Comparative analysis of dna methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Previous reports have shown that DNA methylation profiles within primary human malignant tissues are altered when these cells are transformed into cancer cell lines. However, it is unclear if similar differences in DNA methylation profiles exist between DNA derived from peripheral blood leukocytes (PBLs) and corresponding Epstein-Barr Virus transformed lymphoblastoid cell lines (LCLs). To assess the utility of LCLs as a resource for methylation studies we have compared DNA methylation profiles in promoter and 5' regions of 318 genes in PBL and LCL sample pairs from patients with type 1 diabetes with or without nephropathy. We identified a total of 27 (similar to 8%) genes that revealed different DNA methylation profiles in PBL compared with LCL-derived DNA samples. In conclusion, although the profiles for most promoter regions were similar between PBL-LCL pairs, our results indicate that LCL-derived DNA may not be suitable for DNA methylation studies at least in diabetic nephropathy.

University space planning and space-type profiles

Universities planning the provision of space for their teaching requirements need to do so in a fashion that reduces capital and maintenance costs whilst still providing a high-quality level of service. Space plans should aim to provide sufficient capacity without incurring excessive costs due to over-capacity. A simple measure used to estimate over-provision is utilisation. Essentially, the utilisation is the fraction of seats that are used in practice, or the ratio of demand to supply. However, studies usually find that utilisation is low, often only 20–40%, and this is suggestive of significant over-capacity.

Our previous work has provided methods to improve such space planning. They identify a critical level of utilisation as the highest level that can be achieved whilst still reliably satisfying the demand for places to allocate teaching events. In this paper, we extend this body of work to incorporate the notions of event-types and space-types. Teaching events have multiple ‘event-types’, such as lecture, tutorial, workshop, etc., and there are generally corresponding space-types. Matching the type of an event to a room of a corresponding space-type is generally desirable. However, realistically, allocation happens in a mixed space-type environment where teaching events of a given type are allocated to rooms of another space-type; e.g., tutorials will borrow lecture theatres or workshop rooms.

We propose a model and methodology to quantify the effects of space-type mixing and establish methods to search for better space-type profiles; where the term “space-type profile” refers to the relative numbers of each type of space. We give evidence that these methods have the potential to improve utilisation levels. Hence, the contribution of this paper is twofold. Firstly, we present informative studies of the effects of space-type mixing on utilisation, and critical utilisations. Secondly, we present straightforward though novel methods to determine better space-type profiles, and give an example in which the resulting profiles are indeed significantly improved.

‘A system that works for the sea’? Exploring Stakeholder Engagement in Marine Spatial Planning

This paper aims to contribute to the current debate on Marine Spatial Planning (MSP) by exploring the issue of stakeholder engagement. MSP is an emergent policy field that is subject to an increasing body of research, yet the role, scope and nature of participatory engagement within the process remains a neglected topic. This paper briefly reviews the nature of the ‘marine problem’, to which MSP is seen to be the response and describes the emergence of MSP policy in the UK with specific emphasis on participatory aspects. Drawing on the experience of terrestrial planning it discusses the potential benefits of stakeholder engagement in MSP and highlights some of the key issues that need to be taken into account when shaping stakeholder input into the process. It then goes on to describe the findings from a series of interviews with key stakeholders in the Irish Sea Region, which suggest that we need to develop a more critical and deeper understanding of how various interests frame the ‘marine problem’, and how they see their role in shaping the form of the MSP process. This highlights the importance of encouraging stakeholder involvement in MSP, the need to develop a shared vision of a ‘sea interest’. Priorities are then set for research to support this important policy agenda.

Planning Through Dialogue for Rural Development: The European Citizens’ Panel Initiative

This paper presents a narrative of the operation of the European Citizens’ Panel that reported in 2007 on the future roles of rural areas. This dialogue was located within a wider and recent engagement by the EU with its citizens following rejection of the EU Constitutional Treaty. The paper draws attention to the contemporary rural development challenges in Europe that were debated by eight regional panels as a prelude to a wider European deliberation. The working method of the European Citizens’ Panel is outlined and critical commentary is provided on the interaction between planning through dialogue, EU citizenship renewal, and the shaping of bottom-up development trajectories.

Experiences of parents during diagnosis and forward planning for children with Autism Spectrum Disorder.

Background For families of children diagnosed with autism spectrum disorder (ASD) getting a diagnosis is a traumatic experience on which future care and education plans for the child depend. In this paper parental experiences of diagnosis and forward planning for children with ASD are reported. Method This paper is part of a large cross-sectional study conducted in Northern Ireland and the Republic of Ireland that assessed the needs and experiences of parents of children diagnosed with ASD. Questionnaires were designed and completed by 95 parents, reporting on 100 children, as well as 67 multi-disciplinary professionals. Results Findings confirm that diagnostic and planning processes are extremely stressful for parents, that statutory diagnosis takes a long time, that care and education plans do not include full parental participation, and that reviews of plans do not consistently include intervention data. Conclusion Policy and practice implications of these findings are important for future revisions of diagnostic tools and manuals.

Impact of PSA testing and prostatic biopsy on cancer incidence and mortality: comparative study between the Republic of Ireland and Northern Ireland

Objectives: To investigate the impact of different PSA testing policies and health-care systems on prostate cancer incidence and mortality in two countries with similar populations, the Republic of Ireland (RoI) and Northern Ireland (NI).

Methods: Population-level data on PSA tests, prostate biopsies and prostate cancer cases 1993–2005 and prostate cancer deaths 1979–2006 were compiled. Annual percentage change (APC) was estimated by joinpoint regression.

Results: Prostate cancer rates were similar in both areas in 1994 but increased rapidly in RoI compared to NI. The PSA testing rate increased sharply in RoI (APC = +23.3%), and to a lesser degree in NI (APC = +9.7%) to reach 412 and 177 tests per 1,000 men in 2004, respectively. Prostatic biopsy rates rose in both countries, but were twofold higher in RoI. Cancer incidence rates rose significantly, mirroring biopsy trends, in both countries reaching 440 per 100,000 men in RoI in 2004 compared to 294 in NI. Median age at diagnosis was lower in RoI (71 years) compared to NI (73 years) (p < 0.01) and decreased significantly over time in both countries. Mortality rates declined from 1995 in both countries (APC = -1.5% in RoI, -1.3% in NI) at a time when PSA testing was not widespread.

Conclusions: Prostatic biopsy rates, rather than PSA testing per se, were the main driver of prostate cancer incidence. Because mortality decreases started before screening became widespread in RoI, and mortality remained low in NI, PSA testing is unlikely to be the explanation for declining mortality.

Identification of gene networks associated with acute myeloid leukemia by comparative molecular methylation and expression profiling

Around 80% of acute myeloid leukemia (AML) patients achieve a complete remission, however many will relapse and ultimately die of their disease. The association between karyotype and prognosis has been studied extensively and identified patient cohorts as having favourable [e.g. t(8; 21), inv (16)/t(16; 16), t(15; 17)], intermediate [e.g. cytogenetically normal (NK-AML)] or adverse risk [e.g. complex karyotypes]. Previous studies have shown that gene expression profiling signatures can classify the sub-types of AML, although few reports have shown a similar feature by using methylation markers. The global methylation patterns in 19 diagnostic AML samples were investigated using the Methylated CpG Island Amplification Microarray (MCAM) method and CpG island microarrays containing 12,000 CpG sites. The first analysis, comparing favourable and intermediate cytogenetic risk groups, revealed significantly differentially methylated CpG sites (594 CpG islands) between the two subgroups. Mutations in the NPM1 gene occur at a high frequency (40%) within the NK-AML subgroup and are associated with a more favourable prognosis in these patients. A second analysis comparing the NPM1 mutant and wild-type research study subjects again identified distinct methylation profiles between these two subgroups. Network and pathway analysis revealed possible molecular mechanisms associated with the different risk and/or mutation sub-groups. This may result in a better classification of the risk groups, improved monitoring targets, or the identification of novel molecular therapies.