The analytical approach of the European Court of Human Rights in surveillance cases—the implications, justifications, and future of the Court’s reasoning, with a focus on the legislative impact in Ireland

A notable feature of the surveillance case law of the European Court of Human Rights has been the tendency of the Court to focus on the “in accordance with the law” aspect of the Article 8 ECHR inquiry. This focus has been the subject of some criticism, but the impact of this approach on the manner in which domestic surveillance legislation has been formulated in the Party States has received little scholarly attention. This thesis addresses that gap in the literature through its consideration of the Interception of Postal Packets and Telecommunications Messages (Regulation) Act, 1993 and the Criminal Justice (Surveillance) Act, 2009. While both Acts provide several of the safeguards endorsed by the European Court of Human Rights, this thesis finds that they suffer from a number of crucial weaknesses that undermine the protection of privacy. This thesis demonstrates how the focus of the European Court of Human Rights on the “in accordance with the law” test has resulted in some positive legislative change. Notwithstanding this fact, it is maintained that the legality approach has gained prominence at the expense of a full consideration of the “necessary in a democratic society” inquiry. This has resulted in superficial legislative responses at the domestic level, including from the Irish government. Notably, through the examination of a number of more recent cases, this project discerns a significant alteration in the interpretive approach adopted by the European Court of Human Rights regarding the application of the necessity test. The implications of this development are considered and the outlook for Irish surveillance legislation is assessed.

Redefining military memorials and commemoration and how they have changed since the 19th century with a focus on Anglo-American practice

This thesis is a study of military memorials and commemoration with a focus on Anglo-American practice. The main question is: How has history defined military memorials and commemoration and how have they changed since the 19th century. In an effort to resolve this, the work examines both historic and contemporary forms of memorials and commemoration and establishes that remembrance in sites of collective memory has been influenced by politics, conflicts and religion. Much has been written since the Great War about remembrance and memorialization; however, there is no common lexicon throughout the literature. In order to better explain and understand this complex subject, the work includes an up-to-date literature review and for the first time, terminologies are properly explained and defined. Particular attention is placed on recognizing important military legacies, being familiar with spiritual influences and identifying classic and new signs of remembrance. The thesis contends that commemoration is composed of three key principles – recognition, respect and reflection – that are intractably linked to the fabric of memorials. It also argues that it is time for the study of memorials to come of age and proposes Memorialogy as an interdisciplinary field of study of memorials and associated commemorative practices. Moreover, a more modern, adaptive, General Classification System is presented as a means of identifying and re-defining memorials according to certain groups, types and forms. Lastly, this thesis examines how peacekeeping and peace support operations are being memorialized and how the American tragic events of 11 September 2001 and the war in Afghanistan have forever changed the nature of memorials and commemoration within Canada and elsewhere. This work goes beyond what has been studied and written about over the last century and provides a deeper level of analysis and a fresh approach to understanding the field of Memorialogy.

P-glycoprotein inhibition as a strategy to increase drug delivery across the blood-brain barrier: focus on antidepressants

Depression is among the leading causes of disability worldwide. Currently available antidepressant drugs have unsatisfactory efficacy, with up to 60% of depressed patients failing to respond adequately to treatment. Emerging evidence has highlighted a potential role for the efflux transporter P-glycoprotein (P-gp), expressed at the blood-brain barrier (BBB), in the aetiology of treatment-resistant depression. In this thesis, the potential of P-gp inhibition as a strategy to enhance the brain distribution and pharmacodynamic effects of antidepressant drugs was investigated. Pharmacokinetic studies demonstrated that administration of the P-gp inhibitors verapamil or cyclosporin A (CsA) enhanced the BBB transport of the antidepressants imipramine and escitalopram in vivo. Furthermore, both imipramine and escitalopram were identified as transported substrates of human P-gp in vitro. Contrastingly, human P-gp exerted no effect on the transport of four other antidepressants (amitriptyline, duloxetine, fluoxetine and mirtazapine) in vitro. Pharmacodynamic studies revealed that pre-treatment with verapamil augmented the behavioural effects of escitalopram in the tail suspension test (TST) of antidepressant-like activity in mice. Moreover, pre-treatment with CsA exacerbated the behavioural manifestation of an escitalopram-induced mouse model of serotonin syndrome, a serious adverse reaction associated with serotonergic drugs. This finding highlights the potential for unwanted side-effects which may occur due to increasing brain levels of antidepressants by P-gp inhibition, although further studies are needed to fully elucidate the mechanism(s) at play. Taken together, the research outlined in this thesis indicates that P-gp may restrict brain concentrations of escitalopram and imipramine in patients. Moreover, we show that increasing the brain distribution of an antidepressant by P-gp inhibition can result in an augmentation of antidepressant-like activity in vivo. These findings raise the possibility that P-gp inhibition may represent a potentially beneficial strategy to augment antidepressant treatment in clinical practice. Further studies are now warranted to evaluate the safety and efficacy of this approach.

Modified cyclodextrins as novel non-viral vectors for neuronal siRNA delivery: focus on Huntington’s disease

Huntington’s Disease (HD) is a rare autosomal dominant neurodegenerative disease caused by the expression of a mutant Huntingtin (muHTT) protein. Therefore, preventing the expression of muHTT by harnessing the specificity of the RNA interference (RNAi) pathway is a key research avenue for developing novel therapies for HD. However, the biggest caveat in the RNAi approach is the delivery of short interfering RNA (siRNAs) to neurons, which are notoriously difficult to transfect. Indeed, despite the great advances in the field of nanotechnology, there remains a great need to develop more effective and less toxic carriers for siRNA delivery to the Central Nervous System (CNS). Thus, the aim of this thesis was to investigate the utility of modified amphiphilic β-cyclodextrins (CDs), oligosaccharide-based molecules, as non-viral vectors for siRNA delivery for HD. Modified CDs were able to bind and complex siRNAs forming nanoparticles capable of delivering siRNAs to ST14A-HTT120Q cells and to human HD fibroblasts, and reducing the expression of the HTT gene in these in vitro models of HD. Moreover, direct administration of CD.siRNA nanoparticles into the R6/2 mouse brain resulted in significant HTT gene expression knockdown and selective alleviation of rotarod motor deficits in this mouse model of HD. In contrast to widely used transfection reagents, CD.siRNA nanoparticles only induced limited cytotoxic and neuroinflammatory responses in multiple brain-derived cell-lines, and also in vivo after single direct injections into the mouse brain. Alternatively, we have also described a PEGylation-based formulation approach to further stabilise CD.siRNA nanoparticles and progress towards a systemic delivery nanosystem. Resulting PEGylated CD.siRNA nanoparticles showed increased stability in physiological saltconditions and, to some extent, reduced protein-induced aggregation. Taken together, the work outlined in this thesis identifies modified CDs as effective, safe and versatile siRNA delivery systems that hold great potential for the treatment of CNS disorders, such as HD.

Aspects of the biology of Mya arenaria and Ensis spp. (Mollusca; Bivalvia) in the Irish Sea and adjacent areas

This study was undertaken to investigate the general biology, including the reproductive cycle and health status, of two clam taxa in Irish waters, with particular reference to the Irish Sea area. Monthly samples of the soft shell clam, Mya arenaria, were collected from Bannow Bay, Co. Wexford, Ireland, for sixteen months, and of the razor clam, Ensis spp. from the Skerries region (Irish Sea) between June 2010 and September 2011. In 2010, M. arenaria in Bannow Bay matured over the summer months, with both sexes either ripe or spawning by August. The gonads of both sexes of E. siliqua developed over autumn and winter 2010, with the first spawning individuals being recorded in January 2011. Two unusually cold winters, followed by a warmer than average spring, appear to have affected M. arenaria and E. siliqua gametogenesis at these sites. It was noted that wet weight of E. siliqua dropped significantly in the summer of both 2010 and 2011, after spawning, which may impact on the economic viability of fishing during this period. Additional samples of M. arenaria were collected at Flaxfort (Ireland), and Ensis spp. at Oxwich (Wales), and the pathology of all clams was examined using both histological and molecular methods. No pathogenic conditions were observed in M. arenaria while Prokaryote inclusions, trematode parasites, Nematopsis spp. and inflammatory pathologies were observed at low incidences in razor clams from Ireland but not from Wales; the first time these conditions have been reported in Ensis spp. in northern European waters. Mya arenaria from sites in Europe and eastern and western North America were investigated for genetic variation using both mitochondrial (cytochrome oxidase I (COI) and 16S ribosomal RNA genes) and nuclear markers (10 microsatellite loci). Both mitochondrial CO1 and all nuclear markers showed reduced levels of variation in certain European samples, with significant differences in haplotype and allelic composition between most samples, particularly those from the two different continents, but with the same common haplotypes or alleles throughout the range. The appearance of certain unique rare haplotypes and microsatellite alleles in the European samples suggest a complicated origin involving North American colonization but also possible southern European Pleistocene refugia. Specimens of Ensis spp. were obtained from five coastal areas around Ireland and Wales and species-specific PCR primers were used to amplify the internal transcribed spacer region 1 (ITS1) and the mitochondrial DNA CO1 gene and all but 15 razor clams were identified as Ensis siliqua. Future investigations should focus on continued monitoring of reproductive biology and pathology of the two clam taxa (in particular, to assess the influence of environmental change), and on genetics of southern European M. arenaria and sequencing the CO1 gene in Ensis individuals to clarify species identity

Substance misuse in young people in Ireland - a focus on benzodiazepines

Benzodiazepines are a class of drugs that are prescribed for the treatment of anxiety and insomnia. Due to the powerful tolerance that can develop as a result of sustained use, benzodiazepines can also be dependence-forming. Benzodiazepine dependence can occur from prescribed and from recreational use, and is a significant issue for young people. The consequences of benzodiazepine dependence include cognitive and learning impairment, depressive symptoms, and increased suicide risk. Despite these risks, the nature of youth benzodiazepine use has not been explored to the same extent as other drugs. A review of existing Irish literature revealed that benzodiazepines are one of the five most recreationally-used drugs among young people. Analyses of young people attending a treatment centre indicated that young attendees from urban areas were more likely to be referred to the centre because of benzodiazepines than rural attendees. Further examination of the centre’s attendees showed that regular benzodiazepine users experienced more paranoia, loss of interest in sport, and pallor than non-regular users. Analysis of benzodiazepine prescribing to young people revealed that approximately one in seven young people were prescribed benzodiazepines for periods greater than recommended by national guidelines. Young benzodiazepine users discussed in interviews that they took benzodiazepines to escape from negative feelings and that they are generally taken in a social setting. Further interviews with youth counsellors and general practitioners highlighted that both family and community attitude to benzodiazepine use can impact on a young person’s benzodiazepine usage. Suggestions for reducing benzodiazepine use such as psychological alternatives to medication, public awareness campaigns and prescribing restrictions are provided. Future research can elaborate upon this work to determine other methods of reducing youth benzodiazepine use and the damage that it causes to the young people themselves, but also to their families, their community, and society at large.

The study of molecular variation in Atlantic salmon (Salmo salar L.) and brown trout (Salmo trutta L.)

Polymorphic microsatellite DNA loci were used here in three studies, one on Salmo salar and two on S. trutta. In the case of S. salar, the survival of native fish and non-natives from a nearby catchment, and their hybrids, were compared in a freshwater common garden experiment and subsequently in ocean ranching, with parental assignment utilising microsatellites. Overall survival of non-natives was 35% of natives. This differential survival was mainly in the oceanic phase. These results imply a genetic basis and suggest local adaptation can occur in salmonids across relatively small geographic distances which may have important implications for the management of salmon populations. In the first case study with S trutta, the species was investigated throughout its spread as an invasive in Newfoundland, eastern Canada. Genetic investigation confirmed historical records that the majority of introductions were from a Scottish hatchery and provided a clear example of the structure of two expanding waves of spread along coasts, probably by natural straying of anadromous individuals, to the north and south of the point of human introduction. This study showed a clearer example of the genetic anatomy of an invasion than in previous studies with brown trout, and may have implications for the management of invasive species in general. Finally, the genetics of anadromous S. trutta from the Waterville catchment in south western Ireland were studied. Two significantly different population groupings, from tributaries in geographically distinct locations entering the largest lake in the catchment, were identified. These results were then used to assign very large rod caught sea trout individuals (so called “specimen” sea trout) back to region of origin, in a Genetic Stock Identification exercise. This suggested that the majority of these large sea trout originated from one of the two tributary groups. These results are relevant for the understanding of sea trout population dynamics and for the future management of this and other sea trout producing catchments. This thesis has demonstrated new insights into the population structuring of salmonids both between and within catchments. While these chapters look at the existence and scale of genetic variation from different angles, it might be concluded that the overarching message from this thesis should be to highlight the importance of maintaining genetic diversity in salmonid populations as vital for their long-term productivity and resilience.

Can population-level variation in early childhood development be measured in a manner that supports service planning and intervention?

Background: The Early Development Instrument (EDI) is a population-level measure of five developmental domains at school-entry age. The overall aim of this thesis was to explore the potential of the EDI as an indicator of early development in Ireland. Methods: A cross-sectional study was conducted in 47 primary schools in 2011 using the EDI and a linked parental questionnaire. EDI (teacher completed) scores were calculated for 1,344 children in their first year of full-time education. Those scoring in the lowest 10% of the sample population in one or more domains were deemed to be 'developmentally vulnerable'. Scores were correlated with contextual data from the parental questionnaire and with indicators of area and school-level deprivation. Rasch analysis was used to determine the validity of the EDI. Results: Over one quarter (27.5%) of all children in the study were developmentally vulnerable. Individual characteristics associated with increased risk of vulnerability were being male; under 5 years old; and having English as a second language. Adjusted for these demographics, low birth weight, poor parent/child interaction and mother’s lower level of education showed the most significant odds ratios for developmental vulnerability. Vulnerability did not follow the area-level deprivation gradient as measured by a composite index of material deprivation. Children considered by the teacher to be in need of assessment also had lower scores, which were not significantly different from those of children with a clinical diagnosis of special needs. all domains showed at least reasonable fit to the Rasch model supporting the validity of the instrument. However, there was a need for further refinement of the instrument in the Irish context. Conclusion: This thesis provides a unique snapshot of early development in Ireland. The EDI and linked parental questionnaires are promising indicators of the extent, distribution and determinants of developmental vulnerability.

Efficient delivery of scalable media streaming over lossy networks

Recent years have witnessed a rapid growth in the demand for streaming video over the Internet, exposing challenges in coping with heterogeneous device capabilities and varying network throughput. When we couple this rise in streaming with the growing number of portable devices (smart phones, tablets, laptops) we see an ever-increasing demand for high-definition videos online while on the move. Wireless networks are inherently characterised by restricted shared bandwidth and relatively high error loss rates, thus presenting a challenge for the efficient delivery of high quality video. Additionally, mobile devices can support/demand a range of video resolutions and qualities. This demand for mobile streaming highlights the need for adaptive video streaming schemes that can adjust to available bandwidth and heterogeneity, and can provide us with graceful changes in video quality, all while respecting our viewing satisfaction. In this context the use of well-known scalable media streaming techniques, commonly known as scalable coding, is an attractive solution and the focus of this thesis. In this thesis we investigate the transmission of existing scalable video models over a lossy network and determine how the variation in viewable quality is affected by packet loss. This work focuses on leveraging the benefits of scalable media, while reducing the effects of data loss on achievable video quality. The overall approach is focused on the strategic packetisation of the underlying scalable video and how to best utilise error resiliency to maximise viewable quality. In particular, we examine the manner in which scalable video is packetised for transmission over lossy networks and propose new techniques that reduce the impact of packet loss on scalable video by selectively choosing how to packetise the data and which data to transmit. We also exploit redundancy techniques, such as error resiliency, to enhance the stream quality by ensuring a smooth play-out with fewer changes in achievable video quality. The contributions of this thesis are in the creation of new segmentation and encapsulation techniques which increase the viewable quality of existing scalable models by fragmenting and re-allocating the video sub-streams based on user requirements, available bandwidth and variations in loss rates. We offer new packetisation techniques which reduce the effects of packet loss on viewable quality by leveraging the increase in the number of frames per group of pictures (GOP) and by providing equality of data in every packet transmitted per GOP. These provide novel mechanisms for packetizing and error resiliency, as well as providing new applications for existing techniques such as Interleaving and Priority Encoded Transmission. We also introduce three new scalable coding models, which offer a balance between transmission cost and the consistency of viewable quality.

Synthesis, functionalisation and characterisation of germanium nanocrystals & their applications

In the last two decades, semiconductor nanocrystals have been the focus of intense research due to their size dependant optical and electrical properties. Much is now known about how to control their size, shape, composition and surface chemistry, allowing fine control of their photophysical and electronic properties. However, genuine concerns have been raised regarding the heavy metal content of these materials, which is toxic even at relatively low concentrations and may limit their wide scale use. These concerns have driven the development of heavy metal free alternatives. In recent years, germanium nanocrystals (Ge NCs) have emerged as environmentally friendlier alternatives to II-VI and IV-VI semiconductor materials as they are nontoxic, biocompatible and electrochemically stable. This thesis reports the synthesis and characterisation of Ge NCs and their application as fluorescence probes for the detection of metal ions. A room-temperature method for the synthesis of size monodisperse Ge NCs within inverse micelles is reported, with well-defined core diameters that may be tuned from 3.5 to 4.5 nm. The Ge NCs are chemically passivated with amine ligands, minimising surface oxidation while rendering the NCs dispersible in a range of polar solvents. Regulation of the Ge NCs size is achieved by variation of the ammonium salts used to form the micelles. A maximum quantum yield of 20% is shown for the nanocrystals, and a transition from primarily blue to green emission is observed as the NC diameter increases from 3.5 to 4.5 nm. A polydisperse sample with a mixed emission profile is prepared and separated by centrifugation into individual sized NCs which each showed blue and green emission only, with total suppression of other emission colours. A new, efficient one step synthesis of Ge NCs with in situ passivation and straightforward purification steps is also reported. Ge NCs are formed by co-reduction of a mixture of GeCl4 and n-butyltrichlorogermane; the latter is used both as a capping ligand and a germanium source. The surface-bound layer of butyl chains both chemically passivates and stabilises the Ge NCs. Optical spectroscopy confirmed that these NCs are in the strong quantum confinement regime, with significant involvement of surface species in exciton recombination processes. The PL QY is determined to be 37 %, one of the highest values reported for organically terminated Ge NCs. A synthetic method is developed to produce size monodisperse Ge NCs with modified surface chemistries bearing carboxylic acid, acetate, amine and epoxy functional groups. The effect of these different surface terminations on the optical properties of the NCs is also studied. Comparison of the emission properties of these Ge NCs showed that the wavelength position of the PL maxima could be moved from the UV to the blue/green by choice of the appropriate surface group. We also report the application of water-soluble Ge NCs as a fluorescent sensing platform for the fast, highly selective and sensitive detection of Fe3+ ions. The luminescence quenching mechanism is confirmed by lifetime and absorbance spectroscopies, while the applicability of this assay for detection of Fe3+ in real water samples is investigated and found to satisfy the US Environmental Protection Agency requirements for Fe3+ levels in drinkable water supplies.

Antimicrobial stewardship in Ireland, with a focus on long term care facilities

Background: Antimicrobial resistance is a major public health concern, and its increasing incidence in the Long Term Care Facility (LTCF) setting warrants attention (1). The prescribing of antimicrobials in this setting is often inappropriate and higher in Ireland than the European average (2). The aim of the study was to generate an evidence base for the factors influencing antimicrobial prescribing in LTCFs and to investigate Antimicrobial Stewardship (AMS) strategies for LTCFs. Methods: An initial qualitative study was conducted to determine the factors influencing antimicrobial prescribing in Irish LTCFs. This allowed for the informed implementation of an AMS feasibility study in LTCFs in the greater Cork region. Hospital AMS was also investigated by means of a national survey. A study of LTCF urine sample antimicrobial resistance rates was conducted in order to collate information for incorporation into future LTCF AMS initiatives. Results: The qualitative interviews determined that there are a multitude of factors, unique to the LTCF setting, which influence antimicrobial prescribing. There was a positive response from the doctors and nurses involved in the feasibility study as they welcomed the opportunity to engage with AMS and audit and feedback activities. While the results did not indicate a significant change in antimicrobial prescribing over the study period, important trends and patterns of use were detected. The antimicrobial susceptibility of LTCF urine samples compared to GPs samples found that there was a higher level of antimicrobial resistance in LTCFs. Conclusion: This study has made an important contribution to the development of AMS in LTCFs. The complexity of care and healthcare organisation, and the factors unique to LTCFs must be borne in mind when developing quality improvement strategies.

Variation in the type and frequency of postoperative invasive Staphylococcus aureus infections according to type of surgical procedure.

OBJECTIVE: To determine the epidemiological characteristics of postoperative invasive Staphylococcus aureus infection following 4 types of major surgical procedures.design. Retrospective cohort study. SETTING: Eleven hospitals (9 community hospitals and 2 tertiary care hospitals) in North Carolina and Virginia. PATIENTS: Adults undergoing orthopedic, neurosurgical, cardiothoracic, and plastic surgical procedures. METHODS: We used previously validated, prospectively collected surgical surveillance data for surgical site infection and microbiological data for bloodstream infection. The study period was 2003 through 2006. We defined invasive S. aureus infection as either nonsuperficial incisional surgical site infection or bloodstream infection. Nonparametric bootstrapping was used to generate 95% confidence intervals (CIs). P values were generated using the Pearson chi2 test, Student t test, or Wilcoxon rank-sum test, as appropriate. RESULTS: In total, 81,267 patients underwent 96,455 procedures during the study period. The overall incidence of invasive S. aureus infection was 0.47 infections per 100 procedures (95% CI, 0.43-0.52); 227 (51%) of 446 infections were due to methicillin-resistant S.aureus. Invasive S. aureus infection was more common after cardiothoracic procedures (incidence, 0.79 infections per 100 procedures [95%CI, 0.62-0.97]) than after orthopedic procedures (0.37 infections per 100 procedures [95% CI, 0.32-0.42]), neurosurgical procedures (0.62 infections per 100 procedures [95% CI, 0.53-0.72]), or plastic surgical procedures (0.32 infections per 100 procedures [95% CI, 0.17-0.47]) (P < .001). Similarly, S. aureus bloodstream infection was most common after cardiothoracic procedures (incidence, 0.57 infections per 100 procedures [95% CI, 0.43-0.72]; P < .001, compared with other procedure types), comprising almost three-quarters of the invasive S. aureus infections after these procedures. The highest rate of surgical site infection was observed after neurosurgical procedures (incidence, 0.50 infections per 100 procedures [95% CI, 0.42-0.59]; P < .001, compared with other procedure types), comprising 80% of invasive S.aureus infections after these procedures. CONCLUSION: The frequency and type of postoperative invasive S. aureus infection varied significantly across procedure types. The highest risk procedures, such as cardiothoracic procedures, should be targeted for ongoing preventative interventions.

The humoral response to HIV-1: new insights, renewed focus.

During the past 2 decades, significant advances in our understanding of the humoral immune response to human immunodeficiency virus type 1 (HIV-1) infection have been made, yet a tremendous amount of work lies ahead. Despite these advances, strategies to reliably induce antibodies that can control HIV-1 infection are still critically needed. However, recent advances in our understanding of the kinetics, specificity, and function of early humoral responses offer alternative new approaches to attain this goal. These results, along with the new broadly neutralizing antibody specificities, the role for other antibody functions, the increased understanding of HIV-1-induced changes to B cell biology, and results from the RV144 "Thai" trial showing potential modest sterilizing protection by nonneutralizing antibody responses, have renewed focus on the humoral system. In this review, recent advances in our understanding of the earliest humoral responses are discussed, highlighting presentations from the meeting on the Biology of Acute HIV Infection.

Low demographic variability in wild primate populations: fitness impacts of variation, covariation, and serial correlation in vital rates.

In a stochastic environment, long-term fitness can be influenced by variation, covariation, and serial correlation in vital rates (survival and fertility). Yet no study of an animal population has parsed the contributions of these three aspects of variability to long-term fitness. We do so using a unique database that includes complete life-history information for wild-living individuals of seven primate species that have been the subjects of long-term (22-45 years) behavioral studies. Overall, the estimated levels of vital rate variation had only minor effects on long-term fitness, and the effects of vital rate covariation and serial correlation were even weaker. To explore why, we compared estimated variances of adult survival in primates with values for other vertebrates in the literature and found that adult survival is significantly less variable in primates than it is in the other vertebrates. Finally, we tested the prediction that adult survival, because it more strongly influences fitness in a constant environment, will be less variable than newborn survival, and we found only mixed support for the prediction. Our results suggest that wild primates may be buffered against detrimental fitness effects of environmental stochasticity by their highly developed cognitive abilities, social networks, and broad, flexible diets.

A longitudinal study of epigenetic variation in twins.

DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. Alterations in DNA methylation are established contributors to inter-individual phenotypic variation and have been associated with disease susceptibility. The degree to which changes in loci-specific DNA methylation are under the influence of heritable and environmental factors is largely unknown. In this study, we quantitatively measured DNA methylation across the promoter regions of the dopamine receptor 4 gene (DRD4), the serotonin transporter gene (SLC6A4/SERT) and the X-linked monoamine oxidase A gene (MAOA) using DNA sampled at both ages 5 and 10 years in 46 MZ twin-pairs and 45 DZ twin-pairs (total n=182). Our data suggest that DNA methylation differences are apparent already in early childhood, even between genetically identical individuals, and that individual differences in methylation are not stable over time. Our longitudinal-developmental study suggests that environmental influences are important factors accounting for interindividual DNA methylation differences, and that these influences differ across the genome. The observation of dynamic changes in DNA methylation over time highlights the importance of longitudinal research designs for epigenetic research.