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Simulation research that seeks to solve the problem of silence among interprofessional teams has focused almost exclusively on training subordinate team members to be more courageous and to speak up to team leaders using direct challenge scripts despite the great interpersonal cost. Consequently, the existing literature overemphasizes the responsibility of subordinate team members for speaking up and fails to consider the role and responsibilities of team leaders in sustaining silence. The purpose of this study is to identify and describe the subtle behaviors and actions of team leaders that both promote and discourage speaking up. This study used a simulation-primed qualitative inquiry approach. Obstetricians (OB) at one academic center participated in an interprofessional simulation as an embedded participant. Five challenge moments (CM) were scripted for the OB involving deliberate clinical judgment errors or professionalism infractions. Other participants were unaware of the OB embedded participant role. Thirteen iterations were completed with 39 participants. Twelve faculty members completed a subsequent semi-structured interview. Scenarios were videotaped; debriefs and interviews were audio-recorded and transcribed verbatim. Data were analyzed using an inductive thematic approach. After participating in an interprofessional simulation, faculty participants reflected that being an approachable team leader requires more than simply avoiding disruptive behaviors. We found that approachability necessitates that team leaders actively create the conditions in which team members perceive that speaking up is welcomed, rather than an act of bravery. In practice, this conceptualization of approachability involves the tangible actions of signaling availability through presence, uncertainty through thinking aloud, and vulnerability through debriefing. By using faculty as embedded participants with scripted errors, our simulation design provided an ideal learning opportunity to prompt discussion of the subtle behaviors and actions of team leaders that both promote and discourage speaking up. Faculty participants gained a new appreciation that their actions create the conditions for speaking up to occur before critical incidents through their verbal and non-verbal communication.

Recent studies with normal rats and mouse allograft models have reported that insulin and insulin analogues do not activate the IGF-1 receptor in vivo, and that this characteristic therefore cannot be responsible for the increased incidence of mammary tumours observed for the insulin analogue X10 in chronic toxicity studies with Sprague Dawley rats. This is in clear contrast to reports of insulin and insulin analogues in vitro. Clarification of this is important for understanding the mechanisms behind possible growth-promoting effects of insulin analogues, and will have implications for the development of novel insulin analogues. We established a xenograft model in BALB/c nude mice with the human colon cancer cell line COLO-205, which expresses human insulin and IGF-1 receptors, and explored the acute and chronic effects of treatment with supra-pharmacological doses of human insulin, insulin analogue X10 and human IGF-1. With a novel antibody, acute IGF-1 receptor activation was also examined in various tissues from normal rats treated with human insulin, insulin analogue X10 or human IGF-1. Finally, the effects of pharmacologically relevant doses of human insulin and insulin analogue X10 on receptor activation and growth of COLO-205 xenograft were explored in BALB/c nude mice with alloxan-induced hyperglycaemia. In normal rats and in BALB/c nude mice bearing a COLO-205 cell xenograft, treatment with supra-pharmacological doses of human insulin, insulin analogue X10 or human IGF-1 resulted in activation of insulin receptors as well as IGF-1 receptors. Treatment of diabetic nude mice with pharmacologically relevant doses of human insulin or insulin analogue X10, which decreased blood glucose from hyperglycaemic levels to the normoglycaemic range, did not increase IGF-1 receptor activation. Furthermore, repeated treatment with supra-pharmacological as well as pharmacological doses of human insulin or insulin analogue X10 did not influence the growth of COLO-205 xenografts. This study demonstrates that activation of IGF-1 receptors in cancer cells by insulin and insulin analogues cannot be considered as a purely in vitro phenomenon. It does occur in vivo in animal models, although only after treatment with supra-pharmacological doses. Furthermore, treatment with insulin or insulin analogue X10 did not influence the growth of COLO-205 xenografts under normo- or hypoglycaemic conditions. Further studies are needed before a conclusion can be reached on whether IGF-1 receptor activation by insulin analogues correlates with increased growth in vivo.

Dedifferentiated chondrosarcoma is an unconventional chondrosarcoma of distinctive pathology. The tumor, not previously reported in childhood, is characterized by a very poor prognosis with an average survival of only 6 months. Imaging features include a lytic lesion, focal calcifications, and a soft tissue mass.