Pushrim-activated power-assisted wheel (PAPAW) users ideally require different levels of assistance depending on activity and preference. Therefore, it is important to design and develop adaptive ...PAPAW controllers to account for these differences. The main objective of this work was to integrate a user intention estimation framework into a PAPAW and develop personalized adaptive controllers. We performed experiments to gather kinetics of wheelchair propulsion for a variety of daily life wheelchair activities. The propulsion characteristics (i.e., pushrim forces) were used to train intention estimation models and characterize implicit user intentions when performing daily life wheelchair maneuvers. These intentions included moving straight forward, performing a right/left turn, and braking. The intention estimation framework, based on random forest classification algorithms and kinetic features, was implemented and tested in our laboratory-developed PAPAW. This computationally efficient framework was successfully implemented and tested for each participant in real-time. Our results revealed that the real-time user intention predictions were similar to the offline models. The power-assist ratio of each wheel was adjusted based on which user intention was identified. Data collected from four participants provided evidence regarding the effectiveness of using adaptive intention-based controllers. For instance, the propulsion effort was significantly reduced when using an adaptive PAPAW controller. Subjective views of participants regarding the workload of wheelchair propulsion (e.g., physical/cognitive effort) were also gathered. Our findings suggest that rankings of different controllers varied among different participants and across different wheelchair maneuvers, indicating the need for customized adaptive controllers to fit different users' activities and preferences.
Molecular Genetics and Economics Beauchamp, Jonathan P.; Cesarini, David; Johannesson, Magnus ...
The Journal of economic perspectives,
2011, Letnik:
25, Številka:
4
Journal Article
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The costs of comprehensively genotyping human subjects have fallen to the point where major funding bodies, even in the social sciences, are beginning to incorporate genetic and biological markers ...into major social surveys. How, if at all, should economists use and combine molecular genetic and economic data from these surveys? What challenges arise when analyzing genetically informative data? To illustrate, we present results from a “genome-wide association study” of educational attainment. We use a sample of 7,500 individuals from the Framingham Heart Study; our dataset contains over 360,000 genetic markers per person. We get some initially promising results linking genetic markers to educational attainment, but these fail to replicate in a second large sample of 9,500 people from the Rotterdam Study. Unfortunately such failure is typical in molecular genetic studies of this type, so the example is also cautionary. We discuss a number of methodological challenges that face researchers who use molecular genetics to reliably identify genetic associates of economic traits. Our overall assessment is cautiously optimistic: this new data source has potential in economics. But researchers and consumers of the genoeconomic literature should be wary of the pitfalls, most notably the difficulty of doing reliable inference when faced with multiple hypothesis problems on a scale never before encountered in social science.
Niraparib (Zejula), a selective oral PARP1/2 inhibitor registered for ovarian, fallopian tube, and primary peritoneal cancer treatment, is under investigation for other malignancies, including brain ...tumors. We explored the impact of the ABCB1 and ABCG2 multidrug efflux transporters, the OATP1A/1B uptake transporters, and the CYP3A drug-metabolizing complex on oral niraparib pharmacokinetics, using wild-type and genetically modified mouse and cell line models. In vitro, human ABCB1 and mouse Abcg2 transported niraparib moderately. Compared to wild-type mice, niraparib brain-to-plasma ratios were 6- to 7-fold increased in Abcb1a/1b –/– and Abcb1a/1b;Abcg2–/– but not in single Abcg2–/– mice, while niraparib plasma exposure at later time points was ∼2-fold increased. Niraparib recovery in the small intestinal content was markedly reduced in the Abcb1a/1b-deficient strains. Pretreatment of wild-type mice with oral elacridar, an ABCB1/ABCG2 inhibitor, increased niraparib brain concentration and reduced small intestinal content recovery to levels observed in Abcb1a/1b;Abcg2–/– mice. Oatp1a/1b deletion did not significantly affect niraparib oral bioavailability or liver distribution but decreased metabolite M1 liver uptake. No significant effects of mouse Cyp3a ablation were observed, but overexpression of transgenic human CYP3A4 unexpectedly increased niraparib plasma exposure. Thus, Abcb1 deficiency markedly increased niraparib brain distribution and reduced its small intestinal content recovery, presumably through reduced biliary excretion and/or decreased direct intestinal excretion. Elacridar pretreatment inhibited both processes completely. Clinically, the negligible role of OATP1 and CYP3A could be advantageous for niraparib, diminishing drug–drug interaction or interindividual variation risks involving these proteins. These findings may support the further clinical development and application of niraparib.
Electroencephalography (EEG) is a common neuroimaging technique used in clinical, research, and consumer technology given its noninvasiveness, high temporal resolution, and sensitivity. The main ...challenge in ambulatory EEG monitoring is the presence of substantial motion artifacts, especially for high-intensity movements such as running. This study compared motion artifacts in gold-cup, gel, and dry electrodes during different levels of physical activity. Eight healthy participants were instrumented with a wearable EEG cap and an instrumented mouthguard to measure head kinematics. While all electrode types performed similarly in the resting state, dry electrodes showed high-amplitude motion artifacts and worse performance during walking, running, and jumping. EEG-motion coherence was found to be higher for dry electrodes in low-intensity movements (e.g., walking with 0.1-0.5-g head acceleration, where 1 g =9.81 m/s<inline-formula> <tex-math notation="LaTeX">^{2} </tex-math></inline-formula>), but similar across the three electrode types for medium-to-high-intensity movements (e.g., running and jumping with 0.5-3.5-g head acceleration), with peak coherences at up to 20 Hz. Fast walk trials showed the highest linear correlation between EEG signal and head acceleration, indicating potentially better coupling between the head and the electrode at this movement intensity. Our results imply that dry electrodes require further hardware development to mitigate motion artifacts before reliable application in ambulatory monitoring, and wet electrodes also exhibit clear movement-related artifacts in higher intensity movements. Uniquely, we identified EEG-motion coupling as a contributing factor to motion artifact characteristics, and coherence analysis may be a promising approach for motion artifact identification and quantification. Further characterization, quantification, and mitigation of motion artifacts will aid in higher quality measurement and meaningful interpretation of ambulatory EEG signals for clinical and research applications.
The notion of an optimal difficulty during practice has been articulated in many areas of cognitive psychology: flow theory, the challenge point framework, and desirable difficulties. Delivering ...exercises at a participant's desired difficulty has the potential to improve both motor learning and users' engagement in therapy. Motivation and engagement are among the contributing factors to the success of exercise programs. The authors previously demonstrated that error amplification can be used to introduce levels of challenge into a robotic reaching task, and that machine-learning algorithms can dynamically adjust difficulty to the desired level with 85% accuracy. Building on these findings, we present the results of a proof-of-concept study investigating the impacts of practicing under desirable difficulty conditions. A control condition with a predefined random order for difficulty levels was deemed more suitable for this study (compared to constant or continuously increasing difficulty). By practicing the task at their desirable difficulties, participants in the experimental group perceived their performance at a significantly higher level and reported lower required effort to complete the task, in comparison to a control group. Moreover, based on self-reports, participants in the experimental group were willing, on average, to continue the training session for 4.6 more training blocks (∼45 min) compared to the control group's average. This study demonstrates the efficiency of delivering the exercises at the user's desired difficulty level to improve the user's engagement in exercise tasks. Future work will focus on clinical feasibility of this approach in increasing stroke survivors' engagement in their therapy programs.
Key points
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Electrical vestibular stimulation delivered at the mastoid processes evokes a reflex response in the appendicular muscles only when they are actively involved in keeping the unsupported ...head and body balanced.
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We show that the vestibular‐evoked muscle response was present during a task that simulated the control of standing where sensory feedback was congruent with the motor‐generated expectation to balance the body, and absent when sensory feedback did not match.
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The present results indicate that the task dependency of the vestibular‐evoked muscle response relies on congruent sensory and motor signals, and that this is organised in the absence of a conscious perception of postural control.
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These findings help us understand how our brain combines sensory and motor signals to provide an internal representation of standing balance that can be used to assess whether a perturbation poses a postural threat.
We investigate whether the muscle response evoked by an electrically induced vestibular perturbation during standing is related to congruent sensory and motor signals. A robotic platform that simulated the mechanics of a standing person was used to manipulate the relationship between the action of the calf muscles and the movement of the body. Subjects braced on top of the platform with the ankles sway referenced to its motion were required to balance its simulated body‐like load by modulating ankle plantar‐flexor torque. Here, afferent signals of body motion were congruent with the motor command to the calf muscles to balance the body. Stochastic vestibular stimulation (±4 mA, 0–25 Hz) applied during this task evoked a biphasic response in both soleus muscles that was similar to the response observed during standing for all subjects. When the body was rotated through the same motion experienced during the balancing task, a small muscle response was observed in only the right soleus and in only half of the subjects. However, the timing and shape of this response did not resemble the vestibular‐evoked response obtained during standing. When the balancing task was interspersed with periods of computer‐controlled platform rotations that emulated the balancing motion so that subjects thought that they were constantly balancing the platform, coherence between the input vestibular stimulus and soleus electromyogram activity decreased significantly (P < 0.05) during the period when plantar‐flexor activity did not affect the motion of the body. The decrease in coherence occurred at 175 ms after the transition to computer‐controlled motion, which subjects did not detect until after 2247 ms (Confidence Interval 1801, 2693), and then only half of the time. Our results indicate that the response to an electrically induced vestibular perturbation is organised in the absence of conscious perception when sensory feedback is congruent with the underlying motor behaviour.
Despite there being sufficient evidence for the effectiveness of screening by cytology in preventing cancer of the cervix uteri, screening policies vary widely among European countries, and incidence ...is increasing in younger women. This study analyzes trends in squamous cell carcinoma (SCC) of the cervix uteri in 13 European countries to evaluate effectiveness of screening against a background of changing risk. Age-period-cohort models were fitted and period and cohort effects were estimated; these were considered as primarily indicative of screening interventions and changing etiology, respectively. A unique set of estimates was derived by fixing age slopes to one of several plausible age curves under the assumption that the relation between age and cervical cancer incidence is biologically determined. There were period-specific declines in cervical SCC in several countries, with the largest decreases seen in northern Europe. A pattern emerged across Europe of escalating risk in successive generations born after 1930. In the western European countries, a decrease followed by a stabilization of risk by cohort was accompanied by period-specific declines. In southern Europe, stable period, but increasing cohort trends, were observed. Substantial changes have occurred in cervical SCC incidence in Europe and well-organized screening programs have been highly effective in reducing the incidence of cervical SCC. Screening and changing sexual mores largely explain the changing period- and cohort-specific patterns, respectively. The increasing risk in recent cohorts is of obvious concern particularly in countries where no screening programs are in place. Further investigation of the effectiveness of opportunistic screening is warranted as is the observation of differing risk patterns in young cohorts in countries with relatively similar societal structures.
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