Christopher H. Remien

Woody cover and hominin environments in the past 6 million years

The role of African savannahs in the evolution of early hominins has been debated for nearly a century. Resolution of this issue has been hindered by difficulty in quantifying the fraction of woody cover in the fossil record. Here we show that the fraction of woody cover in tropical ecosystems can be quantified using stable carbon isotopes in soils. Furthermore, we use fossil soils from hominin sites in the Awash and Omo-Turkana basins in eastern Africa to reconstruct the fraction of woody cover since the Late Miocene epoch (about 7 million years ago). 13C/12C ratio data from 1,300 palaeosols at or adjacent to hominin sites dating to at least 6 million years ago show that woody cover was predominantly less than ∼40% at most sites. These data point to the prevalence of open environments at the majority of hominin fossil sites in eastern Africa over the past 6 million years.

History of Animals using Isotope Records (HAIR): A 6-year dietary history of one family of African elephants

The dietary and movement history of individual animals can be studied using stable isotope records in animal tissues, providing insight into long-term ecological dynamics and a species niche. We provide a 6-year history of elephant diet by examining tail hair collected from 4 elephants in the same social family unit in northern Kenya. Sequential measurements of carbon, nitrogen, and hydrogen isotope rations in hair provide a weekly record of diet and water resources. Carbon isotope ratios were well correlated with satellite-based measurements of the normalized difference vegetation index (NDVI) of the region occupied by the elephants as recorded by the global positioning system (GPS) movement record; the absolute amount of C4 grass consumption is well correlated with the maximum value of NDVI during individual wet seasons. Changes in hydrogen isotope ratios coincided very closely in time with seasonal fluctuations in rainfall and NDVI whereas diet shifts to relatively high proportions of grass lagged seasonal increases in NDVI by ≈2 weeks. The peak probability of conception in the population occurred ≈3 weeks after peak grazing. Spatial and temporal patterns of resource use show that the only period of pure browsing by the focal elephants was located in an over-grazed, communally managed region outside the protected area. The ability to extract time-specific longitudinal records on animal diets, and therefore the ecological history of an organism and its environment, provides an avenue for understanding the impact of climate dynamics and land-use change on animal foraging behavior and habitat relations.

Mathematical modeling of liver injury and dysfunction after acetaminophen overdose: early discrimination between survival and death.

Acetaminophen (APAP) is the leading cause of acute liver injury in the developed world. Timely administration of N‐acetylcysteine (N‐Ac) prevents the progression of serious liver injury and disease, whereas failure to administer N‐Ac within a critical time frame allows disease progression and in the most severe cases may result in liver failure or death. In this situation, liver transplantation may be the only life‐saving measure. Thus, the outcome of an APAP overdose depends on the size of the overdose and the time to first administration of N‐Ac. We developed a system of differential equations to describe acute liver injury due to APAP overdose. The Model for Acetaminophen‐induced Liver Damage (MALD) uses a patients aspartate aminotransferase (AST), alanine aminotransferase (ALT), and international normalized ratio (INR) measurements on admission to estimate overdose amount, time elapsed since overdose, and outcome. The mathematical model was then tested on 53 patients from the University of Utah. With the addition of serum creatinine, eventual death was predicted with 100% sensitivity, 91% specificity, 67% positive predictive value (PPV), and 100% negative predictive value (NPV) in this retrospective study. Using only initial AST, ALT, and INR measurements, the model accurately predicted subsequent laboratory values for the majority of individual patients. This is the first dynamical rather than statistical approach to determine poor prognosis in patients with life‐threatening liver disease due to APAP overdose. Conclusion: MALD provides a method to estimate overdose amount, time elapsed since overdose, and outcome from patient laboratory values commonly available on admission in cases of acute liver failure due to APAP overdose and should be validated in multicenter prospective evaluation. (HEPATOLOGY 2012)

Aberrant water homeostasis detected by stable isotope analysis

While isotopes are frequently used as tracers in investigations of disease physiology (i.e., 14C labeled glucose), few studies have examined the impact that disease, and disease-related alterations in metabolism, may have on stable isotope ratios at natural abundance levels. The isotopic composition of body water is heavily influenced by water metabolism and dietary patterns and may provide a platform for disease detection. By utilizing a model of streptozotocin (STZ)-induced diabetes as an index case of aberrant water homeostasis, we demonstrate that untreated diabetes mellitus results in distinct combinations, or signatures, of the hydrogen (δ2H) and oxygen (δ18O) isotope ratios in body water. Additionally, we show that the δ2H and δ18O values of body water are correlated with increased water flux, suggesting altered blood osmolality, due to hyperglycemia, as the mechanism behind this correlation. Further, we present a mathematical model describing the impact of water flux on the isotopic composition of body water and compare model predicted values with actual values. These data highlight the importance of factors such as water flux and energy expenditure on predictive models of body water and additionally provide a framework for using naturally occurring stable isotope ratios to monitor diseases that impact water homeostasis.

Hydrogen and Oxygen Isotope Ratios in Body Water and Hair: Modeling Isotope Dynamics in Nonhuman Primates

The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the isotopic composition of body water (2H/1H, 18O/16O expressed as δ2H and δ18O). In turn, body water influences the isotopic composition of organic matter in tissues, such as hair and teeth, which are often used to reconstruct historical dietary and movement patterns of animals and humans. Here, we used a nonhuman primate system (Macaca fascicularis) to test the robustness of two different mechanistic stable isotope models: a model to predict the δ2H and δ18O values of body water and a second model to predict the δ2H and δ18O values of hair. In contrast to previous human‐based studies, use of nonhuman primates fed controlled diets allowed us to further constrain model parameter values and evaluate model predictions. Both models reliably predicted the δ2H and δ18O values of body water and of hair. Moreover, the isotope data allowed us to better quantify values for two critical variables in the models: the δ2H and δ18O values of gut water and the 18O isotope fractionation associated with a carbonyl oxygen–water interaction in the gut (αow). Our modeling efforts indicated that better predictions for body water and hair isotope values were achieved by making the isotopic composition of gut water approached that of body water. Additionally, the value of αow was 1.0164, in close agreement with the only other previously measured observation (microbial spore cell walls), suggesting robustness of this fractionation factor across different biological systems. Am. J. Primatol. 74:651–660, 2012.

The end of hepatitis C.

We are at a turning point in the management of the hepatitis C virus (HCV) epidemic. HCV can be cured, but treatment up to this point has required a toxic combination of drugs. This is about to change; the second generation of direct-acting antiviral agents promises high cure rates with few side effects. This gives us the historical opportunity to eradicate HCV from the entire population. Our article addresses the advantages of universal eradication of HCV infection from the United States and the steps required to achieve this goal.

Deconvolution of isotope signals from bundles of multiple hairs

Segmental analysis of hair has been used in diverse fields ranging from forensics to ecology to measure the concentration of substances such as drugs and isotopes. Multiple hairs are typically combined into a bundle for segmental analysis to obtain a high-resolution series of measurements. Individual hair strands cycle through multiple phases of growth and grow at different rates when in the growth phase. Variation in growth of hair strands in a bundle can cause misalignment of substance concentration between hairs, attenuating the primary body signal. We developed a mathematical model based on the known physiology of hair growth to describe the signal averaging caused by bundling multiple hairs for segmental analysis. The model was used to form an inverse method to estimate the primary body signal from measurements of a hair bundle. The inverse method was applied to a previously described stable oxygen isotope chronology from the hair of a murder victim and provides a refined interpretation of the data. Aspects of the reconstruction were confirmed when the victim was later identified.

Mathematical modelling of chronic acetaminophen metabolism and liver injury

Acetaminophen (APAP) overdose is the leading cause of acute liver injury in the USA and the UK. Increasingly, liver injury is caused by sustained overuse rather than a single-time overdose. We have recently developed a mathematical model, the Model of APAP-induced Liver Damage (MALD), to predict the outcome of patients with APAP-induced liver damage. The model is based on a single-time overdose and uses measurable markers of liver injury to estimate time since overdose and overdose amount, two variables critical for survival. Here, we extend the model to study liver injury from chronic APAP use. We find that there is a threshold in the model, such that liver injury occurs rapidly or not at all, even with chronic use. Fits of synthetic data derived from chronic use overdose scenarios to MALD lead to accurate predictions of outcome, even when liver injury is the result of sustained overuse.

Modeling time-series data from microbial communities

As sequencing technologies have advanced, the amount of information regarding the composition of bacterial communities from various environments (for example, skin or soil) has grown exponentially. To date, most work has focused on cataloging taxa present in samples and determining whether the distribution of taxa shifts with exogenous covariates. However, important questions regarding how taxa interact with each other and their environment remain open thus preventing in-depth ecological understanding of microbiomes. Time-series data from 16S rDNA amplicon sequencing are becoming more common within microbial ecology, but methods to infer ecological interactions from these longitudinal data are limited. We address this gap by presenting a method of analysis using Poisson regression fit with an elastic-net penalty that (1) takes advantage of the fact that the data are time series; (2) constrains estimates to allow for the possibility of many more interactions than data; and (3) is scalable enough to handle data consisting of thousands of taxa. We test the method on gut microbiome data from white-throated woodrats (Neotoma albigula) that were fed varying amounts of the plant secondary compound oxalate over a period of 22 days to estimate interactions between OTUs and their environment.

Modeling the dynamics of stable isotope tissue-diet enrichment

Reconstructions of dietary composition and trophic level from stable isotope measurements of animal tissue rely on predictable offsets of stable isotope ratios from diet to tissue. Physiological processes associated with metabolism shape tissue stable isotope ratios, and as such the spacing between stable isotope ratios of diet and tissue may be influenced by processes such as growth, nutritional stress, and disease. Here, we develop a model of incorporation stable isotopes in diet to tissues by coupling stable isotope dynamics to a model of macronutrient energy metabolism. We use the model to explore the effect of changes in dietary intake, both composition and amount, and in energy expenditure, on body mass and carbon and nitrogen stable isotope ratios of tissue.