Correlations between imatinib pharmacokinetics, pharmacodynamics, adherence, and clinical response in advanced metastatic gastrointestinal stromal tumor (GIST): An emerging role for drug blood level testing?

Imatinib is the standard of care for patients with advanced metastatic gastrointestinal stromal tumors (GIST), and is also approved for adjuvant treatment in patients at substantial risk of relapse. Studies have shown that maximizing benefit from imatinib depends on long-term administration at recommended doses. Pharmacokinetic (PK) and pharmacodynamic factors, adherence, and drug-drug interactions can affect exposure to imatinib and impact clinical outcomes. This article reviews the relevance of these factors to imatinib's clinical activity and response in the context of what has been demonstrated in chronic myelogenous leukemia (CML), and in light of new data correlating imatinib exposure to response in patients with GIST. Because of the wide inter-patient variability in drug exposure with imatinib in both CML and GIST, blood level testing (BLT) may play a role in investigating instances of suboptimal response, unusually severe toxicities, drug-drug interactions, and suspected non-adherence. Published clinical data in CML and in GIST were considered, including data from a PK substudy of the B2222 trial correlating imatinib blood levels with clinical responses in patients with GIST. Imatinib trough plasma levels <1100ng/mL were associated with lower rates of objective response and faster development of progressive disease in patients with GIST. These findings have been supported by other analyses correlating free imatinib (unbound) levels with response. These results suggest a future application for imatinib BLT in predicting and optimizing therapeutic response. Nevertheless, early estimates of threshold imatinib blood levels must be confirmed prospectively in future studies and elaborated for different patient subgroups.

Legitimacy in question : elite-mass relations, constitutional reform and Canadian democracy /

During the 1980s and 1990s, Canadian political authority orientations underwent a significant transformation. Canadians are no longer deferential towards their political elites. Instead, they are autonomous, challenging, and increasingly participatory, and this continuing trend has brought the procedural legitimacy of the Canadian political process into question. The following study of elite-mass relations within Canadian democracy attempts to provide insight into the meaning of this change and how it should be addressed. An attitudinalbehavioural analysis ofthe electorate presents evidence that popular cynicism and alienation is rooted more deeply in a dissatisfaction with political institutions and traditions than with politicians. A structural analysis of the elected political elite reveals the failure of consociational traditions to provide effective representation as well as the minimal impact which the aforementioned orientation shift has had upon this elite. An event-decisional analysis, or case study, ofelite-mass relations in the arena of constitutional politics augments these complementary profiles and illustrates how the transformed electorate has significantly restricted the elected political elite's role in constitutional reform. The study concludes that the lack ofresponsiveness, representativeness, and inclusiveness ofCanada's elected political elite, political institutions, and political traditions has substantially eroded the procedural legitimacy of Canadian democracy during the 1980s and 1990s. Remedying these three deficiencies in the political system, which are the objects of increasing public demand, may restore legitimacy, but the likelihood that such reforms will be adopted is presently uncertain in the face of formidable difficulties and obstacles.

Why are people liberal? : a motivated social cognition perspective

The present dissertation examined why people adopt or endorse certain political ideologies (i.e., liberal or conservative). According to a motivated social cognition perspective (Jost, Glaser, Kruglanski, & Sulloway, 2003a; Kruglanslliberalism. By focussing on the political right and not considering the political left, there might be other motivational underpinnings of political orientation that have been overlooked. In four studies, the present dissertation ail)1ed to fill this gap by investigating what chronic and situationally induced needs underlie political orientation, with a focus on political liberalism. Based on psychological the9ries of ideology, research examining political conservatism, and experimental research examining differences between liberals and conservatives, it was proposed that four social-cognitive needs (Need for Inclusiveness, Need for Understanding, Need for Change, and Avoidance of Decisional Commitment) would be associated with liberalism. Moreover, research suggests that the relations between the needs and liberalism might be moderated by political sophistication (e.g., Converse, 1964). University students (Study 1; n == 201) and community adults (Study 2; n == 197) completed questionnaires assessing political liberalism, political sophistication, and individual differences 're~ective of the four proposed needs. As predicted, correlation and hierarchical regression analyses in both Studies 1 and 2 indicated that political liberalism was related to Need for Inclusiveness, Need for Understanding, and Need for Change. 11 Avoidance of Decisional Commitment uniquely predicted political liberalism in Study 2; however, contrary to predictions, it was unrelated to political liberalism in Study 1. Furthermore, some of these relations were moderated by political sophistication, such that among individuals with a greater knowledge of politics, the relation between certain needs and liberalism was positive. To explore the role of situationally induced needs on political liberalism, each of the four proposed needs were manipulated in Study 3. Participants (n == 120) completed one of five scrambled-sentence tasks (one for each need condition and control condition), measures of explicit and implicit political liberalism, political sophistication, and state and trait measures indicative of the four proposed needs. The ~anipulation did not successfully prime participants with the needs. Therefore, a replication of the analyses from Studies 1 and 2 was conducted on the dispositional needs. Results showed that Need for Inclusiveness, Need for Understanding, and Need for Change were linked with greater explicit and implicit political liberalism. Study 4 examined the effect of manipulated Need for Inclusiveness on participants' endorsement ofpolitical liberalism, independent of conservatism. Participants (n == 43) were randomly assigned to a Need for Inclusiveness or control condition, and completed separate measures of political liberalism and conservatism, and political sophistication. Participants in the Need for Inclusiveness condition reported greater liberalism than those in a control condition; this effect was not moderated by political sophistication. Generally, the findings from this dissertation suggest that there might be other needs underlying political ideology, especially political liberalism. Thus, consistent with others' (Jost, Glaser et aI., 2003a), individuals might adopt political liberalism as a way of gratifying certain psychological needs. Implications and future research are discussed.

Opening truth to imagination : the pragmatism of John Dewey and Richard Rorty

This study explores in a comparative way the works of two American pragmatist philosophers-John Dewey and Richard Rorty. I have provided a reading of their broader works in order to offer what I hope is a successful sympathetic comparison where very few exist. Dewey is often viewed as the central hero in the classical American pragmatic tradition, while Rorty, a contemporary pragmatist, is viewed as some sort of postmodern villain. I show that the different approaches by the two philosophers-Dewey's experiential focus versus Rorty's linguistic focus-exist along a common pragmatic continuum, and that much of the critical scholarship that pits the two pragmatists against each other has actually created an unwarranted dualism between experience and language. I accomplish this task by following the critical movement by each of the pragmatists through their respective reworking of traditional absolutist truth conceptions toward a more aesthetical, imaginative position. I also show how this shift or "turning" represents an important aspect of the American philosophical tradition-its aesthetic axis. I finally indicate a role for liberal education (focusing on higher nonvocational education) in accommodating this turning, a turning that in the end is necessitated by democracy's future trajectory

The claim of Amasa Stetson, of Massachusetts, on the United States, for money advanced, in fulfilling the orders of the Government while discharging the duties of Commissary General of Purchases, in time of the late war with Great Britain ; and for services rendered. --

Claim relating to the War of 1812.

The role of a minor party : a comparative study of the British Liberal Party and the Australian Country Party since 1918

and the Australian Country Party since 1918. 2. The thesis examines the proposition that the role of a minor party is determined, not by its total strength expressed as a percentage of the national vote, but by how its strength is concentrated. Australia and Britain were chosen for the comparison because of the many similarities in political culture and in the extent of class voting. Each country has a party - the Country Party in Australia and the Liberal Party in Britain - which has had a distinct impact on the political scene in their respective countries. In the period from 1918 to the present day neither party, at the national level, has ever held the largest number of seats in parliament let alone a majority of seats, and it is in this sense that they are herein defined as minor parties. In the thesis the constitutional background of and differences between Australia and Britain are reviewed, followed by a brief historical picture of each of the two parties being studied. The sources of supporc of the two parties are analysed and it is here that real differences emerge. The Country Party in Australia is a deliberately sectional party with a narrow rural base, whereas the British Liberal Party is more broadly based than either the Labour or Conservative Parties in Britain. 3. Party leadership and organisation are then discussed. Both parties have had outstanding leaders, Earle Page and McEwen for the Country Party; Asquith, Lloyd George and Grimond for the Liberal Party. Both parties have had relatively fewer leaders than their major party opponents. However, whereas the Country Party has been free of serious splits the Liberal Party was shattered on the leadership struggles of Asquith and Lloyd George. Both parties have been identified with decentralisation of state power, the Country Party through its support, albeit sometimes lukewarm of the New States Movement; the Liberal Party through its espousal of a federal system for Britain with separate Welsh, Scottish and regional assemblies. Unfortunately for the British Liberal Party the beneficiaries of their policies in this area have been relatively new nationalist parties in both Wales arid Scotland. The major part of the thesis is devoted to a study of how the electoral systems in the two countries have, in practice, worked to the advantage or disadvantage of the Country Party and the British Liberal Party. The Country Party has been as consistently over-represented in the House of Representatives as the Liberal Party has been under-represented in the British House of Commons. With the even distribution of its support the introduction of the single transferable vote, in itself, would bring little benefit to the British Liberal Party in terms of seats. Multimember urban constituencies combined with some type of list system are the only way the Liberals are likely to obtain House of Commons seats in proportion to their votes. 4. Finally, the relations of the two minor parties with their respective major parties are considered. In the conclusion the future of the two parties is reviewed. In general terms it appears that the Country Party is faced with a slow decline. Although the British Liberal Party made a major breakthrough, in terms of votes, in the February 1974 election, they were unable to maintain this momentum in the October election, even though they lost very little ground. In the long term they must make an inroad into Labour held seats if they are to progress further.

Diálogos en el panteón liberal de México

UANL

Diálogos en el panteón liberal de México

UANL

Opiniones sobre los discursos leidos en la Convención Liberal

UANL

Advanced arithmetic

UANL

Catecismo para uso del pueblo, en que se hace una ligera comparación del protestantismo con el catolicismo y se combaten las leyes que el gobierno liberal ha dado en México contra la iglesia católica

UANL

Maximiliano y la toma de Querétaro: recopilación de los artículos que, con motivo de este histórico asunto ha publicado ultimamentetanto la prensa liberal como la conservadora, conteniendo además el informe del sr. General Escobedo sobre la toma de la plaza de Querétaro en 1867

UANL

La política liberal bajo la tiranía de Rosas

UANL

Question period of the Liberal Neutrality Conference (May 1-3, 2008)

This is the audio recording of all discussion sessions of the International Conference on the Re-evaluation of Liberal Neutrality organized by CRÉUM, Montreal May 1-3 2008. (The conference announcement is at http://www.creum.umontreal.ca/spip.php?article765) // Ceci est l'enregistrement audio des périodes de discussion du colloque organisé par le CRÉUM (Montréal, 1-3 mai 2008) et portant sur une ré-évaluation de la neutralité libérale. (L'annonce du colloque est à l'adresse http://www.creum.umontreal.ca/spip.php?article765)