At Crossroads in a Virtual City: Effect of Spatial Disorientation on Gait Variability and Psychophysiological Response among Healthy Older Adults.

INTRODUCTION: Aging has been associated with a decline in cognitive and motor performance, often expressed in multitasking situations, which could include wayfinding. A major challenge to successful wayfinding is spatial disorientation, occurring mostly at crossings. Although gait changes have been observed in various dual-task conditions, little is known about the effect of disorientation on gait and psychophysiological response among older adults during wayfinding. The study aimed at identifying the effect of spatial disorientation on gait variability and psychophysiological response among healthy older adults during wayfinding in a controlled environment. METHOD: We analyzed data of 28 participants (age 70.8 ± 4.6, 18 female), 14 experimental and 14 controls. Participants performed a wayfinding task consisting of 14 major decision points (7 intersections) within a virtual environment (VE) projected on a 180° screen while walking on a self-paced treadmill equipped with a marker-based optical motion-capture system. The VE was held constant for the controls and manipulated for the experimental participants. Disorientation was identified based on a customized annotation scheme. Variability in gait, including the coefficient of variation (CV), was measured as the primary endpoint. Psychophysiological response measures, including heart rate variability (RMSSD) and skin conductance response (SCR), were continuously monitored as secondary endpoints and estimates of cognitive effort. Linear Mixed Effects models were applied to hypothesis-driven outcome measures extracted from decision points. RESULTS: Walking speed and step length decreased when disoriented (p < 0.05), while stride time, stance time, walking speed CV, stance time CV, SCR amplitude, and SCR count increased when disoriented (p < 0.05). A higher RMSSD was associated with being disoriented at crossings (p < 0.05). SCR count was greater in the older experimental group (p < 0.001), including when disoriented (p < 0.001). DISCUSSION/CONCLUSION: The results provide evidence for the impact of spatial disorientation on changes in gait pattern and psychophysiological response among older adults during wayfinding. Location also had implications for the effect of disorientation on gait and cognitive effort. This gives further insight into the substrates of real-world navigation challenges among older adults, with an emphasis on viable features for designing situation-adaptive interventional devices aiding independent mobility.

Prediction of Disorientation by Accelerometric and Gait Features in Young and Older Adults Navigating in a Virtually Enriched Environment.

Objective: To determine whether gait and accelerometric features can predict disorientation events in young and older adults. Methods: Cognitively healthy younger (18-40 years, n = 25) and older (60-85 years, n = 28) participants navigated on a treadmill through a virtual representation of the city of Rostock featured within the Gait Real-Time Analysis Interactive Lab (GRAIL) system. We conducted Bayesian Poisson regression to determine the association of navigation performance with domain-specific cognitive functions. We determined associations of gait and accelerometric features with disorientation events in real-time data using Bayesian generalized mixed effect models. The accuracy of gait and accelerometric features to predict disorientation events was determined using cross-validated support vector machines (SVM) and Hidden Markov models (HMM). Results: Bayesian analysis revealed strong evidence for the effect of gait and accelerometric features on disorientation. The evidence supported a relationship between executive functions but not visuospatial abilities and perspective taking with navigation performance. Despite these effects, the cross-validated percentage of correctly assigned instances of disorientation was only 72% in the SVM and 63% in the HMM analysis using gait and accelerometric features as predictors. Conclusion: Disorientation is reflected in spatiotemporal gait features and the accelerometric signal as a potentially more easily accessible surrogate for gait features. At the same time, such measurements probably need to be enriched with other parameters to be sufficiently accurate for individual prediction of disorientation events.

Context-Aware Human Activity Recognition in Industrial Processes.

The automatic, sensor-based assessment of human activities is highly relevant for production and logistics, to optimise the economics and ergonomics of these processes. One challenge for accurate activity recognition in these domains is the context-dependence of activities: Similar movements can correspond to different activities, depending on, e.g., the object handled or the location of the subject. In this paper, we propose to explicitly make use of such context information in an activity recognition model. Our first contribution is a publicly available, semantically annotated motion capturing dataset of subjects performing order picking and packaging activities, where context information is recorded explicitly. The second contribution is an activity recognition model that integrates movement data and context information. We empirically show that by using context information, activity recognition performance increases substantially. Additionally, we analyse which of the pieces of context information is most relevant for activity recognition. The insights provided by this paper can help others to design appropriate sensor set-ups in real warehouses for time management.

An algorithm for actigraphy-based sleep/wake scoring: Comparison with polysomnography.

OBJECTIVE: To evaluate the accuracy of actigraphy against polysomnography (PSG) as gold standard using a newly developed algorithm for sleep/wake discrimination that explicitly models the temporal structure of sleep. METHODS: PSG was recorded in 11 men and 9 women (age 71.1±5.0) to evaluate suspected neuropsychiatric sleep disturbances. Simultaneously, wrist actigraphy was recorded, from which 37 features were computed for each 1-min epoch. We compared prediction of PSG-derived sleep/wake states for each of these features between our newly developed algorithm, and four state-of-the-art algorithms. The algorithms were evaluated using a leave-one-subject out cross validation. RESULTS: The new algorithm classified 84.9% of sleep epochs (sensitivity) and 74.2% of wake epochs correctly (specificity), leading to a sleep/wake scoring accuracy of 79.0%. Four out of five sleep parameters were estimated more accurately by the new algorithm than by state-of-the-art algorithms. CONCLUSION: The proposed algorithm achieved a significantly higher specificity than state-of-the-art algorithm, with only minor decrease in sensitivity for patients with sleep disorders. We assume this reflects the capability of the algorithm to explicitly model sleep architecture. SIGNIFICANCE: The unobtrusive assessment of sleep/wake cycles is particularly relevant for patients with neuropsychiatric diseases that are associated with sleep disturbances, such as depression or dementia.

Effect of Spatial Disorientation in a Virtual Environment on Gait and Vital Features in Patients with Dementia: Pilot Single-Blind Randomized Control Trial.

BACKGROUND: Orientation deficits are among the most devastating consequences of early dementia. Digital navigation devices could overcome these deficits if adaptable to the user's needs (ie, provide situation-aware, proactive navigation assistance). To fulfill this task, systems need to automatically detect spatial disorientation from sensors in real time. Ideally, this would require field studies consisting of real-world navigation. However, such field studies can be challenging and are not guaranteed to cover sufficient instances of disorientation due to the large variability of real-world settings and a lack of control over the environment. OBJECTIVE: Extending a foregoing field study, we aim to evaluate the feasibility of using a sophisticated virtual reality (VR) setup, which allows a more controlled observation of disorientation states and accompanying behavioral and physiological parameters in cognitively healthy older people and people with dementia. METHODS: In this feasibility study, we described the experimental design and pilot outcomes of an ongoing study aimed at investigating the effect of disorientation on gait and selected physiological features in a virtual laboratory. We transferred a real-world navigation task to a treadmill-based virtual system for gait analysis. Disorientation was induced by deliberately manipulating landmarks in the VR projection. Associated responses in motion behavior and physiological parameters were recorded by sensors. Primary outcomes were variations in motion and physiological parameters, frequency of disorientation, and questionnaire-derived usability estimates (immersion and perceived control of the gait system) for our population of interest. At this time, the included participants were 9 cognitively healthy older participants [5/9 women, 4/9 men; mean age 70 years, SD 4.40; Mini-Mental State Examination (MMSE) mean 29, SD 0.70) and 4 participants with dementia (2/4 women, 2/4 men; mean age 78 years, SD 2.30 years; MMSE mean 20.50, SD 7.54). Recruitment is ongoing, with the aim of including 30 cognitively healthy older participants and 20 participants with dementia. RESULTS: All 13 participants completed the experiment. Patients' route was adapted by shortening it relative to the original route. Average instances of disorientation were 21.40, 36.50, and 37.50 for the cognitively healthy older control, cognitively healthy older experimental participants, and participants with dementia, respectively. Questionnaire outcomes indicated that participants experienced adequate usability and immersion; 4.30 for presence, 3.73 for involvement, and 3.85 for realism of 7 possible points, indicating a good overall ability to cope with the experiment. Variations were also observed in motion and physiological parameters during instances of disorientation. CONCLUSIONS: This study presents the first feasibility outcomes of a study investigating the viability of using a sophisticated VR setup, based on an earlier real-world navigation study, to study spatial disorientation among cognitively healthy older people and people with dementia. Preliminary outcomes give confidence to the notion that our setup can be used to assess motion and physiological markers of disorientation, even in people with cognitive decline. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT04134806.

Cool Farm Tool Water: A global on-line tool to assess water use in crop production.

The agricultural sector accounts for 70% of all water consumption and poses great pressure on ground water resources. Therefore, evaluating agricultural water consumption is highly important as it allows supply chain actors to identify practices which are associated with unsustainable water use, which risk depleting current water resources and impacting future production. However, these assessments are often not feasible for crop producers as data, models and experiments are required in order to conduct them. This work introduces a new on-line agricultural water use assessment tool that provides the water footprint and irrigation requirements at field scale based on an enhanced FAO56 approach combined with a global climate, crop and soil databases. This has been included in the Cool Farm Tool - an online tool which already provides metrics for greenhouse gas emissions and biodiversity impacts and therefore allows for a more holistic assessment of environmental sustainability in farming and agricultural supply chains. The model is tested against field scale and state level water footprint data providing good results. The tool provides a practical, reliable way to assess agricultural water use, and offers a means to engage growers and stakeholders in identifying efficient water management practices.

Analysing Cooking Behaviour in Home Settings: Towards Health Monitoring.

Wellbeing is often affected by health-related conditions. Among them are nutrition-related health conditions, which can significantly decrease the quality of life. We envision a system that monitors the kitchen activities of patients and that based on the detected eating behaviour could provide clinicians with indicators for improving a patient's health. To be successful, such system has to reason about the person's actions and goals. To address this problem, we introduce a symbolic behaviour recognition approach, called Computational Causal Behaviour Models (CCBM). CCBM combines symbolic representation of person's behaviour with probabilistic inference to reason about one's actions, the type of meal being prepared, and its potential health impact. To evaluate the approach, we use a cooking dataset of unscripted kitchen activities, which contains data from various sensors in a real kitchen. The results show that the approach is able to reason about the person's cooking actions. It is also able to recognise the goal in terms of type of prepared meal and whether it is healthy. Furthermore, we compare CCBM to state-of-the-art approaches such as Hidden Markov Models (HMM) and decision trees (DT). The results show that our approach performs comparable to the HMM and DT when used for activity recognition. It outperformed the HMM for goal recognition of the type of meal with median accuracy of 1 compared to median accuracy of 0.12 when applying the HMM. Our approach also outperformed the HMM for recognising whether a meal is healthy with a median accuracy of 1 compared to median accuracy of 0.5 with the HMM.

Sub-ångström-resolution crystallography reveals physical distortions that enhance reactivity of a covalent enzymatic intermediate.

It is recognized widely that enzymes promote reactions by providing a pathway that proceeds through a transition state of lower energy. In principle, further rate enhancements could be achieved if intermediates are prevented from relaxing to their lowest energy state, and thereby reduce the barrier to the subsequent transition state. Here, we report sub-ångström-resolution crystal structures of genuine covalent reaction intermediates of transketolase. These structures reveal a pronounced out-of-plane distortion of over 20° for the covalent bond that links cofactor and substrate, and a specific elongation of the scissile substrate carbon-carbon bond (d > 1.6 Å). To achieve these distortions, the protein's conformation appears to prevent relaxation of a substrate-cofactor intermediate. The results implicate a reduced barrier to the subsequent step that is consistent with an intermediate of raised energy and leads to a more efficient overall process.

A δ38 deletion variant of human transketolase as a model of transketolase-like protein 1 exhibits no enzymatic activity.

Besides transketolase (TKT), a thiamin-dependent enzyme of the pentose phosphate pathway, the human genome encodes for two closely related transketolase-like proteins, which share a high sequence identity with TKT. Transketolase-like protein 1 (TKTL1) has been implicated in cancerogenesis as its cellular expression levels were reported to directly correlate with invasion efficiency of cancer cells and patient mortality. It has been proposed that TKTL1 exerts its function by catalyzing an unusual enzymatic reaction, a hypothesis that has been the subject of recent controversy. The most striking difference between TKTL1 and TKT is a deletion of 38 consecutive amino acids in the N-terminal domain of the former, which constitute part of the active site in authentic TKT. Our structural and sequence analysis suggested that TKTL1 might not possess transketolase activity. In order to test this hypothesis in the absence of a recombinant expression system for TKTL1 and resilient data on its biochemical properties, we have engineered and biochemically characterized a "pseudo-TKTL1" Δ38 deletion variant of human TKT (TKTΔ38) as a viable model of TKTL1. Although the isolated protein is properly folded under in vitro conditions, both thermal stability as well as stability of the TKT-specific homodimeric assembly are markedly reduced. Circular dichroism and NMR spectroscopic analysis further indicates that TKTΔ38 is unable to bind the thiamin cofactor in a specific manner, even at superphysiological concentrations. No transketolase activity of TKTΔ38 can be detected for conversion of physiological sugar substrates thus arguing against an intrinsically encoded enzymatic function of TKTL1 in tumor cell metabolism.

Unexpected tautomeric equilibria of the carbanion-enamine intermediate in pyruvate oxidase highlight unrecognized chemical versatility of thiamin.

Thiamin diphosphate, the vitamin B1 coenzyme, plays critical roles in fundamental metabolic pathways that require acyl carbanion equivalents. Studies on chemical models and enzymes had suggested that these carbanions are resonance-stabilized as enamines. A crystal structure of this intermediate in pyruvate oxidase at 1.1 Å resolution now challenges this paradigm by revealing that the enamine does not accumulate. Instead, the intermediate samples between the ketone and the carbanion both interlocked in a tautomeric equilibrium. Formation of the keto tautomer is associated with a loss of aromaticity of the cofactor. The alternate confinement of electrons to neighboring atoms rather than π-conjugation seems to be of importance for the enzyme-catalyzed, redox-coupled acyl transfer to phosphate, which requires a dramatic inversion of polarity of the reacting substrate carbon in two subsequent catalytic steps. The ability to oscillate between a nucleophilic (carbanion) and an electrophilic (ketone) substrate center highlights a hitherto unrecognized versatility of the thiamin cofactor. It remains to be studied whether formation of the keto tautomer is a general feature of all thiamin enzymes, as it could provide for stable storage of the carbanion state, or whether this feature represents a specific trait of thiamin oxidases. In addition, the protonation state of the two-electron reduced flavin cofactor can be fully assigned, demonstrating the power of high-resolution cryocrystallography for elucidation of enzymatic mechanisms.

Twisted Schiff base intermediates and substrate locale revise transaldolase mechanism.

We examined the catalytic cycle of transaldolase (TAL) from Thermoplasma acidophilum by cryocrystallography and were able to structurally characterize--for the first time, to our knowledge--different genuine TAL reaction intermediates. These include the Schiff base adducts formed between the catalytic lysine and the donor ketose substrates fructose-6-phosphate and sedoheptulose-7-phosphate as well as the Michaelis complex with acceptor aldose erythrose-4-phosphate. These structural snapshots necessitate a revision of the accepted reaction mechanism with respect to functional roles of active site residues, and they further reveal fundamental insights into the general structural features of enzymatic Schiff base intermediates and the role of conformational dynamics in enzyme catalysis, substrate binding and discrimination. A nonplanar arrangement of the substituents around the Schiff base double bond was observed, suggesting that a structurally encoded reactant-state destabilization is a driving force of catalysis. Protein dynamics and the intrinsic hydrogen-bonding pattern appear to be crucial for selective recognition and binding of ketose as first substrate.

The crystal structure of human transketolase and new insights into its mode of action.

The crystal structure of human transketolase (TKT), a thiamine diphosphate (ThDP) and Ca(2+)-dependent enzyme that catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway, has been determined to 1.75 Å resolution. The recombinantly produced protein crystallized in space group C2 containing one monomer in the asymmetric unit. Two monomers form the homodimeric biological assembly with two identical active sites at the dimer interface. Although the protomer exhibits the typical three (α/ß)-domain structure and topology reported for TKTs from other species, structural differences are observed for several loop regions and the linker that connects the PP and Pyr domain. The cofactor and substrate binding sites of human TKT bear high resemblance to those of other TKTs but also feature unique properties, including two lysines and a serine that interact with the ß-phosphate of ThDP. Furthermore, Gln(189) spans over the thiazolium moiety of ThDP and replaces an isoleucine found in most non-mammalian TKTs. The side chain of Gln(428) forms a hydrogen bond with the 4'-amino group of ThDP and replaces a histidine that is invariant in all non-mammalian TKTs. All other amino acids involved in substrate binding and catalysis are strictly conserved. Besides a steady-state kinetic analysis, microscopic equilibria of the donor half-reaction were characterized by an NMR-based intermediate analysis. These studies reveal that formation of the central 1,2-dihydroxyethyl-ThDP carbanion-enamine intermediate is thermodynamically favored with increasing carbon chain length of the donor ketose substrate. Based on the structure of human transketolase and sequence alignments, putative functional properties of the related transketolase-like proteins TKTL1 and -2 are discussed in light of recent findings suggesting that TKTL1 plays a role in cancerogenesis.