ASU Scholarship Showcase

Background: Emerging interventions that rely on and harness variability in behavior to adapt to individual performance over time may outperform interventions that prescribe static goals (e.g., 10,000 steps/day). The purpose of this factorial trial was to compare adaptive vs. static goal setting and immediate vs. delayed, non-contingent financial rewards for increasing free-living physical activity (PA).

Methods: A 4-month 2 × 2 factorial randomized controlled trial tested main effects for goal setting (adaptive vs. static goals) and rewards (immediate vs. delayed) and interactions between factors to increase steps/day as measured by a Fitbit Zip. Moderate-to-vigorous PA (MVPA) minutes/day was examined as a secondary outcome.

Results: Participants (N = 96) were mainly female (77%), aged 41 ± 9.5 years, and all were insufficiently active and overweight/obese (mean BMI = 34.1 ± 6.2). Participants across all groups increased by 2389 steps/day on average from baseline to intervention phase (p < .001). Participants receiving static goals showed a stronger increase in steps per day from baseline phase to intervention phase (2630 steps/day) than those receiving adaptive goals (2149 steps/day; difference = 482 steps/day, p = .095). Participants receiving immediate rewards showed stronger improvement (2762 step/day increase) from baseline to intervention phase than those receiving delayed rewards (2016 steps/day increase; difference = 746 steps/day, p = .009). However, the adaptive goals group showed a slower decrease in steps/day from the beginning of the intervention phase to the end of the intervention phase (i.e. less than half the rate) compared to the static goals group (−7.7 steps vs. -18.3 steps each day; difference = 10.7 steps/day, p < .001) resulting in better improvements for the adaptive goals group by study end. Rate of change over the intervention phase did not differ between reward groups. Significant goal phase x goal setting x reward interactions were observed.

Conclusions: Adaptive goals outperformed static goals (i.e., 10,000 steps) over a 4-month period. Small immediate rewards outperformed larger, delayed rewards. Adaptive goals with either immediate or delayed rewards should be preferred for promoting PA.

Background: An accurate method that can diagnose and predict lupus and its neuropsychiatric manifestations is essential since currently there are no reliable methods. Autoantibodies to a varied panel of antigens in the body are characteristic of lupus. In this study we investigated whether serum autoantibody binding patterns on random-sequence peptide microarrays (immunosignaturing) can be used for diagnosing and predicting the onset of lupus and its central nervous system (CNS) manifestations. We also tested the techniques for identifying potentially pathogenic autoantibodies in CNS-Lupus. We used the well-characterized MRL/lpr lupus animal model in two studies as a first step to develop and evaluate future studies in humans.

Results: In study one we identified possible diagnostic peptides for both lupus and altered behavior in the forced swim test. When comparing the results of study one to that of study two (carried out in a similar manner), we further identified potential peptides that may be diagnostic and predictive of both lupus and altered behavior in the forced swim test. We also characterized five potentially pathogenic brain-reactive autoantibodies, as well as suggested possible brain targets.

Conclusions: These results indicate that immunosignaturing could predict and diagnose lupus and its CNS manifestations. It can also be used to characterize pathogenic autoantibodies, which may help to better understand the underlying mechanisms of CNS-Lupus.

Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed to contain the outbreak. We present a simple concept for rapid development of new antimicrobials. The goal was to produce in as little as one week thousands of doses of an intervention for a new pathogen. We tested the feasibility of a system based on antimicrobial synbodies. The system involves creating an array of 100 peptides that have been selected for broad capability to bind and/or kill viruses and bacteria. The peptides are pre-screened for low cell toxicity prior to large scale synthesis. Any pathogen is then assayed on the chip to find peptides that bind or kill it. Peptides are combined in pairs as synbodies and further screened for activity and toxicity. The lead synbody can be quickly produced in large scale, with completion of the entire process in one week.

Immunosignaturing shows promise as a general approach to diagnosis. It has been shown to detect immunological signs of infection early during the course of disease and to distinguish Alzheimer’s disease from healthy controls. Here we test whether immunosignatures correspond to clinical classifications of disease using samples from people with brain tumors. Blood samples from patients undergoing craniotomies for therapeutically naïve brain tumors with diagnoses of astrocytoma (23 samples), Glioblastoma multiforme (22 samples), mixed oligodendroglioma/astrocytoma (16 samples), oligodendroglioma (18 samples), and 34 otherwise healthy controls were tested by immunosignature. Because samples were taken prior to adjuvant therapy, they are unlikely to be perturbed by non-cancer related affects. The immunosignaturing platform distinguished not only brain cancer from controls, but also pathologically important features about the tumor including type, grade, and the presence or absence of O⁶-methyl-guanine-DNA methyltransferase methylation promoter (MGMT), an important biomarker that predicts response to temozolomide in Glioblastoma multiformae patients.

Introduction: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4∶1 (fat∶ carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas.

Methods: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging.

Results: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days.

Conclusions: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

Cancer therapy selects for cancer cells resistant to treatment, a process that is fundamentally evolutionary. To what extent, however, is the evolutionary perspective employed in research on therapeutic resistance and relapse? We analyzed 6,228 papers on therapeutic resistance and/or relapse in cancers and found that the use of evolution terms in abstracts has remained at about 1% since the 1980s. However, detailed coding of 22 recent papers revealed a higher proportion of papers using evolutionary methods or evolutionary theory, although this number is still less than 10%. Despite the fact that relapse and therapeutic resistance is essentially an evolutionary process, it appears that this framework has not permeated research. This represents an unrealized opportunity for advances in research on therapeutic resistance.

Background: Advancements in geographic information systems over the past two decades have increased the specificity by which an individual’s neighborhood environment may be spatially defined for physical activity and health research. This study investigated how different types of street network buffering methods compared in measuring a set of commonly used built environment measures (BEMs) and tested their performance on associations with physical activity outcomes.

Methods: An internationally-developed set of objective BEMs using three different spatial buffering techniques were used to evaluate the relative differences in resulting explanatory power on self-reported physical activity outcomes. BEMs were developed in five countries using ‘sausage,’ ‘detailed-trimmed,’ and ‘detailed,’ network buffers at a distance of 1 km around participant household addresses (n = 5883).

Results: BEM values were significantly different (p < 0.05) for 96% of sausage versus detailed-trimmed buffer comparisons and 89% of sausage versus detailed network buffer comparisons. Results showed that BEM coefficients in physical activity models did not differ significantly across buffering methods, and in most cases BEM associations with physical activity outcomes had the same level of statistical significance across buffer types. However, BEM coefficients differed in significance for 9% of the sausage versus detailed models, which may warrant further investigation.

Conclusions: Results of this study inform the selection of spatial buffering methods to estimate physical activity outcomes using an internationally consistent set of BEMs. Using three different network-based buffering methods, the findings indicate significant variation among BEM values, however associations with physical activity outcomes were similar across each buffering technique. The study advances knowledge by presenting consistently assessed relationships between three different network buffer types and utilitarian travel, sedentary behavior, and leisure-oriented physical activity outcomes.

Background: The World Health Organization recommends strategies to improve urban design, public transportation, and recreation facilities to facilitate physical activity for non-communicable disease prevention for an increasingly urbanized global population. Most evidence supporting environmental associations with physical activity comes from single countries or regions with limited variation in urban form. This paper documents variation in comparable built environment features across countries from diverse regions.

Methods: The International Physical Activity and the Environment Network (IPEN) study of adults aimed to measure the full range of variation in the built environment using geographic information systems (GIS) across 12 countries on 5 continents. Investigators in Australia, Belgium, Brazil, Colombia, the Czech Republic, Denmark, China, Mexico, New Zealand, Spain, the United Kingdom, and the United States followed a common research protocol to develop internationally comparable measures. Using detailed instructions, GIS-based measures included features such as walkability (i.e., residential density, street connectivity, mix of land uses), and access to public transit, parks, and private recreation facilities around each participant’s residential address using 1-km and 500-m street network buffers.

Results: Eleven of 12 countries and 15 cities had objective GIS data on built environment features. We observed a 38-fold difference in median residential densities, a 5-fold difference in median intersection densities and an 18-fold difference in median park densities. Hong Kong had the highest and North Shore, New Zealand had the lowest median walkability index values, representing a difference of 9 standard deviations in GIS-measured walkability.

Conclusions: Results show that comparable measures can be created across a range of cultural settings revealing profound global differences in urban form relevant to physical activity. These measures allow cities to be ranked more precisely than previously possible. The highly variable measures of urban form will be used to explain individuals’ physical activity, sedentary behaviors, body mass index, and other health outcomes on an international basis. Present measures provide the ability to estimate dose–response relationships from projected changes to the built environment that would otherwise be impossible.

Background: Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia.

Methods: Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet.

Results: Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4.

Conclusions: Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

Background: To more accurately quantify the potential impact of the neighbourhood environment on adults’ physical activity (PA), it is important to compare environment-PA associations between periods of the day or week when adults are more versus less likely to be in their neighbourhood and utilise its PA resources. We examined whether, among adults from 10 countries, associations between objectively-assessed neighbourhood environment attributes and moderate-to-vigorous physical activity (MVPA) varied by time of the day and day of the week. The secondary aim was to examine whether such associations varied by employment status, gender and city.

Methods: This cross-sectional study included 6,712 adults from 14 cities across 10 countries with ≥1 day of valid accelerometer-assessed MVPA and complete information on socio-demographic and objectively-assessed environmental characteristics within 0.5 and 1 km street-network buffers around the home. Accelerometer measures (MVPA min/h) were created for six time periods from early morning until late evening/night, for weekdays and weekend days separately. Associations were estimated using generalized additive mixed models.

Results: Time of the day, day of week, gender and employment status were significant moderators of environment-MVPA associations. Land use mix was positively associated with MVPA in women who were employed and in men irrespective of their employment status. The positive associations between MVPA and net residential density, intersection density and land use mix were stronger in the mornings of weekdays and the afternoon/evening periods of both weekdays and weekend days. Associations between number of parks and MVPA were stronger in the mornings and afternoon/evenings irrespective of day of the week. Public transport density showed consistent positive associations with MVPA during weekends, while stronger effects on weekdays were observed in the morning and early evenings.

Conclusions: This study suggests that space and time constraints in adults’ daily activities are important factors that determine the impact of neighbourhood attributes on PA. Consideration of time-specific associations is important to better characterise the magnitude of the effects of the neighbourhood environment on PA. Future research will need to examine the contribution of built environment characteristics of areas surrounding other types of daily life centres (e.g., workplaces) to explaining adults’ PA at specific times of the day.