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Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children

Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children with ASD, and significantly worsen their behavior and their quality of life. Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut–brain interactions could also be a direct result of microbially produced metabolites.

ContributorsKrajmalnik-Brown, Rosa (Author) / Lozupone, Catherine (Author) / Kang, Dae Wook (Author) / Adams, James (Author) / Biodesign Institute (Contributor)
Created2015-03-12
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Description

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms.

One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.

ContributorsFrye, Richard E. (Author) / Slattery, John (Author) / MacFabe, Derrick F. (Author) / Allen-Vercoe, Emma (Author) / Parker, William (Author) / Rodakis, John (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Bolte, Ellen (Author) / Kahler, Stephen (Author) / Jennings, Jana (Author) / James, Jill (Author) / Cerniglia, Carl E. (Author) / Midtvedt, Tore (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-05-07
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Description

Humans are able to modulate digit forces as a function of position despite changes in digit placement that might occur from trial to trial or when changing grip type for object manipulation. Although this phenomenon is likely to rely on sensing the position of the digits relative to each other

Humans are able to modulate digit forces as a function of position despite changes in digit placement that might occur from trial to trial or when changing grip type for object manipulation. Although this phenomenon is likely to rely on sensing the position of the digits relative to each other and the object, the underlying mechanisms remain unclear. To address this question, we asked subjects (n = 30) to match perceived vertical distance between the center of pressure (CoP) of the thumb and index finger pads (dy) of the right hand (“reference” hand) using the same hand (“test” hand). The digits of reference hand were passively placed collinearly (dy = 0 mm). Subjects were then asked to exert different combinations of normal and tangential digit forces (Fn and Ftan, respectively) using the reference hand and then match the memorized dy using the test hand. The reference hand exerted Ftan of thumb and index finger in either same or opposite direction. We hypothesized that, when the tangential forces of the digits are produced in opposite directions, matching error (1) would be biased toward the directions of the tangential forces; and (2) would be greater when the remembered relative contact points are matched with negligible digit force production. For the test hand, digit forces were either negligible (0.5–1 N, 0 ± 0.25 N; Experiment 1) or the same as those exerted by the reference hand (Experiment 2).Matching error was biased towards the direction of digit tangential forces: thumb CoP was placed higher than the index finger CoP when thumb and index finger Ftan were directed upward and downward, respectively, and vice versa (p < 0.001). However, matching error was not dependent on whether the reference and test hand exerted similar or different forces. We propose that the expected sensory consequence of motor commands for tangential forces in opposite directions overrides estimation of fingertip position through haptic sensory feedback.

ContributorsShibata, Daisuke (Author) / Kappers, Astrid M. L. (Author) / Santello, Marco (Author) / College of Health Solutions (Contributor)
Created2014-08-04
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Description

We develop a general framework to analyze the controllability of multiplex networks using multiple-relation networks and multiple-layer networks with interlayer couplings as two classes of prototypical systems. In the former, networks associated with different physical variables share the same set of nodes and in the latter, diffusion processes take place.

We develop a general framework to analyze the controllability of multiplex networks using multiple-relation networks and multiple-layer networks with interlayer couplings as two classes of prototypical systems. In the former, networks associated with different physical variables share the same set of nodes and in the latter, diffusion processes take place. We find that, for a multiple-relation network, a layer exists that dominantly determines the controllability of the whole network and, for a multiple-layer network, a small fraction of the interconnections can enhance the controllability remarkably. Our theory is generally applicable to other types of multiplex networks as well, leading to significant insights into the control of complex network systems with diverse structures and interacting patterns.

ContributorsYuan, Zhengzhong (Author) / Zhao, Chen (Author) / Wang, Wen-Xu (Author) / Di, Zengru (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-10-24
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Description

Recent studies about sensorimotor control of the human hand have focused on how dexterous manipulation is learned and generalized. Here we address this question by testing the extent to which learned manipulation can be transferred when the contralateral hand is used and/or object orientation is reversed. We asked subjects to

Recent studies about sensorimotor control of the human hand have focused on how dexterous manipulation is learned and generalized. Here we address this question by testing the extent to which learned manipulation can be transferred when the contralateral hand is used and/or object orientation is reversed. We asked subjects to use a precision grip to lift a grip device with an asymmetrical mass distribution while minimizing object roll during lifting by generating a compensatory torque. Subjects were allowed to grasp anywhere on the object’s vertical surfaces, and were therefore able to modulate both digit positions and forces. After every block of eight trials performed in one manipulation context (i.e., using the right hand and at a given object orientation), subjects had to lift the same object in the second context for one trial (transfer trial).

Context changes were made by asking subjects to switch the hand used to lift the object and/or rotate the object 180° about a vertical axis. Therefore, three transfer conditions, hand switch (HS), object rotation (OR), and both hand switch and object rotation (HS+OR), were tested and compared with hand matched control groups who did not experience context changes. We found that subjects in all transfer conditions adapted digit positions across multiple transfer trials similar to the learning of control groups, regardless of different changes of contexts. Moreover, subjects in both HS and HS+OR group also adapted digit forces similar to the control group, suggesting independent learning of the left hand. In contrast, the OR group showed significant negative transfer of the compensatory torque due to an inability to adapt digit forces. Our results indicate that internal representations of dexterous manipulation tasks may be primarily built through the hand used for learning and cannot be transferred across hands.

ContributorsFu, Qiushi (Author) / Choi, Jason (Author) / Gordon, Andrew M. (Author) / Jesunathadas, Mark (Author) / Santello, Marco (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-09-18
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Description

Sensorimotor control theories propose that the central nervous system exploits expected sensory consequences generated by motor commands for movement planning, as well as online sensory feedback for comparison with expected sensory feedback for monitoring and correcting, if needed, ongoing motor output. In our study, we tested this theoretical framework by

Sensorimotor control theories propose that the central nervous system exploits expected sensory consequences generated by motor commands for movement planning, as well as online sensory feedback for comparison with expected sensory feedback for monitoring and correcting, if needed, ongoing motor output. In our study, we tested this theoretical framework by quantifying the functional role of expected vs. actual proprioceptive feedback for planning and regulation of gait in humans. We addressed this question by using a novel methodological approach to deliver fast perturbations of the walking surface stiffness, in conjunction with a virtual reality system that provided visual feedback of upcoming changes of surface stiffness. In the “predictable” experimental condition, we asked subjects to learn associating visual feedback of changes in floor stiffness (sand patch) during locomotion to quantify kinematic and kinetic changes in gait prior to and during the gait cycle. In the “unpredictable” experimental condition, we perturbed floor stiffness at unpredictable instances during the gait to characterize the gait-phase dependent strategies in recovering the locomotor cycle. For the “unpredictable” conditions, visual feedback of changes in floor stiffness was absent or inconsistent with tactile and proprioceptive feedback. The investigation of these perturbation-induced effects on contralateral leg kinematics revealed that visual feedback of upcoming changes in floor stiffness allows for both early (preparatory) and late (post-perturbation) changes in leg kinematics. However, when proprioceptive feedback is not available, the early responses in leg kinematics do not occur while the late responses are preserved although in a, slightly attenuated form. The methods proposed in this study and the preliminary results of the kinematic response of the contralateral leg open new directions for the investigation of the relative role of visual, tactile, and proprioceptive feedback on gait control, with potential implications for designing novel robot-assisted gait rehabilitation approaches.

ContributorsFrost, Ryan (Author) / Skidmore, Jeffrey (Author) / Santello, Marco (Author) / Artemiadis, Panagiotis (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-02-09
Description

Widespread contamination of groundwater by chlorinated ethenes and their biological dechlorination products necessitates the reliable monitoring of liquid matrices; current methods approved by the U.S. Environmental Protection Agency (EPA) require a minimum of 5 mL of sample volume and cannot simultaneously detect all transformative products. This paper reports on the

Widespread contamination of groundwater by chlorinated ethenes and their biological dechlorination products necessitates the reliable monitoring of liquid matrices; current methods approved by the U.S. Environmental Protection Agency (EPA) require a minimum of 5 mL of sample volume and cannot simultaneously detect all transformative products. This paper reports on the simultaneous detection of six chlorinated ethenes and ethene itself, using a liquid sample volume of 1 mL by concentrating the compounds onto an 85-µm carboxen-polydimenthylsiloxane solid-phase microextraction fiber in 5 min and subsequent chromatographic analysis in 9.15 min. Linear increases in signal response were obtained over three orders of magnitude (∼0.05 to ∼50 µM) for simultaneous analysis with coefficient of determination (R2) values of ≥ 0.99. The detection limits of the method (1.3–6 µg/L) were at or below the maximum contaminant levels specified by the EPA. Matrix spike studies with groundwater and mineral medium showed recovery rates between 79–108%. The utility of the method was demonstrated in lab-scale sediment flow-through columns assessing the bioremediation potential of chlorinated ethene-contaminated groundwater. Owing to its low sample volume requirements, good sensitivity and broad target analyte range, the method is suitable for routine compliance monitoring and is particularly attractive for interpreting the bench-scale feasibility studies that are commonly performed during the remedial design stage of groundwater cleanup projects.

ContributorsZiv-El, Michal (Author) / Kalinowski, Tomasz (Author) / Krajmalnik-Brown, Rosa (Author) / Halden, Rolf (Author) / Biodesign Institute (Contributor)
Created2014-02-01
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Description

Objective: To estimate the absolute wealth of households using data from demographic and health surveys.

Methods: We developed a new metric, the absolute wealth estimate, based on the rank of each surveyed household according to its material assets and the assumed shape of the distribution of wealth among surveyed households. Using

Objective: To estimate the absolute wealth of households using data from demographic and health surveys.

Methods: We developed a new metric, the absolute wealth estimate, based on the rank of each surveyed household according to its material assets and the assumed shape of the distribution of wealth among surveyed households. Using data from 156 demographic and health surveys in 66 countries, we calculated absolute wealth estimates for households. We validated the method by comparing the proportion of households defined as poor using our estimates with published World Bank poverty headcounts. We also compared the accuracy of absolute versus relative wealth estimates for the prediction of anthropometric measures.

Findings: The median absolute wealth estimates of 1 403 186 households were 2056 international dollars per capita (interquartile range: 723-6103). The proportion of poor households based on absolute wealth estimates were strongly correlated with World Bank estimates of populations living on less than 2.00 United States dollars per capita per day (R-2=0.84). Absolute wealth estimates were better predictors of anthropometric measures than relative wealth indexes.

Conclusion: Absolute wealth estimates provide new opportunities for comparative research to assess the effects of economic resources on health and human capital, as well as the long-term health consequences of economic change and inequality.

ContributorsHruschka, Daniel (Author) / Gerkey, Drew (Author) / Hadley, Craig (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-07-01
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Description

The intact nervous system has an exquisite ability to modulate the activity of multiple muscles acting at one or more joints to produce an enormous range of actions. Seemingly simple tasks, such as reaching for an object or walking, in fact rely on very complex spatial and temporal patterns of

The intact nervous system has an exquisite ability to modulate the activity of multiple muscles acting at one or more joints to produce an enormous range of actions. Seemingly simple tasks, such as reaching for an object or walking, in fact rely on very complex spatial and temporal patterns of muscle activations. Neurological disorders such as stroke and focal dystonia affect the ability to coordinate multi-joint movements. This article reviews the state of the art of research of muscle synergies in the intact and damaged nervous system, their implications for recovery and rehabilitation, and proposes avenues for research aimed at restoring the nervous system’s ability to control movement.

ContributorsSantello, Marco (Author) / Lang, Catherine E. (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-01-06