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Radiation damage of structural materials leads to mechanical property degradation, eventually inducing failure. Secondary-phase dispersoids or other defect sinks are often added to materials to boost their radiation resistance. We demonstrate that a metal composite made by adding 1D carbon nanotubes (CNTs) to aluminum (Al) exhibits superior radiation resistance. In situ ion irradiation with transmission electron microscopy (TEM) and atomistic simulations together reveal the mechanisms of rapid defect migration to CNTs, facilitating defect recombination and enhancing radiation tolerance. The origin of this effect is an evolving stress gradient in the Al matrix resulting from CNT transformation under irradiation, and the stability of resulting carbides. Extreme value statistics of large defect behavior in our simulations highlight the role of CNTs in reducing accumulated damage. This approach to controlling defect migration represents a promising opportunity to enhance the radiation resistance of nuclear materials without detrimental effects. [ABSTRACT FROM AUTHOR]

Polyphenisms occur when phenotypic plasticity produces morphologically distinct phenotypes from the same genotype. Plasticity is maintained through fitness trade-offs which are conferred to different phenotypes under specific environmental contexts. Predicting the impacts of contemporary climate change on phenotypic plasticity is critical for climate-sensitive animals like amphibians, but elucidating the selective pressures maintaining polyphenisms requires a framework to control for all mechanistic drivers of plasticity. Using a 32-year dataset documenting the larval and adult histories of 717 Arizona tiger salamanders (Ambystoma mavortium nebulosum), we determined how annual variation in climate and density dependence explained the maintenance of two distinct morphs (terrestrial metamorph vs. aquatic paedomorph) in a high-elevation polyphenism. The effects of climate and conspecific density on morph development were evaluated with piecewise structural equation models (SEM) to tease apart the direct and indirect pathways by which these two mechanisms affect phenotypic plasticity. Climate had a direct effect on morph outcome whereby longer growing seasons favoured metamorphic outcomes. Also, climate had indirect effects on morph outcome as mediated through density-dependent effects, such as long overwintering coldspells corresponding to high cannibal densities and light snowpacks corresponding to high larval densities, both of which promoted paedomorphic outcomes. Both climate and density dependence serve as important proxies for growth and resource limitation, which are important underlying drivers of the phenotypic plasticity in animal polyphenisms. Our findings motivate new studies to determine how contemporary climate change will alter the selective pressures maintaining phenotypic plasticity and polyphenisms., (© 2024 The Author(s). Journal of Animal Ecology © 2024 British Ecological Society.)

Fitness trade-offs are a foundation of ecological and evolutionary theory because trade-offs can explain life history variation, phenotypic plasticity, and the existence of polyphenisms. Using a 32-year mark-recapture dataset on lifetime fitness for 1093 adult Arizona tiger salamanders (Ambystoma mavortium nebulosum) from a high elevation, polyphenic population, we evaluated the extent to which two life history morphs (aquatic paedomorphs vs. terrestrial metamorphs) exhibited fitness trade-offs in breeding and body condition with respect to environmental variation (e.g. climate) and internal state-based variables (e.g. age). Both morphs displayed a similar response to higher probabilities of breeding during years of high spring precipitation (i.e. not indicative of a morph-specific fitness trade-off). There were likely no climate-induced fitness trade-offs on breeding state for the two life history morphs because precipitation and water availability are vital to amphibian reproduction. Body condition displayed a contrasting response for the two morphs that was indicative of a climate-induced fitness trade-off. While metamorphs exhibited a positive relationship with summer snowpack conditions, paedomorphs were unaffected. Fitness trade-offs from summer snowpack are likely due to extended hydroperiods in temporary ponds, where metamorphs gain a fitness advantage during the summer growing season by exploiting resources that are unavailable to paeodomorphs. However, paedomorphs appear to have the overwintering fitness advantage because they consistently had higher body condition than metamorphs at the start of the summer growing season. Our results reveal that climate and habitat type (metamorphs as predominately terrestrial, paedomorphs as fully aquatic) interact to confer different advantages for each morph. These results advance our current understanding of fitness trade-offs in this well-studied polyphenic amphibian by integrating climate-based mechanisms. Our conclusions prompt future studies to explore how climatic variation can maintain polyphenisms and promote life history diversity, as well as the implications of climate change for polyphenisms., (© 2023 The Authors. Journal of Animal Ecology © 2023 British Ecological Society.)

Studies predicting how the distribution of aquatic organisms will shift with climate change often use projected increases in air temperature or water temperature. However, the assumed correlations between water temperature change and air temperature change can be problematic, especially for mountainous, high elevation streams. Using stream fish assemblage data from 1,442 surveys across a mountain-plains gradient (Wyoming, USA; 1990-2018), we compared the responsiveness of thermal guilds, native status groups, and assemblage structure to projected climate warming from generalized air temperature models and stream-specific water temperature models. Air temperature models consistently predicted greater range shift differences between warm-water and cold-water species, with air temperatures predicting greater increases in occurrence and greater range expansions for warm-water species. The "over-prediction" of warm-water species expansions resulted in air temperature models predicting higher rates of novel species combinations, greater increases in local species richness, and higher magnitudes of biotic homogenization compared with water temperature models. Despite differences in model predictions for warm-water species, both air and water temperature models predicted that three cold-water species would exhibit similar decreases in occurrence (decline of 1.0% and 1.8% of sites per 1°C warming, respectively) and similar range contractions (16.6 and 21.5 m elevation loss per 1°C warming, respectively). The "over-prediction" for warm-water species is partially attributable to water temperatures warming at slower rates than air temperatures because local, stream-scale factors (e.g., riparian cover, groundwater inputs) buffer high elevation streams from rising air temperatures. Our study provides the first comparison of how inferences about climate-induced biotic change at the species- and assemblage-levels differ when modeling with generalized air temperatures versus stream-specific water temperatures. We recommend that future studies use stream-specific water temperature models, especially for mountainous, high elevation streams, to avoid the "over-prediction" of biotic changes observed from air temperature variables., (© 2021 by the Ecological Society of America.)

Monitoring long-term changes in aquatic biodiversity requires the effective use of historical data that were collected with different methods and varying levels of effort. Aggregating data into different spatial scales can control for such differences and provide a robust framework for monitoring distribution trends. We used a quantitative, multi-scale assessment to evaluate the potential drivers of distribution change for 60 fish species at three spatial scales, using 503 unique sampling events conducted between 1931 and 2019 in a stream biodiversity hotspot (French Creek, Pennsylvania, U.S.A). Trends delineated at multiple scales demonstrated that only one cyprinid species consistently declined through time. In contrast, several species, particularly centrarchids (bass and sunfish), appeared to increase with time. However, evidence for species' increases varied among the different spatial scales, and our observations suggest that differences in effort and detection across time periods may contribute to patterns of species increases. There was agreement among scales that agricultural land use, non-native brown trout (Salmo trutta), and anthropogenic barriers did not explain patterns in biodiversity change from the distribution trends in this study. The lack of species declines is likely due to the limited levels of historical impacts in the watershed compared with other locations in the region that experienced more acute pollution bottlenecks. Species increases were most prevalent for sportfish and baitfish species, suggesting that distribution increases were human mediated. Similar multi-scale assessments should provide more robust insight into patterns of biodiversity loss and distribution changes by maximizing the use of historical data.

There is considerable variation among studies that evaluate how amphibian populations respond to global climate change. We used 23 years of annual survey data to test whether changes in climate have caused predictable shifts in the phenology and population characteristics of adult spotted salamanders (Ambystoma maculatum) during spring breeding migrations. Although we observed year-to-year correlation between seasonal climate variables and salamander population characteristics, there have not been long-term, directional shifts in phenological or population characteristics. Warm winters consistently resulted in early migration dates, but across the 23-year study, there was no overall shift towards warmer winters and thus no advanced migration timing. Warm summers and low variability in summer temperatures were correlated with large salamander body sizes, yet an overall shift towards increasing body sizes was not observed despite rising summer temperatures during the study. This was likely due to the absence of long-term changes of within-year variation in summer temperatures, which was a stronger determinant of body size than summer temperature alone. Climate-induced shifts in population characteristics were thus not observed for this species as long-term changes in important seasonal climate variables were not observed during the 23-years of the study. Different amphibian populations will likely be more resilient to climate change impacts than others, and the probability of amphibians exhibiting long-term population changes will depend on how seasonal climate change interacts with a species' life history, phenology, and geographic location. Linking a wide range of seasonal climatic conditions to species or population characteristics should thus improve our ability for explaining idiosyncratic responses of species to climate change., Competing Interests: The authors have declared that no competing interests exist.

A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes. In theory, therefore, continuous intraocular administration of a normal form of a soluble lysosomal enzyme should be able to cure the molecular defect in the retinas of subjects lacking this enzyme. Experiments were conducted to determine whether genetically modified bone marrow-derived stem cells implanted into the vitreous could be used as -vehicles for continuous delivery of such enzymes to the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice were implanted into the vitreous of mice undergoing retinal degeneration as a result of a mutation in the PPT1 gene. The implanted cells appeared to survive indefinitely in the vitreous without proliferating or invading the retina. This indicates that intravitreal implantation of MSCs is likely a safe means of long-term delivery of proteins synthesized by the implanted cells. Experiments have been initiated to test the efficacy of using genetically modified autologous MSCs to inhibit retinal degeneration in a canine model of neuronal ceroid lipofuscinosis.

Most approaches toward chemical and radiological/nuclear (CRN) incidents focus on the clinical skills of the first receiver. These skills are certainly important and are addressed throughout this article. Management skills are often overlooked. The following are basic competencies in information management for the emergency medicine physician to handle large-scale CRN incidents: planning information; incident management information; toxicant management; disposition/definitive care management; and recovery management. Information management and synthesis are crucial throughout the phases of the disaster cycle: planning, response, mitigation, and recovery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Drug-induced prolongation of the QT interval is frequently encountered after medication overdose. Such toxicity can result in degeneration to torsades de pointes (TdP) and require overdrive pacing. We present 3 cases in which intentional medication overdose resulted in QTc prolongation with subsequent degeneration to TdP. Despite appropriate care, including magnesium therapy, each case required overdrive pacing for resolution of TdP. Although rarely encountered, patients with drug-induced TdP can be successfully managed with overdrive pacing.

A central issue in stem cell biology is the determination of function and activity of differentiated stem cells, features that define the true phenotype of mature cell types. Commonly, physiological mechanisms are used to determine the functionality of mature cell types, including those of the nervous system. Calcium imaging provides an indirect method of determining the physiological activities of a mature cell. Camgaroos are variants of yellow fluorescent protein that act as intracellular calcium sensors in transfected cells. We expressed one version of the camgaroos, Camgaroo-2, in mouse embryonic stem (ES) cells under the control of the CAG promoter system. Under the control of this promoter, Camgaroo-2 fluorescence was ubiquitously expressed in all cell types derived from the ES cells that were tested. In response to pharmacological stimulation, the fluorescence levels in transfected cells correlated with cellular depolarization and hyperpolarization. These changes were observed in both undifferentiated ES cells as well as ES cells that had been neurally induced, including putative neurons that were differentiated from transfected ES cells. The results presented here indicate that Camgaroo-2 may be used like traditional fluorescent proteins to track cells as well as to study the functionality of stem cells and their progeny.

There is well-founded concern that a chemical or radioactive agent will at some point be used as a weapon of terror. There are several antidotes that, if used correctly in a timely fashion, can help lessen the harm caused by these agents. This article is meant to introduce the clinician to several such agents, along with the antidotes useful in the management of exposure to these. It covers the indications, administration, and precautions for using these antidotes.

An accident or a deliberate terrorism attack releasing hazardous chemicals will create chaos, confusion, and seeming unpredictability that complicates the emergency response. Clinicians are challenged to urgently treat patients needing care, even before a chemical is confirmed. Emergency response planning that focuses on preparing for predictable challenges to the health care system and applies basic toxicologic principles to clinical decision-making can bring a sense of order to the chaos and provide medical care that will be best for the most victims of an incident.

Atypical antipsychotics and newer antidepressants are commonly prescribed medications responsible for tens of thousands of adverse drug exposures each year. The emergency medicine physician should have a basic understanding of the pharmacology and toxicity of these agents. This knowledge is crucial to providing proper care and timely management of patients presenting with adverse drug effects from exposure to atypical antipsychotics and newer antidepressants.

The beta-thymosins have been known as actin-sequestering proteins, but now are recognized as molecules with multiple and diverse intracellular and extracellular functions. Two closely related proteins, beta-thymosin(His) and beta-thymosin(Gln), have been de novo sequenced by top-down mass spectrometry in the common neurobiology model, Aplysia californica. As determined by nanoelectrospray quadrupole-enhanced Fourier-Transform mass spectrometry with collisionally activated and electron-capture dissociations, both of these Aplysia beta-thymosins are acetylated and differ by a single residue in the central actin-binding domain. Profiling of individual cells and tissue by matrix-assisted laser desorption/ionization mass spectrometry reveals that these proteins are widely expressed in the Aplysia central nervous system, including in individual identified neurons, neuronal clusters, nerves and connective tissues. Newly identified beta-thymosin(His) and beta-thymosin(Gln) are also detected by mass spectrometry in hemolymph, and in releasates collected from whole ganglia. When applied exogenously, beta-thymosin proteins, purified from nerve cell extract, support the anchoring of neurons, and increase neurite sprouting and total neurite outgrowth in culture. These positive effects on neurite regeneration in cell culture suggest that the beta-thymosin proteins have an extracellular function in the central nervous system of Aplysia californica., (Copyright 2006 John Wiley & Sons, Ltd.)

Acetaminophen (acetyl-para-amino-phenol or APAP), an antipyretic and analgesic, is a common component in hundreds of over-the-counter and prescription medications. The wide usage of this drug results in many potentially toxic exposures. It is therefore critical for the clinician to be comfortable with the diagnosis and treatment of APAP toxicity. Prompt recognition of APAP overdose and institution of appropriate therapy are essential to preventing morbidity and mortality.

Embryonic stem (ES) cells differentiate into all cell types of the body during development, including those of the central nervous system (CNS). After transplantation, stem cells have the potential to replace host cells lost due to injury or disease or to supply host tissues with therapeutic factors and thus provide a functional benefit. In the current study, we assessed whether mouse neuralized ES cells can incorporate into retinal tissue and prevent retinal degeneration in mnd mice. These mice have an inherited lysosomal storage disease characterized by retinal and CNS degeneration. Sixteen weeks after intravitreal transplantation into adult mice, donor cells had incorporated into most layers of the retina, where they resembled retinal neurons in terms of morphology, location in the retina, and expression of cell type-specific marker proteins. Presence of these donor cells was correlated with a reduction in the sizes and numbers of lysosomal storage bodies in host retinal cells. The presence of transplanted donor cells was also accompanied by enhanced survival of host retinal neurons, particularly photoreceptors. These results demonstrate that neuralized ES cells protect host neurons from degeneration and appear to replace at least some types of lost neurons.

APAP is likely to remain a common toxic exposure and continue to cause significant morbidity and mortality. To minimize the harm to patients, it is necessary for the clinician to be aware of the current diagnostic and therapeutic management of APAP poisoning. Despite the bulk of literature on APAP, management strategies are likely to continue to change as more studies are conducted to improve our understanding of nonacute ingestions and the role of prognostic markers in defining those most at risk for life-threatening hepatotoxicity.

Perceived poisoning may manifest in numerous ways; however, all cases share certain characteristics. All are fostered by the wide availability of unreliable information about chemical safety, poor understanding of scientific principles, and ineffective risk communication. Although this problem is still incompletely understood, some approaches have been demonstrated to be useful, such as education about risk, appropriate reassurance, and empathy on the part of the practitioner. Successful management may curtail the spread or exacerbation of symptoms, whereas unsuccessful treatment may cause the problems to escalate, with detrimental effects on both society and patient.

Many systemic and eye-specific genetic disorders are accompanied by retinal degenerations that lead to blindness. In some of these diseases retinal degeneration occurs early in life and is quite rapid, whereas in other disorders, retinal degeneration starts later and progresses very slowly. At present, no therapies are available to patients for preventing or reversing the retinal degeneration that occurs in these diseases. Implantation of neural progenitor cells into the eye may be a means by which to retard or even reverse degeneration of the retina. To evaluate the potential of neural precursor cell implantation for treating retinal degenerative disorders, neuralized mouse embryonic stem cells from green fluorescent protein (GFP) transgenic mice were administered intravitreally to normal mice, mice with early retinal degeneration, and mice with slowly progressing retinal degeneration. In normal mice, the donor cells remained in the vitreous cavity and did not associate with the host retina. In mice with early retinal degeneration, implantation of the neural precursors was performed after the degeneration was almost complete. In these animals, the donor cells primarily associated closely with the inner surface of the retina, although a small fraction of donor cells did integrate into the host retina. Donor cells implanted in mice with slowly progressing retinal degeneration also associated with the inner retinal surface, but many more of the cells integrated into the retina. These findings indicate the importance of host tissue-donor cell interactions in determining the fate of implanted neural precursor cells. These interactions will be a major consideration when devising strategies for using cell implantation therapies for neurodegenerative disorders.

Study Objective: We conduct a study to determine the rate of adverse events (anaphylactoid and cardiorespiratory) associated with the use of oral N-acetylcysteine by the intravenous route for the treatment of suspected acetaminophen poisoning and to examine specific variables that may be associated with adverse events., Methods: We conducted a retrospective medical record review with explicit criteria. All patients who received oral N-acetylcysteine by the intravenous route from September 1995 to September 2001 were included. Patients were identified by cross-matching 3 databases. Adverse events were divided into categories of cutaneous, systemic, or life threatening. Five reviewers abstracted charts by using a standardized data collection form. Interrater reliability was calculated by using 24 medical records abstracted by all 5 reviewers., Results: There were 7 adverse events identified in 187 patients (3.7%; 95% confidence interval 1.0% to 6.5%). Six adverse events were cutaneous and responded rapidly to antihistamines. One adverse event was life threatening but not clearly related to N-acetylcysteine. A high rate of antihistamine exposure (53%) was identified before the administration of N-acetylcysteine. Interrater agreement was higher than 95%., Conclusion: Intravenous administration of an oral solution of N-acetylcysteine is associated with a low rate of adverse events and should be considered for selected patients with suspected acetaminophen poisoning.

Study Objective: Droperidol is a butyrophenone commonly used as an antiemetic and antipsychotic in the United States since US Food and Drug Administration (FDA) approval in 1970. Its labeling has recently been revised, with a black box warning for cases of QT prolongation leading to torsades de pointes and death. A black box warning is applied when serious adverse drug reactions are uncovered for medications. We sought to examine the evidence of a causal association suggested by the black box warning to aid clinicians in their risk-benefit analyses regarding further use of droperidol., Methods: A literature search was undertaken to determine the evidence regarding the association between droperidol and QT prolongation or torsades de pointes. The evidence was then evaluated by using evidence-based medicine principles. In addition, a review of the FDA regulatory process is presented., Results: Three clinical studies, 1 published abstract, and 7 case reports were reviewed. Available postmarketing surveillance data (MedWatch reports) were also reviewed. Applying the criteria of evidence-based medicine and Hill's criteria, the evidence is not convincing for a causal relationship between therapeutic droperidol administration and life-threatening cardiac events., Conclusion: The recent black box warning appears to have originated from postmarketing surveillance data rather than data reported in the peer-reviewed medical literature. Ongoing monitoring of drug safety and more definitive study appear appropriate.

Background and Purpose: Hyperbaric oxygen therapy (HBO) has promise as a treatment for acute stroke. This study was conducted to evaluate the efficacy, safety, and feasibility of using HBO in acute ischemic stroke., Methods: We conducted a randomized, prospective, double-blind, sham-controlled pilot study of 33 patients presenting with acute ischemic stroke who did not receive thrombolytics over a 24-month period. Patients were randomized to treatment for 60 minutes in a monoplace hyperbaric chamber pressurized with 100% O2 to 2.5-atm absolute (ATA) in the HBO group or 1.14 ATA in the sham group. Primary outcomes measured included percentage of patients with improvement at 24 hours (National Institutes of Health Stroke Scale [NIHSS]) and 90 days (NIHSS, Barthel Index, modified Rankin Scale, Glasgow Outcome Scale). Secondary measurements included complications of treatment and mortality at 90 days., Results: Baseline demographics were similar in both groups. There were no differences between the groups at 24 hours (P=0.44). At 3 months, however, a larger percentage of the sham patients had a good outcome defined by their stroke scores compared with the HBO group (NIHSS, 80% versus 31.3%; P=0.04; Barthel Index, 81.8% versus 50%; P=0.12; modified Rankin Scale, 81.8% versus 31.3%; P=0.02; Glasgow Outcome Scale, 90.9% versus 37.5%; P=0.01) with loss of statistical significance in a intent-to-treat analysis., Conclusions: Although our HBO protocol appears feasible and safe, it does not appear to be beneficial and may be harmful in patients with acute ischemic stroke.