L'indicateur EU2020 de suivi de la pauvreté et de l'exclusion: une analyse critique

The reduction of poverty and social exclusion is one of the targets of the European Union's 2020 strategy. The appropriateness and success of such a policy require the choice of relevant indicators that not only highlight poverty gaps between countries but also identify the groups of individuals in each country that need particular attention from social policies. The target retained in the European strategy combines three criteria: people living in households below the monetary poverty threshold, poor people “in terms of standard of living” who live in a situation of severe material deprivation, and those who live in households with very low or zero work intensity. We first show that neither the combination nor the intersection of these three criteria produces an adequate measure of the fight against poverty, or an objective for it. We therefore propose an alternative concept, that of “consistent poverty”, which targets people who simultaneously live below the monetary poverty threshold and above a certain level of material deprivation. The special material deprivation module of the EU-SILC 2009 database allows us to examine two versions of this notion of deprivation: the measurement of “severe” deprivation currently used by the European Union, which adopts a threshold with four items, and an alternative measure of “elementary” material deprivation with a three-item threshold. The intersection between our three-item elementary deprivation criterion and the monetary poverty criterion produces more satisfactory results than those obtained by the European Union approach, in terms of both coherency and profile of the population identified.

Economic Stress and the Great Recession in Ireland: Polarization, Individualization or ‘Middle Class Squeeze’?

Following an unprecedented boom, since 2008 Ireland has experienced a severe economic crisis. Considerable debate persists as to where the heaviest burden of the recession has fallen. Conventional measures of income poverty and inequality have a limited capacity to answer this question. Our analysis, which focuses on economic stress and the mediating role of material deprivation, provides no evidence for individualization or class polarization. Instead we find that while economic stress level are highly stratified in income class and social class terms in both boom and bust periods, the changing impact of class is contingent on life course stage. The affluent income class remained largely insulated from the experience of economic stress. However, it saw its relative advantage overthe income poor class decline at the earlier stage of the life-course. At the other end of the hierarchy, the income poor experienced a relative improvement in their situation in the early life course phases. The precarious income class experienced some improvement in its situation at the earlier life course stages while the outcomes for the middle classes remain unchanged. In the mid-life course stages the precarious and lower middle classes experienced disproportionate increase in their stress levels while at the later life-cycle stage it is the combined middle classes that lost out. Additional effects over time relating to social class are restricted to the deteriorating situation of the petit bourgeoisie at the middle stage of the life-course. The pattern is clearly a good deal more complex that suggested by conventional notions of ‘middle class squeeze’ and points to the distinctive challenges relating to welfare and taxation policy faced by governments in the Great Recession.

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - http://www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.

Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells

Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynecological malignancy. High-grade serous OC (HGSOC) is the most common and aggressive OC subtype, characterized by widespread genome changes and chromosomal instability and is consequently poorly responsive to chemotherapy treatment. The objective of this study was to investigate the role of the microRNA miR-433 in the cellular response of OC cells to paclitaxel treatment. We show that stable miR-433 expression in A2780 OC cells results in the induction of cellular senescence demonstrated by morphological changes, downregulation of phosphorylated retinoblastoma (p-Rb), and an increase in β-galactosidase activity. Furthermore, in silico analysis identified four possible miR-433 target genes associated with cellular senescence: cyclin-dependent kinase 6 (CDK6), MAPK14, E2F3, and CDKN2A. Mechanistically, we demonstrate that downregulation of p-Rb is attributable to a miR-433-dependent downregulation of CDK6, establishing it as a novel miR-433 associated gene. Interestingly, we show that high miR-433 expressing cells release miR-433 into the growth media via exosomes which in turn can induce a senescence bystander effect. Furthermore, in relation to a chemotherapeutic response, quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that only PEO1 and PEO4 OC cells with the highest miR-433 expression survive paclitaxel treatment. Our data highlight how the aberrant expression of miR-433 can adversely affect intracellular signaling to mediate chemoresistance in OC cells by driving cellular senescence.

miR-433 overexpression attenuates the spindle assembly checkpoint response to paclitaxel

Paclitaxel is a microtubule inhibitory chemotherapeutic drug that is increasingly used for the treatment of solid tumours. In vitro studies have demonstrated that attenuating the spindle assemble checkpoint (SAC) alters the post-mitotic responses to paclitaxel. Furthermore, the aberrant expression of a number of the SAC proteins, MAD2, BUBR1, and Aurora A kinase, are associated with poor patient prognosis. We have identified a microRNA, miR-433, that regulates the expression of MAD2. Overexpression of miR-433 in Hela cells induced downregulation of MAD2 mRNA and protein expression. We have also shown that Hela cells overexpressing miR-433 and treated with paclitaxel are no longer capable of cyclin B stabilisation, and thus have lost the ability to activate the SAC in response to paclitaxel. In addition, cell viability assays showed that Hela cells overexpressing miR-433 and treated with paclitaxel have an attenuated response to paclitaxel compared with microRNA scrambled controls. We have characterised the levels of miR-433, MAD2 gene expression and MAD2 protein levels in a cohort of ovarian cancer cell lines. Cell viability assays on this cohort revealed that responsiveness to paclitaxel is associated with high MAD2 protein expression and lower miR-433 expression. We hypothesise that the expression of miR-433 when deregulated in cancer leads to altered MAD2 expression and a compromised SAC, a key feature underlying drug resistance to paclitaxel. In a pilot study of paired human breast tumour and normal breast tissue samples we have shown that expression levels of miR-433 are elevated in cancer tissue. Targeting this microRNA in cancer may improve the efficacy of paclitaxel in treating breast cancer and ovarian cancer.

MiR-433 induces cellular senescence rendering ovarian cancer cells less likely to undergo chemotherapy-induced apoptosis

Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynaecological malignancy. Such mortality is predominantly associated with the development of an intrinsic and acquired resistance to chemotherapy, the lack of targeted therapies and the lack of biomarkers predicting therapeutic response.

Our clinical data demonstrates that increased miR-433 expression in primary high grade serous OC (HGSOCs) is significantly associated with poor PFS (n=46, p=0.024). Interestingly, the IHC analysis of two miR-433 targets: MAD2 [Furlong et al., 2012 PMID:22069160] and HDAC6 shows that low IHC levels of both proteins is also significantly associated with worse outcome (p=0.002 and 0.002 respectively; n=43). Additionally, the analysis of miR 433 in the publicly available TCGA dataset corroborates that high miR-433 is significantly correlated with worse OS for patients presenting with OC (n=558 and p=0.027). In vitro, in a panel of OC cell lines, higher miR-433 and lower MAD2 and HDAC6 levels were associated with resistance to paclitaxel.

To further investigate the role of miR-433 in the cellular response to chemotherapy, we generated an OC cell line stably expressing miR-433, or miR-control. MTT viability assays and Western Blot analyses established that miR-433 cells were more resistant to paclitaxel treatment (50nM) compared to miR-controls. Importantly, we have shown for the first time that miR 433 induced senescence, exemplified by a flattened morphology and down-regulation of phosphorylated Retinoblastoma (p-Rb), a molecular marker of senescence. Surprisingly, miR 433 induced senescence was independent from two well recognised senescent drivers: namely p53/p21 and p16. To explore this further we performed an in silico analysis of seven microRNA platforms which indicated that miR 433 potentially targets Cyclin-dependent kinase CDK6, which promotes sustained phosphorylation of Rb and thus cell cycle progression. In vitro, the overexpression of pre-miR-433 resulted in diminished CDK6 expression demonstrating a novel interaction between miR-433 and CDK6.

In conclusion, this study demonstrates that high miR-433 expression predicts poor outcome in OC patients by putatively rendering OC cells resistant to paclitaxel treatment through the induction of cellular senescence identifying this microRNA as a potential marker of chemoresponse.

Resistance to chemotherapy in ovarian cancer is miRrored by the microRNA miR-433-dependent dysregulation of the cell cycle.

An understanding of the mechanisms underlying the development of resistance to chemotherapy treatment is a gateway to the introduction of novel therapies and improved outcomes for women presenting with ovarian cancer (OC). The desired apoptotic death post-chemotherapy depends on an intact and fully functioning cell cycle machinery.

In this study we demonstrate that stable expression of miR-433 renders OC cells more resistant to paclitaxel treatment. Interestingly, only cells with the highest miR-433 survived paclitaxel suggesting the possible role of miR-433 in cancer recurrence. Importantly, for the first time we demonstrate that miR 433 induces cellular senescence, exemplified by a flattened morphology, the downregulation of phosphorylated Retinoblastoma (p Rb) and increased β galactosidase activity. Surprisingly, miR 433 induced senescence was independent of two well recognised senescent drivers: p21 and p16. Further in silico analysis followed by in vitro experiments identified CKD6 as a novel miR-433 target gene possibly explaining the observed p21 and p16-independent induction of cellular senescence. Another in silico identified miR-433 target gene was CDC27, a protein involved in the regulation of the cell cycle during mitosis. We demonstrate that the overexpression of pre-miR-433 leads to the downregulation of CDC27 in vitro revealing a novel interaction between miR-433 and CDC27, an integral cell cycle regulating protein.

Interestingly, miR-433 expressing cells also demonstrated an ability to impact their tumour microenvironment. We show that miR-433 is present in exosomes released from miR-433 overexpressing and high miR-433 naïve cells. Moreover, growth condition media (GCM) harvested from cells with high miR-433 have higher levels of IL-6 and IL-8, two key cytokines involved in the senescence associated secretory phenotype (SASP). Importantly, GCM from miR-433-enriched cells repressed the growth of co-cultured cells with initial studies showing a GCM-dependent induction of chemoresistance.

In conclusion, data in this study highlights how the aberrant expression miR-433 contributes to chemoresistance in OC cells. We postulate that standard chemotherapy, particularly paclitaxel, used to treat women with OC may have an attenuated ability to kill cells harbouring increased levels of miR-433, allowing for a subsequent chemoresistant phenotype post-therapy.

Family Economic Vulnerability & the Great Recession: An Analysis of the First two Waves of the Growing Up in Ireland Study

In this paper we make use of the first and second waves of the 2008 and 1998 cohorts of the Growing Up in Ireland study, to develop a multidimensional and dynamic approach to understanding the impact on families and children in Ireland of the Great Recession. Economic vulnerability is operationalised as involving a distinctive risk profile in relation to relative income, household joblessness and economic stress. We find that the recession was associated with a significant increase in levels of economic vulnerability and changing risk profiles involving a more prominent role for economic stress for both the 2008 and 1998 cohorts. The factors affecting vulnerability outcomes were broadly similar for both cohorts. Persistent economic vulnerability was significantly associated with lone parenthood, particularly for those with more than one child, lower levels of Primary Care Giver (PCG) education and to a lesser extent younger age of PCG at child’s birth, number of children and a parent leaving or dying. Similar factors were associated with transient vulnerability in the first wave but the magnitude of the effects was significantly weaker particularly in relation to lone parenthood and level of education of the PCG. For entry into vulnerability the impact of these factors was again substantially weaker than for persistent and transient vulnerability indicating a significantly greater degree of socio-economic heterogeneity among the group that became vulnerable during the recession. The findings raise policy and political problems that go beyond those associated with catering for groups that have tended to be characterized by high dependence on social welfare.

European Cystic Fibrosis Society Standards of Care: Quality Management in cystic fibrosis

Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful treatments and patient outcomes to be recognized and improvement programmes to be implemented in specialist CF centres. Over the past decades, the greater volumes of data becoming available through Centre databases and patient registries led to the possibility of making comparisons between different therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons. 

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.

Motivation à apprendre des élèves et modèle d'autorité de l'enseignant étude du lien au travers des perceptions d'élèves de troisième d'enseignement agricole

Cette thèse s'inscrit dans le cadre d'une thématique d'interrelation recherche-formation-pratique. Elle a pour objectif principal d'étudier le lien entre les perceptions motivationnelles à apprendre d'élèves de troisième d'enseignement agricole et leur perception du modèle d'autorité de l'enseignant. Son caractère novateur repose sur l'interculturalité des approches utilisées: la motivation à apprendre empruntée aux études nord-américaines et le modèle d'autorité de l'enseignant empruntée aux études françaises. L'étape de recension des écrits nous a permis de préparer le terrain à un questionnaire de type quantitatif. Il comprend deux sections sur les modèles d'autorité (autoritaire et d'autorité) et trois sections sur les perceptions motivationnelles (valeur, sentiment de compétence et contrôlabilité) en lien avec deux matières: français et STP (sciences et techniques professionnelles). À la suite de cette investigation, les entrevues menées ont permis de découvrir deux cas de figure non envisagés au départ. Le premier est qu'un enseignant de tendance autoritaire sur l'axe relationnel n'altère pas la perception de la valeur de la matière si celui-ci autonomise et responsabilise les élèves et s'il est impliqué dans leur réussite. Il en est de même si cela rejoint les buts éloignés des élèves (brevet, projet personnel ou professionnel). Enfin, il ressort des résultats un troisième modèle d'autorité de l'enseignant inattendu qu'est l'enseignant manquant d'autorité. Il fait apparaître le besoin des élèves d'avoir un enseignant cadrant sur l'axe relationnel afin de contenir les apprentissages. Même si les apprentissages sont variés et novateurs et que l'enseignant est disponible et explique bien ses cours, ils ne sont pas suffisants pour motiver les élèves rencontrés. Il semble que le cadre donné par l'enseignant les sécurise, donne de la fiabilité à l'enseignant et de la valeur à la matière même s'il est de tendance autoritaire.

Alessandro Baricco littérature, musique, peinture, cinéma, etc.

Dans l'oeuvre contemporaine d'Alessandro Baricco, des références de toutes sortes attirent l'attention de ceux et celles qui s'intéressent aux récits et romans de l'écrivain italien. De cette esthétique néo-baroque, c'est la rencontre avec d'autres formes d'art qui nous a ici interpelée. Autant sur le plan formel que thématique, les références à la musique, à la peinture et au cinéma, entre autres, offrent de remarquables exemples d'intermédialité. Cette diversité de disciplines convoquées dans le texte de Châteaux de la colère (1995), Soie (1997), Océan mer (1998), City (2001) et Novecento : pianiste (1997), constitue l'originalité forte de l'oeuvre de Baricco. Ces formes artistiques produisent une ambiance qui plonge le lecteur dans le domaine de l'art et accorde à l'auteur la possibilité de déployer avec une grande maîtrise de moyens et d'effets son style unique. Les renvois intermédiatiques relevant principalement des personnages soutiennent les propos de Baricco au sujet de l'art : ils permettent d'établir l'importance qu'accorde ce dernier au métalangage artistique et à la création sous toutes ses formes. Par là, il devient possible de mieux comprendre sa propre oeuvre littéraire qui valorise, au détriment de la prétention réaliste, une fantaisie ludique qui relève du spectaculaire. Le premier chapitre présente les procédés formels au service de la musicalité dans l'écriture de Baricco et les personnages de musiciens - ou en lien avec la musique - qui évoquent cette forme artistique privilégiée. Dans le deuxième chapitre, il est question des moyens techniques qui permettent aux textes de Baricco de rappeler l'art pictural ainsi que des personnages qui, par le truchement de la peinture, tiennent un discours sur la création artistique. Dans le troisième et dernier chapitre, nous nous intéressons à la structure romanesque qui, par diverses stratégies formelles, imite le scénario. Les personnages qui renvoient à l'art dramatique sont aussi abordés, de façon à tenir compte de la vision artistique qu'ils mettent en place. Enfin, la conclusion nous permet, à la lumière des informations recueillies, de relever les effets entrainés i.e. [entraînés] par ces jeux intermédiatiques. Celle-ci est aussi pour nous l'occasion de dégager, en son caractère unitaire, la vision artistique à l'oeuvre chez Baricco.

Statistique de photons d’une jonction tunnel déduite de mesures de potentiel électrique à l’aide d’un amplificateur paramétrique Josephson

On présente dans ce mémoire la mesure de la statistique de photons des fluctuations électromagnétiques micro-ondes d’une jonction tunnel placée à ultra-basse température. En particulier, on déduit cettedite statistique en mesurant les cumulants des fluctuations de courant générées par une jonction tunnel polarisée en courant continu et photoexcitée par un signal haute fréquence. On utilise un amplificateur paramétrique Josephson en tant que premier maillon de la chaîne d’amplification en raison de son bruit près de la limite quantique. On développe aussi un modèle pour tenir compte de sa saturation, celle-ci étant apparente à des puissances de signal incident très faibles. C’est, à ma connaissance, la première fois qu’un tel amplificateur est utilisé pour étudier la physique au sein du bruit émis par un conducteur mésoscopique. Les résultats mettent en évidence l’apparition d’un excès dans le quatrième cumulant lorsque la photoexcitation s’effectue au double de la fréquence de mesure. Un développement mathématique simple nous permet d’associer cet excès à la statistique de photons, sous la forme d’une augmentation – à nombre de photons fixe – de la variance du nombre moyen de photons contenue dans le signal. C’est en fait une signature de l’émission de paires de photons corrélés par la jonction tunnel photoexcitée. Ces résultats font le pont entre ceux obtenus précédemment par notre groupe de recherche quant aux cumulants d’ordre supérieur du bruit et ceux associées aux parallèles entre l’optique quantique et les fluctuations de courant des dispositifs mésoscopiques. [Gasse et al. PRL 111, 136601 (2013) ; Forgues et al. Scientific Reports 3, 2869 (2013) ; Forgues et al. PRL 113, 043602 (2014)] Ils dressent un portait intéressant du bruit photoexcité en termes normalement associés à l’optique quantique.

A herança de Locke

A organização de um colóquio em torno da “herança de Locke” foi uma ideia que nasceu no Centro de Estudos Anglísticos da Universidade de Lisboa, no âmbito do núcleo de investigação dedicado aos estudos de cultura inglesa. Vários textos de Locke são regularmente incluídos nos programas de graduação e de pósgraduação em Estudos Anglísticos, além de objecto de estudo especializado no Centro de Estudos Anglísticos. Assim, fazia todo o sentido comemorar, no ano de 2004, a passagem de mais um centenário sobre a morte de Locke, e celebrar a vitalidade da sua obra ao longo de três séculos reunindo especialistas que, publicamente, apresentassem e discutissem aspectos dessa obra que continuam activos no presente. O volume que agora se publica reúne as comunicações apresentadas em Janeiro de 2004. A variedade dos temas abordados e a manifesta relevância de que se revestem para o estudo da modernidade demonstram que a herança de Locke continua a produzir riqueza, e que constitui património cultural a ser herdado por novas gerações.