Production and Productive Reason

This article explores two rival understandings of production and what it means to be a rational productive subject. Against ‘technicist’ models of productive reason, it defends a ‘phronetic’ model on both normative and pragmatic grounds. The discussion begins with a description of the general principles underpinning technicist theories of workplace organisation, principles which continue to inform work design approaches to this day. The technicist model is thereafter criticised on three counts: that it represents a specific managerial agenda which privileges sectional interests; that it is suspect morally for a number of reasons; and that despite its aspiration of arriving at ‘one best method’, it represents but one way of organising work processes. The phronetic model is then set out using the notion of ‘practices’ as a guide. This notion is important in providing a view of production in which technical reason is subsumed under a broader practical reason incorporating individual experience and judgement. Against the charge that this view is merely an instance of nostalgic craft romanticism having little relevance to present industrial realities, there are recognisable contemporary instances of phronetic production, one of the most interesting being Volvo’s innovations in automotive assembly systems.

Constitutive and Treatment-Induced CXCL8-Signalling Selectively Modulates the Efficacy of Anti-Metabolite Therapeutics in Metastatic Prostate Cancer

Background: The current study was undertaken to characterize the effect of anti-metabolites on inducing CXCL8 signaling and determining whether the constitutive and/or drug-induced CXCL8 signaling in metastatic prostate cancer (CaP) cells modulates their sensitivity to this class of agent.

Methods: The response of metastatic CaP cells to 5-Fluorouracil (5-FU), Pemetrexed or Tomudex was determined using cell count assays, flow cytometry and PARP cleavage analysis. Quantitative-PCR, ELISA and immunoblots were employed to determine effects of drugs or CXCL8 administration on target gene/protein expression.

Results: Administration of 5-FU but not pemetrexed potentiated CXCL8 secretion and increased CXCR1 and CXCR2 gene expression in metastatic PC3 cells. Consistent with this, the inhibition of CXCL8 signaling using a CXCR2 antagonist, AZ10397767, increased the cytotoxicity of 5-FU by 4-fold (P,0.001), and increased 5-FU-induced apoptosis in PC3 cells (P,0.01). In contrast, while administration of AZ10397767 had no effect on the sensitivity of pemetrexed, the CXCR2 antagonist exerted the greatest effect in increasing the sensitivity of PC3 cells to Tomudex, a directed thymidylate synthase (TS) inhibitor. Subsequent experiments confirmed that administration of recombinant human CXCL8 increased TS expression, a response mediated in part by the CXCR2 receptor. Moreover, siRNA-mediated knockdown of the CXCL8-target gene Bcl-2 increased the sensitivity of PC3 cells to 5-FU.

Conclusions: CXCL8 signaling provides a selective resistance of metastatic prostate cancer cells to specific anti-metabolites by promoting a target-associated resistance, in addition to underpinning an evasion of treatment-induced apoptosis. © 2012 Wilson et al.

Ordering effects and choice set awareness in repeat-response stated preference studies

We present an experiment designed to investigate the presence and nature of ordering effects within repeat-response stated preference (SP) studies. Our experiment takes the form of a large sample, full-factorial, discrete choice SP exercise investigating preferences for tap water quality improvements. Our study simultaneously investigates a variety of different forms of position-dependent and precedent-dependent ordering effect in preferences for attributes and options and in response randomness. We also examine whether advanced disclosure of the choice tasks impacts on the probability of exhibiting ordering effects of those different types. We analyze our data both non-parametrically and parametrically and find robust evidence for ordering effects. We also find that the patterns of order effect in respondents' preferences are significantly changed but not eradicated by the advanced disclosure of choice tasks a finding that offers insights into the choice behaviors underpinning order effects. © 2011 Elsevier Inc.

Good news-bad news:the Yin and Yang of immune privilege in the eye

The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialized function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because its natural defenses are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood-ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics, and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumor-related IP can combine to permit extensive tumor growth and increased risk of metastasis thus threatening the survival of the host.

Millimetre-wave broadband wireless systems and enabling MMIC technologies

Chapter eleven on Mm-wave broadband wireless systems and enabling MMIC technologies, is contributed by Jian Zhang, Mury Thian, Guochi Huang, George Goussetis and Vincent F. Fusco, from Queen's University Belfast, UK. Millimeter wave bands provide large available bandwidths for high data rate wireless communication systems, which are envisaged to shift data throughput well in the GBps range. This capability has over past few years driven rapid developments in the technology underpinning broadband wireless systems as well as in the standardisation activity from various non-governmental consortia and the band allocation from spectrum regulators globally. This chapter provides an overview of the recent developments on V-band broadband wireless systems with the emphasis placed on enabling MMIC technologies. An overview of the key applications and available standards is presented. System-level architectures for broadband wireless applications are being reviewed. Examples of analysis, design and testing on MMIC components in SiGe BiCMOS are presented and the outlook of the technology is discussed.

Older People's Conceptualisation of Elder and neglect

Purpose

To be effective, definitions of elder abuse should be informed by the perspectives of older people themselves.

Methods

This qualitative study used data from eight focus groups involving 58 people aged over 65 years in both urban and rural settings across Northern Ireland and the Republic of Ireland. Following training, four older people assisted in facilitation and analysis as ‘peer-researchers'.

Findings

Increasing lack of respect within society was experienced as abusive. The vulnerability of older people to abuse was perceived as relating to the need for help and support, where standing up for themselves might have repercussions for the person's health or safety. Emotional abusiveness was viewed as underpinning all forms of abuse, and as influencing its experienced severity. Respondents' views as to whether an action was abusive required an understanding of intent; some actions that professionals might view as abusive were regarded as acceptable if they were in the older person's best interests.

Implications

Preventing abuse requires a wide-ranging approach including re-building respect for older people within society. Procedures to prevent elder abuse need to take into account the emotional impact of family relationships and intent, not just a description of behaviours that have occurred.

Meta-Theoretical Paradigms Underpinning Risk in Child Welfare: Towards a Position of Methodological Pragmatism

The aim of this paper is to explore the ‘natural attitude’ underpinning risk practices in child welfare. This refers to various taken-for-granted approaches to risk that social workers and other human service professionals draw upon in their everyday practice. The approach proceeds by identifying and critically examining three key, meta-theoretical paradigms on risk which typically shape the natural attitude. They are labelled ‘objectivist’, ‘subjectivist’ and ‘critical’. The ontological, epistemological, axiological and methodological premises supporting each paradigm, and how they shape risk practices, are then reviewed leading to a composite, meta-theoretical position on risk termed ‘methodological pragmatism’. This position draws on the strengths of each paradigm and is formulated into ten propositions which consider how risk should be approached in child welfare. Within this corpus of thought salient themes are endorsed such as the need for method triangulation, an examination of ‘deep causality’, and the promotion of emancipatory perspectives. By critically reflecting on meta-theory, the paper contributes to the development of substantive theories of risk assessment and management in child welfare.

Offshoring Clinical Trials: The Mutable Ethics, Weak Protections and Vulnerable Subjects of EU Law

In this paper I engage with science and technology studies work on pharmaceuticalisation to explore how European Union (EU) law helps to produce and support the preference for pharmaceutical responses in public health governance, while authorising the production of vulnerable subjects through the growing off-shoring of clinical trials. Drawing on the analysis of legal and policy documents, I demonstrate how EU law allows and legitimates the use of data procured from vulnerable subjects abroad for market authorisation and corporate profitability at home. This is possible because the EU has (de)selected international ethical frameworks in order to support the continued and growing use of clinical trials data from abroad. This has helped to stimulate the revision of international ethical frameworks in light of market needs, inscribing EU public health law within specific politics (that often remained obscured by the joint workings of legal and technological discourses). I suggest that law operates as part of a broader ‘technology’ – encompassing ethics and human rights discourses – that functions to optimise life through resort to market reasoning. Law is thereby reoriented, instrumentalised and deployed as part of a broader project aimed at (re)defining and limiting the boundaries of the EU's responsibility for public health, including the broader social production of public health problems and the unequal global order that the EU represents and helps to depoliticise and perpetuate. Overall, this limits the EU's responsibility and accountability for these failures, as well as another: the weak and mutable protections and insecure legacies for vulnerable trial subjects abroad.

A Case Study in Policy Delivery:Examining Social Inclusion through Interpretation and Practice

The current body of literature regarding social inclusion and the arts tends to focus
on two areas: the lack of clear or common understanding of the terminology involved
(GLLAM, 2000) and the difficulty in measuring impact (Newman 2001). Further, much
of the literature traces the historical evolution of social inclusion policy within the arts
from a political and social perspective (Belfiore & Bennett, 2007), whilst others
examine the situation in the context of the museum as an institution more generally
(Sandell, 2002b). Such studies are essential; however they only touch on the
importance of understanding the context of social inclusion programmes. As each
individual’s experience of exclusion (or inclusion) is argued to be different (Newman
et al., 2005) and any experience is also process-based (SEU 2001), there is a need
for more thorough examination of the processes underpinning project delivery
(Butterfoss, 2006), particularly within a field that has its own issues of exclusion, such
as the arts (Bourdieu & Darbel, 1991). This paper presents case study findings of a
programme of contemporary arts participation for adults with learning difficulties
based at an arts centre in Liverpool. By focusing on practice, the paper applies
Wenger’s (1998) social theory of learning in order to assert that rather than search
for measurable impacts, examining the delivery of programmes within their individual
contexts will provide the basis for a more reflective practice and thus more effective
policy making.

Business Giving, the Tsunami and Corporates as Rock Stars: Some Implications for Arts Funding?

Financial and cultural aspects of corporate giving by UK and non-UK companies in response to the December 2004 South Asia Tsunami disaster are explored in this article. Literatures on corporate giving rationales, concepts of disaster and donor activity in disasters provide an underpinning. The article seeks to make connections between this high profile if short-lived business giving and the funding of the arts that is sought from business; and to draw tentative lessons for arts funding when seeking business support. The giving accounts in the wake of the Tsunami from a non-probability sample of 56 UK companies and 16 non-UK companies were examined. Reported online to the UK charity Business in the Community, these accounts were accessed in February 2005 and scrutinized thematically. Concurrently, company financial profiles to accompany giving figures were constructed. Although linkages between donation levels and financial performance were lacking, emerging themes included the role of employees, influencing company giving and creating a climate of expectation of firms' contributions. These developments may have important implications for business funding for the arts, where leading philanthropists are prominent as individuals in the giving landscapes; but employees' collective involvement is not marked. Alternatively, cultivation of employees as would-be donors, indirectly via their firms, may be a more secure, if lower level route to funding for some arts organizations than dependence on high profile business leaders. The article considers alternative scenarios for company giving in disaster contexts, including as a sustained and lasting giving theme or as company support as a ‘one-off’ event, rock-star style. The likely development of employee power as a key element in company giving is explored; and its wider meanings for funding in arts settings, (where the giver as rock star heroine/hero is also prominent) are considered.

MSC-clustering and forward stepwise regression for virtual metrology in highly correlated input spaces

Increasingly semiconductor manufacturers are exploring opportunities for virtual metrology (VM) enabled process monitoring and control as a means of reducing non-value added metrology and achieving ever more demanding wafer fabrication tolerances. However, developing robust, reliable and interpretable VM models can be very challenging due to the highly correlated input space often associated with the underpinning data sets. A particularly pertinent example is etch rate prediction of plasma etch processes from multichannel optical emission spectroscopy data. This paper proposes a novel input-clustering based forward stepwise regression methodology for VM model building in such highly correlated input spaces. Max Separation Clustering (MSC) is employed as a pre-processing step to identify a reduced srt of well-conditioned, representative variables that can then be used as inputs to state-of-the-art model building techniques such as Forward Selection Regression (FSR), Ridge regression, LASSO and Forward Selection Ridge Regression (FCRR). The methodology is validated on a benchmark semiconductor plasma etch dataset and the results obtained are compared with those achieved when the state-of-art approaches are applied directly to the data without the MSC pre-processing step. Significant performance improvements are observed when MSC is combined with FSR (13%) and FSRR (8.5%), but not with Ridge Regression (-1%) or LASSO (-32%). The optimal VM results are obtained using the MSC-FSR and MSC-FSRR generated models. © 2012 IEEE.

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.

Tumor-derived CXCL8 signaling augments stroma-derived CCL2-promoted proliferation and CXCL12-mediated invasion of PTEN-deficient prostate cancer cells

Impaired PTEN function is a genetic hallmark of aggressive prostate cancers (CaP) and is associated with increased CXCL8 expression and signaling. The current aim was to further characterize biological responses and mechanisms underpinning CXCL8-promoted progression of PTEN-depleted prostate cancer, focusing on characterizing the potential interplay between CXCL8 and other disease-promoting chemokines resident within the prostate tumor microenvironment. Autocrine CXCL8-stimulation (i) increased expression of CXCR1 and CXCR2 in PTEN-deficient CaP cells suggesting a self-potentiating signaling axis and (ii) induced expression of CXCR4 and CCR2 in PTEN-wild-type and PTEN-depleted CaP cells. In contrast, paracrine CXCL8 signaling induced expression and secretion of the chemokines CCL2 and CXCL12 from prostate stromal WPMY-1 fibroblasts and monocytic macrophage-like THP-1 cells. In vitro studies demonstrated functional co-operation of tumor-derived CXCL8 with stromal-derived chemokines. CXCL12-induced migration of PC3 cells and CCL2-induced proliferation of prostate cancer cells were dependent upon intrinsic CXCL8 signaling within the prostate cancer cells. For example, in co-culture experiments, CXCL12/CXCR4 signaling but not CCL2/CCR2 signaling supported fibroblast-mediated migration of PC3 cells while CXCL12/CXCR4 and CCL2/CCR2 signaling underpinned monocyte-enhanced migration of PC3 cells. Combined inhibition of both CXCL8 and CXCL12 signaling was more effective in inhibiting fibroblast-promoted cell motility while repression of CXCL8 attenuated CCL2-promoted proliferation of prostate cancer cells. We conclude that tumor-derived CXCL8 signaling from PTEN-deficient tumor cells increases the sensitivity and responsiveness of CaP cells to stromal chemokines by concurrently upregulating receptor expression in cancer cells and inducing stromal chemokine synthesis. Combined chemokine targeting may be required to inhibit their multi-faceted actions in promoting the invasion and proliferation of aggressive CaP.

Pool Evolution: A Parallel Pattern for Evolutionary and Symbolic Computing

We introduce a new parallel pattern derived from a specific application domain and show how it turns out to have application beyond its domain of origin. The pool evolution pattern models the parallel evolution of a population subject to mutations and evolving in such a way that a given fitness function is optimized. The pattern has been demonstrated to be suitable for capturing and modeling the parallel patterns underpinning various evolutionary algorithms, as well as other parallel patterns typical of symbolic computation. In this paper we introduce the pattern, we discuss its implementation on modern multi/many core architectures and finally present experimental results obtained with FastFlow and Erlang implementations to assess its feasibility and scalability.

Environmental Operations Management and its links with Proactivity and Performance: A study of the UK Food Industry

Two important strands of research within the literature on Environmental Operations Management (EOM) relate to environmental approach and performance. Often in this research the links between environmental approach, environmental performance and EOM are considered separately with little consideration given to the interrelationships between them. This study develops and tests a theoretical framework that combines these two strands to explore how UK food manufacturers approach EOM. The framework considers the relationships between an environmentally pro-active strategic orientation, EOM and environmental and cost performance. A cross-sectional survey was developed to collect data from a sample of 1200 food manufacturing firms located within the UK. Responses were sought from production and operations managers who are knowledgeable about the environmental operations practices within their firms. A total of 149 complete and useable responses were obtained. The reliability and validity of the scales used in the survey were tested using exploratory factor analysis, prior to the testing of the hypotheses underpinning the theoretical framework using hierarchical regression analysis. Our results generate support for a link between environmental proactivity, environmental practices and performance, consistent with the natural resource-based view (NRBV) and a number of studies in the extant literature. In considering environmental proactivity as a standalone concept that influences the implementation of environmental practices outlined in the NRBV, our study generates some novel insights into these links. Further our results provide some interesting insights for managers within the food industry who can identify the potential benefits of certain practices for performance within this unique context.