Modified 3+3 design for phase I clinical trials

Phase I clinical trial is mainly designed to determine the maximum tolerated dose (MTD) of a new drug. Optimization of phase I trial design is crucial to minimize the number of enrolled patients exposed to unsafe dose levels and to provide reliable information to the later phases of clinical trials. Although it has been criticized about its inefficient MTD estimation, nowadays the traditional 3+3 method remains dominant in practice due to its simplicity and conservative estimation. There are many new designs that have been proven to generate more credible MTD estimation, such as the Continual Reassessment Method (CRM). Despite its accepted better performance, the CRM design is still not widely used in real trials. There are several factors that contribute to the difficulties of CRM adaption in practice. First, CRM is not widely accepted by the regulatory agencies such as FDA in terms of safety. It is considered to be less conservative and tend to expose more patients above the MTD level than the traditional design. Second, CRM is relatively complex and not intuitive for the clinicians to fully understand. Third, the CRM method take much more time and need statistical experts and computer programs throughout the trial. The current situation is that the clinicians still tend to follow the trial process that they are comfortable with. This situation is not likely to change in the near future. Based on this situation, we have the motivation to improve the accuracy of MTD selection while follow the procedure of the traditional design to maintain simplicity. We found that in 3+3 method, the dose transition and the MTD determination are relatively independent. Thus we proposed to separate the two stages. The dose transition rule remained the same as 3+3 method. After getting the toxicity information from the dose transition stage, we combined the isotonic transformation to ensure the monotonic increasing order before selecting the optimal MTD. To compare the operating characteristics of the proposed isotonic method and the other designs, we carried out 10,000 simulation trials under different dose setting scenarios to compare the design characteristics of the isotonic modified method with standard 3+3 method, CRM, biased coin design (BC) and k-in-a-row design (KIAW). The isotonic modified method improved MTD estimation of the standard 3+3 in 39 out of 40 scenarios. The improvement is much greater when the target is 0.3 other than 0.25. The modified design is also competitive when comparing with other selected methods. A CRM method performed better in general but was not as stable as the isotonic method throughout the different dose settings. The results demonstrated that our proposed isotonic modified method is not only easily conducted using the same procedure as 3+3 but also outperforms the conventional 3+3 design. It can also be applied to determine MTD for any given TTL. These features make the isotonic modified method of practical value in phase I clinical trials.^

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Re-thinking Argentina's labour and social security reform in the 1990s : agreement on competitive corporatism

This paper will analyze the Menem administration's social policy reforms during the 1990s. Neo-liberal reforms in Argentina are well-known both in the economy and in the social arena, but in the latter we can discern the presence of tripartite negotiations. The form of such negotiations, the type of agreements reached as a result, and the background to those agreements will be discussed. We also pay attention to the concept of competitive corporatism, which was established under the increase in market competition brought about by globalization.

EvAAL: Evaluating AAL Systems through Competitive Benchmarking

Owing to the complexity of Ambient Assisted Living (AAL) systems and platforms, the evaluation of AAL solutions is a complex task that will challenge researchers for years to come. However, the analysis and comparison of proposed solutions is paramount to enable us to assess research results in this area. We have thus organized an international contest called EvAAL: Evaluating AAL Systems through Competitive Benchmarking. Its aims are to raise interest within the research and developer communities in the multidisciplinary research fields enabling AAL, and to create benchmarks for the evaluation and comparison of AAL systems.

Differences and Relationship Between Standard and Specific Throwing Test in Handball According to the Competitive and Professional Level

The present study analyzed the differences in distance throwing with heavy and light medicine ball and throwing velocity between handball players of different competitive and professional level. Likewise, the relationship between the three throwing test of progressive specificity was analyzed: throwing with heavy medicinal ball (TH), throwing with light medicinal ball (TL) and throwing velocity (TV). For this purpose, sixty-five professional (P), semiprofessional (S) and non-professional (N) players were evaluated. El presente estudio analizó las diferencias en la distancia de lanzamiento realizado con balón medicinal pesado y ligero y en la velocidad de lanzamiento entre jugadores de balonmano de diferente nivel competitivo y profesional. Igualmente, la relación entre los tres test de lanzamiento, de progresiva especificidad, fue analizado: lanzamiento con balón medicinal pesado (TH), lanzamiento con balón medicinal ligero (TL) y velocidad de lanzamiento (TV). Para ello, sesenta y cinco jugadores profesionales (P), semi-profesionales (S) y no-profesionales (N) fueron evaluados.

Effect of positioning on the accuracy of decision making of association football top-class referees and assistant referees during competitive matches

The aim of this study was to examine the effect of positioning on the correctness of decision making of top-class referees and assistant referees during international games. Match analyses were carried out during the Fe´de´ration Internationale de Football Association (FIFA) Confederations Cup 2009 and 380 foul play incidents and 165 offside situations were examined. The error percentage for the referees when indicating the incidents averaged 14%. The lowest error percentage occurred in the central area of the field, where the collaboration of the assistant referee is limited, and was achieved when indicating the incidents from a distance of 11–15 m, whereas this percentage peaked (23%) in the last 15-min match period. The error rate for the assistant referees was 13%. Distance of the assistant referee to the offside line did not have an impact on the quality of the offside decision. The risk of making incorrect decisions was reduced when the assistant referees viewed the offside situations from an angle between 46 and 608. Incorrect offside decisions occurred twice as often in the second as in the first half of the games. Perceptual-cognitive training sessions specific to the requirements of the game should be implemented in the weekly schedule of football officials to reduce the overall error rate.

Validity and reliability of AMPET Greek versión: a first examination of learning motivation in Greek PE settings

Validity and reliability of AMPET Greek versión: a first examination of learning motivation in Greek PE settings

Toward a planning model for the peruvian university system as a competitive strategy.

University education in Peru is based on models of teacher-centered teaching and a conception of knowledge which is closed and static and under the dominance of an information model now overwhelmed by multiple factors hastened by international change. The worlds most prestigious universities have chosen cultural diversity as a sign of quality and are hence interested in the mobility of teachers and students through exchange and cooperation with foreign educational institutions. These universities respond more effectively to pressure from the international business sector, better satisfy training demands, introduce new information and communication technologies into education and research and have improved administration and management structures. While there is progress, the university system in Peru is a planning model defined "as a discipline that seeks to respond to the needs of an organization defined by new cultural and social models" (A. Cazorla, et al 2007).This paper studies the non-Euclidean thinking of planning and development of John Friedmann (2001). Based on the four domains of social practice, it proposes a planning model for Peruvian universities that meets international requirements.

Survey on student motivation and approval of educational environment at Universidad Politécnica de Madrid within the European Higher Education area implementation

A recent study elaborated by Vicerrectorado de Ordenación Académica y Planificación Estratégica of Technical University of Madrid (UPM) defines the satisfaction of the university student body as "the response that the University offers to the expectations and demands of service of the students, considered in a general way ". Besides an indicator of academic and institutional insertion of the student, the assessment of student engagement allows us to adapt the academic offer and the extension services of the University to the real needs of the students. The process of convergence towards the European Higher Education Area (EHEA) raises the need to form in competitions, that is to say, of developing in our students capacities and knowledge beyond the purely theoretical-practical thing. Therefore, the perception and experience of the educational process and environment by the students is an important issue to be addressed to accomplish their expectations and achieve a curriculum accordingly to EHEA expectations. The present study aims to explore the student motivation and approval of the educational environment at the UPM. To this end a total of 97 students enrolled in the undergraduate program of Civil Engineering, Computer Engineering and Agronomic Engineering at UPM were surveyed. The survey consisted of 40 questions divided in three blocks. The first one of 20 questions of personal character in that they were gathering, besides the sex and the age, the degree of fulfilment, implication and dedication with the institution and the academic tasks. In the second block we identify 10 questions related to the perception of the student on the teaching quality, and finally a block of 10 questions regarding the Bologna Process. The students personal motivation was moderately high, with a score of 3.6 (all scores are provided on a 5-point scale), being the most valuable items obtaining a university degree (4,3) and the friendship between students (4,2). Any significant difference was shown between sexes (P=0.23) since the averages for this block of questions were of 3.7±0.3 and 3.5±0.4 for women and men respectively. The students are moderately satisfied with their graduate studies with an average score of 3,2, being the questions that reflect a minor satisfaction the research profile of the teachers (2,8) and the organization of the Schools (2,9). The best valued questions are related to the usefulness and quality of the degrees, with 3,5 and 3,4 respectively, and to the interest of the courses within the degree (3,4). For sexes, the results of this block of questions are similar (3.1±0.3 and 3.2±0.3 for men and women respectively=0.79). Also, there were no differences (P=0.39) between the students who arrange work and studies or do not work (3.1±0.2 and 3.2±0.3 respectively). In conclusion, students at UPM present an acceptable degree of motivation and satisfaction with regard to the studies and services that offer their respective Schools. Both characteristics receive the same value both for men and for women and so much for students who arrange work and studies as for those who devote themselves only to studying. In a significant way, students who are more engaged and are in-class attendants present the major degree of satisfaction.Overall, there is a great lack of information regarding the Bologna Process. In fact to the majority, they would like to know more on what it is, what it means and what changes will involve its implementation.

Teamwork competence and academic motivation in computer science engineering studies.

The present work is focused on studying two issues: the “teamwork” generic competence and the “academic motivation”. Currently the professional profile of engineers has a strong component of teamwork. On the other hand, motivational profile of students determines their tendencies when they come to work in team, as well as their performance at work. In this context we suggest four hypotheses: (H1) students improve their teamwork capacity by specific training and carrying out a set of activities integrated into an active learning process; (H2) students with higher mastery motivation have better attitude towards team working; (H3) students with higher mastery motivation obtain better results in academic performance; and (H4) students show different motivation profiles in different circumstances: type of courses, teaching methodologies, different times of the learning process. This study was carried out with computer science engineering students from two Spanish universities. The first results point to an improvement in teamwork competence of students if they have previously received specific training in facets of that competence. Other results indicate that there is a correlation between the motivational profiles of students and their perception about teamwork competence. Finally, and contrary to the initial hypothesis, these profiles appear to not influence significantly the academic performance of students.