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.

Previous empirical evaluations of training programs aimed at improving dog adoption rates assume that dogs exhibiting certain behaviors are more adoptable. However, no systematic data are available to indicate that the spontaneous behavior of shelter dogs has an effect on adopter preference. The aim of the present study was to determine whether any behaviors that dogs exhibit spontaneously in the presence of potential adopters were associated with the dogs' length of stay in the shelter. A sample of 289 dogs was videotaped for 1 min daily throughout their stay at a county shelter. To account for differences in adopter behavior, experimenters varied from solitary passive observers to pairs of interactive observers. Dogs behaved more attentively to active observers. To account for adopter preference for morphology, dogs were divided into “morphologically preferred” and “non-preferred” groups. Morphologically preferred dogs were small, long coated, ratters, herders, and lap dogs. No theoretically significant differences in behavior were observed between the two different dog morphologies. When accounting for morphological preference, three behaviors were found to have a significant effect on length of stay in all dogs: leaning or rubbing on the enclosure wall (increased median length of stay by 30 days), facing away from the front of the enclosure (increased by 15 days), and standing (increased by 7 days). When combinations of behaviors were assessed, back and forth motion was found to predict a longer stay (increased by 24 days). No consistent behavioral changes were observed due to time spent at the shelter. These findings will allow shelters to focus behavioral modification efforts only on behaviors likely to influence adopters' choices.

Background: The influence of occupation and ex/passive smoking on inflammatory phenotype is not well understood. The aim of this study was to examine the relationship between occupation, past smoking and current passive smoking and airway inflammation in a population of adults with refractory asthma.

Methods: Sixty-six participants with refractory asthma were characterized. Occupational exposure to asthma causing or worsening agents were identified with an asthma-specific job exposure matrix. Exposure to passive cigarette smoke was determined by questionnaire and exhaled carbon monoxide assessment. The carbon content of macrophages was assessed in a sub-group of participants.

Results: Nineteen participants had smoked previously with low smoking pack years (median 1.7 years). Ex-smokers more commonly lived with a current smoker (26% vs. 9%, p = 0.11) and were more likely to allow smoking inside their home (26% vs. 4%, p = 0.02) compared to never smokers. Twenty participants had occupations with an identified exposure risk to an asthmagen; thirteen had exposures to irritants such as motor vehicle exhaust and environmental tobacco smoke. Sputum neutrophils were elevated in participants with asthma who had occupational exposures, particularly those who were diagnosed with asthma at a more than 30 years of age.

Conclusions: Sputum neutrophils are elevated in refractory asthma with exposure to occupational asthmagens. In addition to older age, exposure to both environmental and occupational particulate matter may contribute to the presence of neutrophilic asthma. This may help explain asthma heterogeneity and geographical variations in airway inflammatory phenotypes in asthma.

Adult diet quality indices are shown to predict nutritional adequacy of dietary intake as well as all-cause morbidity and mortality. This study describes the reproducibility and validity of a food-based diet quality index, the Australian Recommended Food Score (ARFS). ARFS was developed to reflect alignment with the Australian Dietary Guidelines and is modelled on the US Recommended Food Score. Dietary intakes of 96 adult participants (31 male, 65 female) age 30 to 75 years were assessed in two rounds, five months apart. Diet was assessed using a 120-question semi-quantitative food frequency questionnaire (FFQ). The ARFS diet quality index was derived using a subset of 70 items from the full FFQ. Reproducibility of the ARFS between round one and round two was confirmed by the overall intraclass correlation coefficient of 0.87 (95% CI 0.83, 0.90), which compared favourably to that for the FFQ at 0.85 (95% CI 0.80, 0.89). ARFS was correlated with FFQ nutrient intakes, particularly fiber, vitamin A, beta-carotene and vitamin C (0.53, 95% CI 0.37–0.67), and with mineral intakes, particularly calcium, magnesium and potassium (0.32, 95% CI 0.23–0.40). ARFS is a suitable brief tool to evaluate diet quality in adults and reliably estimates a range of nutrient intakes.

Background: Diet quality tools provide researchers with brief methods to assess the nutrient adequacy of usual dietary intake. This study describes the development and validation of a pediatric diet quality index, the Australian Recommended Food Scores for Pre-schoolers (ARFS-P), for use with children aged two to five years.

Methods: The ARFS-P was derived from a 120-item food frequency questionnaire, with eight sub-scales, and was scored from zero to 73. Linear regressions were used to estimate the relationship between diet quality score and nutrient intakes, in 142 children (mean age 4 years) in rural localities in New South Wales, Australia.

Results: Total ARFS-P and component scores were highly related to dietary intake of the majority of macronutrients and micronutrients including protein, β-carotene, vitamin C, vitamin A. Total ARFS-P was also positively related to total consumption of nutrient dense foods, such as fruits and vegetables, and negatively related to total consumption of discretionary choices, such as sugar sweetened drinks and packaged snacks.

Conclusion: ARFS-P is a valid measure that can be used to characterize nutrient intakes for children aged two to five years. Further research could assess the utility of the ARFS-P for monitoring of usual dietary intake over time or as part of clinical management.

Background: Mating behaviors in simple invertebrate model organisms represent tractable paradigms for understanding the neural bases of sex-specific behaviors, decision-making and sensorimotor integration. However, there are few examples where such neural circuits have been defined at high resolution or interrogated.

Methodology/Principal Findings: Here we exploit the simplicity of the nematode Caenorhabditis elegans to define the neural circuits underlying the male’s decision to initiate mating in response to contact with a mate. Mate contact is sensed by male-specific sensilla of the tail, the rays, which subsequently induce and guide a contact-based search of the hermaphrodite’s surface for the vulva (the vulva search). Atypically, search locomotion has a backward directional bias so its implementation requires overcoming an intrinsic bias for forward movement, set by activity of the sex-shared locomotory system. Using optogenetics, cell-specific ablation- and mutant behavioral analyses, we show that the male makes this shift by manipulating the activity of command cells within this sex-shared locomotory system. The rays control the command interneurons through the male-specific, decision-making interneuron PVY and its auxiliary cell PVX. Unlike many sex-shared pathways, PVY/PVX regulate the command cells via cholinergic, rather than glutamatergic transmission, a feature that likely contributes to response specificity and coordinates directional movement with other cholinergic-dependent motor behaviors of the mating sequence. PVY/PVX preferentially activate the backward, and not forward, command cells because of a bias in synaptic inputs and the distribution of key cholinergic receptors (encoded by the genes acr-18, acr-16 and unc-29) in favor of the backward command cells.

Conclusion/Significance: Our interrogation of male neural circuits reveals that a sex-specific response to the opposite sex is conferred by a male-specific pathway that renders subordinate, sex-shared motor programs responsive to mate cues. Circuit modifications of these types may make prominent contributions to natural variations in behavior that ultimately bring about speciation.

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.

Gompertz’s empirical equation remains the most popular one in describing cancer cell population growth in a wide spectrum of bio-medical situations due to its good fit to data and simplicity. Many efforts were documented in the literature aimed at understanding the mechanisms that may support Gompertz’s elegant model equation. One of the most convincing efforts was carried out by Gyllenberg and Webb. They divide the cancer cell population into the proliferative cells and the quiescent cells. In their two dimensional model, the dead cells are assumed to be removed from the tumor instantly. In this paper, we modify their model by keeping track of the dead cells remaining in the tumor. We perform mathematical and computational studies on this three dimensional model and compare the model dynamics to that of the model of Gyllenberg and Webb. Our mathematical findings suggest that if an avascular tumor grows according to our three-compartment model, then as the death rate of quiescent cells decreases to zero, the percentage of proliferative cells also approaches to zero. Moreover, a slow dying quiescent population will increase the size of the tumor. On the other hand, while the tumor size does not depend on the dead cell removal rate, its early and intermediate growth stages are very sensitive to it.