3 resultados para SUGGESTED EXPLANATION
Resumo:
In many advanced democracies, political scientists have lamented the rise of professional politicians as a challenge to the effective representation of diverse electorates. In contrast, their relative absence from Canadian federal politics gives rise to concerns over high levels of political amateurism among Canadian MPs. This study, thus, seeks to account for the numerical weakness of individuals with an occupational background in politics in the Canadian Parliament. It utilizes both individual-level quantitative data on MPs serving between the 35th and 41st Parliaments, inclusive, as well as material from qualitative interviews with over seventy former MPs. Conceptualizing the field of politics as a career in itself, and drawing on career development theory, the study finds that at the key stages of establishing, maintaining, and disengaging from a federal political career, there are specific challenges that are not significantly ameliorated by the possession of professional experience in politics itself. Professional politicians, therefore, have no major advantage over those with non-political occupational backgrounds in their career development. Furthermore, by acknowledging the existence of different types of professional politician, it finds that those whose primary occupational background was in politics itself to be in a distinct minority, but the extent of political amateurism is challenged by a much larger minority of MPs whose primary occupation was non-political but who still possess some secondary or electoral experience prior to entering Parliament.
Resumo:
Exon 11 KIT mutations are found in a majority of gastrointestinal stromal tumors (GIST) and are usually predictive of response to imatinib, a KIT, PDGFRA and ABL inhibitor. Exon 11 mutations with poor sensitivity to imatinib and poor outcome can be observed on rare occasions, including p.(L576P). In silico and in vitro studies suggested a decreased binding affinity for imatinib in p.(L576P) KIT mutations, thereby offering an explanation for their poor outcome and poor response to standard therapy. These observations were further corroborated with anecdotal case reports of refractoriness or non-durable response to imatinib therapy. However, we describe the favorable response to imatinib and outcome in 5 p.(L576P)-KIT mutant GIST patients treated at a tertiary sarcoma referral center. The sensitivity of p.(L576P)-KIT mutations to imatinib, and the prognostic impact of this mutation need to be further evaluated in a larger cohort. Based on our observations, p.(L576P) mutated GISTs should be treated with standard first line imatinib therapy.