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Background Freezing of gait (FOG) is a common and debilitating gait impairment in Parkinson’s disease. Further insight into this phenomenon is hampered by the difficulty to objectively assess FOG. To meet this clinical need, this paper proposes an automated motion-capture-based FOG assessment method driven by a novel deep neural network. Methods Automated FOG assessment can be formulated as an action segmentation problem, where temporal models are tasked to recognize and temporally localize the FOG segments in untrimmed motion capture trials. This paper takes a closer look at the performance of state-of-the-art action segmentation models when tasked to automatically assess FOG. Furthermore, a novel deep neural network architecture is proposed that aims to better capture the spatial and temporal dependencies than the state-of-the-art baselines. The proposed network, termed multi-stage spatial-temporal graph convolutional network (MS-GCN), combines the spatial-temporal graph convolutional network (ST-GCN) and the multi-stage temporal convolutional network (MS-TCN). The ST-GCN captures the hierarchical spatial-temporal motion among the joints inherent to motion capture, while the multi-stage component reduces over-segmentation errors by refining the predictions over multiple stages. The proposed model was validated on a dataset of fourteen freezers, fourteen non-freezers, and fourteen healthy control subjects. Results The experiments indicate that the proposed model outperforms four state-of-the-art baselines. Moreover, FOG outcomes derived from MS-GCN predictions had an excellent (r = 0.93 [0.87, 0.97]) and moderately strong (r = 0.75 [0.55, 0.87]) linear relationship with FOG outcomes derived from manual annotations. Conclusions The proposed MS-GCN may provide an automated and objective alternative to labor-intensive clinician-based FOG assessment. Future work is now possible that aims to assess the generalization of MS-GCN to a larger and more varied verification cohort.

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Background Although deep neural networks (DNNs) are showing state of the art performance in clinical gait analysis, they are considered to be black-box algorithms. In other words, there is a lack of direct understanding of a DNN’s ability to identify relevant features, hindering clinical acceptance. Interpretability methods have been developed to ameliorate this concern by providing a way to explain DNN predictions. Methods This paper proposes the use of an interpretability method to explain DNN decisions for classifying the movement that precedes freezing of gait (FOG), one of the most debilitating symptoms of Parkinson’s disease (PD). The proposed two-stage pipeline consists of (1) a convolutional neural network (CNN) to model the reduction of movement present before a FOG episode, and (2) layer-wise relevance propagation (LRP) to visualize the underlying features that the CNN perceives as important to model the pathology. The CNN was trained with the sagittal plane kinematics from a motion capture dataset of fourteen PD patients with FOG. The robustness of the model predictions and learned features was further assessed on fourteen PD patients without FOG and fourteen age-matched healthy controls. Results The CNN proved highly accurate in modelling the movement that precedes FOG, with 86.8% of the strides being correctly identified. However, the CNN model was unable to model the movement for one of the seven patients that froze during the protocol. The LRP interpretability case study shows that (1) the kinematic features perceived as most relevant by the CNN are the reduced peak knee flexion and the fixed ankle dorsiflexion during the swing phase, (2) very little relevance for FOG is observed in the PD patients without FOG and the healthy control subjects, and (3) the poor predictive performance of one subject is attributed to the patient’s unique and severely flexed gait signature. Conclusions The proposed pipeline can aid clinicians in explaining DNN decisions in clinical gait analysis and aid machine learning practitioners in assessing the generalization of their models by ensuring that the predictions are based on meaningful kinematic features.

There are concerns about the stability of meropenem in plasma samples, even when frozen at −20 °C. Previous smaller studies suggested significant degradation of meropenem at −20 °C after 3–20 days. However, in several recent clinical studies, meropenem plasma samples were still stored at −20 °C, or the storage temperature and/or time were not mentioned in the paper. The aim of this study was to describe and model meropenem degradation in human plasma at −20 °C over 1 year. Stability of meropenem in human plasma at −20 °C was investigated at seven concentrations (0.44, 4.38, 17.5, 35.1, 52.6, 70.1, and 87.6 mg/L) representative for the range of relevant concentrations encountered in clinical practice. For each concentration, samples were stored for 0, 7, 14, 21, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224, 252, 280, 308, 336, and 364 days at −20 °C before being transferred to −80 °C until analysis. Degradation was modeled using polynomial regression analysis and artificial neural network (ANN). Meropenem showed significant degradation over time in human plasma when stored at −20 °C. Degradation was present over the whole concentration range and increased with higher concentrations until a concentration of 35.1 mg/L. Both models showed accurate prediction of meropenem degradation. In conclusion, this study provides detailed insights into the concentration-dependent degradation of meropenem in human plasma stored at −20 °C over 1 year. Meropenem in human plasma is shown to be stable at least up to approximately 80 days when stored at −20 °C. The polynomial model allows calculating original meropenem concentrations in samples stored for a known period of time at −20 °C.