VHE gamma-ray sources. Analysis of approximately 24 hours of good quality IC 342 data, consisting entirely of ON/OFF observations, was carried out using a number of methods (standard Supercuts, optimised Supercuts, scaled optimised Supercuts and the multivariate kernel analysis technique). No evidence for TeV gamma-ray emission from IC 342 was found. The significance was 0.6 a with a nominal rate of 0.04 ± 0.06 gamma rays per minute. The flux upper limit above 600 GeV (at 99.9 % confidence) was determined to be 5.5 x 10-8 m-2 s-1, corresponding to 8 % of the Crab Nebula flux in the same energy range.

Development of a rehabilitation system for the red mud waste generated at the Aughinish Alumina Bayer Plant

Aughinish Alumina Limited (AAL) have an obligation by terms of their Integrated Pollution Control Licence (IPCL) and Planning Permission to establish vegetation on the red mud stack at their plant at Aughinish, Co. Limerick. High pH and high exchangeable sodium percentage are the main known factors limiting the establishment of vegetation on red mud. Gypsum addition has been known to assist in alleviating these problems in other countries. However, there is no experience or published information on red mud rehabilitation under Irish conditions. Red mud with organic and inorganic waste-derived ameliorants as well as selected grassland species were examined under laboratory controlled environment conditions as well as in field plot trials. Also, in order that it would be economically achievable, the research utilised locally available waste products as the organic amendments. Screening trials found that physical constraints severely limit plant germination and growth in red mud. Gypsum addition effectively lowers pH, exchangeable sodium percentage and the availability of A1 and Fe in the mud. A strong relationship between pH, ESP and A1 levels was also found. Gypsum addition increased germination percentages and plant growth for all species investigated. Greenhouse trials demonstrated that organic wastes alone did not greatly improve conditions for plant growth but when used in conjunction with gypsum plant performances for all species investigated was significantly increased. There was a high mortality rate for grasses in non-gypsum treatments. An emerging trend of preferential iron uptake and calcium deficiency in non-gypsum treatments was found at pot screening stage. Species also displayed manganese and magnesium deficiencies.