Class and Performance in the Age of Global Capitalism

This article addresses the relative absence of class-based analysis in theatre and performance studies, and suggests the reconfiguration of class as performance rather than as it is traditionally conceived as an identity predicated solely on economic stratification. It engages with the occlusion of class by the ascendancy of identity politics based on race, gender and sexuality and its attendant theoretical counterparts in deconstruction and post-structuralism, which became axiomatic as they displaced earlier methodologies to become hegemonic in the arts and humanities. The article proceeds to an assessment of the development of sociological approaches to theatre, particularly the legacy of Raymond Williams and Pierre Bourdieu. The argument concludes with the application of an approach which reconfigures class as performance to the production of Declan Hughes's play Shiver of 2003, which dramatizes the consequences of the dot.com bubble of the late 1990s for ambitious members of the Irish middle class.

Detection of Mixing Dynamics During Pumping of a Flooded Coal Mine

In complex hydrogeological environments the effective management of groundwater quality problems by pump-and-treat operations can be most confidently achieved if the mixing dynamics induced within the aquifer by pumping are well understood. The utility of isotopic environmental tracers (C-, H-, O-, S-stable isotopic analyses and age indicators—14C, 3H) for this purpose is illustrated by the analysis of a pumping test in an abstraction borehole drilled into flooded, abandoned coal mineworkings at Deerplay (Lancashire, UK). Interpretation of the isotope data was undertaken conjunctively with that of major ion hydrochemistry, and interpreted in the context of the particular hydraulic setting of flooded mineworkings to identify the sources and mixing of water qualities in the groundwater system. Initial pumping showed breakdown of initial water quality stratification in the borehole, and gave evidence for distinctive isotopic signatures (d34S(SO4) ~= -1.6‰, d18O(SO4) ~= +15‰) associated with primary oxidation of pyrite in the zone of water table fluctuation—the first time this phenomenon has been successfully characterized by these isotopes in a flooded mine system. The overall aim of the test pumping—to replace an uncontrolled outflow from a mine entrance in an inconvenient location with a pumped discharge on a site where treatment could be provided—was swiftly achieved. Environmental tracing data illustrated the benefits of pumping as little as possible to attain this aim, as higher rates of pumping induced in-mixing of poorer quality waters from more distant old workings, and/or renewed pyrite oxidation in the shallow subsurface.

New prognostic markers, determined using gene expression analyses, reveal two distinct subtypes of chronic myelomonocytic leukaemia patients

Chronic myelomonocytic leukaemia (CMML) is a heterogeneous haematopoietic disorder characterized by myeloproliferative or myelodysplastic features. At present, the pathogenesis of this malignancy is not completely understood. In this study, we sought to analyse gene expression profiles of CMML in order to characterize new molecular outcome predictors. A learning set of 32 untreated CMML patients at diagnosis was available for TaqMan low-density array gene expression analysis. From 93 selected genes related to cancer and cell cycle, we built a five-gene prognostic index after multiplicity correction. Using this index, we characterized two categories of patients with distinct overall survival (94% vs. 19% for good and poor overall survival, respectively; P = 0.007) and we successfully validated its strength on an independent cohort of 21 CMML patients with Affymetrix gene expression data. We found no specific patterns of association with traditional prognostic stratification parameters in the learning cohort. However, the poor survival group strongly correlated with high-risk treated patients and transformation to acute myeloid leukaemia. We report here a new multigene prognostic index for CMML, independent of the gene expression measurement method, which could be used as a powerful tool to predict clinical outcome and help physicians to evaluate criteria for treatments.

Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial

BACKGROUND:
Long-term hormone therapy alone is standard care for metastatic or high-risk, non-metastatic prostate cancer. STAMPEDE--an international, open-label, randomised controlled trial--uses a novel multiarm, multistage design to assess whether the early additional use of one or two drugs (docetaxel, zoledronic acid, celecoxib, zoledronic acid and docetaxel, or zoledronic acid and celecoxib) improves survival in men starting first-line, long-term hormone therapy. Here, we report the preplanned, second intermediate analysis comparing hormone therapy plus celecoxib (arm D) with hormone therapy alone (control arm A).
METHODS:
Eligible patients were men with newly diagnosed or rapidly relapsing prostate cancer who were starting long-term hormone therapy for the first time. Hormone therapy was given as standard care in all trial arms, with local radiotherapy encouraged for newly diagnosed patients without distant metastasis. Randomisation was done using minimisation with a random element across seven stratification factors. Patients randomly allocated to arm D received celecoxib 400 mg twice daily, given orally, until 1 year or disease progression (including prostate-specific antigen [PSA] failure). The intermediate outcome was failure-free survival (FFS) in three activity stages; the primary outcome was overall survival in a subsequent efficacy stage. Research arms were compared pairwise against the control arm on an intention-to-treat basis. Accrual of further patients was discontinued in any research arm showing safety concerns or insufficient evidence of activity (lack of benefit) compared with the control arm. The minimum targeted activity at the second intermediate activity stage was a hazard ratio (HR) of 0·92. This trial is registered with ClinicalTrials.gov, number NCT00268476, and with Current Controlled Trials, number ISRCTN78818544.
FINDINGS:
2043 patients were enrolled in the trial from Oct 17, 2005, to Jan 31, 2011, of whom 584 were randomly allocated to receive hormone therapy alone (control group; arm A) and 291 to receive hormone therapy plus celecoxib (arm D). At the preplanned analysis of the second intermediate activity stage, with 305 FFS events (209 in arm A, 96 in arm D), there was no evidence of an advantage for hormone therapy plus celecoxib over hormone therapy alone: HR 0·94 (95% CI 0·74-1·20). [corrected]. 2-year FFS was 51% (95% CI 46-56) in arm A and 51% (95% CI 43-58) in arm D. There was no evidence of differences in the incidence of adverse events between groups (events of grade 3 or higher were noted at any time in 123 [23%, 95% CI 20-27] patients in arm A and 64 [25%, 19-30] in arm D). The most common grade 3-5 events adverse effects in both groups were endocrine disorders (55 [11%] of patients in arm A vs 19 [7%] in arm D) and musculoskeletal disorders (30 [6%] of patients in arm A vs 15 [6%] in arm D). The independent data monitoring committee recommended stopping accrual to both celecoxib-containing arms on grounds of lack of benefit and discontinuing celecoxib for patients currently on treatment, which was endorsed by the trial steering committee.
INTERPRETATION:
Celecoxib 400 mg twice daily for up to 1 year is insufficiently active in patients starting hormone therapy for high-risk prostate cancer, and we do not recommend its use in this setting. Accrual continues seamlessly to the other research arms and follow-up of all arms will continue to assess effects on overall survival.

Association analysis of proopiomelanocortin (POMC) haplotypes in type 1 diabetes in a UK population

Aim

To assess the association of POMC haplotype-tagged single nucleotide polymorphisms (htSNPs) with the development of type 1 diabetes (T1D) in a Caucasian population.

Methods

All exons, intron 1, and approximately 6-kb upstream and 3-kb downstream of the POMC gene were bidirectionally resequenced to identify DNA polymorphisms in 30 individuals. Allele frequencies were determined (60 chromosomes) and efficient htSNPs were selected using the htSNP2 programme. Genotyping was performed in 390 cases, 339 controls and 245 T1D parent-offspring trios, using Taqman, Sequenom and direct-sequencing technologies.

Results

Thirteen polymorphisms (two novel) with a minor allele frequency greater than 1% were identified. Six POMC htSNPs (rs3754863 G>A, ss161151662 A>G, rs3754860 C>T, rs1009388 G>C, rs3769671 A>C, rs1042571 G>A) were identified. Allele and haplotype frequencies were similar between case and control groups (P>0.60 by permutation test), and assessment of allele transmission distortion from informative parents to affected offspring also failed to find any association. Stratification of these analyses for age-at-onset and HLA-DR risk group (DR3/DR4) revealed no significant associations. A haplotype block of 9.86-kb from rs3754863 to rs1042571 was identified, encompassing the POMC gene. Comparison of haplotype frequencies identified the GGCGAG haplotype as protective against T1D in 12.9% of cases vs. 18.3% of controls: ?2=8.18, Pc=0.03 by permutation test.

Conclusion

The POMC SNP haplotype GGCGAG may have a protective effect against T1D in the UK population. However, this finding needs to be replicated, and the cellular and molecular processes influenced by this POMC haplotype determined to fully appreciate its impact.

A comparison of nitogen fate and transport in catchments underlain by high and low permeability aquifers using chemical and isotopic tools.

Variability in nitrogen fate and transport in different catchments types is often not considered. This research considers the importance of such nitrogen processes within groundwater pathways in two agricultural catchments in Ireland; a well drained catchment, underlain by karstified Carboniferous limestone, and a poorly drained catchment, underlain by Silurian greywacke.
Depth specific low-flow groundwater sampling was used to evaluate the hydrochemical stratification in groundwater. Groundwater samples, as well as surface water samples, along river courses were analysed for nitrogen species (NO3, NH4 and NO2) and nitrate isotopes (d15N and d18O) as well as field parameters and major ions
.
The dominant nitrate (NO3) groundwater pathway in the poorly drained greywacke catchment is through the shallow weathered bedrock, as indicated by transmissivity values and the ionic and isotopic signatures, and a clear reduction in NO3 concentration is observed with depth. A similar chloride trend would suggest dilution is a major factor, however d15N and d18O isotopic values producing an enrichment ratio of 1.8 indicate that denitrification is also an important process involved in the fate of the NO3 within the groundwater flow system. This consistent trend with depth is in contrast to the stratification pattern observed in the karstified catchment. NO3 was not detected in the shallow groundwater pathway; the dominant groundwater pathway is in the deeper groundwater where there is little change in the nitrate isotope values with depth (d15N values range between 4.1 and 4.6 ‰). This deeper groundwater contributes the dominant proportion of the river flow through a number of springs. As a result, the deeper groundwater, springs and river have a similar ionic signature and NO3 concentration range (23 ± 3 mg/l). Despite this pattern, the NO3 isotopes show a distinct difference in isotopic values between the deeper groundwater in the diffuse karst and the springs indicating some denitrification is occurring during groundwater discharge into the river. Furthermore the isotopes give an indication of the variability of the spatial extent of the springs and the complexities of the fissures through which they are fed. The results of this study clearly show the importance of the geology in the fate and transport of NO3 in agricultural catchments.

Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure

The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.

Europeanization of Inequality and Europeanization of Reference Groups

In this article we take advantage of the availability of European Union Statistics on Income and Living Conditions (EU-SILC) data to address both weak and strong versions of the Europeanization of reference groups thesis. The former proposes that common standards of evaluation emerge as a consequence of knowledge of conditions in other societies. The latter argues that people increasingly perceive themselves as part of a larger European stratification system. Our analysis leads us to reject both versions of the thesis. Material deprivation rather than having a uniform effect is highly dependent on national context. If a process of convergence is underway, it is one that as yet has had a limited impact. In circumstances where the Europeanization of inequality is raising issues relating to both national and transnational forms of legitimacy, it is important to understand that there is no necessary relationship between such Europeanization and the Europeanization of reference groups.

Understanding material deprivation: A comparative European analysis

In this paper, taking advantage of the inclusion of a special module on material deprivation in EU-SILC 2009. we provide a comparative analysis of patterns of deprivation. Our analysis identifies six relatively distinct dimensions of deprivation with generally satisfactory overall levels of reliability and mean levels of reliability across countries. Multi-level analysis based on 28 European countries reveals systematic variation in the importance of within and between country variation for a range of deprivation dimensions. The basic deprivation dimension is the sole dimension to display a graduated pattern of variation across countries. It also reveals the highest correlations with national and household income, the remaining deprivation dimensions and economic stress. It comes closest to capturing an underlying dimension of generalized deprivation that can provide the basis for a comparative European analysis of exclusion from customary standards of living. A multilevel analysis revealed that a range of household characteristics and household reference person socio-economic factors were related to basic deprivation and controlling for contextual differences in such factors allowed us to account for substantial proportions of both within and between country variance. The addition of macro-economic factors relating to average levels of disposable income and income inequality contributed relatively little further in the way of explanatory power. Further analysis revealed the existence of a set of significant interactions between micro socioeconomic attributes and country level gross national disposable income per capita. The impact of socio-economic differentiation was significantly greater where average income levels were lower. Or, in other words, the impact of the latter was greater for more disadvantaged socio-economic groups. Our analysis supports the suggestion that an emphasis on the primary role of income inequality to the neglect of differences in absolute levels of income may be misleading in important respects. (C) 2012 International Sociological Association Research Committee 28 on Social Stratification and Mobility. Published by Elsevier Ltd. All rights reserved.

Understanding the socio-economic distribution of multiple deprivation: An application of self-organising maps

In this paper we seek to contribute to recent efforts to develop and implement multi-dimensional approaches to social exclusion by applying self-organising maps (SOMs) to a set of material deprivation indicators from the Irish component of EU-SILC. The first stage of our analysis involves the identification of sixteen clusters that confirm the multi-dimensional nature of deprivation in contemporary Ireland and the limitations of focusing solely on income. In going beyond this mapping stage, we consider both patterns of socio-economic differentiation in relation to cluster membership and the extent to which such membership contributes to our understanding of economic stress. Our analysis makes clear the continuing importance of traditional forms of stratification relating to factors such as income, social class and housing tenure in accounting for patterns of multiple deprivation. However, it also confirms the role of acute life events and life cycle and location influences. Most importantly, it demonstrates that conclusions relating to the relative impact of different kinds of socio-economic influences are highly dependent on the form of deprivation being considered. Our analysis suggests that debates relating to the extent to which poverty and social exclusion have become individualized should take particular care to distinguish between different kinds of outcomes. Further analysis demonstrates that the SOM approach is considerably more successful than a comparable latent class analysis in identifying those exposed to subjective economic stress. (C) 2010 International Sociological Association Research Committee 28 on Social Stratification and Mobility. Published by Elsevier Ltd. All rights reserved.

Understanding Parental Influence on Educational Outcomes Among 9 Year Olds in Ireland: The Mediating Role of Resources, Attitudes and Children's Own Perspectives

The relationship between parental background and children's educational outcomes has been a dominant theme within the sociology of education. There has been an on-going debate as to the relative merits of explanations which focus on the role of socio-cultural reproduction and those which focus on rational choice. However, many empirical studies within the social stratification tradition fail to allow for children's own agency in shaping the relationship between social background and schooling outcomes. This paper draws on the first wave of a large-scale longitudinal study of over 8,000 nine-year-old children in Ireland, which combines information from parents, school principals, teachers and children themselves. Both social class and parental education are found to have significant effects on reading and mathematics test scores among nine year olds. These effects are partly mediated by home-based educational resources and activities, parents' educational expectations for their child, and parents' formal involvement in the school. More importantly, children's own engagement with, and attitudes to, school significantly influence their academic performance. The influence of children's own attitudes and actions can thus reinforce or mitigate the effect of social background factors. The analysis therefore provides a bridge between the large body of research on the intergenerational transmission of inequality and the emerging research and policy literature on children's rights.

The 'Europeanization' of Reference Groups

In this paper we address the question of the relative importance of within and between country differences in income and material deprivation in the European Union in the context of recent suggestions that insufficient attention has been paid to the latter. In particular, we respond to the argument that the 'state bounded' relative income approach obscures the significance of EU-wide reference groups. Making use of EU-SILC 2004, we have sought to quantify the magnitude of relevant within and between country differences and their relative impact. Overall, our analysis supports the view that the predominant frame of reference is a national one. The limited impact of European reference groups observed in our analysis does not require explanation in terms of the emergence of a European social stratification system. Furthermore, the significance of such comparisons depends not only on the expectations of those affected by European inequalities but on the degree of legitimacy afforded to ensuing demands. While an EU-wide income-threshold can provide information regarding progress of the Union towards greater social cohesion, its usage for this purpose does not require a strong sense of European identity. Given the current status of the European Social Model, it would seem unwise to attribute an undue degree of policy relevance to the relatively modest impact of EU-wide reference groups revealed in our analysis.

Economic boom and social mobility:The Irish experience

In this paper we examine the consequences for social mobility of the recent unprecedented period of economic growth experienced in Ireland and the implications of such developments for current theories of social fluidity. Contrary to suggestions that the "Celtic Tiger" experience has been associated with deepening problem marginalization, we found evidence for a substantial upgrading of the class structure, increased levels of social mobility and increased social fluidity in relation to long-range hierarchical mobility. Such increased openness could not be explained by changes in the mediating role of education. The pattern of change suggests that both the upgrading of the class structure and the recent unprecedented tightness of the labour market have led employers to increasingly apply criteria other than education in a manner that has facilitated increased social fluidity. The Irish case provides further support for the argument for reconsidering the balance that mobility research has struck between social fluidity and absolute mobility and encouraging increased attention to the evolution of firms and jobs. It also suggests that, in circumstances where policies in advanced industrial societies have shown an increasing tendency to diverge, increased social fluidity may come about as a consequence of very different economic and social policies. © 2006 Elsevier Ltd. All rights reserved.

Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data

Background: Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding pathologies.

Methods: On the basis of biomarkers, we conducted agglomerative hierarchical clustering to identify patient and biomarker clusters. We then explored the relationship between the patient clusters and clinical characteristics using Chi-square analyses. We determined classification errors and areas under the receiver operating curve of Random Forest Classifiers (RFC) for patient subpopulations using the biomarker clusters to reduce the dimensionality of the data.

Results: Agglomerative clustering identified five patient clusters and seven biomarker clusters. Final diagnoses categories were non-randomly distributed across the five patient clusters. In addition, two of the patient clusters were enriched with patients with ‘low cancer-risk’ characteristics. The biomarkers which contributed to the diagnostic classifiers for these two patient clusters were similar. In contrast, three of the patient clusters were significantly enriched with patients harboring ‘high cancer-risk” characteristics including proteinuria, aggressive pathological stage and grade, and malignant cytology. Patients in these three clusters included controls, that is, patients with other serious disease and patients with cancers other than UC. Biomarkers which contributed to the diagnostic classifiers for the largest ‘high cancer- risk’ cluster were different than those contributing to the classifiers for the ‘low cancer-risk’ clusters. Biomarkers which contributed to subpopulations that were split according to smoking status, gender and medication were different.

Conclusions: The systems biology approach applied in this study allowed the hematuric patients to cluster naturally on the basis of the heterogeneity within their biomarker data, into five distinct risk subpopulations. Our findings highlight an approach with the promise to unlock the potential of biomarkers. This will be especially valuable in the field of diagnostic bladder cancer where biomarkers are urgently required. Clinicians could interpret risk classification scores in the context of clinical parameters at the time of triage. This could reduce cystoscopies and enable priority diagnosis of aggressive diseases, leading to improved patient outcomes at reduced costs. © 2013 Emmert-Streib et al; licensee BioMed Central Ltd.

HOXA/PBX3 knockdown impairs growth and sensitizes cytogenetically normal acute myeloid leukemia cells to chemotherapy

The cytogenetically normal subtype of acute myeloid leukemia (CN-AML) is associated with Intermediate risk which complicates therapeutic options. Lower overall HOX/TALE expression appears to correlate with more favorable prognosis/better response to treatment in some leukemias and solid cancer. The functional significance of the associated gene expression and response to chemotherapy is not known. Three independent microarray datasets obtained from large patient cohorts along with quantitative PCR validation was used to identify a four gene HOXA/TALE signature capable of prognostic stratification. Biochemical analysis was used to identify interactions between the four encoded proteins and targeted knockdown used to examine the functional importance of sustained expression of the signature in leukemia maintenance and response to chemotherapy. An eleven HOXA/TALE code identified in an Intermediate risk (n=315) compared to a Favourable group of patients (n=105) was reduced to a four gene signature of HOXA6, HOXA9, PBX3 and MEIS1 by iterative analysis of independent platforms. This signature maintained the Favorable/Intermediate risk partition and where applicable, correlated with overall survival in CN-AML. We further show that cell growth and function is dependent on maintained levels of these core genes and that direct targeting of HOXA/PBX3 sensitizes CN-AML cells to standard chemotherapy. Together the data support a key role for HOXA/TALE in CN-AML and demonstrate that targeting of clinically significant HOXA/PBX3 elements may provide therapeutic benefit to these patients.