The internationalization process of mychild to São Paulo, Brazil

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Relationships between imatinib plasma levels and efficacy

Purpose: While imatinib has revolutionized the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumors (GIST), its pharmacokinetic-pharmacodynamic relationships have been poorly studied. This study aimed to explore the issue in oncologic patients, and to evaluate the specific influence of the target genotype in a GIST subpopulation. Patients and methods: Data from 59 patients (321 plasma samples) were collected during a previous pharmacokinetic study. Based on a population model purposely developed, individual post-hoc Bayesian estimates of pharmacokinetic parameters were derived, and used to estimate drug exposure (AUC; area under curve). Free fraction parameters were deduced from a model incorporating plasma alpha1-acid glycoprotein levels. Associations between AUC (or clearance) and therapeutic response (coded on a 3-point scale), or tolerability (4-point scale), were explored by ordered logistic regression. Influence of KIT genotype on response was also assessed in GIST patients. Results: Total and free drug exposure correlated with the number of side effects (p < 0.005). A relationship with response was not evident in the whole patient set (with good-responders tending to receive lower doses and bad-responders higher doses). In GIST patients however, higher free drug exposure predicted better responses. A strong association was notably observed in patients harboring an exon 9 mutation or a wild type KIT, known to decrease tumor sensitivity towards imatinib (p < 0.005). Conclusions: Our results are arguments to further evaluate the potential benefit of a therapeutic monitoring program for imatinib. Our data also suggest that stratification by genotype will be important in future trials.

Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohn's disease population: results of the FACTS survey.

Background: Switzerland was the first country to approve certolizumab pegol (Cimzia, CZP) for the treatment of patients with moderate to severe Crohn's disease (CD) in September 2007. This phase IV study aimed to evaluate the efficacy and safety of CZP in a Swiss multicenter cohort of practice-based patients. Methods: Baseline and Week 6 evaluation questionnaires were sent to all Swiss gastroenterologists in hospitals and private practices. Disease activity was assessed with the Harvey-Bradshaw Index (HBI) and adverse events were evaluated according to WHO guidelines. Results: Fifty patients (31 women, 19 men) were included; 56% had complicated disease (stricture or fistula) and 52% had undergone prior CD-related surgery. All patients. had prior exposure to systemic steroids, 96% to immunomodulators, 78% to infliximab, and 50% to adalimumab. A significant decrease in HBI was observed at Week 6 (versus Week 0) following induction therapy with CZP 400 mg subcutaneously at Weeks 0, 2, and 4 (12.6 +/- 4.7 Week 0 versus 6.2 +/- 4.4 Week 6, P < 0.001). Response and remission rates at Week 6 were 54% and 40%, respectively. We identified 8/11 CD patients undergoing a 50% fistula response (P = 0.021). The frequency of adverse drug reactions attributed to CZP was 6%. CZP was continued in 80% of patients beyond Week 6. Conclusions: In a population of CD patients with complicated disease behavior, CZP induced a response and remission in 54% and 40% of patients, respectively. This series provides the first evidence of the effectiveness of CZP in perianal fistulizing CD.

Residual antimalarials in malaria patients from Tanzania--implications on drug efficacy assessment and spread of parasite resistance.

Repeated antimalarial treatment for febrile episodes and self-treatment are common in malaria-endemic areas. The intake of antimalarials prior to participating in an in vivo study may alter treatment outcome and affect the interpretation of both efficacy and safety outcomes. We report the findings from baseline plasma sampling of malaria patients prior to inclusion into an in vivo study in Tanzania and discuss the implications of residual concentrations of antimalarials in this setting. In an in vivo study conducted in a rural area of Tanzania in 2008, baseline plasma samples from patients reporting no antimalarial intake within the last 28 days were screened for the presence of 14 antimalarials (parent drugs or metabolites) using liquid chromatography-tandem mass spectrometry. Among the 148 patients enrolled, 110 (74.3%) had at least one antimalarial in their plasma: 80 (54.1%) had lumefantrine above the lower limit of calibration (LLC = 4 ng/mL), 7 (4.7%) desbutyl-lumefantrine (4 ng/mL), 77 (52.0%) sulfadoxine (0.5 ng/mL), 15 (10.1%) pyrimethamine (0.5 ng/mL), 16 (10.8%) quinine (2.5 ng/mL) and none chloroquine (2.5 ng/mL). The proportion of patients with detectable antimalarial drug levels prior to enrollment into the study is worrying. Indeed artemether-lumefantrine was supposed to be available only at government health facilities. Although sulfadoxine-pyrimethamine is only recommended for intermittent preventive treatment in pregnancy (IPTp), it was still widely used in public and private health facilities and sold in drug shops. Self-reporting of previous drug intake is unreliable and thus screening for the presence of antimalarial drug levels should be considered in future in vivo studies to allow for accurate assessment of treatment outcome. Furthermore, persisting sub-therapeutic drug levels of antimalarials in a population could promote the spread of drug resistance. The knowledge on drug pressure in a given population is important to monitor standard treatment policy implementation.

Impact of enhanced compliance initiatives on the efficacy of rosuvastatin in reducing low density lipoprotein cholesterol levels in patients with primary hypercholesterolaemia.

The effectiveness of lipid-lowering medication critically depends on the patients' compliance and the efficacy of the prescribed drug. The primary objective of this multicentre study was to compare the efficacy of rosuvastatin with or without access to compliance initiatives, in bringing patients to the Joint European Task Force's (1998) recommended low-density lipoprotein cholesterol (LDL-C) level goal (LDL-C, <3.0 mmol/L) at week 24. Secondary objectives were comparison of the number and percentage of patients achieving European goals (1998, 2003) for LDL-C and other lipid parameters. Patients with primary hypercholesterolaemia and a 10-year coronary heart disease risk of >20% received open label rosuvastatin treatment for 24 weeks with or without access to compliance enhancement tools. The initial daily dosage of 10 mg could be doubled at week 12. Compliance tools included: a) a starter pack for subjects containing a videotape, an educational leaflet, a passport/goal diary and details of the helpline and/or website; b) regular personalised letters to provide message reinforcement; c) a toll-free helpline and a website. The majority of patients (67%) achieved the 1998 European goal for LDL-C at week 24. 31% required an increase in dosage of rosuvastatin to 20 mg at week 12. Compliance enhancement tools did not increase the number of patients achieving either the 1998 or the 2003 European target for plasma lipids. Rosuvastatin was well tolerated during this study. The safety profile was comparable with other drugs of the same class. 63 patients in the 10 mg group and 58 in the 10 mg Plus group discontinued treatment. The main reasons for discontinuation were adverse events (39 patients in the 10 mg group; 35 patients in the 10 mg Plus group) and loss to follow-up (13 patients in the 10 mg group; 9 patients in the 10 mg Plus group). The two most frequently reported adverse events were myalgia (34 patients, 3% respectively) and back pain (23 patients, 2% respectively). The overall rate of temporary or permanent study discontinuation due to adverse events was 9% (n = 101) in patients receiving 10 mg rosuvastatin and 3% (n = 9) in patients titrated up to 20 mg rosuvastatin. Rosuvastatin was effective in lowering LDL-C values in patients with hypercholesterolaemia to the 1998 European target at week 24. However, compliance enhancement tools did not increase the number of patients achieving any European targets for plasma lipids.

Cognitive coaching : a multiple case study /

The purpose of this qualitative study was to investigate the application of Cognitive Coaching as a school-based professional development program to improve instructional thought and decision making as well as to enhance staff perceptions, coUegiality and school culture. This topic emerged from personal and professional issues related to the role ofthe reflective practitioner in improving the quality of education, yet cognizant of the fact that little professional development was available to train teachers to become reflective. This case study, positioned within the interpretive sciences, focused on three teachers and how their experiences with cognitive coaching affected their teaching practices. Their knowledge, understanding and use of the four stages of instructional thought (preactive, interactive, reflective and projective) were tested before and at the end of eight coaching cycles, and again after two months to determine whether they had continued to use the reflective process. They were also assessed on whether their attitude towards peer coaching had changed, whether their feelings about teaching had become more positive and whether their professional dialogue had increased. Three methods of data collection were selected to assess growth: interviews, observations and joumaling. Analysis primarily consisted of coding and organizing data according to emerging themes. Although the professed aim of cognitive coaching was to teach the process in order that the teachers would become self-analytical and self-modifying, this study found that the value of the coaching, after trust had been established in both the coach and the process, was in the dialoguing and the time set aside to do it. Once the coaching stopped providing the time to dialogue, to examine one's meanings and beliefs, so did the critical self-reflection. As a result ofthe cognitive coaching experience though, all participants grew in their feelings of efficacy, craftsmanship, flexibility, consciousness and interdependence. The actual and potential significance ofthis study was discussed according to implications for teacher supervision, professional development, school culture, further areas of research and to my personal growth and development.

Moderating effects of gender and general self-efficacy on the relationship between sensation-seeking and adolescent substance use /

This study performed a aecondvy dau analysis of information collected during the Youth Leisure Study (YLS). The purpose of this study was to examine the potential moderating influences of gender and general self-efTicacy on the relationships aoKXig sensation-seeking and various forms of substance use in adolescents. Specifically, the predictive ability of sensation seeking on five adolescents substance use outcomes (alcohol, tobacco, and marijuana use; binge drinking; and number of times drunk) was examined. Moderated hierarchical multiple regression (MHMR) analyses were used to examine the relationships among study variables. The results for this study indicate that the relationships among sensation-seeking and forms of adolescent substance use are more complex than literature suggests. Main effect relationships were found consistently for sensation-seeking and general self-efficacy with each of the outcome variables. Results for gender were not consistent across the substance use outcomes. Gender was a significant predictor for marijuana use only. The moderating effects of general self-efficacy (GSE) on the sensation-seekingsubstance use relationship were inconsistent. While no significant interactions were found for tobacco or alcohol use outcomes, GSE was found to moderate the relationship between sensation-seeking and marijuana use indicating that feelings of high general selfefficacy act as a buffer or guard against marijuana use. A consistent pattern was found among the alcohol use variables (alcohol use. binge drinking, and number of times drunk). Gender was found to moderate each of these variables indicating that higher levels of sensation seeking are more predictive of higher levels of adolescent alcohol use in males only. Implications of this study on the field of education, are discussed further, and suggestions for future research are presented.

Teacher survival : staying alive in the job of teaching /

This study presents information gathered during personal interviews with dynamic and capable teachers in the areas of preparedness for teaching, teaching concerns, survival skills and strategies, and how these teachers support themselves and others in the teaching profession. The data are related to Purkey and Novak's work on invitational education and connections are made to Combs' perceptual orientation. Potential participants were gathered through personal recommendations from their colleagues. All teachers recommended were approached and asked for voluntary participation. Of those who agreed to participate, 6 were selected based on gender and years of experience. There was a male and female participant at each of the following career levels: early, mid, and late. The 4 major survival skills that became apparent were the ability to believe in oneself and others, to act decisively upon that belief through personal and professional goal-setting as well as accessing resources, to actively seek opportunities for interaction with other professionals, and to celebrate personal and professional successes.

Teacher professional growth in an authentic learning environment

The last several decades have been marked by tremendous changes in education - technological, pedagogical, administrative, and social. These changes have led to considerable increments in the budgets devoted to professional development for teachers ~ with the express purpose of helping them accommodate their practices to the new realities oftheir classrooms. However, research has suggested that, in spite of the emphasis placed on encouraging sustained change in teaching practices, little has been accomplished. This begs the question of what ought to be done to not only reverse this outcome, but contribute to transformational change. The literature suggests some possibilities including: a) considering teachers as learners and applying what, is known about cognition and learning; b) modifying the location and nature ofprofessional development so that it is authentic, based in the classroom and focusing on tasks meaningful to the teacher; c) attending to the infrastructure underlying professional development; and d) ensuring opportunities for reflective practice. This dissertation looks at the impact of each ofthese variables through an analysis ofthe learning journeys of a group ofteachers engaged in a program called GrassRoots in one midsized school board in Ontario. Action research was conducted by the researcher in his role as consultant facilitating teacher professional growth around the use of Web sites as culminating performance tasks by students. Research focused on the pedagogical approach to the learning of the teachers involved and the infrastructure underlying their learning. Using grounded theory, a model for professional development was developed that can be used in the future to inform practices and, hopefully, lead to sustained transformational school change.

An after-school literacy program : investigating the experiences of students with literacy difficulties, their volunteer tutors, and the tutors' transition into the teaching profession

This research responds to a pervasive call for our educational institutions to provide students with literacy skills, and teachers with the instructional supports necessary to facilitate this skill acquisition. Questions were posed to gain information concerning the efficacy ofteaching literacy strategies to students with learning difficulties, the impact of this training on their volunteer tutors, and the influence of this experience on these tutors' ensuing instructional practice as teacher candidates in a preservice education program. Study #1 compared a nontreatment group of students with literacy difficulties who participated in the program and found that program participants were superior at reading letter patterns and at comprehending the elements of story grammar. Concurrently, the second study explored the experiences of 19 volunteer tutors and uncovered that they acquired instructional skills as they established a knowledge base in teaching reading and writing, and they affirmed personal goals to become future teachers. Study #3 tracked 6 volunteer tutors into their pre-service year and identified their constructions, and beliefs about literacy instruction. These teacher candidates discussed how they had intended to teach reading and writing strategies based on their position that effective teaching ofthese skills in the primary grades is integral to academic success. The teacher candidates emphasized the need to build rapport with students, and the need to exercise flexibility in lesson plan delivery while including activities to meet emotional and developmental requirements of students. The teacher candidates entered their pre-service education with an initial cognition set based on the limited teaching context of tutoring. This foundational ii perception represented their prior knowledge of literacy instruction, a perception that appeared untenable once they were immersed in a regular instructional setting. This disparity provoked some of the teacher candidates to denounce their teacher mentors for not consistently employing literacy strategies and individualized instruction. This critical perspective could have been a demonstration of cognitive dissonance. In the end, when the teacher candidates began to look toward the future and how they would manage the demands of an inclusive classroom, they recognized the differences in the contexts. With an appreciation for the need for balance between prior and present knowledge, the teacher candidates remained committed to implementing their tutoring strategies in future teaching positions. This document highlights the need for teacher candidates with instructional experience prior to teacher education, to engage in cognitive negotiations to assimilate newly acquired pedagogies into existing pedagogies.

Learning and healing: a wellness pedagogy for Aboriginal teacher education /

During the last 30 years Aboriginal peoples in Canada have made steady progress in reclaiming the responsibility for the education of their young people, especially in primary and secondary school. In comparison the education and or training of adult populations has not kept pace and many socioeconomic and sociocultural indicators demonstrate a ' , continued confinement of those populations to the margins of the dominant society of Canada. It is the adults, the mothers and the fathers, the grandmothers and grandfathers, the aunties and uncles that are the first teachers of the next generation and the nature of these relationships replicates the culture of unwellness in each subsequent generation through those teachers. There are few examples in the Aboriginal adult education literatures that give voice to the educational experience of the Learner. This study addresses that gap by exploring the perspectives embedded in the stories of a Circle of Learners who are, or were enrolled in the Bachelor of Education in Aboriginal Adult Education program at Brock University. That Circle of 1 participants included 9 women and 1 man, 6 of whom were from various i Anishinabek nations while 4 represented the Hotinonshd:ni nations in southern Ontario. They are an eclectic group, representing many professions, age groups, spiritual traditions, and backgrounds. This then is their story, the story of the heaming and Healing pedagogy and an expanded vision of Aboriginal education and research at Brock University.

Why I am not a teacher: a self-study examining why I made the decision to exit the teaching profession /

A good teacher was once described as being like a candle; consuming itself to light the way for others (Author unknown). But as Knox (2005) says, far too many yoimg flames flicker out before they ever get the opportvmity to bum their brightest. This self-study explores the phenomenon of teacher attrition through the stories and lived experiences of one elementary teacher. I strive throughout this self-study to delve deeper into the significance of my story and lived experiences in order to enhance our understanding of why teachers exit the profession. As a result, the guiding question throughout the study is, "Why do teachers, particularly those who have only taught for a few years, leave the classrooms they worked so hard to enter?" Through the writing of a narrative entitled Sarah 's Story, I was able to identify and give voice to a story openly sharing the feelings of despair; disappointment, frustration and disillusionment. This study has identified areas of tension that lead to dissatisfaction, discontent, and teacher disillusionment. It confronts the issues of complexity, uncertainty, and conflict that are experienced in teaching. It discusses the puzzling, powerfiil and upsetting experiences, highlighting the importance of talk between all members of the education system.