In order to achieve a level of community involvement and physical independence, being able to walk is the primary aim of many stroke survivors. It is therefore one of the most important goals during rehabilitation. Falls are common in all stages after stroke. Reported fall rates in the chronic stage after stroke range from 43 to 70% during one year follow up. Moreover, stroke survivors are more likely to become repeated fallers as compared to healthy older adults. Considering the devastating effects of falls in stroke survivors, adequate fall risk assessment is of paramount importance, as it is a first step in targeted fall prevention. As the majority of all falls occur during dynamic activities such as walking, fall risk could be assessed using gait analysis. It is only recent that technology enables us to monitor gait over several consecutive days, thereby allowing us to assess quality of gait in daily life. This thesis studies a variety of gait assessments with respect to their ability to assess fall risk in ambulatory chronic stroke survivors, and explores whether stroke survivors can improve their gait stability through PBT.
Adverse Outcome Pathways (AOPs) are conceptual frameworks that tie an initial perturbation (molecular initiat- ing event) to a phenotypic toxicological manifestation (adverse outcome), through a series of steps (key events). They provide therefore a standardized way to map and organize toxicological mechanistic information. As such, AOPs inform on key events underlying toxicity, thus supporting the development of New Approach Methodologies (NAMs), which aim to reduce the use of animal testing for toxicology purposes. However, the establishment of a novel AOP relies on the gathering of multiple streams of evidence and infor- mation, from available literature to knowledge databases. Often, this information is in the form of free text, also called unstructured text, which is not immediately digestible by a computer. This information is thus both tedious and increasingly time-consuming to process manually with the growing volume of data available. The advance- ment of machine learning provides alternative solutions to this challenge. To extract and organize information from relevant sources, it seems valuable to employ deep learning Natural Language Processing techniques. We review here some of the recent progress in the NLP field, and show how these techniques have already demonstrated value in the biomedical and toxicology areas. We also propose an approach to efficiently and reliably extract and combine relevant toxicological information from text. This data can be used to map underlying mechanisms that lead to toxicological effects and start building quantitative models, in particular AOPs, ultimately allowing animal-free human-based hazard and risk assessment.
Background: Steady-state gait characteristics appear promising as predictors of falls in stroke survivors. However, assessing how stroke survivors respond to actual gait perturbations may result in better fall predictions. We hypothesize that stroke survivors who fall have a diminished ability to adequately adjust gait characteristics after gait is perturbed. This study explored whether gait characteristics of perturbed gait differ between fallers and non fallers. Method: Chronic stroke survivors were recruited by clinical therapy practices. Prospective falls were monitored over a six months follow up period. We used the Gait Real-time Analysis Interactive Lab (GRAIL, Motekforce Link B.V., Amsterdam) to assess gait. First we assessed gait characteristics during steady-state gait and second we examined gait responses after six types of gait perturbations. We assessed base of support gait characteristics and margins of stability in the forward and medio-lateral direction. Findings: Thirty eight stroke survivors complete our gait protocol. Fifteen stroke survivors experienced falls. All six gait perturbations resulted in a significant gait deviation. Forward stability was reduced in the fall group during the second step after a ipsilateral perturbation. Interpretation: Although stability was different between groups during a ipsilateral perturbation, it was caused by a secondary strategy to keep up with the belt speed, therefore, contrary to our hypothesis fallers group of stroke survivors have a preserved ability to cope with external gait perturbations as compared to non fallers. Yet, our sample size was limited and thereby, perhaps minor group differences were not revealed in the present study.
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