ASU Scholarship Showcase

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.

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.

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.

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.

National and state organizations have developed policies calling upon afterschool programs (ASPs, 3–6 pm) to serve a fruit or vegetable (FV) each day for snack, while eliminating foods and beverages high in added-sugars, and to ensure children accumulate a minimum of 30 min/d of moderate-to-vigorous physical activity (MVPA). Few efficacious and cost-effective strategies exist to assist ASP providers in achieving these important public health goals. This paper reports on the design and conceptual framework of Making Healthy Eating and Physical Activity (HEPA) Policy Practice in ASPs, a 3-year group randomized controlled trial testing the effectiveness of strategies designed to improve snacks served and increase MVPA in children attending community-based ASPs. Twenty ASPs, serving over 1800 children (6–12 years) will be enrolled and match-paired based on enrollment size, average daily min/d MVPA, and days/week FV served, with ASPs randomized after baseline data collection to immediate intervention or a 1-year delayed group. The framework employed, STEPs (Strategies To Enhance Practice), focuses on intentional programming of HEPA in each ASPs' daily schedule, and includes a grocery store partnership to reduce price barriers to purchasing FV, professional development training to promote physical activity to develop core physical activity competencies, as well as ongoing technical support/assistance. Primary outcome measures include children's accelerometry-derived MVPA and time spend sedentary while attending an ASP, direct observation of staff HEPA promoting and inhibiting behaviors, types of snacks served, and child consumption of snacks, as well as, cost of snacks via receipts and detailed accounting of intervention delivery costs to estimate cost-effectiveness.

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 (d_y) of the right hand (“reference” hand) using the same hand (“test” hand). The digits of reference hand were passively placed collinearly (d_y = 0 mm). Subjects were then asked to exert different combinations of normal and tangential digit forces (F_n and F_tan, respectively) using the reference hand and then match the memorized d_y using the test hand. The reference hand exerted F_tan 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 F_tan 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.

Recently fabricated two-dimensional phosphorene crystal structures have demonstrated great potential in applications of electronics. In this paper, strain effect on the electronic band structure of phosphorene was studied using first-principles methods including density functional theory (DFT) and hybrid functionals. It was found that phosphorene can withstand a tensile stress and strain up to 10 N/m and 30%, respectively. The band gap of phosphorene experiences a direct-indirect-direct transition when axial strain is applied. A moderate −2% compression in the zigzag direction can trigger this gap transition. With sufficient expansion (+11.3%) or compression (−10.2% strains), the gap can be tuned from indirect to direct again. Five strain zones with distinct electronic band structure were identified, and the critical strains for the zone boundaries were determined. Although the DFT method is known to underestimate band gap of semiconductors, it was proven to correctly predict the strain effect on the electronic properties with validation from a hybrid functional method in this work. The origin of the gap transition was revealed, and a general mechanism was developed to explain energy shifts with strain according to the bond nature of near-band-edge electronic orbitals. Effective masses of carriers in the armchair direction are an order of magnitude smaller than that of the zigzag axis, indicating that the armchair direction is favored for carrier transport. In addition, the effective masses can be dramatically tuned by strain, in which its sharp jump/drop occurs at the zone boundaries of the direct-indirect gap transition.

Deposits of dark material appear on Vesta’s surface as features of relatively low-albedo in the visible wavelength range of Dawn’s camera and spectrometer. Mixed with the regolith and partially excavated by younger impacts, the material is exposed as individual layered outcrops in crater walls or ejecta patches, having been uncovered and broken up by the impact. Dark fans on crater walls and dark deposits on crater floors are the result of gravity-driven mass wasting triggered by steep slopes and impact seismicity. The fact that dark material is mixed with impact ejecta indicates that it has been processed together with the ejected material. Some small craters display continuous dark ejecta similar to lunar dark-halo impact craters, indicating that the impact excavated the material from beneath a higher-albedo surface. The asymmetric distribution of dark material in impact craters and ejecta suggests non-continuous distribution in the local subsurface. Some positive-relief dark edifices appear to be impact-sculpted hills with dark material distributed over the hill slopes.

Dark features inside and outside of craters are in some places arranged as linear outcrops along scarps or as dark streaks perpendicular to the local topography. The spectral characteristics of the dark material resemble that of Vesta’s regolith. Dark material is distributed unevenly across Vesta’s surface with clusters of all types of dark material exposures. On a local scale, some craters expose or are associated with dark material, while others in the immediate vicinity do not show evidence for dark material. While the variety of surface exposures of dark material and their different geological correlations with surface features, as well as their uneven distribution, indicate a globally inhomogeneous distribution in the subsurface, the dark material seems to be correlated with the rim and ejecta of the older Veneneia south polar basin structure. The origin of the dark material is still being debated, however, the geological analysis suggests that it is exogenic, from carbon-rich low-velocity impactors, rather than endogenic, from freshly exposed mafic material or melt, exposed or created by impacts.

The role of ambiguity tolerance in career decision making was examined in a sample of college students (n = 275). Three hypotheses were proposed regarding the direct prediction of ambiguity tolerance on career indecision, the indirect prediction of ambiguity tolerance on career indecision through environmental and self explorations, and the moderation effect of ambiguity tolerance on the link of environmental and self explorations with career indecision. Results supported the significance of ambiguity tolerance with respect to career indecision, finding that it directly predicted general indecisiveness, dysfunctional beliefs, lack of information, and inconsistent information, and moderated the prediction of environmental exploration on inconsistent information. The implications of this study are discussed and suggestions for future research are provided.

Over the last two decades, our knowledge concerning intracellular events that regulate integrin’s affinity to their soluble ligands has significantly improved. However, the mechanism of adhesion-induced integrin clustering and development of focal complexes, which could further mature to form focal adhesions, still remains under-investigated. Here we present a structural model of tandem IgC2 domains of skelemin in complex with the cytoplasmic tails of integrin α[subscript IIb]β[subscript 3]. The model of tertiary assembly is generated based upon NMR data and illuminates a potential link between the essential cell adhesion receptors and myosin filaments. This connection may serve as a basis for generating the mechanical forces necessary for cell migration and remodeling.