Bayesian design and conduct of phase II single-arm clinical trials with binary outcomes: a tutorial

The aim of phase II single-arm clinical trials of a new drug is to determine whether it has sufficient promising activity to warrant its further development. For the last several years Bayesian statistical methods have been proposed and used. Bayesian approaches are ideal for earlier phase trials as they take into account information that accrues during a trial. Predictive probabilities are then updated and so become more accurate as the trial progresses. Suitable priors can act as pseudo samples, which make small sample clinical trials more informative. Thus patients have better chances to receive better treatments. The goal of this paper is to provide a tutorial for statisticians who use Bayesian methods for the first time or investigators who have some statistical background. In addition, real data from three clinical trials are presented as examples to illustrate how to conduct a Bayesian approach for phase II single-arm clinical trials with binary outcomes.

Control of a compliant two-axis robotic arm

In order to ease control, the links between actuators and robotic limbs are generally made to be as stiff as possible. This is in contrast to natural limbs, where compliance is present. Springs have been added to the drive train between the actuator and load to imitate this natural compliance. The majority of these springs have been in series between the actuator and load. However, a more biologically inspired approach is taken, here springs have been used in parallel to oppose each other. The paper will describe the application of parallel extension springs in a robot arm in order to give it compliance. Advantages and disadvantages of this application are discussed along with various control strategies.

Reach and grasp therapy: effects of the Gentle/G System assessing sub-acute stroke whole-arm rehabilitation

This paper reports preliminary results of a reach and grasp study of robot mediated neurorehabilitation. These results are presented on a case-by-case basis and give a good indication of a positive effect of robot mediated therapy. The study investigated both reach and grasp assistance and although it is not possible to attribute the response to the benefits of providing assistance of both modalities the study is a good indicator that this strategy should be pursued. The paper also reports on the benefits of motivational queues such as exercise scores and on subject attitudes to the robot mediated therapy.

The effect of the GENTLE/s robot-mediated therapy system on arm function after stroke

Objective: To evaluate the effect of robot-mediated therapy on arm dysfunction post stroke. Design: A series of single-case studies using a randomized multiple baseline design with ABC or ACB order. Subjects (n = 20) had a baseline length of 8, 9 or 10 data points. They continued measurement during the B - robot-mediated therapy and C - sling suspension phases. Setting: Physiotherapy department, teaching hospital. Subjects: Twenty subjects with varying degrees of motor and sensory deficit completed the study. Subjects attended three times a week, with each phase lasting three weeks. Interventions: In the robot-mediated therapy phase they practised three functional exercises with haptic and visual feedback from the system. In the sling suspension phase they practised three single-plane exercises. Each treatment phase was three weeks long. Main measures: The range of active shoulder flexion, the Fugl-Meyer motor assessment and the Motor Assessment Scale were measured at each visit. Results: Each subject had a varied response to the measurement and intervention phases. The rate of recovery was greater during the robot-mediated therapy phase than in the baseline phase for the majority of subjects. The rate of recovery during the robot-mediated therapy phase was also greater than that during the sling suspension phase for most subjects. Conclusion: The positive treatment effect for both groups suggests that robot-mediated therapy can have a treatment effect greater than the same duration of non-functional exercises. Further studies investigating the optimal duration of treatment in the form of a randomized controlled trial are warranted.

Control of a compliant two-axis robotic arm

It is common to make the links between actuators and robotic limbs as stiff as possible, in complete contrast to natural systems, where compliance is present. In the past, to create some compliance in a drive, springs have been added to the link between the actuator and load. Many of these springs have been in series with the drive, but recently a more 'biological' approach has been taken where two springs have been used in parallel to counteract each other. This paper describes the application of parallel extension springs in a robot arm in order to give it compliance. Advantages and disadvantages of this application are discussed, along with various control strategies.

Spectral invariant behavior of zenith radiance around cloud edges observed by ARM SWS

The ARM Shortwave Spectrometer (SWS) measures zenith radiance at 418 wavelengths between 350 and 2170 nm. Because of its 1-sec sampling resolution, the SWS provides a unique capability to study the transition zone between cloudy and clear sky areas. A spectral invariant behavior is found between ratios of zenith radiance spectra during the transition from cloudy to cloud-free. This behavior suggests that the spectral signature of the transition zone is a linear mixture between the two extremes (definitely cloudy and definitely clear). The weighting function of the linear mixture is a wavelength-independent characteristic of the transition zone. It is shown that the transition zone spectrum is fully determined by this function and zenith radiance spectra of clear and cloudy regions. An important result of these discoveries is that high temporal resolution radiance measurements in the clear-to-cloud transition zone can be well approximated by lower temporal resolution measurements plus linear interpolation.

Enhancement of a telemanipulator design with a human arm model

In this chapter we described how the inclusion of a model of a human arm, combined with the measurement of its neural input and a predictor, can provide to a previously proposed teleoperator design robustness under time delay. Our trials gave clear indications of the superiority of the NPT scheme over traditional as well as the modified Yokokohji and Yoshikawa architectures. Its fundamental advantages are: the time-lead of the slave, the more efficient, and providing a more natural feeling manipulation, and the fact that incorporating an operator arm model leads to more credible stability results. Finally, its simplicity allows less likely to fail local control techniques to be employed. However, a significant advantage for the enhanced Yokokohji and Yoshikawa architecture results from the very fact that it’s a conservative modification of current designs. Under large prediction errors, it can provide robustness through directing the master and slave states to their means and, since it relies on the passivity of the mechanical part of the system, it would not confuse the operator. An experimental implementation of the techniques will provide further evidence for the performance of the proposed architectures. The employment of neural networks and fuzzy logic, which will provide an adaptive model of the human arm and robustifying control terms, is scheduled for the near future.

Design of an active arm support for assisting arm movements

In this paper we have explored areas of application for health care manipulators and possible user groups. We have shown the steps in the design approach to the conceptual mechanism from the AAS. The future work will be measurement from properties of the muscle with the elbow parameterization test-bed to get a database to design one part of the control area from the AAS. More work on the mechanical design is required before a functional prototype can be built.