Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy

The 5T4 oncofoetal antigen is a heavily glycosylated cell surface protein found on human placental trophoblast and on diverse types of human cancer but is not expressed at significant levels on adult human tissues in health. It therefore satisfies the criteria for a tumour-associated antigen and is an ideal target for the immunotherapy of cancer. We report here that 5T4 is strongly expressed on the majority of renal cell carcinomas and therefore this population of patients is suitable for trials of 5T4-targeted therapies. In particular, we have shown that T cells from renal cell carcinoma patients can be genetically modified to kill 5T4 expressing renal cancer cell lines by introduction of a chimeric-signalling protein. This protein consists of a single chain antibody fragment capable of binding antigen directly at the cell surface and then activating the T cell by virtue of a CD3ζ-signalling domain. This is a powerful tool that bypasses a number of mechanisms that allow tumours to escape T-cell killing and can be readily scaled up for clinical use

Three-Wall Segment (TriSeg) Model Describing Mechanics and Hemodynamics of Ventricular Interaction

A mathematical model (TriSeg model) of ventricular mechanics incorporating mechanical interaction of the left and right ventricular free walls and the interventricular septum is presented. Global left and right ventricular pump mechanics were related to representative myofiber mechanics in the three ventricular walls, satisfying the principle of conservation of energy. The walls were mechanically coupled satisfying tensile force equilibrium in the junction. Wall sizes and masses were rendered by adaptation to normalize mechanical myofiber load to physiological standard levels. The TriSeg model was implemented in the previously published lumped closed-loop CircAdapt model of heart and circulation. Simulation results of cardiac mechanics and hemodynamics during normal ventricular loading, acute pulmonary hypertension, and chronic pulmonary hypertension (including load adaptation) agreed with clinical data as obtained in healthy volunteers and pulmonary hypertension patients. In chronic pulmonary hypertension, the model predicted right ventricular free wall hypertrophy, increased systolic pulmonary flow acceleration, and increased right ventricular isovolumic contraction and relaxation times. Furthermore, septal curvature decreased linearly with its transmural pressure difference. In conclusion, the TriSeg model enables realistic simulation of ventricular mechanics including interaction between left and right ventricular pump mechanics, dynamics of septal geometry, and myofiber mechanics in the three ventricular walls

Breaking down professional barriers: Medicine and pharmacy students learning together

Background: This paper reports findings of a pilot interprofessional problem based learning (PBL) study in the faculties of Medicine and Pharmacy at the University of Sydney, New South Wales. The aim of the research was to investigate whether small group interprofessional learning activities with medical and pharmacy students can lead to: changes in attitude toward each other and toward interprofessional education (IPE); added value when learning together; and better understanding of each other's professional roles. Methods: Nineteen medical and 20 pharmacy students participated in two, 2-hour PBL tutorials focussed on conducting a Home Medicines Review. The Attitudes to Health Professionals Questionnaire (AHPQ) was used to measure attitude change pre- and postinterprofessional PBL. Paired t-tests were used to analyse pre- and post-IPE data. Focus groups were conducted with the students after the PBL sessions. These were audio-recorded, transcribed and analysed. Results: Students reported added value from the IPE experience. Pharmacy students reported a small but significant change in attitude toward the medical students on the AHPQ caring scale, rating them as more caring post-IPE (p=0.001). Although medical students rated the pharmacy students more caring after the intervention, this was not statistically significant (p=0.08). Medical students valued the pharmacy students' input and knowledge. Conclusion: There was evidence of a positive change in students' attitudes to the other profession after only two sessions. Aspects of IPE design such as explicit interprofessional learning outcomes, the use of PBL processes, and relevant learning activities were important to the success of this pilot stud

Defining professionalism in medical education: a systematic review

Introduction: We undertook a systematic review and narrative synthesis of the literature to identify how professionalism is defined in the medical education literature. Methods: Eligible studies included any articles published between 1999 and 2009 inclusive presenting viewpoints, opinions, or empirical research on defining medical professionalism. Results: We identified 195 papers on the topic of definition of professionalism in medicine. Of these, we rated 26 as high quality and included these in the narrative synthesis. Conclusion: As yet there is no overarching conceptual context of medical professionalism that is universally agreed upon. The continually shifting nature of the organizational and social milieu in which medicine operates creates a dynamic situation where no definition has yet taken hold as definitive