Nonapical and Cytoplasmic Expression of Interleukin-8, CXCR1, and CXCR2 Correlates with Cell Proliferation and Microvessel Density in Prostate Cancer

Purpose: We characterized interleukin-8 (IL-8) and IL-8 receptor expression (CXCR1 and CXCR2) in prostate cancer to address their significance to this disease. Experimental Design: Immunohistochemistry was conducted on 40 cases of human prostate biopsy containing histologically normal and neoplastic tissue, excised from patients with locally confined or invasive androgen-dependent prostate cancer, and 10 cases of transurethral resection of the prostate material from patients with androgen-independent disease. Results: Weak to moderate IL-8 expression was strictly localized to the apical membrane of normal prostate epithelium. In contrast, membranous expression of IL-8, CXCR1, and CXCR2 was nonapical in cancer cells of Gleason pattern 3 and 4, whereas circumferential expression was present in Gleason pattern 5 and androgen-independent prostate cancer. Each of IL-8, CXCR1, and CXCR2 were also increasingly localized to the cytoplasm of cancer cells in correlation with advancing stage of disease. Cytoplasmic expression (but not apical membrane expression) of IL-8 in Gleason pattern 3 and 4 cancer correlated with Ki-67 expression (R = 0.79; P <0.001), cyclin D1 expression (R = 0.79; P <0.001), and microvessel density (R = 0.81; P <0.001). In vitro studies on androgen-independent PC3 cells confirmed the mitogenic activity of IL-8, increasing the rate of cell proliferation through activation of both CXCR1 and CXCR2 receptors. Conclusions: We propose that the concurrent increase in IL-8 and IL-8 receptor expression in human prostate cancer induces autocrine signaling that may be functionally significant in initiating and promoting the progression of prostate cancer by underpinning cell proliferation and angiogenesis.

Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells

Using a validated tetracycline (tet)-regulated MCF7-founder (MCF7F) expression system to modulate expression of CD44 standard form (CD44s), we report the functional importance of CD44s and that of a novel transcriptional target of hyaluronan (HA)/CD44s signaling, EMS1/cortactin, in underpinning breast cancer metastasis. In functional experiments, tet-regulated induction of CD44s potentiated the migration and invasion of MCF7F cells through HA-supplemented Matrigel. EMS1/cortactin was identified by expression profiling as a novel transcriptional target of HA/CD44 signaling, an association validated by quantitative PCR and immunoblotting experiments in a range of breast cancer cell lines. The mechanistic basis underpinning CD44-promoted transcription of EMS1/cortactin was shown to be dependent upon a NFB mechanism, since pharmacological inhibition of IKinase-2 or suppression of p65 Rel A expression attenuated CD44-induced increases in cortactin mRNA transcript levels. Overexpression of a c-myc tagged murine cortactin construct in the weakly invasive, CD44-deficient MCF7F and T47D cells potentiated their invasion. Furthermore, the functional importance of cortactin to CD44s-promoted metastasis was demonstrated by selective suppression of cortactin in CD44-expressing MCF7F-B5 and MDA-MB-231 breast cancer cells using RNAi, which was shown to result in attenuated CD44-promoted invasion and CD44-promoted adhesion to bone marrow endothelial cells (BMECs).

Auditory sensory memory and working memory processes in children with normal hearing and cochlear implants.

There can be wide variation in the level of oral/aural language ability that prelingually hearing-impaired children develop after cochlear implantation. Automatic perceptual processing mechanisms have come under increasing scrutiny in attempts to explain this variation. Using mismatch negativity methods, this study explored associations between auditory sensory memory mechanisms and verbal working memory function in children with cochlear implants and a group of hearing controls of similar age. Whilst clear relationships were observed in the hearing children between mismatch activation and working memory measures, this association appeared to be disrupted in the implant children. These findings would fit with the proposal that early auditory deprivation and a degraded auditory signal can cause changes in the processes underpinning the development of oral/aural language skills in prelingually hearing-impaired children with cochlear implants and thus alter their developmental trajectory

Educating for peace? Citizenship education in Quebec and Northern Ireland

The article explores particularities of citizenship education in divided societies by comparing key concepts and theoretical frameworks underpinning citizenship education curricula in two divided societies, one of which could be described as relatively peaceful and the other as slowly emerging from political violence. A document analysis of the citizenship education curricula in both societies is conducted to compare differences and commonalities of attempts to promote citizenship and peaceful community relations. Conceptualizations of and interrelationships between citizenship, human rights, and peace education are explored in theory and curricular documents in both societies. The discussion reflects on the value of citizenship education in the context of community divisions and its possible impact on sustainable peace in divided societies.

The Role of Dignity in Equality Law: Lessons from Canada and South Africa

This paper examines the link made on occasion between the concept of dignity and substantive equality; it is further noted that dignity can have very different meanings in different contexts. While the notion of dignity does not often play a substantive role in the resolution of decisions, sometimes the underlying understanding of dignity does matter. However, in all cases, judges should avoid the temptation to rely on unarticulated value judgments or subjective notions of dignity. When judges make reference to dignity, they should articulate the values underpinning their conception of it.

Hanging Flower Baskets, Blowing in the Wind? Third Sector Groups, Cross-Border Partnerships and the EU Peace Programmes in Ireland

The EU’s Peace programmes in Ireland have promoted the cross-border activity of Third sector groups. Potentially, such activity gives substantive meaning to regional cross-border governance and helps to ameliorate ethno-national conflict by providing positive sum outcomes for ‘post-conflict’ communities. The paper mobilizes focused research conducted by the authors to explore this potential. It finds that while regional cross-border governance has indeed developed under the Peace programmes, the sustainability of the social partnerships underpinning this governance is uncertain and its significance for conflict resolution is qualified by difficulties in forming a stable power-sharing arrangement at the political elite level.

Tolstoy, stories, and facilitating insight in end of life care: Exploring ethics through vicarious experience (with Glackin M and Henry R)

Facilitating moral insight in end of life care can be challenging, and the purpose of this paper is to illustrate how this can be nurtured by means of creative literature. Tolstoy's Death of Ivan Ilych is presented as an example of such literature. Aristotle's Nichomean Ethics provides the philosophical underpinning for the method used. Sources also include the nursing literature, and students' evaluations of the impact of Tolstoy's novella on their ability to perceive the ethical issues arising in end of life care. Comments from evaluations were analysed and significant themes emerged. Students' comments clearly support the suggestion that use of this novella has facilitated insight into ethical issues at the end of life. Evaluations also indicate that vicarious experience gained through reading this novella has helped to nurture sensitivity and professional insight into the importance of compassion and offering ‘comfort’ to the dying person.

The Social Politics of Breastfeeding: Norms, Situations and Policy Implications

This paper aims to explore the assumptions concerning the dynamics of human action underpinning breastfeeding promotion campaigns in the UK. Drawing on qualitative interviews with mothers, the ways in which three problematic assumptions shape both the promotion and experience of contemporary breastfeeding promotion campaigns are explored, in the light of Joas’s theorisation of action’s creativity and pragmatism. Public health efforts to establish breastfeeding as a rational standard against which good mothering can be judged, in ways which rely on a de-contextualised understanding of human action as instrumentally rational, where bodies are imagined as pliable instruments of human intentions, are explored as they play out in the experiences of women embarking on motherhood. The paper concludes that a target-driven health-promotion policy, relying on a mechanistic account of social and emotional life, is contributing to the burden of early motherhood in ways that are not conducive to infant and maternal health and attachment.

Combined antenna and localized plasmon resonance in Raman scattering from Random arrays of silver-coated, vertically aligned multiwalled carbon nanotubes

The electric field enhancement associated with detailed structure within novel optical antenna nanostructures is modeled using the surface integral equation technique in the context of surface-enhanced Raman scattering (SERS). The antennae comprise random arrays of vertically aligned, multi-walled carbon nanotubes dressed with highly granular Ag. Different types of "hot-spot" underpinning the SERS are identified, but contrasting characteristics are revealed. Those at the outer edges of the Ag grains are antenna driven with field enhancement amplified in antenna antinodes while intergrain hotspots are largely independent of antenna activity. Hot-spots between the tops of antennae leaning towards each other also appear to benefit from antenna amplification.

Perceived relevance and foods with health-related claims

Although consumer perception of the health claims and nutrition information has been studied widely there is relatively little understanding about the motivational factors underpinning claim perception. The objective of this study is to investigate how levels of perceived relevance influence consumers’ responses to health claims that either promise to reduce a targeted disease risk or improve well-being in comparison to other types of health-related messages, and how attitudes towards nutritionally healthy eating, functional food and previous experience relating to products with health claims affect the consumers’ perceptions of nutrition and health claims. The data (N=2385) were collected by paper and pencil surveys in Finland, the UK, Germany and Italy on a target group of consumers over 35 year old, solely or jointly responsible for the family’s food shopping. The results showed that relevance has a strong influence on perceptions of personal benefit and willingness to buy products with health claims. However the impact of relevance is much stronger when the health risks are relevant to self than when it is relevant to those close to oneself, especially when the claim promises a targeted risk reduction with detailed information about function and health outcome. Previous experience with products with health claims and interest in nutritionally healthy eating promoted the utility of all claims, regardless of whether they were health or nutrition claims. However, to be influenced by health claims consumers also need to have a positive attitude towards functional food products.

Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury

Introduction Changes in the distribution of interstitial cells (IC) are reportedly associated with dysfunctional bladder. The present study investigated whether spinal cord injury (SCI) resulted in changes to IC subpopulations (vimentin-positive with the ultrastructural profile of IC), smooth muscle and nerves within the bladder wall and correlated cellular remodelling with functional properties. Methods Bladders from SCI (T8/9 transection) and sham-operated rats five-weeks post-injury were used for ex vivo pressure-volume experiments or processed for morphological analysis with transmission electron microscopy (TEM) and light/confocal microscopy. Results Pressure-volume relationships revealed low-pressure, hypercompliance in SCI bladders indicative of decompensation. Extensive networks of vimentin-positive IC were typical in sham lamina propria and detrusor but were markedly reduced post-SCI; semi-quantitative analysis showed significant reduction. Nerves labelled with anti-neurofilament and anti-vAChT were notably decreased post-SCI. TEM revealed lamina propria IC and detrusor IC which formed close synaptic-like contacts with vesicle-containing nerve varicosities in shams. Lamina propria and detrusor IC were ultrastructurally damaged post-SCI with retracted/lost cell processes and were adjacent to areas of cellular debris and neuronal degradation. Smooth muscle hypertrophy was common to SCI tissues. Conclusions IC populations in bladder wall were decreased five weeks post-SCI, accompanied with reduced innervation, smooth muscle hypertrophy and increased compliance. These novel findings indicate that bladder wall remodelling post-SCI affects the integrity of interactions between smooth muscle, nerves and IC, with compromised IC populations. Correlation between IC reduction and a hypercompliant phenotype suggests that disruption to bladder IC contribute to pathophysiological processes underpinning the dysfunctional SCI bladder.

Social Work Students Learn about Social Work Values from Service Users and Carers

Teaching on social work values is centrally important in social work education as a core aspect of underpinning knowledge in preparing students for practice. This paper describes an innovative project occurring within the first year of the degree in social work, where service users and carers have assisted students with their understanding of social work values. The positive contribution of service users and carers in facilitating students to make links between theory and practice is now well documented. Applying this user perspective to the educational domain of values, however, is relatively uncharted territory given the challenges that have traditionally accompanied the teaching of values. Importantly, this paper describes the ‘value talk’ which occurred when first-year students sought further meaning from service-user and carer groups in their community settings following classroom teaching on values. The paper not only discusses the detailed preparations involved in the project but also the learning which resulted, drawing on the evaluation findings from the students and participating groups. Whilst the findings show that the students' understanding of social work values has been most significantly influenced by the contributions from service users and carers, it is recognized that further research is needed to monitor the longer term impact on social work students' practice after they qualify.

Oxygen indicators and intelligent inks for packaging food

The detection of oxygen using optical sensors is of increasing interest, especially in modified atmosphere food packaging (MAP), in which the package, usually containing food, is flushed with a gas, such as carbon dioxide or nitrogen. This tutorial review examines the ideal properties of an oxygen optical sensor for MAP and compares them with those developed to date, including the most recent advances. The basic technologies underpinning the different indicator types are described, examples given and their potential for application in MAP assessed. This tutorial review should be of interest to the MAP industry and researchers in optical sensors and oxygen sensing.

Banking in Crisis: The Rise and Fall of British Banking Stability, 1800 to the Present

Can the lessons of the past help us to prevent another banking collapse in the future? This is the first book to tell the story of the rise and fall of British banking stability in the past two centuries, and it sheds new light on why banking systems crash and the factors underpinning banking stability. John Turner shows that there were only two major banking crises in Britain during this time: the crisis of 1825–6 and the Great Crash of 2007–8. Although there were episodic bouts of instability in the interim, the banking system was crisis-free. Why was the British banking system stable for such a long time and why did the British banking system implode in 2008? In answering these questions, the book explores the long-run evolution of bank regulation, the role of the Bank of England, bank rescues and the need to hold shareholders to account.