Assessment of Norwegian People\u27s Aid: Technical Assistance to CMAC 1996-2003

This assessment report of Norwegian People\u27s Aid (NPA) Technical Assistance to the Cambodian Mine Action Centre (CMAC)covers the period from 1996 to 2003. It provides an individual appreciation of each of the NPA Technical Advisors as well as an overall assessment of NPA technical assistance impact to the CMAC. The objective of the assessment is to make recommendations to Technical Advisors on management issues. Based on collected documents and findings, the report tries to present a comprehensive documented assessment of the impact and achievements of the NPA TAs for the target period

Chromosome segregation and recombination in human meiosis: Clinical applications and insight into disjunction errors

Chromosome copy number errors (or aneuploidy) of gametes and embryos occurs in humans more frequently than in any other studied species, with a spectrum of manifestations from implantation failure to affected live births. It is predominantly problem arising in maternal meiosis with at least 20% of oocytes being aneuploid, a proportion that increases dramatically with advancing maternal age. Currently the only intervention to reduce the chances of transmitting aneuploidy is by invasive embryo biopsy procedures in high-risk groups (mainly patients with advanced maternal age) undergoing in-vitro fertilisation. Despite the severity of this problem, aneuploidy of the human preimplantation embryo is relatively poorly understood. With this in mind the purpose of this thesis is to explore the premise underpinning the use of preimplantation genetic screening (PGS) in human embryos and investigate its clinical applications and current methodologies. A series of published works demonstrate what I believe to be a significant contribution to the development of applications for studying human preimplantation aneuploidy, also providing insight into its origins and mechanisms at the earliest stages of human development. Specifically, I present a novel standard set of protocols as a general reference work from practitioners in the fields of embryo biopsy and array comparative genomic hybridisation (CGH - the current ‘gold standard’ for preimplantation aneuploidy screening). I present a summary of work encapsulated in three published clinical papers using a linkage based analysis of Single Nucleotide Polymorphism (SNP) karyotypes (Karyomapping). Karyomapping was designed as a near-universal approach for the simultaneous detection of chromosomal and monogenic disorders in a PGS setting and these results demonstrate the utility of the technique in three separate scenarios. In order to study the underlying mechanisms of female meiosis I present my findings on the use of a calcium ionophore to activate human oocytes artificially. An algorithm based on Karyomapping (termed MeioMapping) is demonstrated for the first time specifically to investigate human female meiosis. By recovering all three products of human female meiosis (oocyte, and both polar biopsies – herein termed “Trios”) using calcium ionophore, I present a novel protocol (commissioned by Nature Protocols) to allow exploration of the full extent of meiotic chromosome recombination and segregation that occurs in the female germline. Finally I present a published set of experiments using this protocol to provide new insight into meiotic segregation patterns and recombination in human oocytes. This work uncovers a previously undescribed pattern of meiotic segregation (termed Reverse Segregation), providing an association between recombination rates and chromosome mis-segregation (aneuploidy). This work demonstrates that there is selection for higher recombination rates in the female germline and that there is a role for meiotic drive for recombinant chromatids at meiosis II in human female meiosis. The work presented in this thesis provides deeper understanding of meiotically derived maternal aneuploidy and recombination. More importantly it provides a vehicle within an ethical framework to continue to expand our knowledge and uncover new insights into the basis of meiotic errors that may aid future reproductive therapies

Enabling quantitative data analysis through e-infrastructures

This paper discusses how quantitative data analysis in the social sciences can engage with and exploit an e-Infrastructure. We highlight how a number of activities which are central to quantitative data analysis, referred to as ‘data management’, can benefit from e-infrastructure support. We conclude by discussing how these issues are relevant to the DAMES (Data Management through e-Social Science) research Node, an ongoing project that aims to develop e-Infrastructural resources for quantitative data analysis in the social sciences

Maximizing the greenhouse gas reductions from biomass: The role of life cycle assessment

Biomass can deliver significant greenhouse gas reductions in electricity, heat and transport fuel supply. However, our biomass resource is limited and should be used to deliver the most strategic and significant impacts. The relative greenhouse gas reduction merits of different bioenergy systems (for electricity, heat, chemical and biochar production) were examined on a common, scientific basis using consistent life cycle assessment methodology, scope of system and assumptions. The results show that bioenergy delivers substantial and cost-effective greenhouse gas reductions. Large scale electricity systems deliver the largest absolute reductions in greenhouse gases per unit of energy generated, while medium scale wood chip district heating boilers result in the highest level of greenhouse gas reductions per unit of harvested biomass. However, ammonia and biochar systems deliver the most cost effective carbon reductions, while biochar systems potentially deliver the highest greenhouse gas reductions per unit area of land. The system that achieves the largest reduction in greenhouse gases per unit of energy does not also deliver the highest greenhouse gas reduction per unit of biomass. So policy mechanisms that incentivize the reductions in the carbon intensity of energy may not result in the best use of the available resource. Life cycle assessment (LCA) is a flexible tool that can be used to answer a wide variety of different policy-relevant, LCA “questions”, but it is essential that care is taken to formulate the actual question being asked and adapt the LCA methodology to suit the context and objective

Cohort profile: rationale and methods of UK Biobank repeat imaging study eye measures to study dementia

PURPOSE: The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study. PARTICIPANTS: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs. FINDINGS TO DATE: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes. FUTURE PLANS: The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia

Britain: racial violence and the politics of hate

Drawing on empirical research into racist attacks in three cities in England, this article reveals a changing geography of racial violence (in terms of new areas and targets), and sets this in the context of the socially destructive impact of neoliberalism as well as government policies to manage the UK’s changing demographic make-up. With racial violence officially defined as a form of ‘hate crime’, it is divorced from any wider political context or racialised climate and reduced to a matter of individual pathology. The changing parameters of racism and the state’s responses present a challenge which the Left and anti-racists have been slow to meet

International Targets for Poverty Reduction and Food Security: A Mildly Sceptical But Resolutely Pragmatic View With a Call for Greater Subsidiarity

Summaries International development targets adopted by UN Conferences provide political impetus, focus expenditure and help in monitoring progress. However, simple targets can misrepresent complex realities and distort policy. Monitoring targets can have a high opportunity cost. Political impetus can be lost if targets are over?ambitious. Food security illustrates the uses of targets and the risks involved. Simple hunger or nutrition targets have been attractive to policymakers but have been problematic conceptually, and routinely overambitious in practice. Greater subsidiarity may be the answer, with simple international targets being used as a platform for local action. Subsidiarity means more than developing national action plans to implement international targets: it is potentially more open, participatory subversive and deviant

HES5 silencing is an early and recurrent change in prostate tumourigenesis.

Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal prostate tumours, we identify promoter methylation of the transcription factor HES5 as an early event in prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86-97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour-normal pairs). Treatment of prostate cancer cells with the demethylating agent 5-aza-2'-deoxycytidine increased HES5 expression and downregulated its transcriptional target HES6, consistent with functional silencing of the HES5 gene in prostate cancer. Finally, we identify and test a transcriptional module involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5 silencing on tumourigenesis as a starting point for future functional studies.The authors are grateful to study volunteers for their participation and staff at the Welcome Trust Clinical Research Facility, Addenbrooke’s Clinical Research Centre, Cambridge. They also thank the NIHR Cambridge Biomedical Research Centre, the DOH HTA (ProtecT grant), and the NCRI/MRC (ProMPT grant) for help with the bio-repository, The University of Cambridge, Hutchison Whampoa Limited and Cancer Research UK for funding. They are grateful to the CRUK Cambridge Institute Genomics and Bioinformatics Core Facilities. Cross-validation of HES5 methylation includes the use of data generated by the TCGA Research Network.This is the final version of the article. It was originally published in the Endocrine-Related Cancer, April 1, 2015 22 131-144 doi: 10.1530/ERC-14-0454