Talking about the genes for cancer. A study of lay and professional knowledge of cancer genetics

This paper is concerned with the ways in which people who work in and use a cancer genetics clinic in the UK talk about the ‘gene for cancer’. By conceptualising such a gene as a boundary object, and using empirical data derived from clinic consultations, observations in a genetics laboratory and interviews with patients, the author seeks to illustrate how the various parties involved adopt different discursive strategies to appropriate, describe and understand what is apparently the ‘same’ thing. The consequent focus on the ways in which the rhetorical and syntactical features of lay and professional talk interlink and diverge, illustrates not merely how our contemporary knowledge of genes and genetics is structured, but also how different publics position themselves with respect to the biochemistry of life.

The Growth, Learning and Development Study: Summary of Research, Findings and Recommendations.

The Growth, Learning and Development (GLAD) study aimed to examine how a broad range of factors influence child weight during the first year of life. Assessments were undertaken within a multidisciplinary team framework. The sample was drawn from the community and data collection was undertaken in the four Greater Belfast Trusts. Twohundred and thirty-four families took part, each receiving a total of five home visits during which physical growth, oral-motor skills and development were assessed. Psychosocial evaluation examined parent-child interaction, feeding and other parental and child characteristics using quantitative and observational techniques. This paper outlines the main findings and recommendations from the GLAD study.

BRCA1: mechanisms of inactivation and implications for management of patients.

The BRCA1 gene was cloned in 1994 as one of the genes that conferred genetic predisposition to early-onset breast and ovarian cancer. Since then, a genetic test for identification of high-risk individuals has been developed. Despite being implicated in many important cellular pathways, including DNA repair and regulation of transcription, the exact mechanism by which inactivation of BRCA1 might lead to malignant transformation of cells remains unknown. We examine the mechanisms that underlie inactivation of BRCA1 and assess how they affect management of patients, in terms of both primary and secondary cancer prevention strategies. Furthermore, we look at the potential usefulness of BRCA1 as a prognostic tool and as a predictive marker of response to different classes of drugs. Finally, throughout this review, we draw links between the functional consequences of BRCA1 inactivation, in terms of key cellular signalling pathways, and how they might explain specific clinical observations in individuals who carry mutations in the gene.

Substitution of pseudokinase domain residue Val-617 by large non-polar amino acids causes activation of JAK2

Explaining the uniqueness of the acquired somatic JAK2 V617F mutation, which is present in more than 95% of polycythemia vera patients, has been a challenge. The V617F mutation in the pseudokinase domain of JAK2 renders the unmutated kinase domain constitutively active. We have performed random mutagenesis at position 617 of JAK2 and tested each of the 20 possible amino acids for ability to induce constitutive signaling in Ba/F3 cells expressing the erythropoietin receptor. Four JAK2 mutants, V617W, V617M, V617I, and V617L, were able to induce cytokine independence and constitutive downstream signaling. Only V617W induced a level of constitutive activation comparable with V617F. Also, only V617W stabilized tyrosine-phosphorylated suppressor of cytokine signaling 3 ( SOCS3), a mechanism by which JAK2 V617F overcomes inhibition by SOCS3. The V617W mutant induced a myeloproliferative disease in mice, mainly characterized by erythrocytosis and megakaryocytic proliferation. Although JAK2 V617W would predictably be pathogenic in humans, the substitution of the Val codon, GTC, by TTG, the codon for Trp, would require three base pair changes, and thus it is unlikely to occur. We discuss how the predicted conformations of the activated JAK2 mutants can lead to better screening assays for novel small molecule inhibitors.

Interaction of directional, neuromuscular and egocentric constraints on the stability of preferred bimanual coordination patterns

We investigated how the relative direction of limb movements in external space (iso- and non-isodirectionality), muscular constraints (the relative timing of homologous muscle activation) and the egocentric frame of reference (moving simultaneously toward/away the longitudinal axis of the body) contribute to the stability of coordinated movements. In the first experiment, we attempted to determine the respective stability of isodirectional and non-isodirectional movements in between-persons coordination. In a second experiment, we determined the effect of the relative direction in external space, and of muscular constraints, on pattern stability during a within-person bimanual coordination task. In the third experiment we dissociated the effects on pattern stability of the muscular constraints, relative direction and egocentric frame of reference. The results showed that (1) simultaneous activation of homologous muscles resulted in more stable performance than simultaneous activation of non-homologous muscles during within-subject coordination, and that (2) isodirectional movements were more stable than non-isodirectional movements during between-persons coordination, confirming the role of the relative direction of the moving limbs in the stability of bimanual coordination. Moreover, the egocentric constraint was to some extent found distinguishable from the effect of the relative direction of the moving limbs in external space, and from the effect of the relative timing of muscle activation. In summary, the present study showed that relative direction of the moving limbs in external space and muscular constraints may interact either to stabilize or destabilize coordination patterns. (C) 2003 Published by Elsevier B.V.

The construction of images of people and place: Labelling Liverpool and stereotyping Scousers.

On 28th August 1207, King John created the Borough of Liverpool by granting its first charter. During the ensuing 800 years Liverpool has experienced a complex and changing social, economic and political history resulting in powerful images of the city and its people. This paper examines the labelling of Liverpool and stereotypes of Scousers. It explains how historical and contemporary events, and their coverage in various arms of the media, construct social and spatial imaginations of the city. This involves a more systematic contribution to the how and why dimensions of negative place imagery and social stereotypes, and enhances our understanding of the processes and issues affecting our interpretations of people and place. The analysis is both historical and contemporaneous in teasing out how previous and current events shape the perceptions of insiders and outsiders. This paper reveals that despite concerted efforts to re-brand Liverpool the city continues to face difficult challenges with ongoing bad publicity and negative place imagery.

Study of the images for the Visual Arts Education in Secondary Education textbooks: educational implications

In this paper we present the first data from the research conducted to determine the relationship between traditional visual arts and other forms of visual culture closer to the experiences of high school youth. The hypothesis of this research is that while students are nurtured and live primarily with the images provided by the media culture, their textbooks basically refer to the more traditional art images. The research has been limited to a review and analysis of the most common educational materials for teaching visual arts in high school. After the systematization and analysis of the images appeared in textbooks, we have detected three major types: the artistics, those who belong to media culture and others. The most relevant conclusions indicate that: there are hardly any connections between different types of images, they offer a very traditional view of art and they are far removed from the experiences of young book users.

Teachers’ understandings of reconciliation and inclusion in four troubled societies.

In this article, the authors examine how teachers in four troubled societies – Israel, Cyprus, Northern Ireland and South Africa – understand and implement reconciliation in light of the increasing diversity of these societies. The authors particularly pay attention to a dialogical encounter between reconciliation and inclusion, as they look for ways to contemplate how each might be of mutual benefit in educational theory and practice. In the first part of the article, the authors give an overview of current thinking on reconciliation and its role in education, and suggest that the notion of inclusiveness can enrich it. The context of the research is then provided by looking briefly at the socio-political and educational settings in which the study was conducted, followed by a discussion of the research methodology. The findings from the study are then presented with the main themes identified as arising across the four research locations. These themes concern understandings of reconciliation and inclusion, student diversity, teachers’ challenges, helping students deal with conflict, and teachers’ development. Finally, whilst acknowledging the exploratory nature of these findings, the authors discuss what policy makers, school leaders and teachers might change about policies and practices for reconciliation education in the four settings studied and, by implication, other comparable settings.

Retrodirective Array Performance in the Presence of Near Field Obstructions

We investigate the situation where there are obstructing elements present in the near field of a retrodirective array. We describe three scattering cases, (1) by an array of straight wires, (2) by low loss medium density fibre board partially obscuring the array, and (3) by concrete blocks, totally and then partially obscuring the array. For all scenarios retrodirective action was shown to be able to provide various degrees of automatic compensation for loss in gain relative to that which would have occurred for a conventional (non-retrodirective) array in the presence of the same scattering screens. Gain improvements of up to 10 dB were observed when the retrodirective array was used. In addition we show how the induced variation of received and re-transmited amplitudes across the array, caused by the scattering screens, is the principle mechanism causing deterioration of the retrodirective arrays monostatic response.

Dynamical instability in surface permeability characteristics of building sandstones in response to salt accumulation over time

This paper explores how the surface permeability of sandstone blocks changes over time in response to repeated salt weathering cycles. Surface permeability controls the amount of moisture and dissolved salt that can penetrate in and facilitate decay. Connected pores permit the movement of moisture (and hence soluble salts) into the stone interior, and where areas are more or less permeable soluble salts may migrate along preferred pathways at differential rates. Previous research has shown that salts can accumulate in the near-surface zone and lead to partial pore blocking which influences subsequent moisture ingress and causes rapid salt accumulation in the near-surface zone.

Two parallel salt weathering simulations were carried out on blocks of Peakmoor Sandstone of different volumes. Blocks were removed from simulations after 2, 5, 10, 20 and 60 cycles. Permeability measurements were taken for these blocks at a resolution of 20 mm, providing a grid of 100 permeability values for each surface. The geostatistical technique of ordinary kriging was applied to the data to produce a smoothed interpolation of permeability for these surfaces, and hence improve understanding of the evolution of permeability over time in response to repeated salt weathering cycles.

Results illustrate the different responses of the sandstone blocks of different volumes to repeated salt weathering cycles. In both cases, after an initial subtle decline in the permeability (reflecting pore blocking), the permeability starts to increase — reflected in a rise in mean, maximum and minimum values. However, between 10 and 20 cycles, there is a jump in the mean and range permeability of the group A block surfaces coinciding with the onset of meaningful debris release. After 60 cycles, the range of permeability in the group A block surface had increased markedly, suggesting the development of a secondary permeability. The concept of dynamic instability and divergent behaviour is applied at the scale of a single block surface, with initial small-scale differences across a surface having larger scale consequences as weathering progresses.

After cycle 10, group B blocks show a much smaller increase in mean permeability, and the range stays relatively steady — this may be explained by the capillary conditions set up by the smaller volume of the stone, allowing salts to migrate to the ‘back’ of the blocks and effectively relieving stress at the ‘front’ face.

Social categorizations, social comparisons and stigma: Presentations of self in people with learning difficulties

Self-categorization theory stresses the importance of the context in which the metacontrast principle is proposed to operate. This study is concerned with how 'the pool of psychologically relevant stimuli' (Turner, Hogg, Oakes, Reicher & Wetherell, 1987, p. 47) comprising the context is determined. Data from interviews with 33 people with learning difficulties were used to show how a positive sense of self might be constructed by members of a stigmatized social category through the social worlds that they describe, and therefore the social comparisons and categorizations that are made possible. Participants made downward comparisons which focused on people with learning difficulties who were less able or who displayed challenging behaviour, and with people who did not have learning difficulties but who, according to the participants, behaved badly, such as beggars, drunks and thieves. By selection of dimensions and comparison others, a positive sense of self and a particular set of social categorizations were presented. It is suggested that when using self-categorization theory to study real-world social categories, more attention needs to be paid to the involvement of the perceiver in determining which stimuli are psychologically relevant since this is a crucial determinant of category salience.

Freedom of Expression and Hate Speech

This is a study of free speech and hate speech with reference to the international standards and to the United States jurisprudence. The study, in a comparative and critical fashion, depicts the historical evolution and the application of the concept of ‘free speech,’ within the context of ‘hate speech.’ The main question of this article is how free speech can be discerned from hate speech, and whether the latter should be restricted. To this end, it examines the regulation of free speech under the First Amendment to the United States Constitution, and in light of the international standards, particularly under the International Convention on the Elimination of All Forms of Racial Discrimination, International Covenant on Civil and Political Rights, and the European Convention on Human Rights and Fundamental Freedoms. The study not only illustrates how elusive the endeavour of striking a balance between free speech and other vital interests could be, but also discusses whether and how hate speech should be eliminated within the ‘marketplace of ideas.’

Punishment, blame and stigma after conflict: the experience of politically motivated former prisoners in Northern Ireland

This paper examines the relationship between the politics of blame in post-conflict Northern Ireland and the treatment of politically motivated former prisoners. Using the examples of direct and indirect discrimination in the areas of employment and access to mental health services, the paper considers how the discursive operation of blaming produces evasions and attributions of guilt. It argues that such blaming practices have very real material consequences for the allocation or withholding of goods and burdens in the community. The paper notes also that the ‘cause of victims’ is often appropriated by the press and other political actors for their own purposes, frequently to block the provision of public goods to one particular group of ex-combatants: ex-politically motivated prisoners. It concludes by posing a series of questions about blaming, justice and the moral authority of the victim in a transitional justice context. The claim of the paper is simply to offer some starting points for understanding the relationship between processes of blame, stigma and social exclusion.

The European Court of Human Rights and Domestic Violence

Domestic violence is an issue that affects vast numbers of women throughout the world. It seems to constitute a clear violation of at least three articles of the European Convention on Human Rights, however it has only been recognised as being a human rights issue relatively recently. Indeed, until 2007 domestic violence had not been directly addressed by the European Court of Human Rights. However, the Court has now addressed the issue in a series of recent cases. This paper discusses what positive obligations states parties to the Convention now have in relation to the issue of domestic violence. It proceeds to discuss the gaps in the Court’s jurisprudence in this area at present and how the case law of the Court may develop in the future.

Refugial persistence and postglacial recolonization of North America by the cold-tolerant herbaceous plant Orthilia secunda

Previous phylogeographical and palaeontological studies on the biota of northern North America have revealed a complex scenario of glacial survival in multiple refugia and differing patterns of postglacial recolonization. Many putative refugial regions have been proposed both north and south of the ice sheets for species during the Last Glacial Maximum, but the locations of many of these refugia remain a topic of great debate. In this study, we used a phylogeographical approach to elucidate the refugial and recolonization history of the herbaceous plant species Orthilia secunda in North America, which is found in disjunct areas in the west and east of the continent, most of which were either glaciated or lay close to the limits of the ice sheets. Analysis of 596-bp of the chloroplast trnS-trnG intergenic spacer and five microsatellite loci in 84 populations spanning the species' range in North America suggests that O.secunda persisted through the Last Glacial Maximum (LGM) in western refugia, even though palaeodistribution modelling indicated a suitable climate envelope across the entire south of the continent. The present distribution of the species has resulted from recolonization from refugia north and south of the ice sheets, most likely in Beringia or coastal regions of Alaska and British Columbia, the Washington/Oregon region in the northwest USA, and possibly from the region associated with the putative 'ice-free corridor' between the Laurentide and Cordilleran ice sheets. Our findings also highlight the importance of the Pacific Northwest as an important centre of intraspecific genetic diversity, owing to a combination of refugial persistence in the area and recolonization from other refugia.