Freshwater Reservoir Effects on the Re-Dating of the Eurasian Steppe Cultures: New Data for the Prehistoric Sites of Kazakhstan and South of Siberia

Freshwater reservoir effects (FRE) can cause a major problem with radiocarbon dating human skeletal material in the Eurasian steppe. Recent research has demonstrated that, for the Eneolithic to Early Bronze Age sites of North-Eastern Kazakhstan, the maximum fish-herbivore freshwater reservoir offset observed equals 301±47 14C yrs, as such indicating that 14C dates from aquatic and human samples from the area apparently need to be interpreted with caution as they are likely to be affected by the offset. The current paper presents the new data on the FRE of the Eneolithic to the Early Iron Age sites of Kazakhstan and South of Siberia.

Re-embedding economic and social constitutionalism:Normative perspectives for the EU

Introduction Tensions between the economic and the social dimensions of European integration are being perceived as increasing, and so is the potential for conflict between national and European levels of policy-making. Both are well illustrated by a highly controversial line of Court of Justice of the European Union (ECJ) cases on industrial relations: Viking and Laval have become symbols for the continuing dominance of the economic over the social dimension of European integration and for an increasing tendency of the EU to diminish national autonomy. As one consequence, demands to protect Member States’ social policy choices from EU law pressures arise. For such demands to be tenable, isolation of national and EU policy-making and of economic and social dimensions of European integration would have to be possible. This is arguably not the case. Economic and social dimensions of integration will thus have to be reconciled across EU and national levels, if the EU and its Member States are to maintain the ability of enhancing social justice against the pulls of economic globalisation.

A Conditional Approach for Modelling Patient Re-admissions in Hospital using a mixture of Coxian phase-type distributions incorporating Bayes Theorem

The number of elderly patients requiring hospitalisation in Europe is rising. With a greater proportion of elderly people in the population comes a greater demand for health services and, in particular, hospital care. Thus, with a growing number of elderly patients requiring hospitalisation competing with non-elderly patients for a fixed (and in some cases, decreasing) number of hospital beds, this results in much longer waiting times for patients, often with a less satisfactory hospital experience. However, if a better understanding of the recurring nature of elderly patient movements between the community and hospital can be developed, then it may be possible for alternative provisions of care in the community to be put in place and thus prevent readmission to hospital. The research in this paper aims to model the multiple patient transitions between hospital and community by utilising a mixture of conditional Coxian phase-type distributions that incorporates Bayes' theorem. For the purpose of demonstration, the results of a simulation study are presented and the model is applied to hospital readmission data from the Lombardy region of Italy.

From the Right to Life to the Right to Livability: Radically Re-approaching ‘Life’ in Human Rights Politics

This article critically reflects on current mainstream debate on abortion in international human rights discourse and the conception of life underpinning it. The public health focus on access to safe abortion which has dominated this discourse can be detected as committed to a fundamentally liberal idea of bounded and individual subjecthood which mirrors the commitments of the liberal right to life more generally. However, feminist challenges to this frame seeking to advance wider access to reproductive freedoms appear equally underpinned by a liberal conception of life. It is asserted that feminists may offer a more radical challenge to the current impasse in international debate on abortion by engaging with the concept of livability which foregrounds life as an interdependent and conditioned process. The trope of the ‘right to livability’ developed in this article presents a means to reposition the relation between rights and life and facilitate such radical engagement which better attends to the socio-political conditions shaping our interdependent living and being.

Modulating mythology in a post-traumatic era: Murals and re-imaging in Northern Ireland.

Arguably the most ancient of the social media, wall paintings have been a persistent vehicle of cultural meaning management. The dynamics of myth markets are reflected in the sectarian murals of Northern Ireland. In this paper, we draw from consumer research literature on mythology and street art to explore the continuous revision of these wallscapes that seeks to address the enduring contradictions of civic ideology in contested political space. In particular, we focus on the use of classical, historical and pop-cultural mythologies to transform private space into public place. We examine the decommissioning of murals occurring in the wake of the Peace Accords, and speculate on the implications of the creation of a shared mythology for the future of mural painting and the state.

Exome sequencing of prostate cancer supports the hypothesis of independent tumour origins

BACKGROUND: Prostate cancer (PCa) is a clinically and pathologically heterogeneous disease. The rapid development of sequencing technology has the potential to deliver new biomarkers with emphasis on aggressive disease and to revolutionise personalised cancer treatment. However, a prostate harbouring cancer commonly contains multiple separate tumour foci, with the potential to aggravate tumour sampling. The level of intraprostatic tumour heterogeneity remains to be determined.

OBJECTIVE: To determine the level of intraprostatic tumour heterogeneity through genome-wide, high-resolution profiling of multiple tumour samples from the same individual.

DESIGN, SETTINGS, AND PARTICIPANTS: Multiple tumour samples were obtained from four individuals following radical prostatectomy. One individual (SWE-1) contained >70% cancer cells in all tumour samples, whereas the other three (SWE-2 to SWE-4) required the use of laser capture microdissection for tumour cell enrichment. Subsequently, DNA was extracted from all tissue samples, and exome sequencing was performed. All tumour foci of SWE-1 were also profiled using a high-resolution array for the identification of copy number alterations (CNA).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Shared somatic high-frequency single nucleotide variants (SNV) and CNAs were used to infer the level of intraprostatic tumour heterogeneity.

RESULTS AND LIMITATIONS: No high-frequency mutations, common for the three tumour samples of SWE-1, were identified. Ten randomly chosen positions were validated with Sanger sequencing in all foci, which verified the exome data. The high level of intraprostatic heterogeneity was consistent in all individuals. In total, three out of four individuals harboured tumours without an apparent common somatic denominator. Although we cannot exclude the presence of common structural rearrangements, a high-density array was used for the detection of deletions and amplifications in SWE-1, which agreed with the exome data.

CONCLUSIONS: We present evidence for the presence of somatically independent tumours within the same prostate. This finding will have implications for personalised cancer treatment and biomarker discovery.

Mapping protein-DNA interactions using ChIP-sequencing

Chromatin immunoprecipitation (ChIP) allows enrichment of genomic regions which are associated with specific transcription factors, histone modifications, and indeed any other epitopes which are present on chromatin. The original ChIP methods used site-specific PCR and Southern blotting to confirm which regions of the genome were enriched, on a candidate basis. The combination of ChIP with genomic tiling arrays (ChIP-chip) allowed a more unbiased approach to map ChIP-enriched sites. However, limitations of microarray probe design and probe number have a detrimental impact on the coverage, resolution, sensitivity, and cost of whole-genome tiling microarray sets for higher eukaryotes with large genomes. The combination of ChIP with high-throughput sequencing technology has allowed more comprehensive surveys of genome occupancy, greater resolution, and lower cost for whole genome coverage. Herein, we provide a comparison of high-throughput sequencing platforms and a survey of ChIP-seq analysis tools, discuss experimental design, and describe a detailed ChIP-seq method.Chromatin immunoprecipitation (ChIP) allows enrichment of genomic regions which are associated with specific transcription factors, histone modifications, and indeed any other epitopes which are present on chromatin. The original ChIP methods used site-specific PCR and Southern blotting to confirm which regions of the genome were enriched, on a candidate basis. The combination of ChIP with genomic tiling arrays (ChIP-chip) allowed a more unbiased approach to map ChIP-enriched sites. However, limitations of microarray probe design and probe number have a detrimental impact on the coverage, resolution, sensitivity, and cost of whole-genome tiling microarray sets for higher eukaryotes with large genomes. The combination of ChIP with high-throughput sequencing technology has allowed more comprehensive surveys of genome occupancy, greater resolution, and lower cost for whole genome coverage. Herein, we provide a comparison of high-throughput sequencing platforms and a survey of ChIP-seq analysis tools, discuss experimental design, and describe a detailed ChIP-seq method.

Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled 'reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers. © 2012 Biek et al.