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Plastic pollution in the oceans is a priority environmental issue. The recent increase in research on the topic, coupled with growing public awareness, has catalyzed policymakers around the world to identify and implement solutions that minimize the harm caused by plastic pollution. To aid and coordinate these efforts, we surveyed experts with scientific experience identified through their peer-reviewed publications. We asked experts about the most pressing research questions relating to how biota interact with plastic pollution that in turn can inform policy decisions and research agendas to best contribute to understanding and reducing the harm of plastic pollution to biota. We used a modified Horizon Scan method that first used a subgroup of experts to generate 46 research questions on aquatic biota and plastics, and then conducted an online survey of researchers globally to prioritize questions in terms of their importance to inform policy development. One hundred and fifteen experts from 29 countries ranked research questions in six themes. The questions were ranked by urgency, indicating which research should be addressed immediately, which can be addressed later, and which are of limited relevance to inform action on plastics as an environmental pollutant. We found that questions relating to the following four themes were the most commonly top-ranked research priorities: (i) sources, circulation and distribution of plastics, (ii) type of harm from plastics, (iii) detection of ingested plastics and the associated problems, and (iv) related economies and policy to ingested plastics. While there are many research questions on the topic of impacts of plastic pollution on biota that could be funded and investigated, our results focus collective priorities in terms of research that experts believe will inform effective policy and on-the-ground conservation.

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Caribou (Rangifer tarandus) are a culturally significant food resource for communities in northern Canada and Greenland. Many barren-ground caribou subpopulations are currently in decline, some dramatically; understanding the influence of stressors, such as toxic trace metals, is important. These contaminants enter Arctic terrestrial environments via atmospheric transport from industrialized areas and from local sources, accumulating there in the environment. Understanding how trace element concentrations interact and are influenced by caribou sex, age and season of collection is essential to evaluating trends in these elements over time and differences among subpopulations. We used path analysis to model the direct and indirect relationships between these variables in the Porcupine subpopulation and in barren-ground caribou from the Canadian Arctic and Greenland. Renal cadmium (Cd), copper (Cu) and mercury (Hg) varied significantly among subpopulations. Hg was positively correlated with Cd, Cu and selenium (Se) in female Porcupine caribou whereas Cd and Cu were negatively correlated in male Porcupine caribou. Age, season and sex influenced all three element concentrations and should be considered when comparing elements among caribou subpopulations or years. Renal Cd decreased slightly from the Canadian Western Arctic to Greenland and increased slightly over time, possibly reflecting patterns of atmospheric deposition. Renal Hg did not change significantly over time, and differences among subpopulations did not follow specific geographical patterns. Renal Cu declined over time, the changes being markedly different among subpopulations, sexes and seasons. This temporal decline is likely due to changes in diet, which could be driven by various environmental factors. Declining Cu concentrations in caribou is of concern as low levels could negatively affect reproductive success and therefore caribou at a population level. Continuing to monitor element concentrations in caribou is essential to better comprehend potential threats facing the species, and to promote food security in communities harvesting this important resource.

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Understanding the impacts of plastic pollution is a global research priority. Previous research has shown that plasticizers such as phthalate esters detected in seabird tissues can be useful non-lethal biochemical markers of plastic ingestion as compared with more standard necropsy techniques. We examined the concentrations of six phthalate esters in the preen oil of Northern Fulmars (Fulmarus glacialis) in relation to their retained plastics. Contrary to a previous study, we found that the phthalates examined were not analytically detectable in fulmar preen oil. Given that the birds we examined had up to 100 pieces of plastics in their stomachs, and all uropygial glands were completely emptied during the necropsies, it does not appear that measuring phthalates in preen oil of Northern Fulmars is a useful, non-lethal technique to determine if individuals ingest plastics, at least not currently given the available commercial analytical detection limits.

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Field experiments where parasites are removed through treatment and contaminant levels in host tissues are recorded can provide insight into the combined effects of parasitism and contaminants in wild populations. In 2013 and 2014, we treated northern common eider ducks (Somateria mollissima) arriving at a breeding colony with either a broad-spectrum antihelminthic (PANACUR®) or distilled water, and measured their blood lead (Pb) levels. Breeding propensity and clutch sizes were inversely related to Pb in both treatment groups. In comparison, a negative effect of Pb on resight probability the following year was observed only in the anti-parasitic treatment (APT) group. These contrasting patterns suggest a long-term benefit to survival of intestinal parasitism in eiders experiencing Pb exposure. The arrival date of hens explained some, but not all, of the effects of Pb. We weigh the merits of different hypotheses in explaining our results, including protective bioaccumulation of Pb by parasites, condition-linked thresholds to costly reproduction and the direct effects of APT on eider health. We conclude that variation in helminth parasitism influences survival in this migratory bird in counterintuitive ways.

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While marine animals are exposed to environmental contaminants via their prey, because plastic pollution in the aquatic environment can concentrate some chemicals, ingested plastics are thought to increase the exposure of biota to contaminants. Currently, in the literature there are contradictory results relating to how higher levels of ingested plastics by birds may lead to higher levels of polychlorinated biphenyl (PCBs). To date none of these have incorporated known Toxic Equivalency Factors (TEFs) for non-ortho and mono-ortho congeners of PCB which is critical to assessing the potential effects from PCBs. We examined northern fulmars (Fulmarus glacialis) from the Labrador Sea region Canada, and the ingested plastics from these same birds for comparative PCB concentrations. We found no significant correlations between the PCB concentrations in the birds and the mass or number of retained ingested plastic pieces in the stomach, this held true when PCBs were considered by a number of different ways, including ∑4PCB, ∑PCB, lower-chlorinated, high-chlorinated, non-ortho PCB, and mono-ortho congeners. PCB concentrations were lower in plastics as compared with livers. We found significant differences in congener profiles between the ingested plastics and seabird livers suggesting that while plastics do not contribute to the PCB concentrations, there may be some interactions between plastics and the chemicals that the birds are exposed to via ingested plastics.

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Plastic debris is recognized as a widespread, common and problematic environmental pollutant. An important consequence of this pollution is the ingestion of plastic debris by wildlife. Assessing the degree to which different species ingest plastics, and the potential effects of these plastics on their health are important research needs for understanding the impacts of plastic pollution. We examined debris (plastic and other types) ingestion in three sympatric overwintering gull species (Herring gulls Larus smithsonianus, Great Black-backed Gulls Larus marinus, and Iceland Gulls Larus glaucoides) to understand how debris ingestion differs among species, age classes and sexes in gulls. We also assessed how plastic burdens were associated with body condition to investigate how gulls may be affected by debris ingestion. There were no differences among the species, age classes or sexes in the incidence of debris ingestion (plastic or otherwise), the mass or number of debris pieces ingested. We found no correlation between ingested plastics burdens and individual condition. Gulls ingested plastic debris, but also showed high levels of other debris types as well, including metal, glass and building materials, including a metal piece of debris found within an abscess in the stomach. Thus, when the health effects of debris ingestion on gulls, and other species that ingest debris, is of interest, either from a physical or chemical perspective, it may be necessary to consider all debris types and not just plastic burdens as is often currently done for seabirds.

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Plastic pollution is global environmental contaminant. Plastic particulates break down into smaller fragments in the environment, and these small pieces are now commonly found to be ingested by animals. To date, most plastic ingestion studies have focused on assessing retained plastics or regurgitated plastics, but it is likely that animals also excrete plastic and other debris items. We examined the terminal portion of the gastrointestinal tract of a seabird known to commonly ingest plastics, the Northern Fulmar (Fulmarus glacialis), to determine if seabirds excrete microplastics and other debris via their guano. We also examine how guano collections may be used as an indicator of retained plastics. The frequency of occurrence of microplastics did not correlate between the gut and faecal precursor samples, but there was a positive relationship between the number of pieces of plastics in the gut and the number of microplastics in the guano. Our findings suggest that seabirds are acting as vectors of microplastics and debris in the marine environment where their guano accumulates around their colonies. This transport of microplastics and debris by colonial seabirds needs to be further examined, and considered when designing environmental monitoring for microplastics in regions where seabird colonies are found.

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Arctic wildlife can be exposed to high mercury (Hg) levels, and are also naturally exposed to gastrointestinal parasites that can reduce condition and negatively affect reproductive output and/or survival in similar ways. Importantly, both Hg and parasites are increasing in wildlife in some Arctic regions. We studied the northern common eider duck (Somateria mollissima) to explore how Hg in association with both natural levels and experimentally reduced parasitic infections, affect reproduction and survival. Female eiders were measured, banded, and blood sampled to determine blood Hg burdens, prior to breeding. Propensity to nest, clutch size, nest survival, nest attendance, and return rates were assessed in relation to both Hg burden and parasite treatment. Neither reproduction nor return rates of females varied with Hg concentrations, but females arriving late to the colony, or in low body condition, showed increased nesting propensity when given the anti-parasite treatment as compared to placebo treatment. Our results suggest that parasites can play a critical role in decisions to invest in avian breeding annually, particularly among individuals with a late onset to breeding, and in poor condition.

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Although physiological traits and phenology are thought to be evolved traits, they often show marked variation within populations, which may be related to extrinsic factors. For example, trace elements such as mercury (Hg) and lead (Pb) alter biochemical processes within wildlife that may affect migration and breeding. While there is a growing understanding of how contaminants may influence wildlife physiology, studies addressing these interactions in free-living species are still limited. We examined how four non-essential trace elements (cadmium, Hg, Pb and selenium) interacted with physiological and breeding measures known to influence breeding in a free-living population of common eider ducks (Somateria mollissima). We collected blood from female eiders as they arrived at a breeding colony in northern Canada. Blood was subsequently assessed for baseline corticosterone (CORT), immunoglobulin Y (IgY), and the four trace elements. We used model selection to identify which elements varied most with CORT, IgY, arrival condition, and arrival timing. We then used path analysis to assess how the top two elements from the model selection process (Hg and Pb) varied with metrics known to influence reproduction. We found that arrival date, blood Hg, CORT, and IgY showed significant inter-annual variation. While blood Pb concentrations were low, blood Pb levels significantly increased with later arrival date of the birds, and varied negatively with eider body condition, suggesting that even at low blood concentrations, Pb may be related to lower investment in reproduction in eiders. In contrast, blood Hg concentrations were positively correlated with eider body condition, indicating that fatter birds also had higher Hg burdens. Overall, our results suggest that although blood Hg and Pb concentrations were below no-effect levels, these low level concentrations of known toxic metals show significant relationships with breeding onset and condition in female eider ducks, factors that could influence reproductive success in this species.

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In many animal species, males and females differ in their levels of contaminants and/or parasitic infections. Most contaminants and gastro-intestinal parasites are obtained through prey ingestion, and thus the causes of sex differences in the distribution of these factors might follow similar pathways. We studied the northern common eider duck (Somateria molissima borealis) as an avian model, and used directed separation path analysis to explore the causes of sex differences in mercury (Hg) and gastro-intestinal helminths. Two trophically transmitted helminths were examined: a cestode (Lateriporus sp.) and an acanthocephalan (Polymorphus sp). We found that the number of Lateriporus sp. varied positively with stable isotope signature (as indicated by δ(15)N in eider breast muscle tissue), and negatively with crustaceans being present in the short term diet. We also found that Polymorphus sp. varied positively with eider tissue stable isotope signature. However, Polymorphus sp. varied negatively with sex indirectly through condition and liver mass. Similarly, Hg concentrations also varied negatively with sex indirectly through condition and liver mass, with both Polymorphus sp. intensity and Hg concentrations significantly higher in males. We found that model fit increased when a negative relationship between the two helminth species was included, suggesting a yet unknown causal mechanism linking these parasites. Our findings suggest that although Hg and gastro-intestinal parasites are both trophically transmitted through the eider's prey items, the factors that contribute towards bioaccumulation of these two burdens differ in source, likely caused by several different factors and may potentially influence each other.

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Plastic is a common item in marine environments. Studies assessing seabird ingestion of plastics have focused on species that ingest plastics mistaken for prey items. Few studies have examined a scavenger and predatory species that are likely to ingest plastics indirectly through their prey items, such as the great skua (Stercorarius skua). We examined 1034 regurgitated pellets from a great skua colony in the Faroe Islands for plastics and found approximately 6% contained plastics. Pellets containing remains of Northern fulmars (Fulmarus glacialis) had the highest prevalence of plastic. Our findings support previous work showing that Northern fulmars have higher loads of plastics than other sympatric species. This study demonstrates that marine plastic debris is transferred from surface feeding seabird species to predatory great skuas. Examination of plastic ingestion in species that do not ingest plastics directly can provide insights into how plastic particles transfer vertically within the food web.

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Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a "hyper-cholinergic" state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.

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CONTEXT: Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. OBJECTIVE: To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. METHODS: Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. RESULTS: The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5-2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. CONCLUSIONS: The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.

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Baseline data on trace element concentrations are lacking for many species of Arctic marine birds. We measured essential and non-essential element concentrations in Arctic tern (Sterna paradisaea) liver tissue and brain tissue (mercury only) from Canada's High Arctic, and recorded the presence/absence of gastrointestinal parasites during four different phases of the breeding season. Arctic terns from northern Canada had similar trace element concentrations to other seabird species feeding at the same trophic level in the same region. Concentrations of bismuth, selenium, lead and mercury in Arctic terns were high compared to published threshold values for birds. Selenium and mercury concentrations were also higher in Arctic terns from northern Canada than bird species sampled in other Arctic areas. Selenium, mercury and arsenic concentrations varied across the time periods examined, suggesting potential regional differences in the exposure of biota to these elements. For unknown reasons, selenium concentrations were significantly higher in birds with gastrointestinal parasites as compared to those without parasites, while bismuth concentrations were higher in Arctic terns not infected with gastrointestinal parasites.

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In addition to monitoring trends in plastic pollution, multi-species surveys are needed to fully understand the pervasiveness of plastic ingestion. We examined the stomach contents of 20 bird species collected from the coastal waters of the eastern North Pacific, a region known to have high levels of plastic pollution. We observed no evidence of plastic ingestion in Rhinoceros Auklet, Marbled Murrelet, Ancient Murrelet or Pigeon Guillemot, and low levels in Common Murre (2.7% incidence rate). Small sample sizes limit our ability to draw conclusions about population level trends for the remaining fifteen species, though evidence of plastic ingestion was found in Glaucous-Winged Gull and Sooty Shearwater. Documenting levels of plastic ingestion in a wide array of species is necessary to gain a comprehensive understanding about the impacts of plastic pollution. We propose that those working with bird carcasses follow standard protocols to assess the levels of plastic ingestion whenever possible.

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We have shown that the epidural (EPI) delivery of morphine encapsulated in multivesicular liposomes (DepoFoam drug delivery system) produces a sustained clearance of morphine and a prolonged analgesia. We have sought to subsequently determine the likelihood of deleterious effects on local tissue of repetitive epidural injections of this encapsulated morphine preparation (C0401). Beagle dogs were prepared according to protocol approved by the Institutional Animal Care and Use Committee under volatile general anesthesia with chronic lumbar EPI catheters and subcutaneous injection ports. Male and female dogs (three groups) received a total of 4 EPI injections at 8-day intervals of 3 mL of C0401 (10 mg/mL morphine) (N = 6), DepoFoam vehicle (N = 6), or 0.9% sodium chloride (N = 6). Following EPI-C0401, but not saline or DepoFoam vehicle, there were transient (< 72 hr) decreases in food consumption, arousal, hindlimb muscle tone, and body temperature. Heart rate was unaltered, but there were modest decreases in blood pressure and respiratory rate, which persisted for 24-72 hr after C0401. No persistent changes in sensory/motor function, body weight, or stool/urine production were observed. Cerebrospinal fluid, blood chemistry, and urinalysis performed at surgery and on the day of sacrifice (24 hr after the last dose) were within normal ranges. Gross pathology at necropsy was unremarkable. Spinal histopathology findings were judged to be minimal (e.g., modest pericatheter inflammation and fibrosis) and present in all dogs. However, a statistical trend in the rank order of pathology scores was noted (Saline < DepoFoam vehicle < C0401). Repeated EPI injection of C0401 at the maximum dose that could be administered (30 mg) resulted in moderate, transient behavioral and physiological effects after each injection, consistent with morphine administration, and a modest effect on cord histopathology. This level of pathology is reflected in the lack of change observed in cerebrospinal fluid and lack of neurological findings. These results suggest that C0401 is without significant pathological effects at this dose after repeated epidural delivery in dogs.

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Traumatic lesions of the spinal cord yield a loss of supraspinal control of voluntary locomotor activity, although the spinal cord contains the necessary circuitry to generate the basic locomotor pattern. In spinal rats, this network, known as central pattern generator (CPG), was shown to be sensitive to serotonergic pharmacological stimulation. In previous works we have shown that embryonic raphe cells transplanted into the sublesional cord of adult rats can reinnervate specific targets, restore the lesion-induced increase in receptor densities of neurotransmitters, promote hindlimb weight support, and trigger a locomotor activity on a treadmill without any other pharmacological treatment or training. With the aim of discriminating whether the action of serotonin on CPG is associated to a specific level of the cord, we have transplanted embryonic raphe cells at two different levels of the sublesional cord (T9 and T11) and then performed analysis of the kinematic and EMG activity synchronously recorded during locomotion. Locomotor performances were correlated to the reinnervated level of the cord and compared to that of intact and transected nontransplanted animals. The movements expressed by T11 transplanted animals correspond to a well defined locomotor pattern comparable to that of the intact animals. On the contrary, T9 transplanted animals developed limited and disorganized movements as those of nontransplanted animals. The correlation of the locomotor performances with the level of reinnervation of the spinal cord suggests that serotonergic reinnervation of the L1-L2 level constitutes a key element in the genesis of this locomotor rhythmic activity. This is the first in vivo demonstration that transplanted embryonic raphe cells reinnervating a specific level of the cord activate a locomotor behavior.

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BACKGROUND: Intrathecally administered adenosine receptor agonists have antinociceptive effects in animals, suggesting that intrathecal adenosine might provide analgesia in humans. The authors performed preclinical neurotoxicity studies to define the safety of intrathecally administered adenosine in rats and dogs. METHODS: Eighteen rats with long-term intrathecal catheters received daily injections of saline or 100 microg adenosine for 4 days and were observed for general behavior and thermal nociception before being killed on day 6. Nine beagle dogs were prepared with long-term, lumbar intrathecal catheters and infused continuously with saline or adenosine, 2.4 mg/day for 48 h, then 7.2 mg/day for 26 days. Animals were then anesthetized and perfused with preservative and their spinal cords were examined systematically. RESULTS: No disturbances in neurologic function were detected in either animal species. intrathecal adenosine caused transient sedation in rats and increased muscle tone in dogs, resolving with continued exposure to drug. Neither adenosine-nor saline-treated rats or dogs showed acute thermal analgesia. Adenosine groups did not differ from saline groups regarding histopathology, although a moderate fibrotic and inflammatory reaction was noted in both, and protein concentrations in cerebrospinal fluid were increased in both. CONCLUSION: The current study in rats and dogs failed to provide behavioral or histologic evidence of neurotoxicity from intrathecal administration of adenosine. This provides evidence for the presumption of safety of adenosine in this dose range, and supports phase I safety trials of acute intrathecal adenosine administration in humans.

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