886 resultados para to-mesenchymal transition
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This is the Report on the Establishment of Hospital Groups as a Transition to Independent Hospital Trusts, as approved by Government on 14 May 2013. Click here to download The Establishment of Hospital Groups as a transition to Independent Hospital Trusts PDF 5.59MB Click here to download Securing the Future of Smaller Hospitals: A Framework for Development PDF 401KB Click here to download Frequently Asked Questions PDF 1.19MB Â
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Supporting A Better Transition From Second Level To Higher Education. Provided by the Department of Education and Skills, Ireland.
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Résumé Le but final de ce projet est d'utiliser des cellules T ou des cellules souches mésenchymateuses modifiées génétiquement afin de surexprimer localement les deux chémokines CXCL13 et CCL2 ensemble ou chacune séparément à l'intérieur d'une tumeur solide. CXCL13 est supposé induire des structures lymphoïdes ectopiques. Un niveau élevé de CCL2 est présumé initier une inflammation aiguë. La combinaison des deux effets amène à un nouveau modèle d'étude des mécanismes régulateur de la tolérance périphérique et de l'immunité tumorale. Les connaissances acquises grâce à ce modèle pourraient permettre le développement ou l'amélioration des thérapies immunes du cancer. Le but premier de ce travail a été l'établissement d'un modèle génétique de la souris permettant d'exprimer spécifiquement dans la tumeur les deux chémokines d'intérêt à des niveaux élevés. Pour accomplir cette tâche, qui est en fait une thérapie génétique de tumeurs solides, deux types de cellules porteuses potentielles ont été évaluées. Des cellules CD8+ T et des cellules mésenchymateuses de la moelle osseuse transférées dans des receveurs portant une tumeur. Si on pouvait répondre aux besoins de la thérapie génétique, indépendamment de la thérapie immune envisagée, on posséderait là un outil précieux pour bien d'autres approches thérapeutiques. Plusieurs lignées de souris transgéniques ont été générées comme source de cellules CD8+ T modifiées afin d'exprimer les chémokines d'intérêt. Dans une approche doublement transgénique les propriétés de deux promoteurs spécifiques de cellules T ont été combinées en utilisant la technologie Cre-loxP. Le promoteur de granzyme B confère une dépendance d'activation et le promoteur distal de lck assure une forte expression constitutive dès que les cellules CD8+ T ont été activées. Les transgènes construits ont montré une bonne performance in vivo et des souris qui expriment CCL2 dans des cellules CD8+ T activées ont été obtenues. Ces cellules peuvent maintenant être utilisées avec différents protocoles pour transférer des cellules T cytotoxiques (CTL) dans des receveurs porteur d'une tumeur, permettant ainsi d'évaluer leur capacité en tant que porteuse de chémokine d'infiltrer la tumeur. L'établissement de souris transgéniques, qui expriment pareillement CXCL13 est prévu dans un avenir proche. L'évaluation de cellules mésenchymateuses de la moelle osseuse a démontré que ces cellules se greffent efficacement dans le stroma tumoral suite à la co-injection avec des cellules tumorales. Cela représente un outil précieux pour la recherche, vu qu'il permet d'introduire des cellules manipulées dans un modèle tumoral. Les résultats confirment partiellement d'autres résultats rapportés dans un modèle amélioré. Cependant, l'efficacité et la spécificité suggérées de la migration systémique de cellules mésenchymateuses de la moelle osseuse dans une tumeur n'ont pas été observées dans notre modèle, ce qui indique, que ces cellules ne se prêtent pas à une utilisation thérapeutique. Un autre résultat majeur de ce travail est l'établissement de cultures de cellules mésenchymateuses de la moelle osseuse in vitro conditionnées par des tumeurs, ce qui a permis à ces cellules de s'étendre plus rapidement en gardant leur capacité de migration et de greffe. Cela offre un autre outil précieux, vu que la culture in vitro est un pas nécessaire pour une manipulation thérapeutique. Abstract The ultimate aim of the presented project is to use genetically modified T cells or mesenchymal stem cells to locally overexpress the two chemokines CXCL13 and CCL2 together or each one alone inside a solid tumor. CXCL13 is supposed to induce ectopic lymphoid structures and a high level of CCL2 is intended to trigger acute inflamation. The combination of these two effects represents a new model for studying mechanisms that regulate peripheral tolerance and tumor immunity. Gained insights may help developing or improving immunotherapy of cancer. The primary goal of the executed work was the establishment of a genetic mouse model that allows tumor-specific expression of high levels of the two chemokines of interest. For accomplishing this task, which represents gene therapy of solid tumors, two types of potentially useful carrier cells were evaluated. CD8+ T cells and mesenchymal bone marrow cells to be used in adoptive cell transfers into tumor-bearing mice. Irrespectively of the envisaged immunotherapy, satisfaction of so far unmet needs of gene therapy would be a highly valuable tool that may be employed by many other therapeutic approaches, too. Several transgenic mouse lines were generated as a source of CD8+ T cells modified to express the chemokines of interest. In a double transgenic approach the properties of two T cell-specific promoters were combined using Cre-loxP technology. The granzyme B promoter confers activation-dependency and the lck distal promoter assures strong constitutive expression once the CD8+ T cell has been activated. The constructed transgenes showed a good performance in vivo and mice expressing CCL2 in activated CD8+ T cells were obtained. These cells can now be used with different protocols for adoptively transferring cytotoxic T cells (CTL) into tumor-bearing recipients, thus allowing to study their capacity as tumor-infiltrating chemokine carrier. The establishment of transgenic mice likewisely expressing CXCL13 is expected in the near future. In addition, T cells from generated single transgenic mice that have high expression of an EGFP reporter in both CD4+ and CD8+ cells can be easily traced in vivo when setting up adoptive transfer conditions. The evaluation of mesenchymal bone marrow cells demonstrated that these cells can efficiently engraft into tumor stroma upon local coinjection with tumor cells. This represents a valuable tool for research purposes as it allows to introduce manipulated stromal cells into a tumor model. Therefore, the established engraftment model is suited for studying the envisaged immunotherapy. These results confirm to some extend previously reported results in an improved model, however, the suggested systemic tumor homing efficiency and specificity of mesenchymal bone marrow cells was not observed in our model indicating that these cells may not be suited for therapeutic use. Another major result of the presented work is the establishment oftumor-conditioned in vitro culture of mesenchymal bone marrow cells, which allowed to more rapidly expand these cells while maintaining their tumor homing and engrafting capacities. This offers another valuable tool as in vitro culture is a necessary step for therapeutic manipulations.
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Previous studies have reported genetic differences between wild-caught sylvatic, domestic and laboratory pop-ulations of several Triatominae species. The differences between sylvatic and laboratory colonies parallel are similar to the differences observed between sylvatic and domestic populations. Laboratory colonies are frequently used as references for field populations, but the consequences of founder events on the genetic makeup of laboratory or domestic populations are rarely quantified. Our goal was to quantify the genetic change in Rhodnius pallescens populations artificially submitted to founder effects via laboratory colonization. We compared the genetic makeup of two sylvatic populations and their laboratory descendants using a panel of 10 microsatellite markers. Both sylvatic populations were initially collected from palm trees, but the colonies differed in the number of founder insects and amount of time kept in the laboratory. We evaluated allelic polymorphism, differences between expected and observed heterozygosity, estimates of population differentiation (Fst) and inbreeding (Fis, Fit) and cluster analyses based on Nei's distances. We found a unique genetic structure for each sample population, with significant differentiation between the field insects and each of the laboratory generations. These analyses showed strong founder effects and showed that genetic drift had led to a genetic equilibrium over several generations of isolation. Our results suggest that laboratory colonies of R. pallescens have a different genetic structure than their wild relatives and similar processes likely affect other Triatominae laboratory stocks.
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Bien que la transition des soins pédiatriques aux soins adultes soit extrêmement importante pour les adolescents souffrant de maladies chroniques, celle-ci se limite le plus souvent à un simple transfert. L'objectif de cet article est de décrire les barrières au bon déroulement de la transition du point de vue du patient et de sa famille, des professionnels de la santé et du système de soins; de détailler les éléments clés pour que la transition soit la moins traumatique possible; et d'énoncer les différentes approches proposées dans la littérature. [Abstract] The transition from pediatric to adult care of chronically ill adolescents Even though the transition from pediatric to adult health care is extremely important for chronically ill adolescents, most of the times it is limited to a simple transfer The objective of this paper is to describe the barriers to a smooth transition from the point of view of the patient and his/her family, the health professionals and the health system, to review the key elements for a smooth transition, and to address the different approaches proposed in the literature.
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Candida albicans is a common member of the human microbiota and may cause invasive disease in susceptible populations. Several risk factors have been proposed for candidaemia acquisition. Previous Candida multifocal colonisation among hospitalised patients may be crucial for the successful establishment of candidaemia. Nevertheless, it is still not clear whether the persistence or replacement of a single clone of C. albicans in multiple anatomical sites of the organism may represent an additional risk for candidaemia acquisition. Therefore, we prospectively evaluated the dynamics of the colonising strains of C. albicans for two groups of seven critically ill patients: group I included patients colonised by C. albicans in multiple sites who did not develop candidaemia and group II included patients who were colonised and who developed candidaemia. ABC and microsatellite genotyping of 51 strains of C. albicans revealed that patients who did not develop candidaemia were multiply colonised by at least two ABC genotypes of C. albicans, whereas candidaemic patients had highly related microsatellites and the same ABC genotype in colonising and bloodstream isolates that were probably present in different body sites before the onset of candidaemia.
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BACKGROUND: Obesity is a contemporary epidemic that does not affect all age groups and sections of society equally. OBJECTIVE: The objective was to examine socioeconomic differences in trajectories of body mass index (BMI; in kg/m(2)) and obesity between the ages of 45 and 65 y. DESIGN: A total of 13,297 men and 4532 women from the French GAZEL (Gaz de France Electricité de France) cohort study reported their height in 1990 and their weight annually over the subsequent 18 y. Changes in BMI and obesity between ages 45 and 49 y, 50 and 54 y, 55 and 59 y, and 60 and 65 y as a function of education and occupational position (at age 35 y) were modeled by using linear mixed models and generalized estimating equations. RESULTS: BMI and obesity rates increased between the ages of 45 and 65 y. In men, BMI was higher in unskilled workers than in managers at age 45 y; this difference in BMI increased from 0.82 (95% CI: 0.66, 0.99) at 45 y to 1.06 (95% CI: 0.85, 1.27) at 65 y. Men with a primary school education compared with those with a high school degree at age 45 y had a 0.75 (95% CI: 0.51, 1.00) higher BMI, and this difference increased to 1.32 (95% CI: 1.03,1.62) at age 65 y. Obesity rates were 3.35% and 7.68% at age 45 y and 9.52% and 18.10% at age 65 y in managers and unskilled workers, respectively; the difference in obesity increased by 4.25% (95% CI: 1.87, 6.52). A similar trend was observed in women. Conclusions: Weight continues to increase in the transition between midlife and old age; this increase is greater in lower socioeconomic groups.
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Understanding how new phenotypes evolve is challenging because intermediate stages in transitions from ancestral to derived phenotypes often remain elusive. Here we describe and evaluate a new mechanism facilitating the transition from sexual reproduction to parthenogenesis. In many sexually reproducing species, a small proportion of unfertilized eggs can hatch spontaneously ('tychoparthenogenesis') and develop into females. Using an analytical model, we show that if females are mate-limited, tychoparthenogenesis can result in the loss of males through a positive feedback mechanism whereby tychoparthenogenesis generates female-biased sex ratios and increasing mate limitation. As a result, the strength of selection for tychoparthenogenesis increases in concert with the proportion of tychoparthenogenetic offspring in the sexual population. We then tested the hypothesis that mate limitation selects for tychoparthenogenesis and generates female-biased sex ratios, using data from natural populations of sexually reproducing Timema stick insects. Across 41 populations, both the tychoparthenogenesis rates and the proportions of females increased exponentially as the density of individuals decreased, consistent with the idea that low densities of individuals result in mate limitation and selection for reproductive insurance through tychoparthenogenesis. Our model and data from Timema populations provide evidence for a simple mechanism through which parthenogenesis can evolve rapidly in a sexual population.
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The aim of this study was to present the initial validation of a new questionnaire, the Transition to Retirement Questionnaire (TRQ) and to study its relationship with resistance to change and personality dimensions. Based on Schlossberg's typology of the retired, the TRQ is designed to assess five dimensions related to personal perceptions of transition to retirement, retirement, and personal plans and activities. The sample consisted of 1,054 professionally active or retired adults from the Swiss French-speaking Canton of Vaud. Exploratory principal components and confirmatory factor analyses highlighted a five-factor solution that fit coherently with Schlossberg's typology. Moreover, TRQ dimensions were related to resistance to change tendencies and personality dimensions. The TRQ seems to be an interesting tool for use in research but also for interventions with young retirees or people preparing for retirement.
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In a previous paper [J.Fort and V.Méndez, Phys. Rev. Lett. 82, 867 (1999)], the possible importance of higher-order terms in a human population wave of advance has been studied. However, only a few such terms were considered. Here we develop a theory including all higher-order terms. Results are in good agreement with the experimental evidence involving the expansion of agriculture in Europe
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This paper is aimed at exploring the determinants of female activity from a dynamic perspective. An event-history analysis of the transition form employment to housework has been made resorting to data from the European Household Panel Survey. Four countries representing different welfare regimes and, more specifically, different family policies, have been selected for the analysis: Britain, Denmark, Germany and Spain. The results confirm the importance of individual-level factors, which is consistent with an economic approach to female labour supply. Nonetheless, there are significant cross-national differences in how these factors act over the risk of abandoning the labour market. First, the number of trnasitions is much lower among Danish working women than among British, German or Spanish ones, revealing the relative importance of universal provision of childcare services, vis-à-vis other elements of the family policy, as time or money.
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Les phacomatoses regroupent des maladies du développement du neurectoderme, engendrant des manifestations cutanées ou du système nerveux central. Les symptômes de ces maladies peuvent affecter les individus atteints à différents moments de leur vie. Il s'agit de maladies, héréditaires ou congénitales, qui sont transmises de façon variable. Effectivement, certaines, telles que la neurofibromatose, la sclérose tubéreuse ou la maladie de von Hippel-Lindau sont autosomiques dominantes, alors que d'autres, telles que la maladie de Sturge-Weber sont sporadiques. Des transmissions autosomiques récessives liées à X ou des formes mosaïques existent également. Une revue de la littérature, comprenant les cinq phacomatoses les plus fréquemment vues par un neurochirurgien (neurofibromatose de type I et II, sclérose tubéreuse de Bourneville, maladie de Sturge-Weber-Krabbe, maladie de von Hippel-Lindau) a été effectuée en se centrant sur le diagnostic, la variabilité de la symptomatologie selon l'âge du patient et son traitement. Les cas de patients adultes et pédiatriques vus aux consultations de neurologie et neurochirurgie de l'hôpital de Lille (France) et Lausanne (Suisse), de 1961 à nos jours, ont été revus pour illustrer les différentes pathologies rencontrées, selon l'âge des patients atteints. Le phénotype de ces maladies se modifie avec l'âge, car les gènes incriminés sont des gènes impliqués dans la différentiation tissulaire et sont activés à des âges différents suivant les tissus. Le rôle du neurochirurgien sera variable selon l'âge et le syndrome du patient. Il importe de connaître les variations du phénotype de ces maladies avec l'âge ainsi que les conséquences à long terme des traitements pour proposer au patient un suivi neurochirurgical personnalisé. Phacomatoses, or neurocutaneous disorders, are a group of congenital and hereditary diseases characterized by developmental lesions of the neuroectoderm, leading to pathologies affecting the skin and the central nervous system. There is a wide range of pathologies affecting individuals at different moments of life. The genetics is variable: while neurofibromatosis 1 and 2, tuberous sclerosis and von Hippel-Lindau disease are all inherited as autosomal dominant traits, Sturge-Weber syndrome is sporadic. Other neurocutaneous disorders can be inherited as autosomal recessive traits (i.e., ataxia-telangiectasia), X-linked (i.e., incontinentia pigmenti) or explained by mosaicism (i.e., hypomelanosis of Ito, McCune-Albright syndrome). In this review, we discuss the major types of neurocutaneous disorders most frequently encountered by the neurosurgeon and followed beyond childhood. They include neurofibromatosis types 1 and 2, tuberous sclerosis, Sturge-Weber syndrome and von Hippel-Lindau disease. In each case, a review of the literature, including diagnosis, genetics and treatment will be presented. The lifespan of the disease with the implications for neurosurgeons will be emphasized. A review of cases, including both pediatric and adult patients, seen in neurosurgical practices in the Lille, France and Lausanne, Switzerland hospitals between 1961 and 2007 is presented to illustrate the pathologies seen in different age-groups. Because the genes mutated in most phacomatoses are involved in development and are activated following a timed schedule, the phenotype of these diseases evolves with age. The implication of the neurosurgeon varies depending on the patient's age and pathology. While neurosurgeons tend to see pediatric patients affected with neurofibromatosis type 1, tuberous sclerosis and Sturge-Weber syndrome, there will be a majority of adult patients with von Hippel-Lindau disease or neurofibromatosis type 2
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The deep drop of the fertility rate in Italy to among the lowest in the world challenges contemporary theories of childbearing and family building. Among high-income countries, Italy was presumed to have characteristics of family values and female labor force participation that would favor higher fertility than its European neighbors to the north. We test competing economic and cultural explanations, drawing on new nationally representative, longitudinal data to examine first union, first birth, and second birth. Our event history analysis finds some support for economic determinants of family formation and fertility, but the clear importance of regional differences and of secularization suggests that such an explanation is at best incomplete and that cultural and ideational factors must be considered.
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Objective To understand the trajectories that women go through from entering into to leaving relationships involving intimate partner violence (IPV), and identify the stages of the transition process. Method We utilized a constructivist paradigm based on grounded theory. We ensured that the ethical guidelines of the World Health Organization for research on domestic violence were followed. The analysis focused on narratives of 28 women survivors of IPV, obtained from in-depth interviews. Results The results showed that the trajectories experienced by women were marked by gender issues, (self) silencing, hope and suffering, which continued after the end of the IPV. Conclusion The transition process consists of four stages: entry - falls in love and becomes trapped; maintenance - silences own self, consents and remains in the relationship; decides to leave - faces the problems and struggles to be rescued; (re) balance - (re) finds herself with a new life. This (long) process was developed by wanting (and being able to have) self-determination.