202 research outputs found
Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK-inhibitors
No full textMany new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on hypertension and ejection fraction reduction development. Then, it follows the examination of published data for each combination therapy. A Literature research was carried out using Pubmed selecting review articles, original studies and clinical trials, but mainly focusing on phase 3 studies. This work aims to summarize the knowledge about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity to make it usable and give the basic tools to Cardiologists and Oncologists for a better management of cancer patient undergoing this treatment. Besides a deeper knowledge of the cardiovascular adverse events linked to this treatment and the magnitude of their expression and frequency can lead to a targeted cardiological treatment
GENETIC, VIROLOGICAL AND CLINICAL FACTORS ASSOCIATED WITH HEPATOCELLULAR CARCINOMA DEVELOPEMENT IN PATIENTS WITH CHRONIC HBV AND HCV INFECTION
No full textEmily Brontë : the mind of a visionary
No full textBibliography: leaves 216-226.This dissertation is an investigation of the visionary and philosophical aspects of Emily Brontë's works. The first five chapters deal with the visionary process such as visions, spirit guides, dreams, imagination, encounters with the darker side of the self and a union with the divine. There is considerable evidence of these mystical avenues in both her poetry and in Wuthering Heights which have been explored. It is shown how Emily Brontë's mysticism is a direct result of personal experiences which augment her reputation as one of the leading mystics in the world of literature. There are however tensions in her works, such as the cynicism of her own intellect in accepting the visionary experiences as authentic and periods of suffering when her faith is tested. These tensions have been considered within the context of her mystical encounters and philosophy. The remaining four chapters deal with the philosophy of Emily Brontë per se. Her beliefs in respect of heaven and hell, mercy and justice, power and survival, and pantheism are considered in depth. It is argued that she is an unorthodox thinker who does not believe in an eternal hell and that she has drawn inspiration for this idea from Frederick Maurice and Ralph Waldo Emerson. It is also shown how issues of power have been of interest to her from a young age and how this needs to be integrated within her philosophy. To the writer power needs to be tempered by compassion if it is to be of use to society or the individual. Her pantheistic spirit is also investigated and related to the mystical ideas
Charlotte Bronte: The Evolution of Her Heroes
No full textCharlotte Bronte, through her novels The Professor (published posthumously in 1857), Jane Eyre (1847) and Villette (1853), attempted to resolve the issues she faced as a plain, unmarried, independent-thinking woman in the nineteenth century. As each story is told the author takes another step toward defining her ideal of love and coming to terms with what she was not given by her father Patrick, brother Branwell, and first love M. Heger. William Crimsworth, Edward Rochester and M. Paul Emmanuel have much in common with the men in Bronte's life, yet these similarities end when they overcome their selfishness, egotism, and weakness to win the women they love. The heroes transform for love and in the process grow to be better men that deserve the heroines' love and devotion as well as becoming the ideal man Bronte longed for.SUNY BrockportEnglishMaster of Arts (MA)English Master’s These
What links BRAF to the heart function? New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment
No full textThe RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation
Graphical and Grammatical Means of Expressing Emotions in Novels Sh. Bronte and E. Bronte
No full textУ статті проаналізовані графічні та граматичні засоби вираження емоцій у романах Шарлоти Бронте «Джейн Ейр», «Ширлі», «Вільєтт» та Емілі Бронте «Буремний перевал». Емоції все частіше досліджують у лінгвістиці, оскільки автор завжди передає емоції своїх героїв у художніх творах. Автори використовують різні мовні засоби вираження емоцій, а саме: лексичні, лексико-стилістичні, графічні, граматичні. Графічні засоби вираження емоцій представлені в романах переважно капіталізацією. Граматичні засоби поділяють на морфологічні та синтаксичні. Морфологічні представлені модальними дієсловами, а синтаксичні – окличними реченнями. Наше дослідження дало змогу встановити, що в романах сестер Бронте графічні та граматичні засоби вираження емоцій займають не перше місце серед мовних засобів, але привертають особливу увагу до їх вивчення. The article analyzed the graphical and grammatical means of expressing emotions in Bronte sisters’ novels. Emotions are increasingly studied in linguistics, as the author always represents the emotions of his characters in novels. The authors use different linguistic means of expressing emotions, namely lexical, lexical-stylistic, grammatical and graphical. Graphical means of expressing emotions presented in the novels using capitalization. Grammatical are divided into morphological and syntactical. Modal verbs are morphological and syntactic – exclamatory sentences. Active research made it possible to establish that in Bronte sisters’ novels, graphical and grammatical means of expressing emotions do not occupy the first place among expressive means, but attract attention to their study
A Discourse Analysis of Lexical Cohesion In The Novel ‘Jane Eyre’ By Charlotte Bronte
No full textThe aims of this research were to describe the reiteration and to know the collocation in the novel ‗Jane Eyre‘ by Charlotte Bronte and it was analyzed by using the descriptive method. It was to indicate the lexical cohesion. This research described the methods which commonly consisted of two techniques, namely data collection and data analysis. Data collection consisted of the text of the novel Jane Eyre‘ by Charlotte Bronte and data analysis consisted of the tables of cohesive items through the novel, 80 sentences taken from the first chapter. The results of this study found out that there were two types of lexical cohesion, namely reiteration and collocation. It could be seen in the novel Jane Eyre‘ by Charlotte Bronte that there were 4 kinds of reiteration which had found, they were 5 items of repetition, 17 items of synonym, 4 items of superordinate, and 6 items of general word. Besides, there were 6 items of collocation. So that, the writer concluded that the author (Charlotte Bronte) mostly used synonym to avoid repetition in her novel especially in the first chapter under the title Gateshead. Meanwhile, this result hopefully would motivate the people to learn about discourse analysis moreover to know about lexical cohesion itself
The Philosophy of Life Reflected in The Poetry of Emily Jane Bronte and Christina Georgina Rossetti
No full textThe writer of this thesis became interested in the poetry of Christina Georgina Rossetti through the study of The Blessed Damozel,” a poem by her brother Dante Gabriel. After receiving some helpful suggestions from her adviser, the writer decided to make a rather thorough and careful study of Miss Rossetti\u27s poems. In the meantime, the adviser, Dr. Myrta E. McGinnis, head of the English Department, selected Dr. Clarice Short as director and guide for the study. Dr. Clarice Short suggested that the writer make an additional study of the poetry of Emily Jane Bronte to ascertain likenesses and unlikeness in the two poets, thereby making it a comparative study. After utilizing every available source in Forsyth Library to gain knowledge about the two poets and after a rapid reading of the poems of these two women, the writer decided upon making a comparative study of the religion or philosophy of life of Emily Jane Bronte and Christina Georgina Rossetti through the medium of their literary works. In pursuing this study, the author read practically all the poems of Emily Jane Bronte and Christina Georgina Rossetti. During a rapid reading of the poems, she selected for a more detailed and thorough study those poems of each poet which seemed to be pertinent to and illustrative of the proposed problem. As far as the writer could learn, there are not many graduate students who have written theses on these two poets. In consulting the lists of theses available in Forsyth Library, the author found that Miss Wilhelmina Rose Schreiner wrote a thesis in 1937 entitled : The Criticism of Emily Bronte, 11 and Miss Mary Louise McCluskey on Christina G. Rossetti: The Development of her Character and its Effect on her Poetry in 1941. Both of these studies were made at the University of Pittsburgh, Pennsylvania. In 1931, Miss Eleanor Walter Thomas wrote a doctoral dissertation: Christina Rossetti at Columbia University
Targeted Therapies in Hepatocellular Carcinoma
No full textThe onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients are conflicting. To date various new target drugs are under developed and other biological treatments normally indicated in other malignancies are under investigation also for HCC. These strategies aim to target the different biological pathways implicated in HCC development and progression. The target drugs studied in HCC include anti-VEGF and anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors and mTOR inhibitors. The most important challenge is represented by the best integration of these drugs with standard treatments to achieve improvement in overall survival and quality of life
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