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Telomere length and DNA methylation (DNAm) are two promising biomarkers of biological age. Environmental factors and life history traits are known to affect variation in both these biomarkers, especially during early life, yet surprisingly little is known about their reciprocal association, especially in natural populations. Here, we explore how variation in DNAm, growth rate, and early-life conditions are associated with telomere length changes during development. We tested these associations by collecting data from wild, nestling zebra finches in the Australian desert. We found that increases in the level of DNAm were negatively correlated with telomere length changes across early life. We also confirm previously documented effects of post hatch growth rate and clutch size on telomere length in a natural ecological context for a species that has been extensively studied in the laboratory. However, we did not detect any effect of ambient temperature during developmental on telomere length dynamics. We also found that the absolute telomere length of wild zebra finches, measured using the in-gel TRF method, was similar to that of captive birds. Our findings highlight exciting new opportunities to link and disentangle potential relationships between DNA based biomarkers of ageing, and of physiological reactions to environmental change., (© 2021 John Wiley & Sons Ltd.)

We report a case of myasthenia gravis, myocarditis, and myositis following the treatment of melanoma with nivolumab. The patient was a 68-year-old Caucasian male with stage 3 melanoma status after two doses of nivolumab with shortness of breath, intermittent palpitations, dizziness, and nausea. During his initial evaluation, he was found to have atrial fibrillation with rapid ventricular response along with new-onset proximal muscle weakness, double vision, dysphagia, and ptosis of the right eye. Further diagnostic workup of the pleural effusion with CT of the chest showed large right pleural effusion with adjacent atelectasis. Thoracentesis was completed without complications and resulted in an exudative effusion with negative cytology and cultures. Serologic studies showed elevated troponin and serum creatine kinase, negative acetylcholine receptor antibody, and negative modulating antibody. Despite negative antibody tests, the patient's symptoms suggested a clinical diagnosis of myasthenia gravis. The ice pack test was performed, which showed temporary improvement of the patient's ptosis. Given the suspicion for myasthenia gravis and positive ice pack test, he was treated with corticosteroids, intravenous immunoglobulin (IVIG), and pyridostigmine. He completed a total of three doses of IVIG with improvement in diplopia. Despite steroids and respiratory support with BiPAP (bilevel positive airway pressure), on the 14th day of hospitalization, the patient had multiple organ failure along with worsening respiratory failure. The patient discussed the situation with his family, and they decided on hospice care. The patient was discharged to hospice on admission day 14., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Bawek et al.)

Human-induced climate change is increasing the frequency, duration, and intensity of heat waves and exposure to these extreme temperatures impacts individual physiology and performance (e.g., metabolism, water balance, and growth). These traits may be susceptible to thermal conditions experienced during embryonic development, but experiments focusing on post-natal development are scant. Documented effects of heat waves on whole-body metabolism may reflect changes in mitochondrial function, but most studies do not measure physiological traits at both the cellular and whole organism levels. Here, we exposed nests of zebra finches to experimentally simulated heat waves for 18 days after hatching and measured body mass, growth rate, whole-body metabolic rate, body temperature, wet thermal conductance, evaporative water loss, and relative water economy of chicks at three ages corresponding to ectothermic (day 5), poikilothermic (day 12), and homoeothermic (day 50) stages. Additionally, we measured mitochondrial bioenergetics of blood cells 80 days post-hatch. While early-life exposure to heat wave conditions did not impact whole body metabolic and hygric physiology, body temperature was lower for birds from heated compared with control nests at both 12 and 50 days of age. There was also an effect of nest heating at the cellular level, with mitochondria from heated birds having higher endogenous and proton-leak related respiration, although oxidative phosphorylation, maximum respiratory capacity, and coupling efficiency were not impacted. Our results suggest that early-life exposure to high ambient temperature induces programming effects on cellular-level and thermal physiology that may not be apparent for whole-animal metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ton, Stier, Cooper and Griffith.)

Metabolism is thought to mediate the connection between environmental selection pressures and a broad array of life history tradeoffs, but tests are needed. High juvenile predation correlates with fast growth, which may be achieved via fast juvenile metabolism. Fast offspring metabolism and growth can create physiological costs later in life that should be minimized in species with low adult mortality. Yet, relationships between juvenile metabolism and mortality at offspring versus adult stages are unexplored. We found that post-natal metabolism was positively correlated with adult mortality but not nest predation rates among 43 songbird species on three continents. Nest predation, but not adult mortality, explained additional variation in growth rates beyond metabolism. Our results suggest that metabolism may not be the mechanism underlying the relationships between growth and mortality at different life stages., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Converging research suggests that the resting brain operates at the cusp of dynamic instability, as signified by scale-free temporal correlations. We asked whether the scaling properties of these correlations differ between amplitude and phase fluctuations, which may reflect different aspects of cortical functioning. Using source-reconstructed magneto-encephalographic signals, we found power-law scaling for the collective amplitude and for phase synchronization, both capturing whole-brain activity. The temporal changes of the amplitude comprise slow, persistent memory processes, whereas phase synchronization exhibits less temporally structured and more complex correlations, indicating a fast and flexible coding. This distinct temporal scaling supports the idea of different roles of amplitude and phase fluctuations in cortical functioning., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Modeling and interpreting (partial) synchronous neural activity can be a challenge. We illustrate this by deriving the phase dynamics of two seminal neural mass models: the Wilson-Cowan firing rate model and the voltage-based Freeman model. We established that the phase dynamics of these models differed qualitatively due to an attractive coupling in the first and a repulsive coupling in the latter. Using empirical structural connectivity matrices, we determined that the two dynamics cover the functional connectivity observed in resting state activity. We further searched for two pivotal dynamical features that have been reported in many experimental studies: (1) a partial phase synchrony with a possibility of a transition towards either a desynchronized or a (fully) synchronized state; (2) long-term autocorrelations indicative of a scale-free temporal dynamics of phase synchronization. Only the Freeman phase model exhibited scale-free behavior. Its repulsive coupling, however, let the individual phases disperse and did not allow for a transition into a synchronized state. The Wilson-Cowan phase model, by contrast, could switch into a (partially) synchronized state, but it did not generate long-term correlations although being located close to the onset of synchronization, i.e. in its critical regime. That is, the phase-reduced models can display one of the two dynamical features, but not both., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The relative importance of intrinsic constraints imposed by evolved physiological trade-offs versus the proximate effects of temperature for interspecific variation in embryonic development time remains unclear. Understanding this distinction is important because slow development due to evolved trade-offs can yield phenotypic benefits, whereas slow development from low temperature can yield costs. We experimentally increased embryonic temperature in free-living tropical and north temperate songbird species to test these alternatives. Warmer temperatures consistently shortened development time without costs to embryo mass or metabolism. However, proximate effects of temperature played an increasingly stronger role than intrinsic constraints for development time among species with colder natural incubation temperatures. Long development times of tropical birds have been thought to primarily reflect evolved physiological trade-offs that facilitate their greater longevity. In contrast, our results indicate a much stronger role of temperature in embryonic development time than currently thought.

Long-range temporal and spatial correlations have been reported in a remarkable number of studies. In particular power-law scaling in neural activity raised considerable interest. We here provide a straightforward algorithm not only to quantify power-law scaling but to test it against alternatives using (Bayesian) model comparison. Our algorithm builds on the well-established detrended fluctuation analysis (DFA). After removing trends of a signal, we determine its mean squared fluctuations in consecutive intervals. In contrast to DFA we use the values per interval to approximate the distribution of these mean squared fluctuations. This allows for estimating the corresponding log-likelihood as a function of interval size without presuming the fluctuations to be normally distributed, as is the case in conventional DFA. We demonstrate the validity and robustness of our algorithm using a variety of simulated signals, ranging from scale-free fluctuations with known Hurst exponents, via more conventional dynamical systems resembling exponentially correlated fluctuations, to a toy model of neural mass activity. We also illustrate its use for encephalographic signals. We further discuss confounding factors like the finite signal size. Our model comparison provides a proper means to identify power-law scaling including the range over which it is present., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Parental behavior and effort vary extensively among species. Life-history theory suggests that age-specific mortality could cause this interspecific variation, but past tests have focused on fecundity as the measure of parental effort. Fecundity can cause costs of reproduction that confuse whether mortality is the cause or the consequence of parental effort. We focus on a trait, parental allocation of time and effort in warming embryos, that varies widely among species of diverse taxa and is not tied to fecundity. We conducted studies on songbirds of four continents and show that time spent warming eggs varies widely among species and latitudes and is not correlated with clutch size. Adult and offspring (nest) mortality explained most of the interspecific variation in time and effort that parents spend warming eggs, measured by average egg temperatures. Parental effort in warming eggs is important because embryonic temperature can influence embryonic development period and hence exposure time to predation risk. We show through correlative evidence and experimental swapping of embryos between species that parentally induced egg temperatures cause interspecific variation in embryonic development period. The strong association of age-specific mortality with parental effort in warming eggs and the subsequent effects on embryonic development time are unique results that can advance understanding of broad geographic patterns of life-history variation.

Minimally invasive gynecologic surgeons who perform laparoscopic intraperitoneal morcellation should be aware of the recent US Food and Drug Administration (FDA) warning and litigation arising from use of morcellation devices with claims of intraperitoneal dissemination of cancerous cells. On November 24, 2014, the FDA issued a statement warning against using laparoscopic power morcellators in the majority of women undergoing hysterectomy or myomectomy for uterine fibroids. Despite the best intentions in regards to their patients, gynecologists who continue to use power morcellation devices expose themselves to liability. This article is not meant to further deter gynecologists from using laparoscopic power morcellators, but rather to provide an interpretation of the FDA statement as to the patients for whom the use of power morcellation may still be permitted under the FDA guidelines. This article also offers protective measures from a legal perspective for those who choose to continue to use power morcellation in the face of the recent FDA warning and litigation., (Published by Elsevier Inc.)

The discrepancy between structural and functional connectivity in neural systems forms the challenge in understanding general brain functioning. To pinpoint a mapping between structure and function, we investigated the effects of (in)homogeneity in coupling structure and delays on synchronization behavior in networks of oscillatory neural masses by deriving the phase dynamics of these generic networks. For homogeneous delays, the structural coupling matrix is largely preserved in the coupling between phases, resulting in clustered stationary phase distributions. Accordingly, we found only a small number of synchronized groups in the network. Distributed delays, by contrast, introduce inhomogeneity in the phase coupling so that clustered stationary phase distributions no longer exist. The effect of distributed delays mimicked that of structural inhomogeneity. Hence, we argue that phase (de-)synchronization patterns caused by inhomogeneous coupling cannot be distinguished from those caused by distributed delays, at least not by the naked eye. The here-derived analytical expression for the effective coupling between phases as a function of structural coupling constitutes a direct relationship between structural and functional connectivity. Structural connectivity constrains synchronizability that may be modified by the delay distribution. This explains why structural and functional connectivity bear much resemblance albeit not a one-to-one correspondence. We illustrate this in the context of resting-state activity, using the anatomical connectivity structure reported by Hagmann and others.

Causes of interspecific variation in growth rates within and among geographic regions remain poorly understood. Passerine birds represent an intriguing case because differing theories yield the possibility of an antagonistic interaction between nest predation risk and food delivery rates on evolution of growth rates. We test this possibility among 64 Passerine species studied on three continents, including tropical and north and south temperate latitudes. Growth rates increased strongly with nestling predation rates within, but not between, sites. The importance of nest predation was further emphasized by revealing hidden allometric scaling effects. Nestling predation risk also was associated with reduced total feeding rates and per-nestling feeding rates within each site. Consequently, faster growth rates were associated with decreased per-nestling food delivery rates across species, both within and among regions. These relationships suggest that Passerines can evolve growth strategies in response to predation risk whereby food resources are not the primary limit on growth rate differences among species. In contrast, reaction norms of growth rate relative to brood size suggest that food may limit growth rates within species in temperate, but not tropical, regions. Results here provide new insight into evolution of growth strategies relative to predation risk and food within and among species., (© 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.)

Humans spontaneously select a step frequency that minimizes the energy expenditure of walking. This selection might be embedded within the neural circuits that generate gait so that the optimum is pre-programmed for a given walking speed. Or perhaps step frequency is directly optimized, based on sensed feedback of energy expenditure. Direct optimization is expected to be slow due to the compounded effect of delays and iteration, whereas a pre-programmed mechanism presumably allows for faster step frequency selection, albeit dependent on prior experience. To test for both pre-programmed selection and direct optimization, we applied perturbations to treadmill walking to elicit transient changes in step frequency. We found that human step frequency adjustments (n = 7) occurred with two components, the first dominating the response (66 ± 10% of total amplitude change; mean ± SD) and occurring quite quickly (1.44 ± 1.14 s to complete 95% of total change). The other component was of smaller amplitude (35 ± 10% of total change) and took tens of seconds (27.56 ± 16.18 s for 95% completion). The fast process appeared to be too fast for direct optimization and more indicative of a pre-programmed response. It also persisted even with unusual closed-loop perturbations that conflicted with prior experience and rendered the response energetically suboptimal. The slow process was more consistent with the timing expected for direct optimization. Our interpretation of these results is that humans may rely heavily on pre-programmed gaits to rapidly select their preferred step frequency and then gradually fine-tune that selection with direct optimization.