ASU Scholarship Showcase

A data set of observed daily precipitation, maximum and minimum temperature, gridded to a 1/16° (~6 km) resolution, is described that spans the entire country of Mexico, the conterminous U.S. (CONUS), and regions of Canada south of 53° N for the period 1950-2013. The dataset improves previous products in spatial extent, orographic precipitation adjustment over Mexico and parts of Canada, and reduction of transboundary discontinuities. The impacts of adjusting gridded precipitation for orographic effects are quantified by scaling precipitation to an elevation-aware 1981-2010 precipitation climatology in Mexico and Canada. Differences are evaluated in terms of total precipitation as well as by hydrologic quantities simulated with a land surface model. Overall, orographic correction impacts total precipitation by up to 50% in mountainous regions outside CONUS. Hydrologic fluxes show sensitivities of similar magnitude, with discharge more sensitive than evapotranspiration and soil moisture. Because of the consistent gridding methodology, the current product reduces transboundary discontinuities as compared with a commonly used reanalysis product, making it suitable for estimating large-scale hydrometeorologic phenomena.

Introduction: Abundance of immune cells has been shown to have prognostic and predictive significance in many tumor types. Beyond abundance, the spatial organization of immune cells in relation to cancer cells may also have significant functional and clinical implications. However there is a lack of systematic methods to quantify spatial associations between immune and cancer cells.

Methods: We applied ecological measures of species interactions to digital pathology images for investigating the spatial associations of immune and cancer cells in breast cancer. We used the Morisita-Horn similarity index, an ecological measure of community structure and predator–prey interactions, to quantify the extent to which cancer cells and immune cells colocalize in whole-tumor histology sections. We related this index to disease-specific survival of 486 women with breast cancer and validated our findings in a set of 516 patients from different hospitals.

Results: Colocalization of immune cells with cancer cells was significantly associated with a disease-specific survival benefit for all breast cancers combined. In HER2-positive subtypes, the prognostic value of immune-cancer cell colocalization was highly significant and exceeded those of known clinical variables. Furthermore, colocalization was a significant predictive factor for long-term outcome following chemotherapy and radiotherapy in HER2 and Luminal A subtypes, independent of and stronger than all known clinical variables.

Conclusions: Our study demonstrates how ecological methods applied to the tumor microenvironment using routine histology can provide reproducible, quantitative biomarkers for identifying high-risk breast cancer patients. We found that the clinical value of immune-cancer interaction patterns is highly subtype-specific but substantial and independent to known clinicopathologic variables that mostly focused on cancer itself. Our approach can be developed into computer-assisted prediction based on histology samples that are already routinely collected.

In a meta-analysis published by myself and co-authors, we report differences in the life history risk factors for estrogen receptor negative (ER−) and estrogen receptor positive (ER+) breast cancers. Our meta-analysis did not find the association of ER− breast cancer risk with fast life history characteristics that Hidaka and Boddy suggest in their response to our article. There are a number of possible explanations for the differences between their conclusions and the conclusions we drew from our meta-analysis, including limitations of our meta-analysis and methodological challenges in measuring and categorizing estrogen receptor status. These challenges, along with the association of ER+ breast cancer with slow life history characteristics, may make it challenging to find a clear signal of ER− breast cancer with fast life history characteristics, even if that relationship does exist. The contradictory results regarding breast cancer risk and life history characteristics illustrate a more general challenge in evolutionary medicine: often different sub-theories in evolutionary biology make contradictory predictions about disease risk. In this case, life history models predict that breast cancer risk should increase with faster life history characteristics, while the evolutionary mismatch hypothesis predicts that breast cancer risk should increase with delayed reproduction. Whether life history tradeoffs contribute to ER− breast cancer is still an open question, but current models and several lines of evidence suggest that it is a possibility.

It has long been accepted that modern reproductive patterns are likely contributors to breast cancer susceptibility because of their influence on hormones such as estrogen and the importance of these hormones in breast cancer. We conducted a meta-analysis to assess whether this ‘evolutionary mismatch hypothesis’ can explain susceptibility to both estrogen receptor positive (ER-positive) and estrogen receptor negative (ER-negative) cancer. Our meta-analysis includes a total of 33 studies and examines parity, age of first birth and age of menarche broken down by estrogen receptor status. We found that modern reproductive patterns are more closely linked to ER-positive than ER-negative breast cancer. Thus, the evolutionary mismatch hypothesis for breast cancer can account for ER-positive breast cancer susceptibility but not ER-negative breast cancer.

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: Medical and public health scientists are using evolution to devise new strategies to solve major health problems. But based on a 2003 survey, medical curricula may not adequately prepare physicians to evaluate and extend these advances. This study assessed the change in coverage of evolution in North American medical schools since 2003 and identified opportunities for enriching medical education.

Methods: In 2013, curriculum deans for all North American medical schools were invited to rate curricular coverage and perceived importance of 12 core principles, the extent of anticipated controversy from adding evolution, and the usefulness of 13 teaching resources. Differences between schools were assessed by Pearson’s chi-square test, Student’s t-test, and Spearman’s correlation. Open-ended questions sought insight into perceived barriers and benefits.

Results: Despite repeated follow-up, 60 schools (39%) responded to the survey. There was no evidence of sample bias. The three evolutionary principles rated most important were antibiotic resistance, environmental mismatch, and somatic selection in cancer. While importance and coverage of principles were correlated (r = 0.76, P < 0.01), coverage (at least moderate) lagged behind importance (at least moderate) by an average of 21% (SD = 6%). Compared to 2003, a range of evolutionary principles were covered by 4 to 74% more schools. Nearly half (48%) of responders anticipated igniting controversy at their medical school if they added evolution to their curriculum. The teaching resources ranked most useful were model test questions and answers, case studies, and model curricula for existing courses/rotations. Limited resources (faculty expertise) were cited as the major barrier to adding more evolution, but benefits included a deeper understanding and improved patient care.

Conclusion: North American medical schools have increased the evolution content in their curricula over the past decade. However, coverage is not commensurate with importance. At a few medical schools, anticipated controversy impedes teaching more evolution. Efforts to improve evolution education in medical schools should be directed toward boosting faculty expertise and crafting resources that can be easily integrated into existing curricula.

Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.

The sensitivity of Earth’s wetlands to observed shifts in global precipitation and temperature patterns and their ability to produce large quantities of methane gas are key global change questions. We present a microwave satellite-based approach for mapping fractional surface water (FW) globally at 25-km resolution. The approach employs a land cover-supported, atmospherically-corrected dynamic mixture model applied to 20+ years (1992–2013) of combined, daily, passive/active microwave remote sensing data. The resulting product, known as Surface Water Microwave Product Series (SWAMPS), shows strong microwave sensitivity to sub-grid scale open water and inundated wetlands comprising open plant canopies. SWAMPS’ FW compares favorably (R² = 91%–94%) with higher-resolution, global-scale maps of open water from MODIS and SRTM-MOD44W. Correspondence of SWAMPS with open water and wetland products from satellite SAR in Alaska and the Amazon deteriorates when exposed wetlands or inundated forests captured by the SAR products were added to the open water fraction reflecting SWAMPS’ inability to detect water underneath the soil surface or beneath closed forest canopies. Except for a brief period of drying during the first 4 years of observation, the inundation extent for the global domain excluding the coast was largely stable. Regionally, inundation in North America is advancing while inundation is on the retreat in Tropical Africa and North Eurasia. SWAMPS provides a consistent and long-term global record of daily FW dynamics, with documented accuracies suitable for hydrologic assessment and global change-related investigations.

A realistic simulation of snow cover and its thermal properties are important for accurate modelling of permafrost. We analyse simulated relationships between air and near-surface (20  cm) soil temperatures in the Northern Hemisphere permafrost region during winter, with a particular focus on snow insulation effects in nine land surface models, and compare them with observations from 268 Russian stations. There are large cross-model differences in the simulated differences between near-surface soil and air temperatures (ΔT; 3 to 14 °C), in the sensitivity of soil-to-air temperature (0.13 to 0.96 °C °^C-1), and in the relationship between ΔT and snow depth. The observed relationship between ΔT and snow depth can be used as a metric to evaluate the effects of each model's representation of snow insulation, hence guide improvements to the model's conceptual structure and process parameterisations. Models with better performance apply multilayer snow schemes and consider complex snow processes. Some models show poor performance in representing snow insulation due to underestimation of snow depth and/or overestimation of snow conductivity. Generally, models identified as most acceptable with respect to snow insulation simulate reasonable areas of near-surface permafrost (13.19 to 15.77 million  km²). However, there is not a simple relationship between the sophistication of the snow insulation in the acceptable models and the simulated area of Northern Hemisphere near-surface permafrost, because several other factors, such as soil depth used in the models, the treatment of soil organic matter content, hydrology and vegetation cover, also affect the simulated permafrost distribution.

From cells to societies, several general principles arise again and again that facilitate cooperation and suppress conflict. In this study, I describe three general principles of cooperation and how they operate across systems including human sharing, cooperation in animal and insect societies and the massively large-scale cooperation that occurs in our multicellular bodies. The first principle is that of Walk Away: that cooperation is enhanced when individuals can leave uncooperative partners. The second principle is that resource sharing is often based on the need of the recipient (i.e., need-based transfers) rather than on strict account-keeping. And the last principle is that effective scaling up of cooperation requires increasingly sophisticated and costly cheater suppression mechanisms. By comparing how these principles operate across systems, we can better understand the constraints on cooperation. This can facilitate the discovery of novel ways to enhance cooperation and suppress cheating in its many forms, from social exploitation to cancer.