14 research outputs found
Cost And Resource Utilization Of Chronic Obstructive Pulmonary Disease (COPD) In Canada: A Systematic Review
No full textLa femme lettrée au 18e siècle : fiction et théorie chez S. de Genlis
No full textStephanie de Genlis (1746--1830) is amongst the most productive women authors of her generation. We will base our work upon the research of Catherine Rubinger and Roland Bonnel (in Femmes savantes et femmes d'esprit) in order to describe the society of women authors at the end of the 18th century; we will also look at their literary practices, as well as analyze the environment which contributed to their discourse. We will then study the literary styles favored by de Genlis; Georges May's study on the novel (Le Dilemme du roman) will be used as a first step towards understanding de Genlis' choices as an author. Our third chapter will be dedicated to De l'influence des femmes sur la litterature francaise, in which the author develops her theory about the institution of French literature, about the status of women authors, and about literature in general. Finally, we will put forward an analysis of the ways in which women authors are portrayed in selected narrative texts. (Abstract shortened by UMI.
Very Distal Femoral Periprosthetic Fractures: Replacement Versus Fixation: A Systematic Review
No full textBiomarker use is associated with reduced clinical trial failure risk in metastatic melanoma
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The role of biomarkers in improving clinical trial success: A study of 1,079 oncology drugs
No full textDoes biomarker use in oncology improve clinical trial failure risk? A large‐scale analysis
No full textTo date there has not been an extensive analysis of the outcomes of biomarker use in oncology.
Data were pooled across four indications in oncology drawing upon trial outcomes from www.clinicaltrials.gov: breast cancer, non-small cell lung cancer (NSCLC), melanoma and colorectal cancer from 1998 to 2017. We compared the likelihood drugs would progress through the stages of clinical trial testing to approval based on biomarker status. This was done with multi-state Markov models, tools that describe the stochastic process in which subjects move among a finite number of states.
Over 10000 trials were screened, which yielded 745 drugs. The inclusion of biomarker status as a covariate significantly improved the fit of the Markov model in describing the drug trajectories through clinical trial testing stages. Hazard ratios based on the Markov models revealed the likelihood of drug approval with biomarkers having nearly a fivefold increase for all indications combined. A 12, 8 and 7-fold hazard ratio was observed for breast cancer, melanoma and NSCLC, respectively. Markov models with exploratory biomarkers outperformed Markov models with no biomarkers.
This is the first systematic statistical evidence that biomarkers clearly increase clinical trial success rates in three different indications in oncology. Also, exploratory biomarkers, long before they are properly validated, appear to improve success rates in oncology. This supports early and aggressive adoption of biomarkers in oncology clinical trials
ROS-Mediated p53 Induction of Lpin1 Regulates Fatty Acid Oxidation in Response to Nutritional Stress
No full textThe p53 protein is activated by stress signals and exhibits both protective and death-promoting functions that are considered important for its tumor suppressor function. Emerging evidence points toward an additional role for p53 in metabolism. Here, we identify Lpin1 as a p53-responsive gene that is induced in response to DNA damage and glucose deprivation. Lpin1 is essential for adipocyte development and fat metabolism, and mutation in this gene is responsible for the lypodystrophy phenotype in fld mice. We show that p53 and Lpin1 regulate fatty acid oxidation in mouse C2C12 myoblasts. p53 phosphorylation on Ser18 in response to low glucose is ROS and ATM dependent. Lpin1 expression in response to nutritional stress is controlled through the ROS-ATM-p53 pathway and is conserved in human cells. Lpin1 provides a critical link between p53 and metabolism that may be an important component in mediating the tumor suppressor function of p53. © 2011 Elsevier Inc.link_to_OA_fulltex
Three-dimensional Nuclear Telomere Organization in Multiple Myeloma
No full textAbstractMultiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Up to date, it is difficult to predict an individual's time to disease progression and the treatment response. To examine whether the nuclear telomeric architecture will unravel some of these questions, we carried out. Three-dimensional (3D) telomere analysis on samples from patients diagnosed with MGUS and MM, as well as from patients who went into relapse. Telomere signal intensity, number of telomere aggregates, nuclear volume, and the overall nuclear telomere distribution (a/c ratio) were analyzed. The telomeric profiles allowed for the differentiation of the disease stages. The telomeric profiles of myeloma cells obtained from blood and bone marrow aspirates were identical. Based on this study, we discuss the use of 3D telomere profiling as a potential future tool for risk stratification and personalized treatment decisions
Crossing boundaries: Suzuki Bokushi (1770-1842) and the rural elite of Tokugawa Japan
No full textThis thesis centres on a member of the rural elite, Suzuki Bokushi (1770-1842) of Echigo, and his social environment in Tokugawa Japan (1603-1868). Through a case study of the interaction between one individual’s life and his social conditions, the thesis participates in the ongoing scholarly reassessment of Tokugawa society, which had an apparently rigid political and social structure, yet many features that suggest a prototype of modernity. Bokushi’s life was multifaceted. He was a village administrator, landlord, pawnbroker, poet, painter, and great communicator, with a nation-wide correspondence network that crossed various social classes. His remote location and humble lifestyle notwithstanding, he was eventually able to publish a book about his region, Japan’s ‘snow country’. This thesis argues that Bokushi’s life epitomises both the potentiality and the restrictions of his historical moment for a well-placed member of the rural elite. An examination of Bokushi’s life and texts certainly challenges residual notions of the rigidity of social boundaries between the urban and the rural, between social statuses, and between cultural and intellectual communities. But Bokushi’s own actions and attitudes also show the force of conservative social values in provincial life. His activities were also still restrained by the external environment in terms of geographical remoteness, infrastructural limitation, political restrictions, cultural norms and the exigencies of human relationships. Bokushi’s life shows that in his day, Tokugawa social frameworks were being shaken and reshaped by people’s new attempts to cross conventional boundaries, within, however, a range of freedom that had both external and internal limits
Dois lados da moeda?: Versus, um jornal alternativo, e Cultura, uma revista do MEC (1976 - 1978)
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em LiteraturaEsta dissertação é uma leitura comparativa de dois periódicos: Cultura, revista publicada pelo MEC (Ministério da Educação e Cultura) entre 1971 e 1984, e Versus, jornal alternativo que circulou entre 1975 e 1979. O recorte proposto se deteve nos anos de 1976, 1977 e 1978, ou, números 20 a 30 de Cultura e 01 a 23 de Versus. A partir do que os periódicos entendiam pelo termo "cultura", foram detectadas não só diferenças, mas, também, semelhanças entre ambos. Ainda com relação ao significado e função atribuídos à cultura por Cultura e Versus, detectamos as diferenças de posicionamento internas (isto é, dentro das publicações). Ao final, percebe-se que a "cultura", tanto por parte do Estado, como por parte dos opositores ao regime militar, é relegada a um segundo plano, seja pela conjuntura econômica, no primeiro caso, seja pela conjuntura política, no segundo
