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Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases

Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.

ContributorsFrye, Richard E. (Author) / Rossignol, Daniel (Author) / Casanova, Manuel F. (Author) / Brown, Gregory L. (Author) / Martin, Victoria (Author) / Edelson, Stephen (Author) / Coben, Robert (Author) / Lewine, Jeffrey (Author) / Slattery, John C. (Author) / Lau, Chrystal (Author) / Hardy, Paul (Author) / Fatemi, S. Hossein (Author) / Folsom, Timothy D. (Author) / MacFabe, Derrick (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-09-13
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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

Background: Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other

Background: Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other clinical factor relevant to ASD, we developed a comprehensive on-line seizure survey.

Methods: Announcements (by email and websites) by ASD support groups asked parents of children with ASD to complete the on-line surveys. Survey responders choose one of two surveys to complete: a survey about treatments for individuals with ASD and clinical or subclinical seizures or abnormal electroencephalograms, or a control survey for individuals with ASD without clinical or subclinical seizures or abnormal electroencephalograms. Survey responders rated the perceived effect of traditional antiepileptic drug (AED), non-AED seizure treatments and non-traditional ASD treatments on seizures and other clinical factors (sleep, communication, behavior, attention and mood), and listed up to three treatment side effects.

Results: Responses were obtained concerning 733 children with seizures and 290 controls. In general, AEDs were perceived to improve seizures but worsened other clinical factors for children with clinical seizure. Valproic acid, lamotrigine, levetiracetam and ethosuximide were perceived to improve seizures the most and worsen other clinical factors the least out of all AEDs in children with clinical seizures. Traditional non-AED seizure and non-traditional treatments, as a group, were perceived to improve other clinical factors and seizures but the perceived improvement in seizures was significantly less than that reported for AEDs. Certain traditional non-AED treatments, particularly the ketogenic diet, were perceived to improve both seizures and other clinical factors. For ASD individuals with reported subclinical seizures, other clinical factors were reported to be worsened by AEDs and improved by non-AED traditional seizure and non-traditional treatments. The rate of side effects was reportedly higher for AEDs compared to traditional non-AED treatments.

Conclusion: Although this survey-based method only provides information regarding parental perceptions of effectiveness, this information may be helpful for selecting seizure treatments in individuals with ASD.

ContributorsFrye, Richard E. (Author) / Sreenivasula, Swapna (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2011-05-18
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Cognitive theories in visual attention and perception, categorization, and memory often critically rely on concepts of similarity among objects, and empirically require measures of “sameness” among their stimuli. For instance, a researcher may require similarity estimates among multiple exemplars of a target category in visual search, or targets and lures

Cognitive theories in visual attention and perception, categorization, and memory often critically rely on concepts of similarity among objects, and empirically require measures of “sameness” among their stimuli. For instance, a researcher may require similarity estimates among multiple exemplars of a target category in visual search, or targets and lures in recognition memory. Quantifying similarity, however, is challenging when everyday items are the desired stimulus set, particularly when researchers require several different pictures from the same category. In this article, we document a new multidimensional scaling database with similarity ratings for 240 categories, each containing color photographs of 16–17 exemplar objects. We collected similarity ratings using the spatial arrangement method. Reports include: the multidimensional scaling solutions for each category, up to five dimensions, stress and fit measures, coordinate locations for each stimulus, and two new classifications. For each picture, we categorized the item's prototypicality, indexed by its proximity to other items in the space. We also classified pairs of images along a continuum of similarity, by assessing the overall arrangement of each MDS space. These similarity ratings will be useful to any researcher that wishes to control the similarity of experimental stimuli according to an objective quantification of “sameness.”

ContributorsHout, Michael C. (Author) / Goldinger, Stephen (Author) / Brady, Kyle (Author) / Department of Psychology (Contributor)
Created2014-11-12
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Studies on urban heat island (UHI) have been more than a century after the phenomenon was first discovered in the early 1800s. UHI emerges as the source of many urban environmental problems and exacerbates the living environment in cities. Under the challenges of increasing urbanization and future climate changes, there

Studies on urban heat island (UHI) have been more than a century after the phenomenon was first discovered in the early 1800s. UHI emerges as the source of many urban environmental problems and exacerbates the living environment in cities. Under the challenges of increasing urbanization and future climate changes, there is a pressing need for sustainable adaptation/mitigation strategies for UHI effects, one popular option being the use of reflective materials. While it is introduced as an effective method to reduce temperature and energy consumption in cities, its impacts on environmental sustainability and large-scale non-local effect are inadequately explored. This paper provides a synthetic overview of potential environmental impacts of reflective materials at a variety of scales, ranging from energy load on a single building to regional hydroclimate. The review shows that mitigation potential of reflective materials depends on a set of factors, including building characteristics, urban environment, meteorological and geographical conditions, to name a few. Precaution needs to be exercised by city planners and policy makers for large-scale deployment of reflective materials before their environmental impacts, especially on regional hydroclimates, are better understood. In general, it is recommended that optimal strategy for UHI needs to be determined on a city-by-city basis, rather than adopting a “one-solution-fits-all” strategy.

ContributorsYang, Jiachuan (Author) / Wang, Zhi-Hua (Author) / Kaloush, Kamil (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-07-01
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Land surface energy balance in a built environment is widely modelled using urban canopy models with representation of building arrays as big street canyons. Modification of this simplified geometric representation, however, leads to challenging numerical difficulties in improving physical parameterization schemes that are deterministic in nature. In this paper, we

Land surface energy balance in a built environment is widely modelled using urban canopy models with representation of building arrays as big street canyons. Modification of this simplified geometric representation, however, leads to challenging numerical difficulties in improving physical parameterization schemes that are deterministic in nature. In this paper, we develop a stochastic algorithm to estimate view factors between canyon facets in the presence of shade trees based on Monte Carlo simulation, where an analytical formulation is inhibited by the complex geometry. The model is validated against analytical solutions of benchmark radiative problems as well as field measurements in real street canyons. In conjunction with the matrix method resolving infinite number of reflections, the proposed model is capable of predicting the radiative exchange inside the street canyon with good accuracy. Modeling of transient evolution of thermal filed inside the street canyon using the proposed method demonstrate the potential of shade trees in mitigating canyon surface temperatures as well as saving of building energy use. This new numerical framework also deepens our insight into the fundamental physics of radiative heat transfer and surface energy balance for urban climate modeling.

ContributorsWang, Zhi-Hua (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-12-01
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The phenomenon of Fano resonance is ubiquitous in a large variety of wave scattering systems, where the resonance profile is typically asymmetric. Whether the parameter characterizing the asymmetry should be complex or real is an issue of great experimental interest. Using coherent quantum transport as a paradigm and taking into

The phenomenon of Fano resonance is ubiquitous in a large variety of wave scattering systems, where the resonance profile is typically asymmetric. Whether the parameter characterizing the asymmetry should be complex or real is an issue of great experimental interest. Using coherent quantum transport as a paradigm and taking into account of the collective contribution from all available scattering channels, we derive a universal formula for the Fano-resonance profile. We show that our formula bridges naturally the traditional Fano formulas with complex and real asymmetry parameters, indicating that the two types of formulas are fundamentally equivalent (except for an offset). The connection also reveals a clear footprint for the conductance resonance during a dephasing process. Therefore, the emergence of complex asymmetric parameter when fitting with experimental data needs to be properly interpreted. Furthermore, we have provided a theory for the width of the resonance, which relates explicitly the width to the degree of localization of the close-by eigenstates and the corresponding coupling matrices or the self-energies caused by the leads. Our work not only resolves the issue about the nature of the asymmetry parameter, but also provides deeper physical insights into the origin of Fano resonance. Since the only assumption in our treatment is that the transport can be described by the Green’s function formalism, our results are also valid for broad disciplines including scattering problems of electromagnetic waves, acoustics, and seismology.

ContributorsHuang, Liang (Author) / Lai, Ying-Cheng (Author) / Luo, Hong-Gang (Author) / Grebogi, Celso (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-01-01
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Persistent currents (PCs), one of the most intriguing manifestations of the Aharonov-Bohm (AB) effect, are known to vanish for Schrödinger particles in the presence of random scatterings, e.g., due to classical chaos. But would this still be the case for Dirac fermions? Addressing this question is of significant value due

Persistent currents (PCs), one of the most intriguing manifestations of the Aharonov-Bohm (AB) effect, are known to vanish for Schrödinger particles in the presence of random scatterings, e.g., due to classical chaos. But would this still be the case for Dirac fermions? Addressing this question is of significant value due to the tremendous recent interest in two-dimensional Dirac materials. We investigate relativistic quantum AB rings threaded by a magnetic flux and find that PCs are extremely robust. Even for highly asymmetric rings that host fully developed classical chaos, the amplitudes of PCs are of the same order of magnitude as those for integrable rings, henceforth the term superpersistent currents (SPCs). A striking finding is that the SPCs can be attributed to a robust type of relativistic quantum states, i.e., Dirac whispering gallery modes (WGMs) that carry large angular momenta and travel along the boundaries. We propose an experimental scheme using topological insulators to observe and characterize Dirac WGMs and SPCs, and speculate that these features can potentially be the base for a new class of relativistic qubit systems. Our discovery of WGMs in relativistic quantum systems is remarkable because, although WGMs are common in photonic systems, they are relatively rare in electronic systems.

ContributorsXu, Hongya (Author) / Huang, Liang (Author) / Lai, Ying-Cheng (Author) / Grebogi, Celso (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-03-11
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While expert groups often make recommendations on a range of non-controversial as well as controversial issues, little is known about how the level of expert consensus-the level of expert agreement-influences perceptions of the recommendations. This research illustrates that for non-controversial issues expert groups that exhibit high levels of agreement are

While expert groups often make recommendations on a range of non-controversial as well as controversial issues, little is known about how the level of expert consensus-the level of expert agreement-influences perceptions of the recommendations. This research illustrates that for non-controversial issues expert groups that exhibit high levels of agreement are more persuasive than expert groups that exhibit low levels of agreement. This effect is mediated by the perceived entitativity-the perceived cohesiveness or unification of the group-of the expert group. But for controversial issues, this effect is moderated by the perceivers' implicit assumptions about the group composition. When perceivers are provided no information about a group supporting the Affordable Care Act-a highly controversial piece of U.S. legislation that is divided by political party throughout the country-higher levels of agreement are less persuasive than lower levels of agreement because participants assume there were more democrats and fewer republicans in the group. But when explicitly told that the group was half republicans and half democrats, higher levels of agreement are more persuasive.

ContributorsVotruba, Ashley (Author) / Kwan, Sau (Author) / Department of Psychology (Contributor)
Created2015-03-26