A model of gender prejudice, power, and discrimination: How hierarchy-enhancing factors predominate over hierarchy-attenuating factors

Gender inequalities remain an issue in our society and particularly in the workplace. Several factors can explain this gender difference in top-level managerial positions such as career ambitions but also biases against women. In our chapter, we propose a model explaining why gender inequalities and particularly discrimination against women is still present in our societies despite social norms and existing legislation on gender equality. To this purpose, we review research on discrimination through two different approaches, (a) a prejudice approach through the justification-suppression model developed by Crandall and Eshleman (2003) and (b) a power approach through the social dominance theory (Pratto, Sidanius, Stallworth, & Malle, 1994; Sidanius & Pratto, 1999). In our work, we integrate these two approaches and propose a model of gender prejudice, power and discrimination. The integration of these two approaches contributes to a better understanding of how discrimination against women is formed and maintained over time.

Image quality in CT: From physical measurements to model observers.

Evaluation of image quality (IQ) in Computed Tomography (CT) is important to ensure that diagnostic questions are correctly answered, whilst keeping radiation dose to the patient as low as is reasonably possible. The assessment of individual aspects of IQ is already a key component of routine quality control of medical x-ray devices. These values together with standard dose indicators can be used to give rise to 'figures of merit' (FOM) to characterise the dose efficiency of the CT scanners operating in certain modes. The demand for clinically relevant IQ characterisation has naturally increased with the development of CT technology (detectors efficiency, image reconstruction and processing), resulting in the adaptation and evolution of assessment methods. The purpose of this review is to present the spectrum of various methods that have been used to characterise image quality in CT: from objective measurements of physical parameters to clinically task-based approaches (i.e. model observer (MO) approach) including pure human observer approach. When combined together with a dose indicator, a generalised dose efficiency index can be explored in a framework of system and patient dose optimisation. We will focus on the IQ methodologies that are required for dealing with standard reconstruction, but also for iterative reconstruction algorithms. With this concept the previously used FOM will be presented with a proposal to update them in order to make them relevant and up to date with technological progress. The MO that objectively assesses IQ for clinically relevant tasks represents the most promising method in terms of radiologist sensitivity performance and therefore of most relevance in the clinical environment.

The effect of learning on the evolution of new courtship behavior: a simulation model

The fact that individuals learn can change the relationship between genotype and phenotype in the population, and thus affect the evolutionary response to selection. Here we ask how male ability to learn from female response affects the evolution of a novel male behavioral courtship trait under pre-existing female preference (sensory drive). We assume a courtship trait which has both a genetic and a learned component, and a two-level female response to males. With individual-based simulations we show that, under this scenario, learning generally increases the strength of selection on the genetic component of the courtship trait, at least when the population genetic mean is still low. As a consequence, learning not only accelerates the evolution of the courtship trait, but also enables it when the trait is costly, which in the absence of learning results in an adaptive valley. Furthermore, learning can enable the evolution of the novel trait in the face of gene flow mediated by immigration of males that show superior attractiveness to females based on another, non-heritable trait. However, rather than increasing monotonically with the speed of learning, the effect of learning on evolution is maximized at intermediate learning rates. This model shows that, at least under some scenarios, the ability to learn can drive the evolution of mating behaviors through a process equivalent to Waddington's genetic assimilation.

Waddlia chondrophila induces systemic infection, organ pathology, and elicits Th1-associated humoral immunity in a murine model of genital infection.

Waddlia chondrophila is a known bovine abortigenic Chlamydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W. chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W. chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial-induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver, and spleen), necrosis (liver) and extramedullary hematopoiesis (spleen). Immunohistochemistry demonstrated the presence of a large number of W. chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W. chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.

Com explicar un sistema CLIL: un model dinàmic newtonià

En la implementació del CLIL a l’educació superior, apart d’estudis sobre el nivell de l’estudiantat i la disponibilitat del professorat, i de l’elaboració de material educatiu interdisciplinari, el repte actual és aconseguir que s’involucrin activament en CLIL els professors de contingut d’un ventall ampli de disciplines. En aquesta comunicació es presenten les bases d’un model per un sistema CLIL, utilitzant la dinàmica newtoniana. Pot ser un model interessant i plausible en un context universitari científic i tecnològic, on fins ara el CLIL s’ha implementat només lleugerament.

Integrating quantitative proteomics and metabolomics in a cellular model of diabetic retinopathy

Diabetic retinopathy is the leading cause of visual loss in individuals under the age of 55. Most investigations into the pathogenesis of diabetic retinopathy have been concentrated on the neural retina since this is where clinical lesions are manifested. Recently, however, various abnormalities in the structural and secretory functions of retinal pigment epithelium that are essential for neuroretina survival, have been found in diabetic retinopathy. In this context, here we study the effect of hyperglycemic and hypoxic conditions on the metabolism of a human retinal pigment epithelial cell line (ARPE-19) by integrating quantitative proteomics using tandem mass tagging (TMT), untargeted metabolomics using MS and NMR, and 13C-glucose isotopic labeling for metabolic tracking. We observed a remarkable metabolic diversification under our simulated in vitro hyperglycemic conditions of diabetes, characterized increased flux through polyol pathways and inhibition of the Krebs cycle and oxidative phosphorylation. Importantly, under low oxygen supply RPE cells seem to consume rapidly glycogen storages and stimulate anaerobic glycolysis. Our results therefore pave the way to future scenarios involving new therapeutic strategies addressed to modulating RPE metabolic impairment, with the aim of regulating structural and secretory alterations of RPE. Finally, this study shows the importance of tackling biomedical problems by integrating metabolomic and proteomics results.

Characterization of a MAF1 knockout mouse model

L'ARN polymérase 3 transcrit un petit groupe de gènes fortement exprimés et impliqués dans plusieurs mécanismes moléculaires. Les ARNs de transfert ou ARNt représentent plus ou moins la moitié du transcriptome de l'ARN polymérase 3. Ils sont directement impliqués dans la traduction des protéines en agissant comme transporteurs d'acides aminés qui sont incorporés à la chaîne naissante de polypeptides. Chez des levures cultivées dans un milieu jusqu'à épuisement des nutriments, Maf1 réprime la transcription par l'ARN polymérase 3, favorisant ainsi l'économie énergétique cellulaire. Dans un modèle de cellules de mammifères, MAF1 réprime aussi la transcription de l'ARN polymérase 3 dans des conditions de stress, cependant il n'existe aucune donnée quant à son rôle chez un mammifère vivant. Pendant mon doctorat, j'ai utilisé une souris délétée pour le gène Maf1 afin de connaître les effets de ce gène chez un mammifère. Etonnamment, la souris Maf1-­‐/-­‐ est résistante à l'obésité même si celle-­‐ci est nourrie avec une nourriture riche en matières grasses. Des études moléculaires et de métabolomiques ont montré qu'il existe des cycles futiles de production et dégradation des lipides et des ARNt, ce qui entraîne une augmentation de la dépense énergique et favorise la résistance à l'obésité. En plus de la caractérisation de la souris Maf1-­‐/-­‐, pendant ma thèse j'ai également développé une méthode afin de normaliser les données de ChIP-­‐sequencing. Cette méthode est fondée sur l'utilisation d'un contrôle interne, représenté ici par l'ajout d'une quantité fixe de chromatine provenant d'un organisme différent de celui étudié. La méthode a amélioré considérablement la reproductibilité des valeurs entre réplicas biologiques. Elle a aussi révélé des différences entre échantillons issus de conditions différentes. Une occupation supérieure de l'ARN polymérase 3 sur les gènes Pol 3 chez les souris Maf1 KO entraîne une augmentation du niveau de précurseurs d'ARNt, ayant pour effet probable la saturation de la machinerie de maturation des ARNt. En effet, chez les souris Maf1 KO, le pourcentage d'ARNt modifiés est plus faible que chez les souris type sauvage. Ce déséquilibre entre le niveau de précurseurs et d'ARNt matures entraîne une diminution de la traduction protéique. Ces résultats ont permis d'identifier de nouvelles fonctions pour la protéine MAF1, comme étant une protéine régulatrice à la fois de la transcription mais aussi de la traduction et en étant un cible potentielle au traitement à l'obésité. -- RNA polymerase III (Pol 3) transcribes a small set of highly expressed genes involved in different molecular mechanisms. tRNAs account for almost half of the Pol 3 transcriptome and are involved in translation, bringing a new amino into the nascent polypeptide chain. In yeast, under nutrient deprivation, Maf1 acts for cell energetic economy by repressing Pol 3 transcription. In mammalian cells, MAF1 also represses Pol 3 activity under conditions of serum deprivation or DNA damages but nothing is known about its role in a mammalian organism. During my thesis studies, I used a Maf1 KO mouse model to characterize the effects of Maf1 deletion in a living animal. Surprisingly, the MAF1 KO mouse developed an unexpected phenotype, being resistant to high fat diet-­‐induced obesity and displaying an extended lifespan. Molecular and metabolomics characterizations revealed futile cycles of lipids and tRNAs, which are produced and immediately degraded, which increases energy consumption in the Maf1 KO mouse and probably explains in part the protection to obesity. Additionally to the mouse characterization, I also developed a method to normalize ChIP-­‐seq data, based on the addition of a foreign chromatin to be used as an internal control. The method improved reproducibility between replicates and revealed differences of Pol 3 occupancy between WT and Maf1 KO samples that were not seen without normalization to the internal control. I then established that increased Pol 3 occupancy in the Maf1 KO mouse liver was associated with increased levels of tRNA precursor but not of mature tRNAs, the effective molecules involved in translation. The overproduction of precursor tRNAs associated with the deletion of Maf1 apparently overwhelms the tRNA processing machinery as the Maf1 KO mice have lower levels of fully modified tRNAs. This maturation defect directly impacts on translation efficiency as polysomic fractions and newly synthetized protein levels were reduced in the liver of the Maf1 KO mouse. Altogether, these results indicate new functions for MAF1, a regulator of both transcription and translation as well as a potential target for obesity treatment.

Iterative reconstruction in CT : using mathematical model observers to determine low dose images' trustworthiness

La tomodensitométrie (TDM) est une technique d'imagerie pour laquelle l'intérêt n'a cessé de croitre depuis son apparition au début des années 70. De nos jours, l'utilisation de cette technique est devenue incontournable, grâce entre autres à sa capacité à produire des images diagnostiques de haute qualité. Toutefois, et en dépit d'un bénéfice indiscutable sur la prise en charge des patients, l'augmentation importante du nombre d'examens TDM pratiqués soulève des questions sur l'effet potentiellement dangereux des rayonnements ionisants sur la population. Parmi ces effets néfastes, l'induction de cancers liés à l'exposition aux rayonnements ionisants reste l'un des risques majeurs. Afin que le rapport bénéfice-risques reste favorable au patient il est donc nécessaire de s'assurer que la dose délivrée permette de formuler le bon diagnostic tout en évitant d'avoir recours à des images dont la qualité est inutilement élevée. Ce processus d'optimisation, qui est une préoccupation importante pour les patients adultes, doit même devenir une priorité lorsque l'on examine des enfants ou des adolescents, en particulier lors d'études de suivi requérant plusieurs examens tout au long de leur vie. Enfants et jeunes adultes sont en effet beaucoup plus sensibles aux radiations du fait de leur métabolisme plus rapide que celui des adultes. De plus, les probabilités des évènements auxquels ils s'exposent sont également plus grandes du fait de leur plus longue espérance de vie. L'introduction des algorithmes de reconstruction itératifs, conçus pour réduire l'exposition des patients, est certainement l'une des plus grandes avancées en TDM, mais elle s'accompagne de certaines difficultés en ce qui concerne l'évaluation de la qualité des images produites. Le but de ce travail est de mettre en place une stratégie pour investiguer le potentiel des algorithmes itératifs vis-à-vis de la réduction de dose sans pour autant compromettre la qualité du diagnostic. La difficulté de cette tâche réside principalement dans le fait de disposer d'une méthode visant à évaluer la qualité d'image de façon pertinente d'un point de vue clinique. La première étape a consisté à caractériser la qualité d'image lors d'examen musculo-squelettique. Ce travail a été réalisé en étroite collaboration avec des radiologues pour s'assurer un choix pertinent de critères de qualité d'image. Une attention particulière a été portée au bruit et à la résolution des images reconstruites à l'aide d'algorithmes itératifs. L'analyse de ces paramètres a permis aux radiologues d'adapter leurs protocoles grâce à une possible estimation de la perte de qualité d'image liée à la réduction de dose. Notre travail nous a également permis d'investiguer la diminution de la détectabilité à bas contraste associée à une diminution de la dose ; difficulté majeure lorsque l'on pratique un examen dans la région abdominale. Sachant que des alternatives à la façon standard de caractériser la qualité d'image (métriques de l'espace Fourier) devaient être utilisées, nous nous sommes appuyés sur l'utilisation de modèles d'observateurs mathématiques. Nos paramètres expérimentaux ont ensuite permis de déterminer le type de modèle à utiliser. Les modèles idéaux ont été utilisés pour caractériser la qualité d'image lorsque des paramètres purement physiques concernant la détectabilité du signal devaient être estimés alors que les modèles anthropomorphes ont été utilisés dans des contextes cliniques où les résultats devaient être comparés à ceux d'observateurs humain, tirant profit des propriétés de ce type de modèles. Cette étude a confirmé que l'utilisation de modèles d'observateurs permettait d'évaluer la qualité d'image en utilisant une approche basée sur la tâche à effectuer, permettant ainsi d'établir un lien entre les physiciens médicaux et les radiologues. Nous avons également montré que les reconstructions itératives ont le potentiel de réduire la dose sans altérer la qualité du diagnostic. Parmi les différentes reconstructions itératives, celles de type « model-based » sont celles qui offrent le plus grand potentiel d'optimisation, puisque les images produites grâce à cette modalité conduisent à un diagnostic exact même lors d'acquisitions à très basse dose. Ce travail a également permis de clarifier le rôle du physicien médical en TDM: Les métriques standards restent utiles pour évaluer la conformité d'un appareil aux requis légaux, mais l'utilisation de modèles d'observateurs est inévitable pour optimiser les protocoles d'imagerie. -- Computed tomography (CT) is an imaging technique in which interest has been quickly growing since it began to be used in the 1970s. Today, it has become an extensively used modality because of its ability to produce accurate diagnostic images. However, even if a direct benefit to patient healthcare is attributed to CT, the dramatic increase in the number of CT examinations performed has raised concerns about the potential negative effects of ionising radiation on the population. Among those negative effects, one of the major risks remaining is the development of cancers associated with exposure to diagnostic X-ray procedures. In order to ensure that the benefits-risk ratio still remains in favour of the patient, it is necessary to make sure that the delivered dose leads to the proper diagnosis without producing unnecessarily high-quality images. This optimisation scheme is already an important concern for adult patients, but it must become an even greater priority when examinations are performed on children or young adults, in particular with follow-up studies which require several CT procedures over the patient's life. Indeed, children and young adults are more sensitive to radiation due to their faster metabolism. In addition, harmful consequences have a higher probability to occur because of a younger patient's longer life expectancy. The recent introduction of iterative reconstruction algorithms, which were designed to substantially reduce dose, is certainly a major achievement in CT evolution, but it has also created difficulties in the quality assessment of the images produced using those algorithms. The goal of the present work was to propose a strategy to investigate the potential of iterative reconstructions to reduce dose without compromising the ability to answer the diagnostic questions. The major difficulty entails disposing a clinically relevant way to estimate image quality. To ensure the choice of pertinent image quality criteria this work was continuously performed in close collaboration with radiologists. The work began by tackling the way to characterise image quality when dealing with musculo-skeletal examinations. We focused, in particular, on image noise and spatial resolution behaviours when iterative image reconstruction was used. The analyses of the physical parameters allowed radiologists to adapt their image acquisition and reconstruction protocols while knowing what loss of image quality to expect. This work also dealt with the loss of low-contrast detectability associated with dose reduction, something which is a major concern when dealing with patient dose reduction in abdominal investigations. Knowing that alternative ways had to be used to assess image quality rather than classical Fourier-space metrics, we focused on the use of mathematical model observers. Our experimental parameters determined the type of model to use. Ideal model observers were applied to characterise image quality when purely objective results about the signal detectability were researched, whereas anthropomorphic model observers were used in a more clinical context, when the results had to be compared with the eye of a radiologist thus taking advantage of their incorporation of human visual system elements. This work confirmed that the use of model observers makes it possible to assess image quality using a task-based approach, which, in turn, establishes a bridge between medical physicists and radiologists. It also demonstrated that statistical iterative reconstructions have the potential to reduce the delivered dose without impairing the quality of the diagnosis. Among the different types of iterative reconstructions, model-based ones offer the greatest potential, since images produced using this modality can still lead to an accurate diagnosis even when acquired at very low dose. This work has clarified the role of medical physicists when dealing with CT imaging. The use of the standard metrics used in the field of CT imaging remains quite important when dealing with the assessment of unit compliance to legal requirements, but the use of a model observer is the way to go when dealing with the optimisation of the imaging protocols.

Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila.

Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 108 W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium.

An evaluation of the Swiss staging model for hypothermia using case reports from the literature.

BACKGROUND: Core body temperature is used to stage and guide the management of hypothermic patients, however obtaining accurate measurements of core temperature is challenging, especially in the pre-hospital context. The Swiss staging model for hypothermia uses clinical indicators to stage hypothermia. The proposed temperature range for clinical stage 1 is <35-32 °C (95-90 °F), for stage 2, <32-28 °C (<90-82 °F) for stage 3, <28-24 °C (<82-75 °F), and for stage 4 below 24 °C (75 °F). However, the evidence relating these temperature ranges to the clinical stages needs to be strengthened. METHODS: Medline was used to retrieve data on as many cases of accidental hypothermia (core body temperature <35 °C (95 °F)) as possible. Cases of therapeutic or neonatal hypothermia and those with confounders or insufficient data were excluded. To evaluate the Swiss staging model for hypothermia, we estimated the percentage of those patients who were correctly classified and compared the theoretical with the observed ranges of temperatures for each clinical stage. The number of rescue collapses was also recorded. RESULTS: We analysed 183 cases; the median temperature for the sample was 25.2 °C (IQR 22-28). 95 of the 183 patients (51.9 %; 95 % CI = 44.7 %-59.2 %) were correctly classified, while the temperature was overestimated in 36 patients (19.7 %; 95 % CI = 13.9 %-25.4 %). We observed important overlaps among the four stage groups with respect to core temperature, the lowest observed temperature being 28.1 °C for Stage 1, 22 °C for Stage 2, 19.3 °C for Stage 3, and 13.7 °C for stage 4. CONCLUSION: Predicting core body temperature using clinical indicators is a difficult task. Despite the inherent limitations of our study, it increases the strength of the evidence linking the clinical hypothermia stage to core temperature. Decreasing the thresholds of temperatures distinguishing the different stages would allow a reduction in the number of cases where body temperature is overestimated, avoiding some potentially negative consequences for the management of hypothermic patients.

Spinal Cord T-Cell Infiltration in the Rat Spared Nerve Injury Model: A Time Course Study.

The immune system is involved in the development of neuropathic pain. In particular, the infiltration of T-lymphocytes into the spinal cord following peripheral nerve injury has been described as a contributor to sensory hypersensitivity. We used the spared nerve injury (SNI) model of neuropathic pain in Sprague Dawley adult male rats to assess proliferation, and/or protein/gene expression levels for microglia (Iba1), T-lymphocytes (CD2) and cytotoxic T-lymphocytes (CD8). In the dorsal horn ipsilateral to SNI, Iba1 and BrdU stainings revealed microglial reactivity and proliferation, respectively, with different durations. Iba1 expression peaked at D4 and D7 at the mRNA and protein level, respectively, and was long-lasting. Proliferation occurred almost exclusively in Iba1 positive cells and peaked at D2. Gene expression observation by RT-qPCR array suggested that T-lymphocytes attracting chemokines were upregulated after SNI in rat spinal cord but only a few CD2/CD8 positive cells were found. A pronounced infiltration of CD2/CD8 positive T-cells was seen in the spinal cord injury (SCI) model used as a positive control for lymphocyte infiltration. Under these experimental conditions, we show early and long-lasting microglia reactivity in the spinal cord after SNI, but no lymphocyte infiltration was found.

A conceptual model for grid learning services automatic composition

Peer-reviewed