The Cost of Sustainability Capital and the Creation of Sustainable Value by Companies

We develop and apply a valuation methodology to calculate the cost of sustainability capital, and, eventually, sustainable value creation of companies. Sustainable development posits that decisions must take into account all forms of capital rather than just economic capital. We develop a methodology that allows calculation of the costs that are associated with the use of different forms of capital. Our methodology borrows the idea from financial economics that the return on capital has to cover the cost of capital. Capital costs are determined as opportunity costs, that is, the forgone returns that would have been created by alternative investments. We apply and extend the logic of opportunity costs to the valuation not only of economic capital but also of other forms of capital. This allows (a) integrated analysis of use of different forms of capital based on a value-based aggregation of different forms of capital, (b) determination of the opportunity cost of a bundle of different forms of capital used in a company, called cost of sustainability capital, (c) calculation of sustainability efficiency of companies, and (d) calculation of sustainable value creation, that is, the value above the cost of sustainability capital. By expanding the well-established logic of the valuation of economic capital in financial markets to cover other forms of capital, we provide a methodology that allows determination of the most efficient allocation of sustainability capital for sustainable value creation in companies. We demonstrate the practicability of the methodology by the valuation of the sustainability performance of British Petroleum (BP).

The mitochondrial and autosomal mutation landscapes of prostate cancer

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men. PCa is strongly age associated; low death rates in surveillance cohorts call into question the widespread use of surgery, which leads to overtreatment and a reduction in quality of life. There is a great need to increase the understanding of tumor characteristics in the context of disease progression.

OBJECTIVE: To perform the first multigenome investigation of PCa through analysis of both autosomal and mitochondrial DNA, and to integrate exome sequencing data, and RNA sequencing and copy-number alteration (CNA) data to investigate how various different tumor characteristics, commonly analyzed separately, are interconnected.

DESIGN, SETTING, AND PARTICIPANTS: Exome sequencing was applied to 64 tumor samples from 55 PCa patients with varying stage and grade. Integrated analysis was performed on a core set of 50 tumors from which exome sequencing, CNA, and RNA sequencing data were available.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Genes, mutated at a significantly higher rate relative to a genomic background, were identified. In addition, mitochondrial and autosomal mutation rates were correlated to CNAs and proliferation, assessed as a cell cycle gene expression signature.

RESULTS AND LIMITATIONS: Genes not previously reported to be significantly mutated in PCa, such as cell division cycle 27 homolog (Saccharomyces cerevisiae) (CDC27), myeloid/lymphoid or mixed-lineage leukemia 3 (MLL3), lysine (K)-specific demethylase 6A (KDM6A), and kinesin family member 5A (KIF5A) were identified. The mutation rate in the mitochondrial genome was 55 times higher than that of the autosomes. Multilevel analysis demonstrated a tight correlation between high reactive-oxygen exposure, chromosomal damage, high proliferation, and in parallel, a transition from multiclonal indolent primary PCa to monoclonal aggressive disease. As we only performed targeted sequence analysis; copy-number neutral rearrangements recently described for PCa were not accounted for.

CONCLUSIONS: The mitochondrial genome displays an elevated mutation rate compared to the autosomal chromosomes. By integrated analysis, we demonstrated that different tumor characteristics are interconnected, providing an increased understanding of PCa etiology.

Gene regulatory mechanisms underpinning prostate cancer susceptibility

Molecular characterization of genome-wide association study (GWAS) loci can uncover key genes and biological mechanisms underpinning complex traits and diseases. Here we present deep, high-throughput characterization of gene regulatory mechanisms underlying prostate cancer risk loci. Our methodology integrates data from 295 prostate cancer chromatin immunoprecipitation and sequencing experiments with genotype and gene expression data from 602 prostate tumor samples. The analysis identifies new gene regulatory mechanisms affected by risk locus SNPs, including widespread disruption of ternary androgen receptor (AR)-FOXA1 and AR-HOXB13 complexes and competitive binding mechanisms. We identify 57 expression quantitative trait loci at 35 risk loci, which we validate through analysis of allele-specific expression. We further validate predicted regulatory SNPs and target genes in prostate cancer cell line models. Finally, our integrated analysis can be accessed through an interactive visualization tool. This analysis elucidates how genome sequence variation affects disease predisposition via gene regulatory mechanisms and identifies relevant genes for downstream biomarker and drug development.

Negotiating difference in post-conflict Northern Ireland: an analysis of approaches to integrated education

In this article, the author critically examines a variety of approaches to multicultural education noted in integrated (mixed Catholic and Protestant) schools in Northern Ireland and considers their implications in the context of the wider debate around multiculturalism. She argues that educators should challenge sectarianism, but should also resist the essentialization of group identities.

The integrated school in a conflict society: a comparative analysis of two integrated primary schools in Northern Ireland

The purpose of this paper is to compare the approach to promoting positive relationships between Catholics and Protestants in two types of integrated primary school in Northern Ireland. Drawing on qualitative interviews with teachers, governors and parents in one transforming school and one grant maintained integrated school, i.e. one representative of each of the two types, the paper shows that whilst there are distinctions in the ways that the schools promote their image and ethos, the ‘lived reality’ of the schools, as reported by the research participants, is almost indistinguishable. The paper suggests that both schools tend not to refer to or explore cultural difference and that this tendency to ‘minimise difference’ seems to have the potential to silence school members who do wish to explore their own and other cultures. It is argued that such practices are likely to impede rather than facilitate the progress of good inter-community relations.

Exploring the adoption and implementation of discrete and integrated IT systems: A Framework for analysis

Despite the substantial organisational benefits of integrated IT, the implementation of such systems – and particularly Enterprise Resource Planning (ERP) systems – has tended to be problematic, stimulating an extensive body of research into ERP implementation. This research has remained largely separate from the main IT implementation literature. At the same time, studies of IT implementation have generally adopted either a factor or process approach; both have major limitations. To address these imitations, factor and process perspectives are combined here in a unique model of IT implementation. We argue that • the organisational factors which determine successful implementation differ for integrated and traditional, discrete IT • failure to manage these differences is a major source of integrated IT failure. The factor/process model is used as a framework for proposing differences between discrete and integrated IT.

An integrated transcriptomics and proteomics analysis of the secretome of the helminth pathogen Fasciola hepatica: Proteins associated with invasion and infection of the mammalian host

To infect their mammalian hosts, Fasciola hepatica larvae must penetrate and traverse the intestinal wall of the duodenum, move through the peritoneum, and penetrate the liver. After migrating through and feeding on the liver, causing extensive tissue damage, the parasites move to their final niche in the bile ducts where they mature and produce eggs. Here we integrated a transcriptomics and proteomics approach to profile Fasciola secretory proteins that are involved in host-pathogen interactions and to correlate changes in their expression with the migration of the parasite. Prediction of F. hepatica secretory proteins from 14,031 expressed sequence tags (ESTs) available from the Wellcome Trust Sanger Centre using the semiautomated EST2Secretome pipeline showed that the major components of adult parasite secretions are proteolytic enzymes including cathepsin L, cathepsin B, and asparaginyl endopeptidase cysteine proteases as well as novel trypsin-like serine proteases and carboxypeptidases. Proteomics analysis of proteins secreted by infective larvae, immature flukes, and adult F. hepatica showed that these proteases are developmentally regulated and correlate with the passage of the parasite through host tissues and its encounters with different host macromolecules. Proteases such as FhCL3 and cathepsin B have specific functions in larvae activation and intestinal wall penetration, whereas FhCL1, FhCL2, and FhCL5 are required for liver penetration and tissue and blood feeding. Besides proteases, the parasites secrete an array of antioxidants that are also highly regulated according to their migration through host tissues. However, whereas the proteases of F. hepatica are secreted into the parasite gut via a classical endoplasmic reticulum/Golgi pathway, we speculate that the antioxidants, which all lack a signal sequence, are released via a non-classical trans-tegumental pathway.

Spatial and Temporal Changes in Soil Organic Carbon Assessment using an Integrated Geostatistical and Compositional Data Analysis Approach

The Irish and UK governments, along with other countries, have made a commitment to limit the concentrations of greenhouse gases in the atmosphere by reducing emissions from the burning of fossil fuels. This can be achieved (in part) through increasing the sequestration of CO2 from the atmosphere including monitoring the amount stored in vegetation and soils. A large proportion of soil carbon is held within peat due to the relatively high carbon density of peat and organic-rich soils. This is particularly important for a country such as Ireland, where some 16% of the land surface is covered by peat. For Northern Ireland, it has been estimated that the total amount of carbon stored in vegetation is 4.4Mt compared to 386Mt stored within peat and soils. As a result it has become increasingly important to measure and monitor changes in stores of carbon in soils. The conservation and restoration of peat covered areas, although ongoing for many years, has become increasingly important. This is summed up in current EU policy outlined by the European Commission (2012) which seeks to assess the relative contributions of the different inputs and outputs of organic carbon and organic matter to and from soil. Results are presented from the EU-funded Tellus Border Soil Carbon Project (2011 to 2013) which aimed to improve current estimates of carbon in soil and peat across Northern Ireland and the bordering counties of the Republic of Ireland.
Historical reports and previous surveys provide baseline data. To monitor change in peat depth and soil organic carbon, these historical data are integrated with more recently acquired airborne geophysical (radiometric) data and ground-based geochemical data generated by two surveys, the Tellus Project (2004-2007: covering Northern Ireland) and the EU-funded Tellus Border project (2011-2013) covering the six bordering counties of the Republic of Ireland, Donegal, Sligo, Leitrim, Cavan, Monaghan and Louth. The concept being applied is that saturated organic-rich soil and peat attenuate gamma-radiation from underlying soils and rocks. This research uses the degree of spatial correlation (coregionalization) between peat depth, soil organic carbon (SOC) and the attenuation of the radiometric signal to update a limited sampling regime of ground-based measurements with remotely acquired data. To comply with the compositional nature of the SOC data (perturbations of loss on ignition [LOI] data), a compositional data analysis approach is investigated. Contemporaneous ground-based measurements allow corroboration for the updated mapped outputs. This provides a methodology that can be used to improve estimates of soil carbon with minimal impact to sensitive habitats (like peat bogs), but with maximum output of data and knowledge.