From twitch to tetanus for human muscle - experimental data and model predictions for m. triceps surae

In models describing the excitation of muscle by the central nervous system, it is often assumed that excitation during a tetanic contraction can be obtained by the linear summation of responses to individual stimuli, from which the active state of the muscle is calculated. We investigate here the extent to which such a model describes the excitation of human muscle in vivo. For this purpose, experiments were performed on the calf muscles of four healthy subjects. Values of parameters in the model describing the behaviour of the contractile element (CE) and the series elastic element (SEE) of this muscle group were derived on the basis of a set of isokinetic release contractions performed on a special-purpose dynamometer as well as on the basis of morphological data. Parameter values describing the excitation of the calf muscles were optimized such that the model correctly predicted plantar flexion moment histories in an isometric twitch, elicited by stimulation of the tibial nerve. For all subjects, the model using these muscle parameters was able to make reasonable predictions of isometric moment histories at higher stimulation frequencies. These results suggest that the linear summation of responses to individual stimuli can indeed give an adequate description of the process of human muscle excitation in vivo

Sensity of vertical jumping performance to changes in muscle stimulation onset times: a simulation study

The effect of muscle stimulation dynamics on the sensitivity of jumping achievement to variations in timing of muscle stimulation onsets was investigated. Vertical squat jumps were simulated using a forward dynamic model of the human musculoskeletal system. The model calculates the motion of body segments corresponding to STIM(t) of six major muscle groups of the lower extremity, where STIM is muscle stimulation level. For each muscle, STIM was allowed to switch "on" only once. The subsequent rise of STIM to its maximum was described using a sigmoidal curve, the dynamics of which was expressed as rise time (RT). For different values of stimulation RT, the optimal set of onset times was determined using dynamic optimization with height reached by the center of mass as performance criterion. Subsequently, 200 jumps were simulated in which the optimal muscle stimulation onset times were perturbed by adding to each a small number taken from a Gaussian-distributed set of pseudo-random numbers. The distribution of heights achieved in these perturbed jumps was used to quantify the sensitivity of jump height to variations in timing of muscle stimulation onsets. It was found that with increasing RT, the sensitivity of jump height to timing of stimulation onset times decreased. To try and understand this finding, a post-hoc analysis was performed on the perturbed jumps. Jump height was most sensitive to errors in the delay between stimulation onset times of proximal muscles and stimulation onset times of plantar flexors. It is explained how errors in this delay cause aberrations in the configuration of the system, which are regenerative and lead to relatively large jump height deficits. With increasing RT, the initial aberrations due to erroneous timing of muscle stimulation are smaller, and the regeneration is less pronounced. Finally, it is speculated that human subjects decrease or increase RT depending on the relative importance of different performance criteria

Predictions of mechanical output of human m. triceps surae on the basis of electromyographic sign: the role of stimulation dynamics

In order to assess the significance of the dynamics of neural control signals for the rise time of muscle moment, simulations of isometric and dynamic plantar flexion contractions were performed using electromyographic signals (EMG signals) of m. triceps surae as input. When excitation dynamics of the muscle model was optimized for an M-wave of the medial head of m. gastrocnemius (GM), the model was able to make reasonable predictions of the rise time of muscle moment during voluntary isometric plantar flexion contractions on the basis of voluntary GM EMG signals. The rise time of muscle moment in the model was for the greater part determined by the amplitude of the first EMG burst. For dynamic jumplike movements of the ankle joint, however, no relationship between rise time of muscle moment in the experiment and muscle moment predicted by the model on the basis of GM EMG signals was found. Since rise time of muscle moment varied over a small range for this movement, it cannot be completely excluded that stimulation dynamics plays a role in control of these simple single-joint movements

Quality assurance of thoracic radiotherapy in EORTC 08941: a randomised trial of surgery versus thoracic radiotherapy in patients with stage IIIA non-small-cell lung cancer (NSCLC) after response to induction chemotherapy.

Contains fulltext : 50144.pdf (publisher's version ) (Closed access)The aim of this study was to investigate the improvement of quality of radiotherapy and compliance to the protocol amendment of EORTC study 08941. The radiotherapy-specific data were analysed from 154 patients with stage IIIA-N2 Non-Small-Cell Lung Cancer who were actually irradiated after response to 3 cycles of platinum-based induction chemotherapy. The parameters of quality, assessed in 93 patients before and in 61 after protocol amendment, included: time interval between last chemotherapy course and start of thoracic radiotherapy, the use of a 3-D planning CT, dose and fractionation scheme to the primary tumour, the involved and uninvolved mediastinum, duration of radiotherapy and toxicity. A significant improvement of all quality parameters was noted, except for the overall treatment time, which decreased slightly. Protocol amendment resulted in an improvement of the quality and the compliance of most observed parameters, at the cost of some increase in overall treatment time. The latter reflects logistical problems rather than poor compliance

The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC.

Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced NSCLC, particularly those who have progressed during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab, and nintedanib). It is hypothesized that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. In this review, we explore the theory and potential of this novel treatment option for patients with advanced NSCLC. We discuss the growing body of evidence that proangiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumor microenvironment and through systemic effects on immune-regulatory cell function), and we examine the preclinical evidence for combining these treatments. Potential challenges are also considered, and we review the preliminary evidence of clinical efficacy and safety with this novel combination in a variety of solid tumor types