Assessing the Activity of Agonistic Autoantibodies in Systemic Sclerosis and their Effects on Cultured Vascular Smooth Muscle Cells

La sclérose systémique (ScS) est une maladie auto-immune dévastatrice d'étiologie inconnue. Le dysfonctionnement immunitaire, la fibrose et la vasculopathie sont les trois principales caractéristiques de cette maladie. Une récente étude a révélé un nouveau lien entre l'auto-immunité et la fibrose, par la présence d'auto-anticorps stimulant le récepteur du facteur de croissance dérivé des plaquettes (PDGFR) des fibroblastes. Ces auto-anticorps sont capables de stimuler les espèces réactives de l'oxygène et d’activer la kinase régulée par un signal extracellulaire (ERK1/2). L’hypothèse que nous formulons est que les cellules musculaires lisses vasculaires (VSMCs) exprimant conjointement les PDGFR, répondront elles aussi aux autoanticorps anti-PDGF-R. Le travail présenté ici vise à valider la présence d'auto-anticorps PDGFR dans les sérums de patients ScS, et à caractériser ensuite la réponse de VSMCs exposées à de l'immunoglobuline G (IgG) de ces sérums, en mesurant l’activation des cascades de signalisation spécifiques, ainsi que l'induction des gènes impliqués dans la réponse fibrotique. Nos résultats démontrent la présence d'une fraction IgG stimulant une réponse phénotypique dans les cultures de VSMCs. Notamment, d’importantes régulations positive et négative des gènes pro-fibrotiques tgfb1 et tgfb2 respectivement, ont été observées dans les VSMCs exposées à des fractions de ScS-IgG. Les fractions de IgG positives pour l'activation de ERK étaient présentes dans la plupart, mais pas dans tous les échantillons de SSc (68%, 19/28), et moins présentes dans les contrôles 27% (11/3). Bien que, les fractions de SSc-IgG ont pu considérablement immunoprécipiter le PDGFR, l'utilisation d'un inhibiteur spécifique des récepteurs au PDGF (AG1296), n'a pas inhibé l'activation de ERK médiée par les fractions de SSc-IgG. Globalement, nos résultats indiquent la présence d'autoanticorps stimulants avec activité pro-fibrotique dans les sérums des patients ScS. Des travaux sont en cours pour identifier l'entité moléculaire responsable de la réponse d’IgG observée dans les cultures de VSMCs.

The work of psychologists in social policy in Brazil

This study verses on the meeting of psychology with the social policy area. The objective is to discuss how psychologists that work in the Basic Health Units and in the Social Assistance Reference Centers experience their daily practices. Using the interview and participant observation methods, we investigated the modes of action of 13 psychologists involved in these service units. The results indicate that because these contexts are adverse to the traditional forms of action, many professionals experience daily strangeness and discomfort, resulting from their encounters with limiting situations of difficult management. Furthermore, we observed practices and experiences that were marked by feelings of compassion, pity, and resentment. We consider, finally, that the encounter between psychology and social policies requires flexibility in traditional acting modes as well as the pursuit of strategies that consider cultural contexts characteristics, avoiding capture, fatigue and saturation process that stifle the worker.

Overcoming Gender Disadvantages. Social Policy Analysis of urban middle-class women in Colombia

The World Bank Report 2012 starts with this statement: “Gender equality matters in itself andit matters for development because, in today’s globalized worlds, countries that use the skillsand talents of their women would have an advantage over those which do not use it.” With theframe that suggest that gender equality matters, this paper describes some policy alternativesoriented to overcome gender disadvantages in the formal labor market incorporation of theurban middle class women in Colombia. On balance, the final recommendation suggest that itis desirable to adopt policy alternatives as Community Centers, which are programs orientedto a social redistribution of the domestic work as a way to encourage women participationin the formal labor market with the social support of the members of their own community.The problem that the social policy needs to address is the segregation of women in the formallabor market in Colombia. Although the evidence shows that the women overcome theeducational gap by showing better performance in education that their male peers, womenare still segregated of the labor market. The persistence of high rates of unemployment on thefemale population, the prevalence of the informal labor market as a women labor market, andthe presence of the payment difference between men and women with similar professionaltrainings are circumstances that sustain the segregation statement. These circumstances areinefficient for the society because an economic analysis shows that the cost of maintain the statuquo is externalized in the social security system that includes health, pension and maternityleave regimens. Therefore, the women segregation involves a market failure.This paper evaluates five policy alternatives each directed to the progress of a different causaldimension of the problem: (i) Quotas in the private market, (ii) Flexible working hours,(iii) replace the maternity leave with a family leave, (iv) Increase the Community Centers forredistributing the care work, and (v) Equal payment enforcement. The first alternative looksto increase women’s participation in the formal labor market. The second, third, and fourthalternatives constitute a package addressed at redistributing care work by reducing women’sresponsibility for reproductive work in the household with the help of husbands and the localgovernment. The fifth alternative intervenes to resolve the equal payment problem.After a four criteria evaluation that measure effectiveness, robustness and improbability inimplementation, efficiency and political acceptability or social opposition, the strongest alternativeis the fostering of Community Centers that promote a redistribution of care work. Thispolicy performs well in the assessment process because it combines gender focus with importantindirect effects: child support and human capabilities. The policy also shows a bottomup implementation process that overcomes the main adoption difficulties in the gender focusprograms and is supported by strong evidence of success in the Colombian context; this evidenceis produced by both transnational actors as a World Bank and also in local accountabilityreporters executed by local institutions like Colombian Institute of Family Welfare (ICBF).

Supporting Computer-supported collaborative work (CSCW) in conceptual design

In order to gain a better understanding of online conceptual collaborative design processes this paper investigates how student designers make use of a shared virtual synchronous environment when engaged in conceptual design. The software enables users to talk to each other and share sketches when they are remotely located. The paper describes a novel methodology for observing and analysing collaborative design processes by adapting the concepts of grounded theory. Rather than concentrating on narrow aspects of the final artefacts, emerging “themes” are generated that provide a broader picture of collaborative design process and context descriptions. Findings on the themes of “grounding – mutual understanding” and “support creativity” complement findings from other research, while important themes associated with “near-synchrony” have not been emphasised in other research. From the study, a series of design recommendations are made for the development of tools to support online computer-supported collaborative work in design using a shared virtual environment.

Visualizing knowledge in project-based work

This article considers how visual practices are used to manage knowledge in project-based work. It compares project-based work in a capital goods manufacturer and an architectural firm. Visual representations are used extensively in both cases, but the nature of visual practice differs significantly between the two. The research explores the kinds of knowledge that are (and aren't) developed and made visible in strategizing and planning activities. For example, whereas the emphasis of project-based work in the former firm is on exploitation of knowledge and it visualizes its project context largely in commercial and processual terms, the emphasis in the latter is on exploration and it uses a wide range of visual materials to understand physical interdependencies across the project boundary. We contend particular kinds of visual tools can help project teams step between exploration and exploitation within a project, and articulate the types of representations, foci of attention and patterns of interaction involved. The findings suggest that business managers can make more deliberate choices about how knowledge is made visible, and can change visual practice to align the project with exploring and exploiting opportunities. It raises the question: What don't you see within your organization? The work contributes to academic debates about managing through projects, strategising and organizing, while the focus on visual representation disrupts the tacit-codified dichotomy in the broad debate on knowledge and learning, and highlights the craft skills central to strategizing and organizing.

Supporting ad hoc collaborations in peer-to-peer networks

Traditionally, applications and tools supporting collaborative computing have been designed only with personal computers in mind and support a limited range of computing and network platforms. These applications are therefore not well equipped to deal with network heterogeneity and, in particular, do not cope well with dynamic network topologies. Progress in this area must be made if we are to fulfil the needs of users and support the diversity, mobility, and portability that are likely to characterise group work in future. This paper describes a groupware platform called Coco that is designed to support collaboration in a heterogeneous network environment. The work demonstrates that progress in the p development of a generic supporting groupware is achievable, even in the context of heterogeneous and dynamic networks. The work demonstrates the progress made in the development of an underlying communications infrastructure, building on peer-to-peer concept and topologies to improve scalability and robustness.

Language capital and development: the case of African language publishing for children in South Africa

In recognizing 11 official languages, the 1996 South African Constitution provides a context for the management of diversity with important implications for the redistribution of wealth and power. The development and implementation of the language-in-education policies which might be expected to flow from the Constitution, however, have been slow and ineffective. One of the casualties of government procrastination has been African language publishing. In the absence of well-resourced bilingual education, most learners continue to be taught through the medium of English as a second language. Teachers are reluctant to use more innovative pedagogies without the support of adequate African language materials and publishers are cautious about producing such materials. Nonetheless, activity in this sector offers many opportunities for African language speakers. This paper explores the challenges and constraints for African language publishing for children and argues that market forces and language policy need to work in mutually reinforcing ways. Further progress is necessarily dependent on the political will to implement language-in-education policies that promote additive bilingualism and, in the process, guarantee sales for risk-averse publishers.

Playing with history: negotiating subjectivity in contemporary lens based work

Contemporary artists exploring Jewish identity in the UK are caught between two exclusions, broadly speaking: an art community that that sees itself as ‘post –identity’ and a ‘black’ art scene that revolves around the organizations that emerged out of the Identity debates of the 1980s and 1990s, namely Iniva, Third Text, Autograph. These organizations and those debates, don’t usually include Jewish identity within their remit as Jewish artists are considered to be well represented in the British art scene and, in any case, white. Out of these assumptions, questions arise in relation to the position of Jews in Britain and what is at stake for an artist in exploring Jewish Identity in their work. There is considerable scholarship, relatively speaking on art and Jewish Identity in the US (such as Lisa Bloom; Norman Kleeblatt; Catherine Sousslouf), which inform the debates on visual culture and Jews. In this chapter, I will be drawing out some of the distinctions between the US and the UK debates within my analysis, building on my own writing over the last ten years as well as the work of Juliet Steyn, Jon Stratton and Griselda Pollock. In short, this chapter aims to explore the problematic of what Jewish Identity can offer the viewer as art; what place such art inhabits within a wider artistic context and how, if at all, it is received. There is a predominance of lens based work that explores Identity arising out of the provenance of feminist practices and the politics of documentary that will be important in the framing of the work. I do not aim to consider what constitutes a Jewish artist, that has been done elsewhere and is an inadequate and somewhat spurious conversation . I will also not be focusing on artists whose intention is to celebrate an unproblematised Jewishness (however that is constituted in any given work). Recent artworks and scholarship has in any case rendered the trumpeting of attachment to any singular identity anachronistic at best. I will focus on artists working in the UK who incorporate questions of Jewishness into a larger visual enquiry that build on Judith Butler’s notion of identity as process or performative as well as the more recent debates and artwork that consider the intersectionality of identifications that co-constitute provisional identities (Jones, Modood, Sara Ahmed, Braidotti/Nikki S Lee, Glenn Ligon). The case studies to think through these questions of identity, will be artworks by Susan Hiller, Doug Fishbone and Suzanne Triester. In thinking through works by these artists, I will also serve to contextualise them, situating them briefly within the history of the landmark exhibition in the UK, Rubies and Rebels and the work of Ruth Novaczek, Lily Markewitz, Oreet Ashery and myself.

ATD: a multiplatform for semiautomatic 3-D detection of kidneys and their pathology in real time

This research presents a novel multi-functional system for medical Imaging-enabled Assistive Diagnosis (IAD). Although the IAD demonstrator has focused on abdominal images and supports the clinical diagnosis of kidneys using CT/MRI imaging, it can be adapted to work on image delineation, annotation and 3D real-size volumetric modelling of other organ structures such as the brain, spine, etc. The IAD provides advanced real-time 3D visualisation and measurements with fully automated functionalities as developed in two stages. In the first stage, via the clinically driven user interface, specialist clinicians use CT/MRI imaging datasets to accurately delineate and annotate the kidneys and their possible abnormalities, thus creating “3D Golden Standard Models”. Based on these models, in the second stage, clinical support staff i.e. medical technicians interactively define model-based rules and parameters for the integrated “Automatic Recognition Framework” to achieve results which are closest to that of the clinicians. These specific rules and parameters are stored in “Templates” and can later be used by any clinician to automatically identify organ structures i.e. kidneys and their possible abnormalities. The system also supports the transmission of these “Templates” to another expert for a second opinion. A 3D model of the body, the organs and their possible pathology with real metrics is also integrated. The automatic functionality was tested on eleven MRI datasets (comprising of 286 images) and the 3D models were validated by comparing them with the metrics from the corresponding “3D Golden Standard Models”. The system provides metrics for the evaluation of the results, in terms of Accuracy, Precision, Sensitivity, Specificity and Dice Similarity Coefficient (DSC) so as to enable benchmarking of its performance. The first IAD prototype has produced promising results as its performance accuracy based on the most widely deployed evaluation metric, DSC, yields 97% for the recognition of kidneys and 96% for their abnormalities; whilst across all the above evaluation metrics its performance ranges between 96% and 100%. Further development of the IAD system is in progress to extend and evaluate its clinical diagnostic support capability through development and integration of additional algorithms to offer fully computer-aided identification of other organs and their abnormalities based on CT/MRI/Ultra-sound Imaging.

Essays on labour market dualisation in Western Europe: active labour market policies, temporary work regulation and inequality

European labour markets are increasingly divided between insiders in full-time permanent employment and outsiders in precarious work or unemployment. Using quantitative as well as qualitative methods, this thesis investigates the determinants and consequences of labour market policies that target these outsiders in three separate papers. The first paper looks at Active Labour Market Policies (ALMPs) that target the unemployed. It shows that left and right-wing parties choose different types of ALMPs depending on the policy and the welfare regime in which the party is located. These findings reconcile the conflicting theoretical expectations from the Power Resource approach and the insider-outsider theory. The second paper considers the regulation and protection of the temporary work sector. It solves the puzzle of temporary re-regulation in France, which contrasts with most other European countries that have deregulated temporary work. Permanent workers are adversely affected by the expansion of temporary work in France because of general skills and low wage coordination. The interests of temporary and permanent workers for re-regulation therefore overlap in France and left governments have an incentive to re-regulate the sector. The third paper then investigates what determines inequality between median and bottom income workers. It shows that non-inclusive economic coordination increases inequality in the absence of compensating institutions such as minimum wage regulation. The deregulation of temporary work as well as spending on employment incentives and rehabilitation also has adverse effects on inequality. Thus, policies that target outsiders have important economic effects on the rest of the workforce. Three broader contributions can be identified. First, welfare state policies may not always be in the interests of labour, so left parties may not always promote them. Second, the interests of insiders and outsiders are not necessarily at odds. Third, economic coordination may not be conducive to egalitarianism where it is not inclusive.