TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.We acknowledge GENZYME for funding our work through a research project. This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology

THINK4JOBS TRAINING: Critical Thinking Training Packages for Higher Education Instructors and Labour Market Tutors

This Report presents the findings of the “Critical Thinking for Successful Jobs-Think4Jobs” Partnership regarding the development of Critical Thinking Training Packages for Higher Education Instructors and Labour Market Organisations Tutors, namely Intellectual Output II. Considering previous research findings, it is suggested that despite HE and LMO instructors’ willingness to promote CT, they both might lack conceptual as well as procedural knowledge regarding CT. In order to assume that a common understanding between HE and LMOs can be achieved to promote CT skills development effectively in future graduates, the aim of this project was to develop a training course for HE instructors as well as LMO tutors. More specifically, the project aims to strengthen University-Business Collaboration for the effective promotion, development, support and assessment of students’ CT through their transition into a professional context using apprenticeships as a privileged interface in order to “bridge the gap” between their skills and those needed by the labour market. The specific objective of the second Intellectual Output was to develop a training curriculum for Higher Education Instructors and Labour Market Organisations Tutors on how to promote, develop, support and assess students’ CT in apprenticeships curricula as well as on how to develop blended curricula using Moodle. The training aimed at reaching 30 participants from the Partnership (i.e., 15 from Higher Education and 15 from Labour Market Organisations). To reach the aforementioned objective for the delivery of the Output, five activities were originally designed: 1. Define the goals, outcomes and assessment criteria of the training packages. 2. Identify the training subjects and design the activities to be held. 3. Identify, select and/or create training resources, which will support the activities during the training packages. 4. Develop a transnational training course. 5. Delivery of the training course. University of Western Macedonia (UOWM) was the leading Organisation for the delivery of the second Intellectual Output. A Participatory Co-Design (PC-D Methodology was implemented to map the participants’ requirements and needs for the training. For the implementation of the training course, participants from both the Higher Education and the Labor Market Organisations from the five countries partake as Trainers providing various workshops focusing on experiential learning. More specifically, workshops concerned the deconstruction and reconstruction of previously held ideas regarding CT, the development of a working definition on CT for the Think4Jobs project, instructional approaches and teaching strategies that promote CT, blended learning and Moodle, the assessment of CT as well as the preparation of the Memorandum of Understanding (MoU) between HE and LMOs. Finally, a reflective session on the work carried out for the MoU and a session for the design and development of the CT blended apprenticeship curricula were scheduled. According to the registrations, on a daily basis, 35 participants engaged in the LTTA. Participants' knowledge on conceptual and procedural knowledge regarding CT, evaluation of CT, as well as blended learning, University-Business Collaboration and Moodle were evaluated in a pre-post measurement. In order to assess participants’ previous knowledge as well as the knowledge acquired during the LTTA, two online questionnaires were used. The first questionnaire (pre-measurement) was administered to participants at the beginning of the training course, while the second questionnaire (post-measurement) at the end of the LTTA (122 items for the pre-test, 130 items for the post-test, including questions about participants’ commitment during LTTA and their evaluation of the LTTA). The data collection tool consisted of seven distinct parts. The first part concerned demographic information, while the second part assessed participants’ level of perceived self-confidence in the issues addressed in the LTTA, the Moodle’s ease of use and perceived self-efficacy. Parts three to five of the tool explored participants’ conceptions regarding myths and facts about conceptual and procedural knowledge of CT, the evaluation of CT, blended learning and the University and Business Collaboration. Moreover, participants’ level of confidence about their answers was also assessed. Statistical analysis of data collected suggested that participants’ knowledge about CT, blended learning and the University and Business Collaboration increased after their participation in the LTTA. However, these results were not statistically significant. A statistically significant median increase elicited only in participants’ perceived self-confidence on the topics addressed during the LTTA, only for HE participants. Finally, the administrative and management of the implemented LTTA was evaluated highlighting that the event reached the predefined objectives and goals, met participants’ expectations and offered a high quality learning and training experience to the participants. Apart from the measurable data, a significant outcome of the LTTA was the development of a Memorandum of Understanding (MoU) between each pair of HEIs and LMOs partner per country. The MoU set a specific framework on the expected collaboration between HE and LMOs for the design-development (IO3), implementation and evaluation (IO4) of the CT blended apprenticeships curricula. The development of MoUs suggest that a common understanding on the design and delivery of CT blended apprenticeships curricula has been achieved and that UBC has been tailored to each pair of contributors. Overall, the CT training course presented in the current report has contributed to the existing research and literature in numerous ways. First, it presented a course designed to address the specific needs of its participants, by employing a PC-D approach. Second, it presented a training course that can also be applied in the future, as an intensive program aiming to enhance CT in educational and LMO settings. Third, it actively engaged HE Instructors and LMOs in a common training course, trying to reach a common understanding. Finally, the current report contributes to the literature with the exploitation of a multiple-choice instrument incorporating a Certainty Response Index identifying not only participants’ alternative concepts but also their level of confidence on aspects of CT, blended learning and UBC