An in-depth characterisation of neonatal seizures by early continuous video-EEG analysis

Introduction Seizures are harmful to the neonatal brain; this compels many clinicians and researchers to persevere further in optimizing every aspects of managing neonatal seizures. Aims To delineate the seizure profile between non-cooled versus cooled neonates with hypoxic-ischaemic encephalopathy (HIE), in neonates with stroke, the response of seizure burden to phenobarbitone and to quantify the degree of electroclinical dissociation (ECD) of seizures. Methods The multichannel video-EEG was used in this research study as the gold standard to detect seizures, allowing accurate quantification of seizure burden to be ascertained in term neonates. The entire EEG recording for each neonate was independently reviewed by at least 1 experienced neurophysiologist. Data were expressed in medians and interquartile ranges. Linear mixed models results were presented as mean (95% confidence interval); p values <0.05 were deemed as significant. Results Seizure burden in cooled neonates was lower than in non-cooled neonates [60(39-224) vs 203(141-406) minutes; p=0.027]. Seizure burden was reduced in cooled neonates with moderate HIE [49(26-89) vs 162(97-262) minutes; p=0.020] when compared with severe HIE. In neonates with stroke, the background pattern showed suppression over the infarcted side and seizures demonstrated a characteristic pattern. Compared with 10 mg/kg, phenobarbitone doses at 20 mg/kg reduced seizure burden (p=0.004). Seizure burden was reduced within 1 hour of phenobarbitone administration [mean (95% confidence interval): -14(-20 to -8) minutes/hour; p<0.001], but seizures returned to pre-treatment levels within 4 hours (p=0.064). The ECD index in cooled, non-cooled neonates with HIE, stroke and in neonates with other diagnoses were 88%, 94%, 64% and 75% respectively. Conclusions Further research exploring the treatment effects on seizure burden in the neonatal brain is required. A change to our current treatment strategy is warranted as we continue to strive for more effective seizure control, anchored with use of the multichannel EEG as the surveillance tool.

An exploratory study on the impact of an early years' preschool intervention programme in the Republic of Ireland

Early years’ education has increasingly been identified as a mechanism to alleviate educational disadvantage in areas of social exclusion. Early years’ intervention programmes are now a common government social policy for addressing social problems (Reynolds, Mann, Miedel, and Smokowski, 1997). In particular, state provided early years’ programmes such as Head Start in the United States and Early Start in Ireland have been established to combat educational disadvantage for children experiencing poverty and socio-economic inequality. The focus of this research is on the long-term outcomes of an early years’ intervention programme in Ireland. It aims to assess whether participation in the programme enhances the life course of children at-risk of educational disadvantage. It involves an in-depth analysis of one Early Start project which was included in the original eight projects established by the Department of Education and Science in 1994. The study utilises a multi-group design to provide a detailed analysis of both the academic and social progress of programme participants. It examines programme outcomes from a number of perspectives by collecting the views of the three main stakeholders involved in the education process; students who participated in Early Start in 1994/5, their parents and their teachers. To contribute to understanding the impact of the programme from a community perspective interviews were also conducted with local community educators and other local early years’ services. In general, Early Start was perceived by all participants in this study as making a positive contribution to parent involvement in education and to strengthening educational capital in the local area. The study found that parents and primary school teachers identified aspects of school readiness as the main benefit of participation in Early Start and parents and teachers were very positive about the role of Early Start in preparing children for the transition to formal school. In addition to this, participation in Early Start appears to have made a positive contribution to academic attainment in Maths and Science at Junior Certificate level. Students who had participated in Early Start were also rated more highly by their second level teachers in terms of goal-setting and future orientation which are important factors in educational attainment. Early Start then can be viewed as providing a positive contribution to the long-term social and academic outcomes for its participants.

Reviewing mHealth in developing countries: A stakeholder perspective

Infrastructural deficiencies, limited access to medicare, and shortage of health care workers are just a few of the barriers to health care in developing countries. As a consequence, the burden of disease and its impact on the livelihoods and the economic productivity of people are staggering. mHealth has been extolled as one possible solution to overcoming these challenges, yet discussion of mHealth systems is often limited to specific tasks and user groups. To address this, we adopt a stakeholder perspective and analyze existing research on the mHealth process in developing countries. Specifically, we focus on three key stakeholder groups, i.e. healthcare workers, patients, and system developers. We perform an in-depth analysis of 60 peer-reviewed studies to determine the extent to which different mHealth stakeholder interactions are researched, and to identify high-level themes emerging within these interactions. This analysis illustrates two key gaps in existing mHealth research. First, while interactions involving healthcare workers and/or patients have received significant attention, relatively little research has looked at the role of patient-to-patient interactions. Second, the interactions between system developers and the other stakeholder groups are strikingly under-represented. We conclude by calling for more mHealth research that explicitly addresses these stakeholder interactions.

Irish neo-paganism: worldview, ritual and identity

Neo-paganism is a vibrant, dynamic global movement, which has had a significant cultural impact. Neo-paganism is an umbrella term for a wide range of spiritual practices, often described as nature- or earth-based spirituality. There are different “paths” or spiritual traditions within this movement, of which Druidry, Wicca and other forms of Pagan Witchcraft are included in this research. The present work is an ethnographic study of the worldview and ritual practices of the Irish neo-pagan community. It is an enquiry into (a) what characterises the neo-pagan worldview and (b) how this worldview is expressed through ritual behaviour. In order to collect data, the methodology of participant observation and ethnographic interviewing was employed. The thesis comprises a collection of “insider” accounts of what it is like to be a neo-pagan in Ireland and analysis of these narratives, which gives insight into different aspects of neopagan culture. In the discussion, the use of mythology is examined in regard to how mythic narrative is connected to identity formation. Irish cultural symbols are observed as resources utilised in the construction of the movement’s overall character. The interconnectedness of the natural landscape, the numinous and mythology gives rise to creative expression through various forms of neo-pagan artworks, which are discussed herein. The identifying features and key issues of Irish neo-pagan culture are addressed. These key issues are expressed as prominent themes and symbols of their discourse. Neo-pagan dialogue often features discussion of the relationship that this cultural group has with the Irish landscape, history, and indigenous and popular Irish religion. Some of the specific aspects of neo-pagan culture examined are magical worldview, the notion of holism, different types of ritual practices (festivals, life cycle rituals, healing), and material culture. The thesis presents an in-depth analysis of neopagan cultural expressions and their significance as cultural processes

A qualitative analysis of parental coping with an early diagnosis of hearing loss in Ireland

The recent implementation of Universal Neonatal Hearing Screening (UNHS) in all 19 maternity hospitals across Ireland has precipitated early identification of paediatric hearing loss in an Irish context. This qualitative, grounded theory study centres on the issue of parental coping as families receive and respond to (what is typically) an unexpected diagnosis of hearing loss in their newborn baby. Parental wellbeing is of particular concern as the diagnosis occurs in the context of recovery from birth and at a time when the parent-child relationship is being established. As the vast majority of children with a hearing loss are born into hearing families with no prior history of deafness, parents generally have had little exposure to childhood hearing loss and often experience acute emotional vulnerability as they respond to the diagnosis. The researcher conducted in-depth interviews primarily with parents (and to a lesser extent with professionals), as well as a follow-up postal questionnaire for parents. Through a grounded theory analysis of data, the researcher subsequently fashioned a four-stage model depicting the parental journey of receiving and coping with a diagnosis. The four stages (entitled Anticipating, Confirming, Adjusting and Normalising) are differentiated by the chronology of service intervention and defined by the overarching parental experience. Far from representing a homogenous trajectory, this four-stage model is multifaceted and captures a wide diversity of parental experiences ranging from acute distress to resilient hopefulness

Molecular genetic analysis of DNA alterations in Irish colorectal cancer

Colorectal cancer is the most common cause of death due to malignancy in nonsmokers in the western world. In 1995 there were 1,757 cases of colon cancer in Ireland. Most colon cancer is sporadic, however ten percent of cases occur where there is a previous family history of the disease. In an attempt to understand the tumorigenic pathway in Irish colon cancer patients, a number of genes associated with colorectal cancer development were analysed in Irish sporadic and HNPCC colon cancer patients. The hereditary forms of colon cancer include Familial adenomatous polyposis coli (FAP) and Hereditary Non-Polyposis Colon Cancer (HNPCC). Genetic analysis of the gene responsible for FAP, (the APC gene) has been previously performed on Irish families, however the genetic analysis of HNPCC families is limited. In an attempt to determine the mutation spectrum in Irish HNPCC pedigrees, the hMSH2 and hMLHl mismatch repair genes were screened in 18 Irish HNPCC families. Using SSCP analysis followed by DNA sequencing, five mutations were identified, four novel and a previously reported mutation. In families where a mutation was detected, younger asyptomatic members were screened for the presence of the predisposing mutation (where possible). Detection of mutations is particularly important for the identification of at risk individuals as the early diagnosis of cancer can vastly improve the prognosis. The sensitive and efficient detection of multiple different mutations and polymorphisms in DNA is of prime importance for genetic diagnosis and the identification of disease genes. A novel mutation detection technique has recently been developed in our laboratory. In order to assess the efficacy and application of the methodology in the analysis of cancer associated genes, a protocol for the analysis of the K-ras gene was developed and optimised. Matched normal and tumour DNA from twenty sporadic colon cancer patients was analysed for K-ras mutations using the Glycosylase Mediated Polymorphism Detection technique. Five mutations of the K-ras gene were detected using this technology. Sequencing analysis verified the presence of the mutations and SSCP analysis of the same samples did not identify any additional mutations. The GMPD technology proved to be highly sensitive, accurate and efficient in the identification of K-ras gene mutations. In order to investigate the role of the replication error phenomenon in Irish colon cancer, 3 polyA tract repeat loci were analysed. The repeat loci included a 10 bp intragenic repeat of the TGF-β-RII gene. TGF-β-RII is involved in the TGF-β epithelial cell growth pathway and mutation of the gene is thought to play a role in cell proliferation and tumorigenesis. Due to the presence of a repeat sequence within the gene, TGFB-RII defects are associated with tumours that display the replication error phenomenon. Analysis of the TGF-β-RII 10 bp repeat failed to identify mutations in any colon cancer patients. Analysis of the Bat26 and Bat 40 polyA repeat sequences in the sporadic and HNPCC families revealed that instability is associated with HNPCC tumours harbouring mismatch repair defects and with 20 % of sporadic colon cancer tumours. No correlation between K-ras gene mutations and the RER+ phenotype was detected in sporadic colon cancer tumours.

The quality of diabetes care in the community: practice, policy and culture

Aim: Diabetes is an important barometer of health system performance. This chronic condition is a source of significant morbidity, premature mortality and a major contributor to health care costs. There is an increasing focus internationally, and more recently nationally, on system, practice and professional-level initiatives to promote the quality of care. The aim of this thesis was to investigate the ‘quality chasm’ around the organisation and delivery of diabetes care in general practice, to explore GPs’ attitudes to engaging in quality improvement activities and to examine efforts to improve the quality of diabetes care in Ireland from practice to policy. Methods: Quantitative and qualitative methods were used. As part of a mixed methods sequential design, a postal survey of 600 GPs was conducted to assess the organization of care. This was followed by an in-depth qualitative study using semi-structured interviews with a purposive sample of 31 GPs from urban and rural areas. The qualitative methodology was also used to examine GPs’ attitudes to engaging in quality improvement. Data were analysed using a Framework approach. A 2nd observation study was used to assess the quality of care in 63 practices with a special interest in diabetes. Data on 3010 adults with Type 2 diabetes from 3 primary care initiatives were analysed and the results were benchmarked against national guidelines and standards of care in the UK. The final study was an instrumental case study of policy formulation. Semi-structured interviews were conducted with 15 members of the Expert Advisory Group (EAG) for Diabetes. Thematic analysis was applied to the data using 3 theories of the policy process as analytical tools. Results: The survey response rate was 44% (n=262). Results suggested care delivery was largely unstructured; 45% of GPs had a diabetes register (n=157), 53% reported using guidelines (n=140), 30% had formal call recall system (n=78) and 24% had none of these organizational features (n=62). Only 10% of GPs had a formal shared protocol with the local hospital specialist diabetes team (n=26). The lack of coordination between settings was identified as a major barrier to providing optimal care leading to waiting times, overburdened hospitals and avoidable duplication. The lack of remuneration for chronic disease management had a ripple effect also creating costs for patients and apathy among GPs. There was also a sense of inertia around quality improvement activities particularly at a national level. This attitude was strongly influenced by previous experiences of change in the health system. In contrast GP’s spoke positively about change at a local level which was facilitated by a practice ethos, leadership and special interest in diabetes. The 2nd quantitative study found that practices with a special interest in diabetes achieved a standard of care comparable to the UK in terms of the recording of clinical processes of care and the achievement of clinical targets; 35% of patients reached the HbA1c target of <6.5% compared to 26% in England and Wales. With regard to diabetes policy formulation, the evolving process of action and inaction was best described by the Multiple Streams Theory. Within the EAG, the formulation of recommendations was facilitated by overarching agreement on the “obvious” priorities while the details of proposals were influenced by personal preferences and local capacity. In contrast the national decision-making process was protracted and ambiguous. The lack of impetus from senior management coupled with the lack of power conferred on the EAG impeded progress. Conclusions: The findings highlight the inconsistency of diabetes care in Ireland. The main barriers to optimal diabetes management center on the organization and coordination of care at the systems level with consequences for practice, providers and patients. Quality improvement initiatives need to stimulate a sense of ownership and interest among frontline service providers to address the local sense of inertia to national change. To date quality improvement in diabetes care has been largely dependent the “special interest” of professionals. The challenge for the Irish health system is to embed this activity as part of routine practice, professional responsibility and the underlying health care culture.

Characterisation of bacteriophage-host interactions in Lactococcus lactis

Lactococcus lactis is used extensively world-wide for the production of fermented dairy products. Bacteriophages (phages) infecting L. lactis can result in slow or incomplete fermentations, or may even cause total fermentation failure. Therefore, bacteriophages disrupting L. lactis fermentation are of economic concern. This thesis employed a multifaceted approach to investigate various molecular aspects of phage-host interaction in L. lactis. The genome sequence of an Irish dairy starter strain, the prophage-cured L. lactis subsp. cremoris UC509.9, was studied. The 2,250,427 bp circular chromosome represents the smallest among its sequenced lactococcal equivalents. The genome displays clear genetic adaptation to the dairy niche in the form of extensive reductive evolution. Gene prediction identified 2066 protein-encoding genes, including 104 which showed significant homology to transposase-specifying genes. Over 9 % of the identified genes appear to be inactivated through stop codons or frame shift mutations. Many pseudogenes were found in genes that are assigned to carbohydrate and amino acid transport and metabolism orthologous groups, reflecting L. lactis UC509.9’s adaptation to the lactose and casein-rich dairy environment. Sequence analysis of the eight plasmids of L. lactis revealed extensive adaptation to the dairy environment. Key industrial phenotypes were mapped and novel lactococcal plasmid-associated genes highlighted. In addition to chromosomally-encoded bacteriophage resistance systems, six functional such systems were identified, including two abortive infection systems, AbiB and AbiD1, explaining the observed phage resistance of L. lactis UC509.9 Molecular analysis suggests that the constitutive expression of AbiB is not lethal to cells, suggesting the protein is expressed in an un/inactivated form. Analysis of 936 species phage sk1-escape mutants of AbiB revealed that all such mutants harbour mutations in orf6, which encodes the major capsid protein. Results suggest that the major capsid protein is required for activation of the AbiB system, although this requires furrther investigations. Temporal transcriptomes of L. lactis UC509.9 undergoing lytic infection with either one of two distinct bacteriophages, Tuc2009 and c2, was determined and compared to the transcriptome of uninfected UC509.9 cells. Whole genome microarrays performed at various time-points post-infection demonstrated a rather modest impact on host transcription. Alterations in the UC509.9 transcriptome during lytic infection appear phage-specific, with a relatively small number of differentially transcribed genes shared between infection with either Tuc2009 or c2. Transcriptional profiles of both bacteriophages during lytic infection was shown to generally correlate with previous studies and allowed the confirmation of previously predicted promoter sequences. Bioinformatic analysis of genomic regions encoding the presumed cell wall polysaccharide (CW PS) biosynthesis gene cluster of several strains of L. lactis was performed. Results demonstrate the presence of three dominant genetic types of this gene cluster, termed type A, B and C. These regions were used for the development of a multiplex PCR to identify CW PS genotype of various lactococcal strains. Analysis of 936 species phage receptor binding protein phylogeny (RBP) and CW PS genotype revealed an apparent correlation between RBP phylogeny and CW PS type, thereby providing a partial explanation for the observed narrow host range of 936 phages. Further analysis of the genetic locus encompassing the presumed CW PS biosynthesis operon of eight strains identified as belonging to the CW PS C (geno)type, revealed the presence of a variable region among the examined strains. The obtained comparative analysis allowed for the identification of five subgroups of the C type, named C1 to C5. We purified an acidic polysaccharide from the cell wall of L. lactis 3107 (C2 subtype) and confirmed that it is structurally different from the CW PS of the C1 subtype L. lactis MG1363. Combinations of genes from the variable region of C2 subtype were amplified from L. lactis 3107 and introduced into a mutant of the C1 subtype L. lactis NZ9000 (a direct derivative of MG1363) deficient in CW PS biosynthesis. The resulting recombinant mutant synthesized a CW PS with a composition characteristic for that of the C2 subtype L. lactis 3107 and not the wildtype C1 L. lactis NZ9000. The recombinant mutant exhibited a changed phage resistance/sensitivity profile consistent with that of L. lactis 3107, which unambiguously demonstrated that L. lactis 3107 CW PS is the host cell surface receptor of two bacteriophages belonging to the P335 species as well as phages that are member of the 936 species. The research presented in this thesis has significantly advanced our understanding of L. lactis bacteriophage-host interactions in several ways. Firstly, the examination of plasmidencoded bacteriophage resistance systems has allowed inferences to be made regarding the mode of action of AbiB, thereby providing a platform for further elucidation of the molecular trigger of this system. Secondly, the phage infection transcriptome data presented, in addition to previous work, has made L. lactis a model organism in terms of transcriptomic studies of bacteriophage-host interactions. And finally, the research described in this thesis has for the first time explicitly revealed the nature of a carbohydrate bacteriophage receptor in L. lactis, while also providing a logical explanation for the observed narrow host ranges exhibited by 936 and P335 phages. Future research in discerning the structures of other L. lactis CW PS, combined with the determination of the molecular interplay between receptor binding proteins of these phages and CW PS will allow an in depth understanding of the mechanism by which the most prevalent lactococcal phages identify and adsorb to their specific host.

Synthesis and characterisation of novel superficially porous silica based stationary phases for use in liquid chromatography

The concept of pellicular particles was suggested by Horváth and Lipsky over fifty years ago. The reasoning behind the idea of these particles was to improve column efficiency by shortening the pathways analyte molecules can travel, therefore reducing the effect of the A and C terms. Several types of shell particles were successfully marketed around this time, however with the introduction of high quality fully porous silica under 10 μm, shell particles faded into the background. In recent years a new generation of core shell particles have become popular within the separation science community. These particles allow fast and efficient separations that can be carried out on conventional HPLC systems. Chapter 1 of this thesis introduces the chemistry of chromatographic stationary phases, with an emphasis on silica bonded phases, particularly focusing on the current state of technology in this area. The main focus is on superficially porous silica particles as a support material for liquid chromatography. A summary of the history and development of these particles over the past few decades is explored, along with current methods of synthesis of shell particles. While commercial shell particles have a rough outer surface, Chapter 2 focuses on the novel approach to growth of smooth surface superficially porous particles in a step-by-step manner. From the Stöber methodology to the seeded growth technique, and finally to the layer-bylayer growth of the porous shell. The superficially porous particles generated in this work have an overall diameter of 2.6 μm with a 350 nm porous shell; these silica particles were characterised using SEM, TEM and BET analysis. The uniform spherical nature of the particles along with their surface area, pore size and particle size distribution are examined in this chapter. I discovered that these smooth surface shell particles can be synthesised to give comparable surface area and pore size in comparison to commercial brands. Chapter 3 deals with the bonding of the particles prepared in Chapter 2 with C18 functionality; one with a narrow and one with a wide particle size distribution. This chapter examines the chromatographic and kinetic performance of these silica stationary phases, and compares them to a commercial superficially porous silica phase with a rough outer surface. I found that the particle size distribution does not seem to be the major contributor to the improvement in efficiency. The surface morphology of the particles appears to play an important role in the packing process of these particles and influences the Van Deemter effects. Chapter 4 focuses on the functionalisation of 2.6 μm smooth surface superficially porous particles with a variety of fluorinated and phenyl silanes. The same processes were carried out on 3.0 μm fully porous silica particles to provide a comparison. All phases were accessed using elemental analysis, thermogravimetric analysis, nitrogen sorption analysis and chromatographically evaluated using the Neue test. I observed comparable results for the 2.6 μm shell pentaflurophenyl propyl silica when compared to 3.0 μm fully porous silica. Chapter 5 moves towards nano-particles, with the synthesis of sub-1 μm superficially porous particles, their characterisation and use in chromatography. The particles prepared are 750 nm in total with a 100 nm shell. All reactions and testing carried out on these 750 nm core shell particles are also carried out on 1.5 μm fully porous particles in order to give a comparative result. The 750 nm core shell particles can be synthesised quickly and are very uniform. The main drawback in their use for HPLC is the system itself due to the backpressure experienced using sub – 1 μm particles. The synthesis of modified Stöber particles is also examined in this chapter with a range of non-porous silica and shell silica from 70 nm – 750 nm being tested for use on a Langmuir – Blodgett system. These smooth surface shell particles have only been in existence since 2009. The results displayed in this thesis demonstrate how much potential smooth surface shell particles have provided more in-depth optimisation is carried out. The results on packing studies reported in this thesis aims to be a starting point for a more sophisticated methodology, which in turn can lead to greater chromatographic improvements.

Leisure and surveillance in Irish childhoods: A cross-class study of Cork city

This research provides an interpretive cross-class analysis of the leisure experience of children, aged between six and ten years, living in Cork city. This study focuses on the cultural dispositions underpinning parental decisions in relation to children’s leisure activities, with a particular emphasis on their child-surveillance practices. In this research, child-surveillance is defined as the adult monitoring of children by technological means, physical supervision, community supervision, or adult supervised activities (Nelson, 2010; Lareau, 2003; Fotel and Thomsen, 2004). This research adds significantly to understandings of Irish childhood by providing the first in-depth qualitative analysis of the surveillance of children’s leisure-time. Since the 1990s, international research on children has highlighted the increasingly structured nature of children’s leisure-time (Lareau, 2011; Valentine & McKendrick, 1997). Furthermore, research on child-surveillance has found an increase in the intensive supervision of children during their unstructured leisure-time (Nelson, 2010; Furedi, 2008; Fotel and Thomsen, 2004). This research bridges the gap between these two key bodies of literature, providing a more integrated overview of children’s experience of leisure in Ireland. Using Bourdieu’s (1992) model of habitus, field and capital, the dispositions that shape parents’ decisions about their children’s leisure time are interrogated. The holistic view of childhood adopted in this research echoes the ‘Whole Child Approach’ by analysing the child’s experience within a wider set of social relationships including family, school, and community. Underpinned by James and Prout’s (1990) paradigm on childhood, this study considers Irish children’s agency in negotiating with parents’ decisions regarding leisure-time. The data collated in this study enhances our understanding of the micro-interactions between parents and children and, the ability of the child to shape their own experience. Moreover, this is the first Irish sociological research to identify and discuss class distinctions in children’s agentic potential during leisure-time.

Current methods and advances in forecasting of wind power generation

Wind power generation differs from conventional thermal generation due to the stochastic nature of wind. Thus wind power forecasting plays a key role in dealing with the challenges of balancing supply and demand in any electricity system, given the uncertainty associated with the wind farm power output. Accurate wind power forecasting reduces the need for additional balancing energy and reserve power to integrate wind power. Wind power forecasting tools enable better dispatch, scheduling and unit commitment of thermal generators, hydro plant and energy storage plant and more competitive market trading as wind power ramps up and down on the grid. This paper presents an in-depth review of the current methods and advances in wind power forecasting and prediction. Firstly, numerical wind prediction methods from global to local scales, ensemble forecasting, upscaling and downscaling processes are discussed. Next the statistical and machine learning approach methods are detailed. Then the techniques used for benchmarking and uncertainty analysis of forecasts are overviewed, and the performance of various approaches over different forecast time horizons is examined. Finally, current research activities, challenges and potential future developments are appraised.

Beyond simple imaging with energetic beams – nanopatterning, correlative microscopy and statistical analysis of inclusions

Electron microscopy (EM) has advanced in an exponential way since the first transmission electron microscope (TEM) was built in the 1930’s. The urge to ‘see’ things is an essential part of human nature (talk of ‘seeing is believing’) and apart from scanning tunnel microscopes which give information about the surface, EM is the only imaging technology capable of really visualising atomic structures in depth down to single atoms. With the development of nanotechnology the demand to image and analyse small things has become even greater and electron microscopes have found their way from highly delicate and sophisticated research grade instruments to key-turn and even bench-top instruments for everyday use in every materials research lab on the planet. The semiconductor industry is as dependent on the use of EM as life sciences and pharmaceutical industry. With this generalisation of use for imaging, the need to deploy advanced uses of EM has become more and more apparent. The combination of several coinciding beams (electron, ion and even light) to create DualBeam or TripleBeam instruments for instance enhances the usefulness from pure imaging to manipulating on the nanoscale. And when it comes to the analytic power of EM with the many ways the highly energetic electrons and ions interact with the matter in the specimen there is a plethora of niches which evolved during the last two decades, specialising in every kind of analysis that can be thought of and combined with EM. In the course of this study the emphasis was placed on the application of these advanced analytical EM techniques in the context of multiscale and multimodal microscopy – multiscale meaning across length scales from micrometres or larger to nanometres, multimodal meaning numerous techniques applied to the same sample volume in a correlative manner. In order to demonstrate the breadth and potential of the multiscale and multimodal concept an integration of it was attempted in two areas: I) Biocompatible materials using polycrystalline stainless steel and II) Semiconductors using thin multiferroic films. I) The motivation to use stainless steel (316L medical grade) comes from the potential modulation of endothelial cell growth which can have a big impact on the improvement of cardio-vascular stents – which are mainly made of 316L – through nano-texturing of the stent surface by focused ion beam (FIB) lithography. Patterning with FIB has never been reported before in connection with stents and cell growth and in order to gain a better understanding of the beam-substrate interaction during patterning a correlative microscopy approach was used to illuminate the patterning process from many possible angles. Electron backscattering diffraction (EBSD) was used to analyse the crystallographic structure, FIB was used for the patterning and simultaneously visualising the crystal structure as part of the monitoring process, scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed to analyse the topography and the final step being 3D visualisation through serial FIB/SEM sectioning. II) The motivation for the use of thin multiferroic films stems from the ever-growing demand for increased data storage at lesser and lesser energy consumption. The Aurivillius phase material used in this study has a high potential in this area. Yet it is necessary to show clearly that the film is really multiferroic and no second phase inclusions are present even at very low concentrations – ~0.1vol% could already be problematic. Thus, in this study a technique was developed to analyse ultra-low density inclusions in thin multiferroic films down to concentrations of 0.01%. The goal achieved was a complete structural and compositional analysis of the films which required identification of second phase inclusions (through elemental analysis EDX(Energy Dispersive X-ray)), localise them (employing 72 hour EDX mapping in the SEM), isolate them for the TEM (using FIB) and give an upper confidence limit of 99.5% to the influence of the inclusions on the magnetic behaviour of the main phase (statistical analysis).