Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma.

Multiple myeloma is characterized by genomic alterations frequently involving gains and losses of chromosomes. Single nucleotide polymorphism (SNP)-based mapping arrays allow the identification of copy number changes at the sub-megabase level and the identification of loss of heterozygosity (LOH) due to monosomy and uniparental disomy (UPD). We have found that SNP-based mapping array data and fluorescence in situ hybridization (FISH) copy number data correlated well, making the technique robust as a tool to investigate myeloma genomics. The most frequently identified alterations are located at 1p, 1q, 6q, 8p, 13, and 16q. LOH is found in these large regions and also in smaller regions throughout the genome with a median size of 1 Mb. We have identified that UPD is prevalent in myeloma and occurs through a number of mechanisms including mitotic nondisjunction and mitotic recombination. For the first time in myeloma, integration of mapping and expression data has allowed us to reduce the complexity of standard gene expression data and identify candidate genes important in both the transition from normal to monoclonal gammopathy of unknown significance (MGUS) to myeloma and in different subgroups within myeloma. We have documented these genes, providing a focus for further studies to identify and characterize those that are key in the pathogenesis of myeloma.

Performance Management in the UK Public Sector: addressing multiple stakeholder complexity

Purpose The aim of this paper is to explore the issues involved in developing and applying performance management approaches within a large UK public sector department using a multiple stakeholder perspective and an accompanying theoretical framework. Design/methodology/approach An initial short questionnaire was used to determine perceptions about the implementation and effectiveness of the new performance management system across the organisation. In total, 700 questionnaires were distributed. Running concurrently with an ethnographic approach, and informed by the questionnaire responses, was a series of semi-structured interviews and focus groups. Findings Staff at all levels had an understanding of the new system and perceived it as being beneficial. However, there were concerns that the approach was not continuously managed throughout the year and was in danger of becoming an annual event, rather than an ongoing process. Furthermore, the change process seemed to have advanced without corresponding changes to appraisal and reward and recognition systems. Thus, the business objectives were not aligned with motivating factors within the organisation. Research limitations/implications Additional research to test the validity and usefulness of the theoretical model, as discussed in this paper, would be beneficial. Practical implications The strategic integration of the stakeholder performance measures and scorecards was found to be essential to producing an overall stakeholder-driven strategy within the case study organisation. Originality/value This paper discusses in detail the approach adopted and the progress made by one large UK public sector organisation, as it attempts to develop better relationships with all of its stakeholders and hence improve its performance. This paper provides a concerted attempt to link theory with practice.

Combining multiple prioritized knowledge bases by negotiation.

Recently, several belief negotiation models have been introduced to deal with the problem of belief merging. A negotiation model usually consists of two functions: a negotiation function and a weakening function. A negotiation function is defined to choose the weakest sources and these sources will weaken their point of view using a weakening function. However, the currently available belief negotiation models are based on classical logic, which makes them difficult to define weakening functions. In this paper, we define a prioritized belief negotiation model in the framework of possibilistic logic. The priority between formulae provides us with important information to decide which beliefs should be discarded. The problem of merging uncertain information from different sources is then solved by two steps. First, beliefs in the original knowledge bases will be weakened to resolve inconsistencies among them. This step is based on a prioritized belief negotiation model. Second, the knowledge bases obtained by the first step are combined using a conjunctive operator which may have a reinforcement effect in possibilistic logic.

Cognitive functioning in subjects with recent-onset psychosis from a low-middle-income environment: Multiple-domain deficits and longitudinal evaluation

Cognitive deficits are a key feature of recent-onset psychosis, but there is no consensus on whether such deficits are generalized or confined to specific domains. Besides, it is unclear whether cognitive deficits: a) are found in psychotic patients in samples from outside high-income countries; and b) whether they progress uniformly over time in schizophrenia and affective psychoses. We applied 12 tests organized into eight cognitive domains, comparing psychosis patients (n = 56, time from initial contact = 677.95+/-183.27 days) versus healthy controls (n = 70) recruited from the same area of Sao Paulo, Brazil. Longitudinal comparisons (digit span and verbal fluency) were conducted between a previous assessment of the subjects carried out at their psychosis onset, and the current follow-up evaluation. Psychosis patients differed significantly from controls on five domains, most prominently on verbal memory. Cognitive deficits remained detectable in separate comparisons of the schizophrenia subgroup and, to a lesser extent, the affective psychosis subjects against controls. Longitudinal comparisons indicated significant improvement in schizophrenia, affective psychoses, and control subjects, with no significant group-by-time interactions. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non-affective nature, which persist over time. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Economic and social integration the challenge for EU constitutional law

'At a time of crisis and therefore a crucial juncture in European politics, Dagmar Schiek offers us an inspiring vision of the potential of the European Union. In her brilliant study, she exposes the obstacles that economic integration has posed for achievement of social justice, and provides a bold solution. Rejecting more limited models of constitutionalism, she presents a convincing alternative which is socially embedded, allowing space for action by manifold actors at multiple levels of governance.' - Tonia Novitz, University of Bristol, UK. © Dagmar Schiek 2012. All rights reserved.

Enhancing performance: The moderating effect of environmental integration and environmental capabilities on the performance outcomes of pollution prevention

Over the last two decades there has been ongoing debate about the impact of environmental practices on operational performance. In recent years, studies have started to move beyond assessing the direct impact of environmental management on different dimensions of performance to consider factors that might moderate or mediate this relationship. This study considers the extent to which environmental integration and environmental capabilities moderate the relationship between pollution prevention and environmental performance outcomes. The mediating influence of environmental performance on the relationship between pollution prevention and cost and flexibility performance is also considered. Data were collected from a sample of UK food manufacturers and analysed using multiple regression analysis. The findings indicate the existence of some moderated and mediated relationships suggesting that there is more to improving performance than implementing environmental practices.

POINTS OF VIEW: Multi-Roling Performance in Ireland in the 1990s, Part 1 (Layering)

This series of posts will consider the acting techniques required for this style of performance with reference to four productions from the 1990s in which two actors took on multiple roles: Frank Pig Says Hello (1992), Co-Motion’s stage adaptation of Pat McCabe’s novel; The Butcher Boy, Corca Dorca’s production of Disco Pigs (1996) by Enda Walsh; DubbleJoint’s production of Stones in his Pockets by Marie Jones (1996) and its subsequent award-winning revival which I produced at Belfast’s Lyric Theatre in 1999; and Kabosh’s production of Mojo Mickybo by Owen McCafferty (1998). The discussion will focus primarily on my own empirical exploration of the demands multi-roling places on an actor through the direction of recent revivals of Mojo Mickybo for Belfast’s Chatterbox Theatre Company (2013) and Bedlam Productions (2015).

Progressing from internal to supply chain level environmental strategies: The influence of internal support processes

The need for companies to consider the environmental impact of their operations and supply chains has been highlighted in the literature. However, few studies appear to consider how companies’ progress from proactive environmental strategies implemented at the internal, operations level to proactive environmental strategies implemented at the supply chain level. This study assesses the implementation process through the lens of the natural resource-based view and dynamic capabilities perspective. First, the link between the internal strategy ‘pollution prevention’ and the supply chain strategy ‘process stewardship’ is assessed. Second, the mediating influence of the internal support processes ‘integration’ and ‘learning’ on the implementation process is considered. Data collected from a sample of 1200 UK-based food manufacturing companies is analysed using multiple regression analysis. The findings suggest that the progression to environmental efforts at the supply chain level begins with internally-based environmental efforts and that the integration of these efforts and experience gained from them are important supporting factors in this progression.

Measuring healthcare integration: Operationalization of a framework for a systems evaluation of palliative care structures, processes, and outcomes

BACKGROUND: Healthcare integration is a priority in many countries, yet there remains little direction on how to systematically evaluate this construct to inform further development. The examination of community-based palliative care networks provides an ideal opportunity for the advancement of integration measures, in consideration of how fundamental provider cohesion is to effective care at end of life.

AIM: This article presents a variable-oriented analysis from a theory-based case study of a palliative care network to help bridge the knowledge gap in integration measurement.

DESIGN: Data from a mixed-methods case study were mapped to a conceptual framework for evaluating integrated palliative care and a visual array depicting the extent of key factors in the represented palliative care network was formulated.

SETTING/PARTICIPANTS: The study included data from 21 palliative care network administrators, 86 healthcare professionals, and 111 family caregivers, all from an established palliative care network in Ontario, Canada.

RESULTS: The framework used to guide this research proved useful in assessing qualities of integration and functioning in the palliative care network. The resulting visual array of elements illustrates that while this network performed relatively well at the multiple levels considered, room for improvement exists, particularly in terms of interventions that could facilitate the sharing of information.

CONCLUSION: This study, along with the other evaluative examples mentioned, represents important initial attempts at empirically and comprehensively examining network-integrated palliative care and healthcare integration in general.