ASU Scholarship Showcase

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm³ to 62 mm³, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

Background:
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.

Results:
We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.

Conclusions:
The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.

Periodicities (repeating patterns) are observed in many human behaviors. Their strength may capture untapped patterns that incorporate sleep, sedentary, and active behaviors into a single metric indicative of better health. We present a framework to detect periodicities from longitudinal wrist-worn accelerometry data. GENEActiv accelerometer data were collected from 20 participants (17 men, 3 women, aged 35–65) continuously for 64.4±26.2 (range: 13.9 to 102.0) consecutive days. Cardiometabolic risk biomarkers and health-related quality of life metrics were assessed at baseline. Periodograms were constructed to determine patterns emergent from the accelerometer data. Periodicity strength was calculated using circular autocorrelations for time-lagged windows. The most notable periodicity was at 24 h, indicating a circadian rest-activity cycle; however, its strength varied significantly across participants. Periodicity strength was most consistently associated with LDL-cholesterol (r’s = 0.40–0.79, P’s < 0.05) and triglycerides (r’s = 0.68–0.86, P’s < 0.05) but also associated with hs-CRP and health-related quality of life, even after adjusting for demographics and self-rated physical activity and insomnia symptoms. Our framework demonstrates a new method for characterizing behavior patterns longitudinally which captures relationships between 24 h accelerometry data and health outcomes.

Background: Falls are a major public health concern in older adults. Recent fall prevention guidelines recommend the use of multifactorial fall prevention programs (FPPs) that include exercise for community-dwelling older adults; however, the availability of sustainable, community-based FPPs is limited.

Methods: We conducted a 24-week quasi-experimental study to evaluate the efficacy of a community-based, multifactorial FPP [Stay in Balance (SIB)] on dynamic and functional balance and muscular strength. The SIB program was delivered by allied health students and included a health education program focused on fall risk factors and a progressive exercise program emphasizing lower-extremity strength and balance. All participants initially received the 12-week SIB program, and participants were non-randomly assigned at baseline to either continue the SIB exercise program at home or as a center-based program for an additional 12 weeks. Adults aged 60 and older (n = 69) who were at-risk of falling (fall history or 2+ fall risk factors) were recruited to participate. Mixed effects repeated measures using Statistical Application Software Proc Mixed were used to examine group, time, and group-by-time effects on dynamic balance (8-Foot Up and Go), functional balance (Berg Balance Scale), and muscular strength (30 s chair stands and 30 s arm curls). Non-normally distributed outcome variables were log-transformed.

Results: After adjusting for age, gender, and body mass index, 8-Foot Up and Go scores, improved significantly over time [F_(2,173) = 8.92, p = 0.0; T0 − T2 diff = 1.2 (1.0)]. Berg Balance Scores [F_(2,173) = 29.0, p < 0.0001; T0 − T2 diff = 4.96 (0.72)], chair stands [F_(2,171) = 10.17, p < 0.0001; T0 − T2 diff = 3.1 (0.7)], and arm curls [F_(2,171) = 12.7, p < 0.02; T0 − T2 diff = 2.7 (0.6)] also all improved significantly over time. There were no significant group-by-time effects observed for any of the outcomes.

Conclusion: The SIB program improved dynamic and functional balance and muscular strength in older adults at-risk for falling. Our findings indicate continuing home-based strength and balance exercises at home after completion of a center-based FPP program may be an effective and feasible way to maintain improvements in balance and strength parameters.

Mobile devices are a promising channel for delivering just-in-time guidance and support for improving key daily health behaviors. Despite an explosion of mobile phone applications aimed at physical activity and other health behaviors, few have been based on theoretically derived constructs and empirical evidence. Eighty adults ages 45 years and older who were insufficiently physically active, engaged in prolonged daily sitting, and were new to smartphone technology, participated in iterative design development and feasibility testing of three daily activity smartphone applications based on motivational frames drawn from behavioral science theory and evidence. An “analytically” framed custom application focused on personalized goal setting, self-monitoring, and active problem solving around barriers to behavior change. A “socially” framed custom application focused on social comparisons, norms, and support.

An “affectively” framed custom application focused on operant conditioning principles of reinforcement scheduling and emotional transference to an avatar, whose movements and behaviors reflected the physical activity and sedentary levels of the user. To explore the applications' initial efficacy in changing regular physical activity and leisure-time sitting, behavioral changes were assessed across eight weeks in 68 participants using the CHAMPS physical activity questionnaire and the Australian sedentary behavior questionnaire. User acceptability of and satisfaction with the applications was explored via a post-intervention user survey. The results indicated that the three applications were sufficiently robust to significantly improve regular moderate-to-vigorous intensity physical activity and decrease leisure-time sitting during the 8-week behavioral adoption period. Acceptability of the applications was confirmed in the post-intervention surveys for this sample of midlife and older adults new to smartphone technology. Preliminary data exploring sustained use of the applications across a longer time period yielded promising results. The results support further systematic investigation of the efficacy of the applications for changing these key health-promoting behaviors.

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury rates, disease, and habitat variables to adequately assess changes through time. We cultured and identified microorganisms isolated from abnormal/injured and repressed tissue regeneration sites of the endangered Ozark Hellbender, Cryptobranchus alleganiensis bishopi, to discover potential causative agents responsible for their significant decline in health and population. This organism and our study site were chosen because the population and habitat of C. a. bishopi have been intensively studied from 1969–2009, and the abnormality/injury rate and apparent lack of regeneration were established.

Although many bacterial and fungal isolates recovered were common environmental organisms, several opportunistic pathogens were identified in association with only the injured tissues of C.a. bishopi. Bacterial isolates included Aeromonas hydrophila, a known amphibian pathogen, Granulicetella adiacens, Gordonai terrae, Stenotrophomonas maltophilia, Aerococcus viridans, Streptococcus pneumoniae and a variety of Pseudomonads, including Pseudomonas aeruginosa, P. stutzeri, and P. alcaligenes. Fungal isolates included species in the genera Penicillium, Acremonium, Cladosporium, Curvularia, Fusarium, Streptomycetes, and the Class Hyphomycetes. Many of the opportunistic pathogens identified are known to form biofilms. Lack of isolation of the same organism from all wounds suggests that the etiological agent responsible for the damage to C. a. bishopi may not be a single organism. To our knowledge, this is the first study to profile the external microbial consortia cultured from a Cryptobranchid salamander. The incidence of abnormalities/injury and retarded regeneration in C. a. bishopi may have many contributing factors including disease and habitat degradation. Results from this study may provide insight into other amphibian population declines.

A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD⁵⁰ of D23580 in female BALB/c mice was 4.7 x 10⁵ CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580.

Background: The Nike + Fuelband is a commercially available, wrist-worn accelerometer used to track physical activity energy expenditure (PAEE) during exercise. However, validation studies assessing the accuracy of this device for estimating PAEE are lacking. Therefore, this study examined the validity and reliability of the Nike + Fuelband for estimating PAEE during physical activity in young adults. Secondarily, we compared PAEE estimation of the Nike + Fuelband with the previously validated SenseWear Armband (SWA).

Methods: Twenty-four participants (n = 24) completed two, 60-min semi-structured routines consisting of sedentary/light-intensity, moderate-intensity, and vigorous-intensity physical activity. Participants wore a Nike + Fuelband and SWA, while oxygen uptake was measured continuously with an Oxycon Mobile (OM) metabolic measurement system (criterion).

Results: The Nike + Fuelband (ICC = 0.77) and SWA (ICC = 0.61) both demonstrated moderate to good validity. PAEE estimates provided by the Nike + Fuelband (246 ± 67 kcal) and SWA (238 ± 57 kcal) were not statistically different than OM (243 ± 67 kcal). Both devices also displayed similar mean absolute percent errors for PAEE estimates (Nike + Fuelband = 16 ± 13 %; SWA = 18 ± 18 %). Test-retest reliability for PAEE indicated good stability for Nike + Fuelband (ICC = 0.96) and SWA (ICC = 0.90).

Conclusion: The Nike + Fuelband provided valid and reliable estimates of PAEE, that are similar to the previously validated SWA, during a routine that included approximately equal amounts of sedentary/light-, moderate- and vigorous-intensity physical activity.

Predicting the timing of a castrate resistant prostate cancer is critical to lowering medical costs and improving the quality of life of advanced prostate cancer patients. We formulate, compare and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA). We accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT). While these models are simplifications of a previously published model, they fit data with similar accuracy and improve forecasting results. Both models describe the progression of androgen resistance. Although Model 1 is simpler than the more realistic Model 2, it can fit clinical data to a greater precision. However, we found that Model 2 can forecast future PSA levels more accurately. These findings suggest that including more realistic mechanisms of androgen dynamics in a two population model may help androgen resistance timing prediction.

The ongoing Zika virus (ZIKV) epidemic in the Americas poses a major global public health emergency. While ZIKV is transmitted from human to human by bites of Aedes mosquitoes, recent evidence indicates that ZIKV can also be transmitted via sexual contact with cases of sexually transmitted ZIKV reported in Argentina, Canada, Chile, France, Italy, New Zealand, Peru, Portugal, and the USA. Yet, the role of sexual transmission on the spread and control of ZIKV infection is not well-understood. We introduce a mathematical model to investigate the impact of mosquito-borne and sexual transmission on the spread and control of ZIKV and calibrate the model to ZIKV epidemic data from Brazil, Colombia, and El Salvador. Parameter estimates yielded a basic reproduction number R_0 = 2.055 (95% CI: 0.523–6.300), in which the percentage contribution of sexual transmission is 3.044% (95% CI: 0.123–45.73). Our sensitivity analyses indicate that R_0 is most sensitive to the biting rate and mortality rate of mosquitoes while sexual transmission increases the risk of infection and epidemic size and prolongs the outbreak. Prevention and control efforts against ZIKV should target both the mosquito-borne and sexual transmission routes.