Manual The Regan Factor

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In the love-trial of Act 1, Scene 1, both Goneril and Regan make huge claims about their love for their father, claiming that it surpasses any other kind of happiness they can imagine:. Goneril Sir, I love you more than [words] can wield the matter, Dearer than eyesight, space, and liberty, Beyond what can be valued, rich or rare, No less than life, with grace, health, beauty, honour; As much as child e'er lov'd, or father found; A love that makes breath poor, and speech unable: Beyond all manner of so much I love you. In my true heart I find she names my very deed of love; Only she comes too short, that I profess Myself an enemy to all other joys Which the most precious square of sense [possesses], And find I am alone felicitate In your dear Highness' love.

Edmund, meanwhile, uses his quick-wittedness to outsmart his father and brother, dominating the scenes in which they appear.

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When my dimensions are as well compact, My mind as generous, and my shape as true, As honest madam's issue? Edmund, however, tries to assert an alternative morality. Francis Bacon, the celebrated philosopher and statesman, wrote about the envious and often villainous nature of bastards in his Essays.

Usage terms Public Domain. As Edmund is characterised by the language of bastardy, Goneril and Regan are associated with disease. The Machiavel uses his cunning to manipulate others and ensure that he gets what he wants, being driven entirely by self-interest. Edmund takes advantage of the credulous natures of both Gloucester and Edgar, and revels in the fact that he is able to do so. Significantly, Edmund is fully aware of his unscrupulous nature, and sees it not as a result of his illegitimacy but simply as who he is:.

Many feminist critics have explored the patriarchal society in which Goneril and Regan have grown up. Is it really so surprising that people who seem to have had little power in either the domestic or political spheres should behave inappropriately when power is given to them? The TEXT and SOFT trial results were also considered separately according to chemotherapy use, which was determined by physician and patient choice and reflected an assessment of recurrence risk.

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To better inform selection among three adjuvant endocrine therapy options for premenopausal patients, we investigated the absolute magnitude of treatment benefit in TEXT and SOFT according to a quantitative composite measure of recurrence risk. The composite measure was a means to systematically characterize the spectrum of recurrence risk of all trial patients, as done previously for postmenopausal women.

We focused here on patients with human epidermal growth factor receptor 2 HER2 —negative disease because adjuvant trastuzumab with chemotherapy is now indicated for most patients with HER2-positive disease, a practice that changed during trial conduct; the HER2-positive population will be the subject of a separate investigation.

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The designs and conduct of the trials have been described previously. TEXT was designed to determine the role of adjuvant therapy with the AI exemestane versus tamoxifen in premenopausal women treated with OFS from the start of adjuvant therapy. Between November and March , 2, eligible women were randomly assigned at a ratio to 5 years of exemestane plus OFS or 5 years of tamoxifen plus OFS. OFS was performed through gonadotropin-releasing hormone agonist triptorelin administration, bilateral oophorectomy, or ovarian irradiation.

Chemotherapy was optional and, if administered, was started concurrently with triptorelin. Random assignment was stratified according to intended use of adjuvant chemotherapy and lymph node status. SOFT was designed to determine the value of adding OFS to tamoxifen and the role of exemestane plus OFS in two cohorts of premenopausal women: those who remained premenopausal after completion of neo adjuvant chemotherapy and those for whom adjuvant tamoxifen alone was considered suitable treatment.

Between December and January , 3, eligible women were randomly assigned at a ratio to 5 years of exemestane plus OFS, tamoxifen plus OFS, or tamoxifen alone.

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Random assignment was stratified according to use of prior chemotherapy, lymph node status, and intended initial method of OFS if randomly assigned to OFS. The ethics committee at each participating center approved the study protocols, and all patients provided written informed consent for trial participation, including protocol-mandated central pathology review. The analysis population included 4, patients with hormone receptor—positive, HER2-negative tumors. Fig 1. OFS, ovarian function suppression. The end point for this analysis was BCFI, defined as time from random assignment to first appearance of invasive breast cancer recurrence local, regional, or distant or invasive contralateral breast cancer; in the absence of an event, patients were censored at date of last follow-up.

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BCFI, rather than disease-free survival, was chosen as the end point to disregard second nonbreast malignancies that occurred at similar frequencies across treatment groups and the few deaths that occurred without a prior cancer event. To define the composite measure of recurrence risk hereafter referred to as composite risk , a Cox proportional hazards model for BCFI, stratified by cohort defined by trial and chemotherapy use and treatment assignment, was estimated for the entire hormone receptor—positive, HER2-negative analytic population.

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This stratified model, rather than a model estimated in the control group patients only, 11 , 12 was necessary because the two trials did not have a common control group, and we preferred to examine the two trial populations using the same risk scale. Prognostic factors included in the model and their groupings were specified a priori on the basis of usual clinical cutpoints and prior St Gallen Consensus statements, and there was no intention to optimize the model on the basis of model selection procedures Table 1.

Unknown categories were included because of unavailable data. For tumor grade and ER and PgR expression, the centrally determined values were used when available, and locally determined values were used otherwise; Ki expression was available only from central assessment. For each trial patient, the value of composite risk was calculated by summing the model parameter estimates corresponding to her observed clinicopathologic factor values. The nonparametric sliding-window subpopulation treatment effect pattern plot STEPP methodology 13 , 14 was used to investigate patterns in absolute treatment effect, as measured by Kaplan-Meier estimates of 5-year BCFI y -axis , across the continuum of the values of composite risk x -axis.

Table 1. Values for grade and ER and PgR expression were centrally determined if available and locally determined otherwise; Ki expression was available only by central determination. Characteristics of the 4, patients in the hormone receptor—positive, HER2-negative analysis population according to cohort, as defined by trial and chemotherapy use, are summarized in Table 1. The relation of each factor with BCFI, without regard for cohort or treatment assignment, is summarized in Figure 2.

Fig 2. Kaplan-Meier estimates of breast cancer—free interval BCFI in the overall hormone receptor—positive, human epidermal growth factor receptor 2—negative analysis population according to patient and tumor characteristics.

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A Age at random assignment, B nodal status, C tumor size, D estrogen receptor expression, E progesterone expression, F tumor grade, and G Ki expression. Table 2. Overall, the 5-year BCFI was As expected from the distributions of the individual factors Table 1 and their role in decision making about chemotherapy, the composite risk distributions were shifted lower in the cohorts that did not receive chemotherapy and higher in those that did Fig 4. Fig 3. Breast cancer—free interval BCFI in the overall hormone receptor—positive, human epidermal growth factor receptor 2 HER2 —negative population according to composite risk.

B Subpopulation treatment effect pattern plot of 5-year BCFI y -axis according to composite risk subpopulation x -axis. C distribution of composite risk scores with quartiles of the distribution marked by horizontal lines. The vertical dashed line indicates the median composite risk of 1. In keeping with findings in children with P falciparum malaria, acute endothelial cell activation was an early and consistent feature in the murine model of cerebral malaria CM , resulting in significantly increased plasma VWF levels. Given the significant morbidity and mortality associated with CM, these novel data may have direct translational significance.

National Center for Biotechnology Information , U. Didn't get the message? Find out why Add to Clipboard. Add to Collections. Order articles. Fetching bibliography My Bibliography Add to Bibliography. Generate a file for use with external citation management software. Create File. Epub Oct Comment in The heads and the tails of malaria and VWF. Images from this publication.