Young people's self-reported experiences of sexual exploitation and sexual violence: a view from Northern Ireland

The issue of young people’s experiences of sexual exploitation and sexual violence has received increasing political and media attention within recent years. However, whilst many studies have identified this to be an emerging issue of concern, the collation of prevalence data on the extent of these issues is still very much in its infancy. In this article we report on the findings of a large-scale project on the sexual exploitation of young people, undertaken in Northern Ireland from 2009 to 2011. The article primarily explores young people’s self-reported experiences of sexual violence and exploitation, collated from their responses to a module of questions placed in the 2010 Young Life and Times Survey. The quantitative dataset from the survey covers both prevalence of sexually exploitative experiences and young people’s reports about the type of individuals perpetrating these incidents. This dataset is illustrated and contextualised with reference to the qualitative findings from interviews with young people and professionals conducted as part of the wider sexual exploitation study. The article concludes with a consideration of the implications of the findings, with particular reference to the need for further preventative work in this field.

Discovery of WASP-113b and WASP-114b, two inflated hot-Jupiters with contrasting densities

We present the discovery and characterisation of the exoplanets WASP-113b and WASP-114b by the WASP survey, SOPHIE and CORALIE. The planetary nature of the systems was established by performing follow-up photometric and spectroscopic observations. The follow-up data were combined with the WASP-photometry and analysed with an MCMC code to obtain system parameters. The host stars WASP-113 and WASP-114 are very similar. They are both early G-type stars with an effective temperature of ~5900K, [Fe/H] ~0.12 and T_{eff} ~4.1 dex. However, WASP-113 is older than WASP-114. Although the planetary companions have similar radii, WASP-114b is almost 4 times heavier than WASP-113b. WASP-113b has a mass of 0.48 M_{Jup} and an orbital period of ~4.5 days; WASP-114b has a mass of 1.77 M_{Jup} and an orbital period of ~1.5 days. Both planets have inflated radii, in particular WASP-113 with a radius anomaly of Re=0.35. The high scale height of WASP-113b (~950 km ) makes it a good target for follow-up atmospheric observations.

Ferroelectrics at the Nanoscale

There are several factors which make the investigation and understanding of nanoscale ferroelectrics particularly timely and important. Firstly, there is a market pressure, primarily from the electronics industry, to integrate ferroelectrics into devices with progressive decreases in size and increases in morphological complexity. This is perhaps best illustrated through the roadmaps for product development in FeRAM (Ferroelectric Randorn Access Memory) where the need for increases in bit density will require a move from 2D planar capacitor structures to 3D trenched capacitors in the next few years. Secondly, there is opportunity for novel exploration, as it is only relatively recently that developments in thin film growth of complex oxides, self-assembly techniques and high-resolution 'top-down' patterning have converged to allow the fabrication of isolated and well-defined ferroelectric nanoshapes, the properties of which are not known. Thirdly, there is an expectation that the behaviour of small scale ferroelectrics will be different from bulk, as this group of functional materials is highly sensitive to boundary/surface conditions, which are expected to dominate the overall response when sizes are reduced into the nanoscale regime. This feature article attempts to introduce some of the current areas of discovery and debate surrounding studies on ferroelectrics at the nanoscale. The focus is directed primarily at the search for novel size-related properties and behaviour which are not necessarily observed in bulk.

Ligand and structure-based methodologies for the prediction of the activity of G protein-coupled receptor ligands

Accurate in silico models for the quantitative prediction of the activity of G protein-coupled receptor (GPCR) ligands would greatly facilitate the process of drug discovery and development. Several methodologies have been developed based on the properties of the ligands, the direct study of the receptor-ligand interactions, or a combination of both approaches. Ligand-based three-dimensional quantitative structure-activity relationships (3D-QSAR) techniques, not requiring knowledge of the receptor structure, have been historically the first to be applied to the prediction of the activity of GPCR ligands. They are generally endowed with robustness and good ranking ability; however they are highly dependent on training sets. Structure-based techniques generally do not provide the level of accuracy necessary to yield meaningful rankings when applied to GPCR homology models. However, they are essentially independent from training sets and have a sufficient level of accuracy to allow an effective discrimination between binders and nonbinders, thus qualifying as viable lead discovery tools. The combination of ligand and structure-based methodologies in the form of receptor-based 3D-QSAR and ligand and structure-based consensus models results in robust and accurate quantitative predictions. The contribution of the structure-based component to these combined approaches is expected to become more substantial and effective in the future, as more sophisticated scoring functions are developed and more detailed structural information on GPCRs is gathered.

Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Subclassification of Leukemia: Report From the International Microarray Innovations in Leukemia Study Group

The Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories of myeloid and lymphoid malignancies. METHODS: The investigation was performed in 11 laboratories across three continents and included 3,334 patients. An exploratory retrospective stage I study was designed for biomarker discovery and generated whole-genome expression profiles from 2,143 patients with leukemias and myelodysplastic syndromes. The gene expression profiling-based diagnostic accuracy was further validated in a prospective second study stage of an independent cohort of 1,191 patients. RESULTS: On the basis of 2,096 samples, the stage I study achieved 92.2% classification accuracy for all 18 distinct classes investigated (median specificity of 99.7%). In a second cohort of 1,152 prospectively collected patients, a classification scheme reached 95.6% median sensitivity and 99.8% median specificity for 14 standard subtypes of acute leukemia (eight acute lymphoblastic leukemia and six acute myeloid leukemia classes, n = 693). In 29 (57%) of 51 discrepant cases, the microarray results had outperformed routine diagnostic methods. CONCLUSION: Gene expression profiling is a robust technology for the diagnosis of hematologic malignancies with high accuracy. It may complement current diagnostic algorithms and could offer a reliable platform for patients who lack access to today's state-of-the-art diagnostic work-up. Our comprehensive gene expression data set will be submitted to the public domain to foster research focusing on the molecular understanding of leukemias

An eye on RNAi in nematode parasites

RNA interference (RNAi) has revolutionised approaches to gene function determination. From a parasitology perspective, gene function studies have the added dimension of providing validation data, increasingly deemed essential to the initial phases of drug target selection, pre-screen development. Notionally advantageous to those working on nematode parasites is the fact that Caenorhabditis elegans research spawned RNAi discovery and continues to seed our understanding of its fundamentals. Unfortunately, RNAi data for nematode parasites illustrate variable and inconsistent susceptibilities which undermine confidence and exploitation. Now well-ensconced in an era of nematode parasite genomics, we can begin to unscramble this variation.

Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS

This Letter describes the discovery and SAR of three novel series of mGluR5 non-competitive antagonists/negative allosteric modulators (NAMs) not based on manipulation of an MPEP/MTEP chemotype identified by a functional HTS approach. This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and further examples of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold. (C) 2009 Elsevier Ltd. All rights reserved.

Design of potent GlyT1 inhibitors: In vitro and in vivo profiles

Inhibitors of Gly transporter type-1 (GlyT1) for the treatment of schizophrenia have been pursued on the basis of the NMDA receptor (R) hypofunction hypothesis, which stems largely from the observation that NMDAR antagonists induce symptoms that more closely mimic those characteristic of schizophrenia than do other classes of psychotic agents. GlyT1 is responsible for uptake of synaptic Gly, an NMDAR co-agonist amino acid, in neuronal populations throughout the forebrain. GlyT1 inhibition thereby potentiates NMDAR activity by increasing synaptic Gly levels. Correspondingly, a large body of data suggests that GlyT1 inhibitors likely confer more comprehensive symptom alleviation than current antipsychotics. To date, a number of small-molecule GlyT1 inhibitors have been reported by the pharmaceutical industry. Developments in the discovery and characterization of GlyT1 inhibitors are discussed in this review.

Mass limits for the progenitor star of supernova 2001du and other Type II-P supernovae

The supernova SN 2001du was discovered in the galaxy NGC 1365 at a distance of 19 +/- 2 Mpc, and is a core-collapse event of Type II-P. Images of this galaxy, of moderate depth, have been taken with the Hubble Space Telescope approximately 6.6 yr before discovery and include the supernova position on the WFPC2 field of view. We have observed the supernova with the WFPC2 to allow accurate differential astrometry of SN 2001du on the pre-explosion frames. As a core-collapse event it is expected that the progenitor was a massive, luminous star. There is a marginal detection (3sigma) of a source close to the supernova position on the pre-discovery V -band frame, but it is not precisely coincident and we do not believe it to be a robust detection of a point source. We conclude that there is no stellar progenitor at the supernova position and derive sensitivity limits of the pre-discovery images that provide an upper mass limit for the progenitor star. We estimate that the progenitor had a mass of less than 15 M-circle dot . We revisit two other nearby Type II-P supernovae that have high-quality pre-explosion images, and refine the upper mass limits for the progenitor stars. Using a new distance determination for SN 1999gi from the expanding photosphere method, we revise the upper mass limit to 12 M-circle dot . We present new HST images of the site of SN 1999em, which validate the use of lower spatial resolution ground-based images in the progenitor studies and use a new Cepheid distance to the galaxy to measure an upper mass limit of 15 M-circle dot for that progenitor. Finally we compile all the direct information available for the progenitors of eight nearby core-collapse supernovae and compare their mass estimates. These are compared with the latest stellar evolutionary models of pre-supernova evolution which have attempted to relate metallicity and mass to the supernovae type. Although this is statistically limited at present, reasonable agreement is already found for the lower-mass events (generally the II-P), but some discrepancies appear at higher masses.

Heritability and Genome-Wide Association Study to Assess Genetic Differences between Advanced Age-Related Macular Degeneration Subtypes

PURPOSE: To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes. DESIGN: Sibling correlation study and genome-wide association study (GWAS). PARTICIPANTS: For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls. METHODS: Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts. MAIN OUTCOME MEASURES: Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes. RESULTS: The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree (P = 4.2×10(-5)), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3×10(-9)), which was confirmed in the replication samples (OR, 1.38; P = 7.4×10(-14) for combined discovery and replication analysis). CONCLUSIONS: Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Beyond Sex, Bond and Star Wars : Exhibition Data from the Southampton Odeon 1972-1980

This article uses the personal ledgers of a cinema manager to explore programming and film exhibition at the Southampton Odeon in the 1970s. The detailed accounts provide a rare insight into cinema exhibition and challenge the notion that 1970s cinema was all about sex, violence, horror and exploitation, suggesting instead that audiences at this cinema, favoured very different fare.

Knowledge, innovation and emulation in the evolutionary thought of Bernard Mandeville

Of the early modern writers on the division of labour, Bernard Mandeville alone extended it to all aspects of human activity and emphasised its role in a cumulative process of evolution in which each generation modified and built on what had been achieved by earlier generations. This required exploration of the mechanisms through which new knowledge was developed as well as the means by which knowledge was transmitted between the generations. The present article examines Mandeville’s treatment of these mechanisms and explores their theoretical origins. It examines Mandeville’s understanding of the role of the division of labour in facilitating discovery and learning and the role of education and imitation in transmitting social knowledge. It shows that, for Mandeville, innovators were people of ordinary capacity who were alert to the opportunities and challenges of their environment. As a result of specialisation, they possessed tacit knowledge which was actualised in what they did rather than in theoretical propositions. Mandeville’s evolutionary thought influenced subsequent writers on political economy and evolutionary social thinkers. It may also have had some influence on Charles Darwin, though it is not, in itself, Darwinian. © The Author 2013. Published by Oxford University Press on behalf of the Cambridge Political Economy Society. All rights reserved.

Unveiling Fairness for the Consumer:The Law, Economics and Justice of Expanded Arbitration

In recent years, the US Supreme Court has rather controversially extended the ambit of the Federal Arbitration Act to extend arbitration’s reach into, inter alia¸ consumer matters, with the consequence that consumers are often (and unbeknownst to them) denied remedies which would otherwise be available. Such denied remedies include recourse to class action proceedings, effective denial of punitive damages, access to discovery and the ability to resolve the matter in a convenient forum.

The court’s extension of arbitration’s ambit is controversial. Attempts to overturn this extension have been made in Congress, but to no avail. In contrast to American law, European consumer law looks at pre-dispute agreements to arbitrate directed at consumers with extreme suspicion, and does so on the grounds of fairness. In contrast, some argue that pre-dispute agreements in consumer (and employment) matters are consumer welfare enhancing: they decrease the costs of doing business, which is then passed on to the consumer. This Article examines these latter claims from both an economic and normative perspective.

The economic analysis of these arguments shows that their assumptions do not hold. Rather than being productive of consumer surplus, the use of arbitration is likely to have the opposite effect. The industries from which the recent Supreme Court cases originated not only do not exhibit the industrial structure assumed by the proponents of expanded arbitration, but are also industries which exhibit features that facilitate consumer welfare reducing collusion.

The normative analysis addresses the fairness concerns. It is explicitly based upon John Rawls’ notion of “justice as fairness,” which can provide a lens to evaluate social institutions. This Rawlsian analysis considers the use of extended arbitration in consumer matters in the light of the earlier economic results. It suggests that the asymmetries present in the contractual allocation of rights serve as prima facie evidence that such arbitration–induced exclusions are prima facie unjust/unfair. However, as asymmetry is only a prima facie test, a generalized criticism of the arbitration exclusions (of the sort found in Congress and underlying the European regime) is overbroad.

Digital pathology and image analysis in tissue biomarker research

Digital pathology and the adoption of image analysis have grown rapidly in the last few years. This is largely due to the implementation of whole slide scanning, advances in software and computer processing capacity and the increasing importance of tissue-based research for biomarker discovery and stratified medicine. This review sets out the key application areas for digital pathology and image analysis, with a particular focus on research and biomarker discovery. A variety of image analysis applications are reviewed including nuclear morphometry and tissue architecture analysis, but with emphasis on immunohistochemistry and fluorescence analysis of tissue biomarkers. Digital pathology and image analysis have important roles across the drug/companion diagnostic development pipeline including biobanking, molecular pathology, tissue microarray analysis, molecular profiling of tissue and these important developments are reviewed. Underpinning all of these important developments is the need for high quality tissue samples and the impact of pre-analytical variables on tissue research is discussed. This requirement is combined with practical advice on setting up and running a digital pathology laboratory. Finally, we discuss the need to integrate digital image analysis data with epidemiological, clinical and genomic data in order to fully understand the relationship between genotype and phenotype and to drive discovery and the delivery of personalized medicine.

From the past to the Future: integrating archaeology and conflict resolution in Northern Ireland

Contested understandings about the past continue to reify the divided character of post-Troubles Northern Ireland. In particular, the unresolved legacies of the extension of English control over Ireland in the late sixteenth and early seventeenth centuries through warfare and plantation continue to structure daily lives in the province. Yet the archaeological record of this period complicates the accepted dichotomous narratives through highlighting complexity. These nuances, however, have been lost in recent decades as an overly simplistic model of colonizer versus colonized has emerged as the dominant political paradigm. The management and presentation of sites associated with the process of plantation can arguably create the space necessary to bridge the divide, and to challenge accepted understandings. Cross-community engagement in the process of archaeological discovery and interpretation on plantation-period sites in Northern Ireland highlights the critical role archaeology can play in peace and reconciliation in post-conflict societies.