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2 results

  • Chapter 7 - Platform Trials

  • from Part III - Basic Ingredients for Master Protocols
  • Jay J. H. Park, McMaster University, Ontario, Edward J. Mills, McMaster University, Ontario, J. Kyle Wathen, Cytel, Cambridge, Massachusetts
  • Book:
    Introduction to Adaptive Trial Designs and Master Protocols
    Published online:
    20 March 2023
    Print publication:
    06 April 2023, pp 73-86

  • Summary

    In this chapter, we review the concept of platform trials in close detail. Platform trials refer to clinical trials that allow new interventions to be added to the platform over time even, if they are not pre-specified in the design stage. Platform trials can be applied to all phases of clinical trial research. While they are most often conducted as randomised clinical trials with adaptive trial designs (adaptive platform randomised trials), they can be conducted with non-randomised or fixed sample trial designs as well. As a general goal, platform trials aim to establish a shared trial infrastructure where multiple interventions can be evaluated. Independent clinical trial evaluation would result in multiple separate teams creating shorter term infrastructure and trials that would otherwise compete against each other. Platform trials represent an exciting turning point for clinical research. The key design considerations of platform trials are outlined in this chapter.

  • Membrane associated complexes : new approach to calciumdynamics modelling

  • M. Dyzma, P. Szopa, B. Kaźmierczak
  • Journal:
    Mathematical Modelling of Natural Phenomena / Volume 7 / Issue 6 / 2012
    Published online by Cambridge University Press:
    20 December 2012, pp. 167-186
    Print publication:
    2012

  • Mitochondria are one of the most important organelles determining Ca2+regulatory pathway in the cell. Recent experiments suggested the existence of cytosolicmicrodomains with locally elevated calcium concentration (CMDs) in the nearest vicinity ofthe outer mitochondrial membrane (OMM). These intermediate physical connections betweenendoplasmic reticulum (ER) and mitochodria are called MAM (mitochondria-associated ERmembrane) complexes.

    The aim of this paper is to take into account the direct calcium flowfrom ER to mitochondria implied by the existence of MAMs and perform detailed numericalanalysis of the influence of this flow on the type and shape of calcium oscillations.Depending on the permeability of MAMs interface and ER channels, different patterns ofoscillations appear (simple, bursting and chaotic). For some parameters the oscillatorypattern disappear and the system tends to a steady state with extremely high calcium levelin mitochondria, which can be interpreted as a crucial point at the beginning of anapoptotic pathway.