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.

Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R² = 0.14-0.28). However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R² = 0.50-0.74). Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.

Background: The transition from the home to college is a phase in which emerging adults shift toward more unhealthy eating and physical activity patterns, higher body mass indices, thus increasing risk of overweight/obesity. Currently, little is understood about how changing friendship networks shape weight gain behaviors. This paper describes the recruitment, data collection, and data analytic protocols for the SPARC (Social impact of Physical Activity and nutRition in College) study, a longitudinal examination of the mechanisms by which friends and friendship networks influence nutrition and physical activity behaviors and weight gain in the transition to college life.

Methods: The SPARC study aims to follow 1450 university freshmen from a large university over an academic year, collecting data on multiple aspects of friends and friendship networks. Integrating multiple types of data related to student lives, ecological momentary assessments (EMAs) are administered via a cell phone application, devilSPARC. EMAs collected in four 1-week periods (a total of 4 EMA waves) are integrated with linked data from web-based surveys and anthropometric measurements conducted at four times points (for a total of eight data collection periods including EMAs, separated by ~1 month). University databases will provide student card data, allowing integration of both time-dated data on food purchasing, use of physical activity venues, and geographical information system (GIS) locations of these activities relative to other students in their social networks.

Discussion: Findings are intended to guide the development of more effective interventions to enhance behaviors among college students that protect against weight gain during college.

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.

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.

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.

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.

Background: Improving perinatal health is the key to achieving the Millennium Development Goal for child survival. Recently, several reviews suggest that scaling up available effective perinatal interventions in an integrated approach can substantially reduce the stillbirth and neonatal death rates worldwide. We evaluated the effect of packaged interventions given in pregnancy, delivery and post-partum periods through integration of community- and facility-based services on perinatal mortality.

Methods: This study took advantage of an ongoing health and demographic surveillance system (HDSS) and a new Maternal, Neonatal and Child Health (MNCH) Project initiated in 2007 in Matlab, Bangladesh in half (intervention area) of the HDSS area. In the other half, women received usual care through the government health system (comparison area). The MNCH Project strengthened ongoing maternal and child health services as well as added new services. The intervention followed a continuum of care model for pregnancy, intrapartum, and post-natal periods by improving established links between community- and facility-based services. With a separate pre-post samples design, we compared the perinatal mortality rates between two periods--before (2005-2006) and after (2008-2009) implementation of MNCH interventions. We also evaluated the difference-of-differences in perinatal mortality between intervention and comparison areas.

Results: Antenatal coverage, facility delivery and cesarean section rates were significantly higher in the post- intervention period in comparison with the period before intervention. In the intervention area, the odds of perinatal mortality decreased by 36% between the pre-intervention and post-intervention periods (odds ratio: 0.64; 95% confidence intervals: 0.52-0.78). The reduction in the intervention area was also significant relative to the reduction in the comparison area (OR 0.73, 95% CI: 0.56-0.95; P = 0.018).

Conclusion: The continuum of care approach provided through the integration of service delivery modes decreased the perinatal mortality rate within a short period of time. Further testing of this model is warranted within the government health system in Bangladesh and other low-income countries.

Background: Androgens bind to the androgen receptor (AR) in prostate cells and are essential survival factors for healthy prostate epithelium. Most untreated prostate cancers retain some dependence upon the AR and respond, at least transiently, to androgen ablation therapy. However, the relationship between endogenous androgen levels and cancer etiology is unclear. High levels of androgens have traditionally been viewed as driving abnormal proliferation leading to cancer, but it has also been suggested that low levels of androgen could induce selective pressure for abnormal cells. We formulate a mathematical model of androgen regulated prostate growth to study the effects of abnormal androgen levels on selection for pre-malignant phenotypes in early prostate cancer development.

Results: We find that cell turnover rate increases with decreasing androgen levels, which may increase the rate of mutation and malignant evolution. We model the evolution of a heterogeneous prostate cell population using a continuous state-transition model. Using this model we study selection for AR expression under different androgen levels and find that low androgen environments, caused either by low serum testosterone or by reduced 5α-reductase activity, select more strongly for elevated AR expression than do normal environments. High androgen actually slightly reduces selective pressure for AR upregulation. Moreover, our results suggest that an aberrant androgen environment may delay progression to a malignant phenotype, but result in a more dangerous cancer should one arise.

Conclusions: The model represents a useful initial framework for understanding the role of androgens in prostate cancer etiology, and it suggests that low androgen levels can increase selection for phenotypes resistant to hormonal therapy that may also be more aggressive. Moreover, clinical treatment with 5α-reductase inhibitors such as finasteride may increase the incidence of therapy resistant cancers.