Data gaps and opportunities for comparative and conservation biology.

Biodiversity loss is a major challenge. Over the past century, the average rate of vertebrate extinction has been about 100-fold higher than the estimated background rate and population declines continue to increase globally. Birth and death rates determine the pace of population increase or decline, thus driving the expansion or extinction of a species. Design of species conservation policies hence depends on demographic data (e.g., for extinction risk assessments or estimation of harvesting quotas). However, an overview of the accessible data, even for better known taxa, is lacking. Here, we present the Demographic Species Knowledge Index, which classifies the available information for 32,144 (97%) of extant described mammals, birds, reptiles, and amphibians. We show that only 1.3% of the tetrapod species have comprehensive information on birth and death rates. We found no demographic measures, not even crude ones such as maximum life span or typical litter/clutch size, for 65% of threatened tetrapods. More field studies are needed; however, some progress can be made by digitalizing existing knowledge, by imputing data from related species with similar life histories, and by using information from captive populations. We show that data from zoos and aquariums in the Species360 network can significantly improve knowledge for an almost eightfold gain. Assessing the landscape of limited demographic knowledge is essential to prioritize ways to fill data gaps. Such information is urgently needed to implement management strategies to conserve at-risk taxa and to discover new unifying concepts and evolutionary relationships across thousands of tetrapod species.

Cross-species transcriptomics uncovers genes underlying genetic accommodation of developmental plasticity in spadefoot toads.

That hardcoded genomes can manifest as plastic phenotypes responding to environmental perturbations is a fascinating feature of living organisms. How such developmental plasticity is regulated at the molecular level is beginning to be uncovered aided by the development of -omic techniques. Here, we compare the transcriptome-wide responses of two species of spadefoot toads with differing capacity for developmental acceleration of their larvae in the face of a shared environmental risk: pond drying. By comparing gene expression profiles over time and performing cross-species network analyses, we identified orthologues and functional gene pathways whose environmental sensitivity in expression have diverged between species. Genes related to lipid, cholesterol and steroid biosynthesis and metabolism make up most of a module of genes environmentally responsive in one species, but canalized in the other. The evolutionary changes in the regulation of the genes identified through these analyses may have been key in the genetic accommodation of developmental plasticity in this system.

Parallel diversification of the African tree toad genus Nectophryne (Bufonidae).

African amphibian diversity remains underestimated with many cryptic lineages awaiting formal description. An important hotspot of amphibian diversification is the Guineo-Congolian rainforest in Central Africa, its richness attributable to present day and ancestral range fragmentation through geological barriers, habitat expansion and contraction, and the presence of steep ecological gradients. The charismatic Nectophryne tree toads present an interesting case study for diversification in this region. The two formally described species comprising this genus show nearly identical geographic distributions extending across most of the Guineo-Congolian rainforest, but show little morphological disparity. Both species harbour extensive genetic diversity warranting taxonomic revisions, and interestingly, when comparing the subclades within each, the two species show remarkably parallel diversification histories, both in terms of timing of phylogenetic splits and their geographic distributions. This indicates that common processes may have shaped the evolutionary history of these lineages.

Telomere attrition with age in a wild amphibian population.

Telomere shortening with age has been documented in many organisms, but few studies have reported telomere length measurements in amphibians, and no information is available for growth after metamorphosis, nor in wild populations. We provide both cross-sectional and longitudinal evidence of net telomere attrition with age in a wild amphibian population of natterjack toads (Epidalea calamita). Based on age-estimation by skeletochronology and qPCR telomere length measurements in the framework of an individual-based monitoring programme, we confirmed telomere attrition in recaptured males. Our results support that toads experience telomere attrition throughout their ontogeny, and that most attrition occurs during the first 1-2 years. We did not find associations between telomere length and inbreeding or body condition. Our results on telomere length dynamics under natural conditions confirm telomere shortening with age in amphibians and provide quantification of wide telomere length variation within and among age-classes in a wild breeding population.

Opposite and synergistic physiological responses to water acidity and predator cues in spadefoot toad tadpoles.

Organisms are exposed to multiple environmental factors simultaneously to which they often respond behaviorally, morphologically and/or physiologically. Amphibian larvae are quite plastic and efficiently adjust their phenotype and physiology to the reigning local conditions. Here we tested whether the combination of predator presence and low water pH induces alterations in the morphology and physiology of spadefoot toad tadpoles. We raised Pelobates cultripes tadpoles in the laboratory in water at either pH 4 or 7, and in the presence or absence of caged dragonfly nymphs, and determined their changes in shape through geometric morphometrics to assess whether predator recognition was impaired or not at low pH. We also measured levels of plasma corticosterone, activity of four antioxidant enzymes, as well as markers of oxidative damage and redox status. We found that tadpoles altered their body shape in response to predator cues even at low pH, indicating that predator recognition was not interfered by water acidity and developmental responses were robust even under abiotic stress. Water acidity was associated with increased corticosterone levels in tadpoles, whereas predator presence consistently reduced corticosterone levels. Predator presence was linked to reduced antioxidant enzyme activity, whereas the combination of both factors resulted in negative synergistic effects on lipid peroxidation and the antioxidant capacity of tadpoles. Here we show that tadpoles detect predators even at low pH but that the development of adaptive anti-predatory morphology can magnify physiological imbalances when other stressors co-occur. These results emphasize the need to understand how multiple environmental perturbations can affect animal homeostasis.

Physiological mechanisms of adaptive developmental plasticity in Rana temporaria island populations.

BACKGROUND: Adaptive plasticity is essential for many species to cope with environmental heterogeneity. In particular, developmental plasticity allows organisms with complex life cycles to adaptively adjust the timing of ontogenetic switch points. Size at and time to metamorphosis are reliable fitness indicators in organisms with complex cycles. The physiological machinery of developmental plasticity commonly involves the activation of alternative neuroendocrine pathways, causing metabolic alterations. Nevertheless, we have still incomplete knowledge about how these mechanisms evolve under environments that select for differences in adaptive plasticity. In this study, we investigate the physiological mechanisms underlying divergent degrees of developmental plasticity across Rana temporaria island populations inhabiting different types of pools in northern Sweden. METHODS: In a laboratory experiment we estimated developmental plasticity of amphibian larvae from six populations coming from three different island habitats: islands with only permanent pools, islands with only ephemeral pools, and islands with a mixture of both types of pools. We exposed larvae of each population to either constant water level or simulated pool drying, and estimated their physiological responses in terms of corticosterone levels, oxidative stress, and telomere length. RESULTS: We found that populations from islands with only temporary pools had a higher degree of developmental plasticity than those from the other two types of habitats. All populations increased their corticosterone levels to a similar extent when subjected to simulated pool drying, and therefore variation in secretion of this hormone does not explain the observed differences among populations. However, tadpoles from islands with temporary pools showed lower constitutive activities of catalase and glutathione reductase, and also showed overall shorter telomeres. CONCLUSIONS: The observed differences are indicative of physiological costs of increased developmental plasticity, suggesting that the potential for plasticity is constrained by its costs. Thus, high levels of responsiveness in the developmental rate of tadpoles have evolved in islands with pools at high but variable risk of desiccation. Moreover, the physiological alterations observed may have important consequences for both short-term odds of survival and long term effects on lifespan.

Should I Change or Should I Go? Phenotypic Plasticity and Matching Habitat Choice in the Adaptation to Environmental Heterogeneity.

It can be challenging for organisms to achieve a good match between their phenotypic characteristics and environmental requirements that vary in space and time. The evolution of adaptive phenotypes can result from genetic differentiation at the population level. Individuals, however, could also change their phenotype (adaptive plasticity) or select an environment because it matches with their phenotype (matching habitat choice). It is poorly known under which conditions these different solutions to environmental heterogeneity evolve and whether they operate together. Using an individual-based simulation model, we assessed which solutions evolved depending on degree of temporal variation, costs of multiple underlying traits, and order of dispersal and development. Population genetic divergence was superseded by plasticity or matching habitat choice as temporal variation increased. Plasticity and matching habitat choice were limited by their trait costs, even when this involved only a part of the underlying traits. Independent of the order of dispersal and development, plasticity evolved more commonly than matching habitat choice, in part because the match a phenotype can achieve by matching habitat choice is limited by the types of environments available. Our results explain the apparent relative rarity of matching habitat choice in nature. At the same time, our results can be used to look for matching habitat choice in those biological systems where the conditions for other solutions seem unfavorable.

A heuristic model on the role of plasticity in adaptive evolution: plasticity increases adaptation, population viability and genetic variation.

An ongoing new synthesis in evolutionary theory is expanding our view of the sources of heritable variation beyond point mutations of fixed phenotypic effects to include environmentally sensitive changes in gene regulation. This expansion of the paradigm is necessary given ample evidence for a heritable ability to alter gene expression in response to environmental cues. In consequence, single genotypes are often capable of adaptively expressing different phenotypes in different environments, i.e. are adaptively plastic. We present an individual-based heuristic model to compare the adaptive dynamics of populations composed of plastic or non-plastic genotypes under a wide range of scenarios where we modify environmental variation, mutation rate and costs of plasticity. The model shows that adaptive plasticity contributes to the maintenance of genetic variation within populations, reduces bottlenecks when facing rapid environmental changes and confers an overall faster rate of adaptation. In fluctuating environments, plasticity is favoured by selection and maintained in the population. However, if the environment stabilizes and costs of plasticity are high, plasticity is reduced by selection, leading to genetic assimilation, which could result in species diversification. More broadly, our model shows that adaptive plasticity is a common consequence of selection under environmental heterogeneity, and hence a potentially common phenomenon in nature. Thus, taking adaptive plasticity into account substantially extends our view of adaptive evolution.

Plastic changes in tadpole trophic ecology revealed by stable isotope analysis.

Amphibian larvae constitute a large fraction of the biomass of wetlands and play important roles in their energy flux and nutrient cycling. Interactions with predators and competitors affect their abundance but also their foraging behaviour, potentially leading to non-consumptive cascading effects on the whole trophic web. We experimentally tested for plastic changes in larval trophic ecology of two anuran species in response to competitors and the non-lethal presence of native and non-native predators, using stable isotope analysis. We hypothesized that tadpoles would alter their diet in the presence of competitors and native predators, and to a lesser extent or not at all in the presence of non-native predators. First, we conducted a controlled diet experiment to estimate tadpole turnover rates and discrimination factors using Pelobates cultripes and Bufo calamita. Turnover rates yielded a half-life of 15-20 days (attaining a quasi-isotopic equilibrium after 2 months), whereas discrimination factors for natural controlled diets resulted in different isotopic values essential for calibration. Second, we did an experiment with P. cultripes and Rana perezi (=Pelophylax perezi) where we manipulated the presence/absence of predators and heterospecific tadpoles using microcosms in the laboratory. We detected a significant shift in trophic status of both amphibian species in the presence of non-native crayfish: the δ(15)N values and macrophyte consumption of tadpoles increased, whereas their detritus consumption decreased. This suggests that tadpoles could have perceived crayfish as a predatory risk or that crayfish acted as competitors for algae and zooplankton. No dietary changes were observed in the presence of native dragonflies or when both tadpole species co-occurred. Stable isotopic analysis is an efficient way to assess variation in tadpoles' tropic status and hence understand their role in freshwater ecosystems. Here we provide baseline isotopic information for future trophic studies and show evidence for plastic changes in tadpoles' use of food resources under different ecological scenarios.

Larval plastic responses to warming and desiccation delay gonadal maturation in postmetamorphic spadefoot toads.

Developmental plasticity allows organisms to adjust life-history traits to varying environmental conditions, which can have concomitant effects across life stages. Many amphibians are suitable model systems to study plasticity because their larvae can adjust growth and differentiation under fluctuating environments. It is unknown, however, whether somatic and gonadal differentiation are equally affected by environmentally induced plasticity or whether their decoupling alters gonadal maturation postmetamorphosis, which may affect fitness. We tested if developmental acceleration in response to warming and desiccation risk results in shifts in gonadal maturation during metamorphosis and postmetamorphic growth in western spadefoot toads (Pelobates cultripes). We found additive effects of increased temperature and desiccation risk on development and growth at metamorphosis, which largely constrained gonadal maturation in metamorphic and postmetamorphic individuals of both sexes. Furthermore, the conditions experienced by larvae incurred sex-specific carryover effects on the gonadal maturation of juveniles 5 months after metamorphosis. In females, high temperature delayed ovarian maturation regardless of the water level. In males, exposure to high temperature and high water levels slightly delayed the testes' maturation. These results highlight the relevance of larval plasticity in the gonadal maturation of species undergoing metamorphosis, which may have implications for population demographics and the evolution of life histories.

Exploring water-borne corticosterone collection as a non-invasive tool in amphibian conservation physiology: benefits, limitations and future perspectives.

Global change exposes wildlife to a variety of environmental stressors and is affecting biodiversity worldwide, with amphibian population declines being at the forefront of the global biodiversity crisis. The use of non-invasive methods to determine the physiological state in response to environmental stressors is therefore an important advance in the field of conservation physiology. The glucocorticoid hormone corticosterone (CORT) is one useful biomarker to assess physiological stress in amphibians, and sampling water-borne (WB) CORT is a novel, non-invasive collection technique. Here, we tested whether WB CORT can serve as a valid proxy of organismal levels of CORT in larvae of the common frog (Rana temporaria). We evaluated the association between tissue and WB CORT levels sampled from the same individuals across ontogenetic stages, ranging from newly hatched larvae to froglets at 10 days after metamorphosis. We also investigated how both tissue and WB CORT change throughout ontogeny. We found that WB CORT is a valid method in pro-metamorphic larvae as values for both methods were highly correlated. In contrast, there was no correlation between tissue and WB CORT in newly hatched, pre-metamorphic larvae, metamorphs or post-metamorphic froglets probably due to ontogenetic changes in respiratory and skin morphology and physiology affecting the transdermal CORT release. Both collection methods consistently revealed a non-linear pattern of ontogenetic change in CORT with a peak at metamorphic climax. Thus, our results indicate that WB CORT sampling is a promising, non-invasive conservation tool for studies on late-stage amphibian larvae. However, we suggest considering that different contexts might affect the reliability of WB CORT and consequently urge future studies to validate this method whenever it is used in new approaches. We conclude proposing some recommendations and perspectives on the use of WB CORT that will aid in broadening its application as a non-invasive tool in amphibian conservation physiology.

Widespread learned predator recognition to an alien predator across populations in an amphibian species.

Alien predators are a major cause of decline and extinction of species worldwide, since native organisms are rarely equipped with specific antipredatory strategies to cope with them. However, phenotypic plasticity and learned predator recognition may help prey populations to survive novel predators. Here we examine geographical variation in the learning ability of larval spadefoot toads (Pelobates cultripes) to recognize invasive predatory crayfish (Procambarus clarkii). We compare the learning-mediated behavioural responses of tadpoles from six populations across two regions in Spain (central and southern), with different histories of exposure to the presence of the invasive species. Two of the populations showed innate recognition of chemical cues from the invasive crayfish, whereas three of them learned to recognize such cues as a threat after conditioning with conspecific alarm cues. Learning abilities did not differ among southern populations, but they did among central populations. We assessed patterns of genetic variation within and among these two regions through microsatellite markers and found low genetic divergence among the southern populations but greater differentiation among the central ones. We hypothesize that similar responses to the invasive crayfish in southern populations may have arisen from a combination of extended historical exposure to this introduced predator (~ 50 y) and higher levels of gene flow, as they inhabit a highly interconnected pond network. In contrast, populations from central Spain show lower connectivity, have been exposed to the invasive crayfish for a shorter period of time, and are more divergent in their plastic responses.

Background matching through fast and reversible melanin-based pigmentation plasticity in tadpoles comes with morphological and antioxidant changes.

Facultative colour change is widespread in the animal kingdom, and has been documented in many distantly related amphibians. However, experimental data testing the extent of facultative colour change, and associated physiological and morphological implications are comparatively scarce. Background matching in the face of spatial and temporal environmental variation is thought to be an important proximate function of colour change in aquatic amphibian larvae. This is particularly relevant for species with long larval periods such as the western spadefoot toad, Pelobates cultripes, whose tadpoles spend up to six months developing in temporary waterbodies with temporally variable vegetation. By rearing tadpoles on different coloured backgrounds, we show that P. cultripes larvae can regulate pigmentation to track fine-grained differences in background brightness, but not hue or saturation. We found that colour change is rapid, reversible, and primarily achieved through changes in the quantity of eumelanin in the skin. We show that this increased eumelanin production and/or maintenance is also correlated with changes in morphology and oxidative stress, with more pigmented tadpoles growing larger tail fins and having an improved redox status.

Life in plastic, it's not fantastic: Sublethal effects of polyethylene microplastics ingestion throughout amphibian metamorphosis.

Microplastics (MP) are an abundant, long-lasting, and widespread type of environmental pollution that is of increasing concern as it might pose a serious threat to ecosystems and species. However, these threats are still largely unknown for amphibians. Here, we used the African clawed frog (Xenopus laevis) as a model species to investigate whether polyethylene MP ingestion affects amphibian growth and development and leads to metabolic changes across two consecutive life stages (larvae and juveniles). Furthermore, we examined whether MP effects were more pronounced at higher rearing temperatures. Larval growth, development, and body condition were recorded, and standard metabolic rate (SMR) and levels of stress hormone (corticosterone, CORT) were measured. We determined variation in size, morphology, and hepatosomatic index in juveniles to identify any potential consequences of MP ingestion across metamorphosis. In both life stages, MP accumulation in the body was assessed. MP ingestion was found to result in sublethal effects on larval growth, development, and metabolism, to lead to allometric carry-over effects on juvenile morphology, and to accumulate in the specimens at both life stages. In larvae, SMR and developmental rate increased in response to MP ingestion; there additionally was a significant interaction of MP ingestion and temperature on development. CORT levels were higher in larvae that ingested MP, except at higher temperature. In juveniles, body was wider, and extremities were longer in animals exposed to MP during the larval stage; a high rearing temperature in combination with MP ingestion counteracted this effect. Our results provide first insights into the effects of MP on amphibians throughout metamorphosis and demonstrate that juvenile amphibians may act as a pathway for MP from freshwater to terrestrial environments. To allow for generalizations across amphibian species, future experiments need to consider the field prevalence and abundance of different MP in amphibians at various life stages.

Irreversibility of a bad start: early exposure to osmotic stress limits growth and adaptive developmental plasticity.

Harsh environments experienced early in development have immediate effects and potentially long-lasting consequences throughout ontogeny. We examined how salinity fluctuations affected survival, growth and development of Fejervarya limnocharis tadpoles. Specifically, we tested whether initial salinity effects on growth and rates of development were reversible and whether they affected the tadpoles' ability to adaptively accelerate development in response to deteriorating conditions later in development. Tadpoles were initially assigned to either low or high salinity, and then some were switched between salinity levels upon reaching either Gosner stage 30 (early switch) or 38 (late switch). All tadpoles initially experiencing low salinity survived whereas those initially experiencing high salinity had poor survival, even if switched to low salinity. Growth and developmental rates of tadpoles initially assigned to high salinity did not increase after osmotic stress release. Initial low salinity conditions allowed tadpoles to attain a fast pace of development even if exposed to high salinity afterwards. Tadpoles experiencing high salinity only late in development metamorphosed faster and at a smaller size, indicating an adaptive acceleration of development to avoid osmotic stress. Nonetheless, early exposure to high salinity precluded adaptive acceleration of development, always causing delayed metamorphosis relative to those in initially low salinity. Our results thus show that stressful environments experienced early in development can critically impact life history traits, having long-lasting or irreversible effects, and restricting their ability to produce adaptive plastic responses.

The evolution of reproductive modes and life cycles in amphibians.

Amphibians have undergone important evolutionary transitions in reproductive modes and life-cycles. We compare large-scale macroevolutionary patterns in these transitions across the three major amphibian clades: frogs, salamanders, and caecilians. We analyse matching reproductive and phylogenetic data for 4025 species. We find that having aquatic larvae is ancestral for all three groups and is retained by many extant species (33-44%). The most frequent transitions in each group are to relatively uncommon states: live-bearing in caecilians, paedomorphosis in salamanders, and semi-terrestriality in frogs. All three groups show transitions to more terrestrial reproductive modes, but only in caecilians have these evolved sequentially from most-to-least aquatic. Diversification rates are largely independent of reproductive modes. However, in salamanders direct development accelerates diversification whereas paedomorphosis decreases it. Overall, we find a widespread retention of ancestral modes, decoupling of trait transition rates from patterns of species richness, and the general independence of reproductive modes and diversification.

Chromosome-level assembly, annotation and phylome of Pelobates cultripes, the western spadefoot toad.

Genomic resources for amphibians are still hugely under-represented in vertebrate genomic research, despite being a group of major interest for ecology, evolution and conservation. Amphibians constitute a highly threatened group of vertebrates, present a vast diversity in reproductive modes, are extremely diverse in morphology, occupy most ecoregions of the world, and present the widest range in genome sizes of any major group of vertebrates. We combined Illumina, Nanopore and Hi-C sequencing technologies to assemble a chromosome-level genome sequence for an anuran with a moderate genome size (assembly span 3.09 Gb); Pelobates cultripes, the western spadefoot toad. The genome has an N50 length of 330 Mb with 98.6% of the total sequence length assembled into 14 super scaffolds, and 87.7% complete BUSCO genes. We use published transcriptomic data to provide annotations, identifying 32,684 protein-coding genes. We also reconstruct the P. cultripes phylome and identify 2,527 gene expansions. We contribute the first draft of the genome of the western spadefoot toad, P. cultripes. This species represents a relatively basal lineage in the anuran tree with an interesting ecology and a high degree of developmental plasticity, and thus is an important resource for amphibian genomic research.

Invasive predatory crayfish do not trigger inducible defences in tadpoles.

Invasive species cause deep impacts on ecosystems worldwide, contributing to the decline and extinction of indigenous species. Effective defences against native biological threats in indigenous species, whether structural or inducible, often seem inoperative against invasive species. Here, we show that tadpoles of the Iberian green frog detect chemical cues from indigenous predators (dragonfly nymphs) and respond by reducing their activity and developing an efficient defensive morphology against them (increased tail depth and pigmentation). Those defensive responses, however, were not activated against a highly damaging invasive predator (red swamp crayfish). Induced defences increased tadpole survival when faced against either indigenous dragonflies or invasive crayfish, so its inactivation in the presence of the invasive predator seems to be due to failure in cue recognition. Furthermore, we tested for local adaptation to the invasive predator by comparing individuals from ponds either exposed to or free from crayfish. In both cases, tadpoles failed to express inducible defences against crayfish, indicating that ca 30 years of contact with the invasive species (roughly 10-15 frog generations) have been insufficient for the evolution of recognition of invasive predator cues.

Comparisons between Q(ST) and F(ST) --how wrong have we been?

The comparison between quantitative genetic divergence (Q(ST) ) and neutral genetic divergence (F(ST) ) among populations has become the standard test for historical signatures of selection on quantitative traits. However, when the mutation rate of neutral markers is relatively high in comparison with gene flow, estimates of F(ST) will decrease, resulting in upwardly biased comparisons of Q(ST) vs. F(ST) . Reviewing empirical studies, the difference between Q(ST) and F(ST) is positively related to marker heterozygosity. After refuting alternative explanations for this pattern, we conclude that marker mutation rate indeed has had a biasing effect on published Q(ST) -F(ST) comparisons. Hence, it is no longer clear that populations have commonly diverged in response to divergent selection. We present and discuss potential solutions to this bias. Comparing Q(ST) with recent indices of neutral divergence that statistically correct for marker heterozygosity (Hedrick's G'st and Jost's D) is not advised, because these indices are not theoretically equivalent to Q(ST) . One valid solution is to estimate F(ST) from neutral markers with mutation rates comparable to those of the loci underlying quantitative traits (e.g. SNPs). Q(ST) can also be compared to Φ(ST) (Phi(ST) ) of amova, as long as the genetic distance among allelic variants used to estimate Φ(ST) reflects evolutionary history: in that case, neutral divergence is independent of mutation rate. In contrast to their common usage in comparisons of Q(ST) and F(ST) , microsatellites typically have high mutation rates and do not evolve according to a simple evolutionary model, so are best avoided in Q(ST) -F(ST) comparisons.

Differences in complexity of glycemic profile in survivors and nonsurvivors in an intensive care unit: a pilot study.

OBJECTIVE: To investigate glycemic dynamics and its relation with mortality in critically ill patients. We searched for differences in complexity of the glycemic profile between survivors and nonsurvivors in patients admitted to a multidisciplinary intensive care unit. DESIGN: Prospective, observational study, convenience sample. SETTINGS: Multidisciplinary intensive care unit of a teaching hospital in Madrid, Spain. PATIENTS: A convenience sample of 42 patients, aged 29 to 86 yrs, admitted to an intensive care unit with an Acute Physiology and Chronic Health Evaluation II score of >or=14 and with an anticipated intensive care unit stay of >72 hrs. INTERVENTIONS: A continuous glucose monitoring system was used to measure subcutaneous interstitial fluid glucose levels every 5 mins for 48 hrs during the first days of intensive care unit stay. A 24-hr period (n = 288 measurements) was used as time series for complexity analysis of the glycemic profile. MEASUREMENTS: Complexity of the glycemic profile was evaluated by means of detrended fluctuation analysis. Other conventional measurements of variability (range, sd, and Mean Amplitude of Glycemic Excursions) were also calculated. MAIN RESULTS: Ten patients died during their intensive care unit stay. Glycemic profile was significantly more complex (lower detrended fluctuation analysis) in survivors (mean detrended fluctuation analysis, 1.49; 95% confidence interval, 1.44-1.53) than in nonsurvivors (1.60; 95% confidence interval, 1.52-1.68). This difference persisted after accounting for the presence of diabetes. In a logistic regression model, the odds ratio for death was 2.18 for every 0.1 change in detrended fluctuation analysis.Age, gender, Simplified Acute Physiologic Score 3 or Acute Physiologic and Chronic Health Evaluation II scores failed to explain differences in survivorship. Conventional variability measurements did not differ between survivors and nonsurvivors. CONCLUSIONS: Complexity of the glycemic profile of critically ill patients varies significantly between survivors and nonsurvivors. Loss of complexity in glycemia time series, evaluated by detrended fluctuation analysis, is associated with higher mortality.