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Summary: Background: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 [–0·32 percentage points, −0·59 to −0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26–53]), but consistently high with CamAPS FX (93% [88–96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.

Background: Cystic fibrosis (CF) is a chronic, life-limiting disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene leading to abnormal airway surface ion transport, chronic lung infections, inflammation and eventual respiratory failure. With the exception of the small-molecule potentiator, ivacaftor (Kalydeco®, Vertex Pharmaceuticals, Boston, MA, USA), which is suitable for a small proportion of patients, there are no licensed therapies targeting the basic defect. The UK Cystic Fibrosis Gene Therapy Consortium has taken a cationic lipid-mediated CFTR gene therapy formulation through preclinical and clinical development. Objective: To determine clinical efficacy of the formulation delivered to the airways over a period of 1 year in patients with CF. Design: This was a randomised, double-blind, placebo-controlled Phase IIb trial of the CFTR gene–liposome complex pGM169/GL67A. Randomisation was performed via InForm™ version 4.6 (Phase Forward Incorporated, Oracle, CA, USA) and was 1 : 1, except for patients in the mechanistic subgroups (2 : 1). Allocation was blinded by masking nebuliser chambers. Settings: Data were collected in the clinical and scientific sites and entered onto a trial-specific InForm, version 4.6 database. Participants: Patients with CF aged ≥ 12 years with forced expiratory volume in the first second (FEV1) between 50% and 90% predicted and any combination of CFTR mutations. The per-protocol group (≥ 9 doses) consisted of 54 patients receiving placebo (62 randomised) and 62 patients receiving gene therapy (78 randomised). Interventions: Subjects received 5 ml of nebulised pGM169/G67A (active) or 0.9% saline (placebo) at 28 (±5)-day intervals over 1 year. Main outcome measures: The primary end point was the relative change in percentage predicted FEV1 over the 12-month period. A number of secondary clinical outcomes were assessed alongside safety measures: other spirometric values; lung clearance index (LCI) assessed by multibreath washout; structural disease on computed tomography (CT) scan; the Cystic Fibrosis Questionnaire – Revised (CFQ-R), a validated quality-of-life questionnaire; exercise capacity and monitoring; systemic and sputum inflammatory markers; and adverse events (AEs). A mechanistic study was performed in a subgroup in whom transgene deoxyribonucleic acid (DNA) and messenger ribonucleic acid (mRNA) was measured alongside nasal and lower airway potential difference. Results: There was a significant (p = 0.046) treatment effect (TE) of 3.7% [95% confidence interval (CI) 0.1% to 7.3%] in the primary end point at 12 months and in secondary end points, including forced vital capacity (FVC) (p = 0.031) and CT gas trapping (p = 0.048). Other outcomes, although not reaching statistical significance, favoured active treatment. Effects were noted by 1 month and were irrespective of sex, age or CFTR mutation class. Subjects with a more severe baseline FEV1 had a FEV1 TE of 6.4% (95% CI 0.8% to 12.1%) and greater changes in many other secondary outcomes. However, the more mildly affected group also demonstrated benefits, particularly in small airway disease markers such as LCI. The active group showed a significantly (p = 0.032) greater bronchial chloride secretory response. No difference in treatment-attributable AEs was seen between the placebo and active groups. Conclusions: Monthly application of the pGM169/GL67A gene therapy formulation was associated with an improvement in lung function, other clinically relevant parameters and bronchial CFTR function, compared with placebo. Limitations: Although encouraging, the improvement in FEV1 was modest and was not accompanied by detectable improvement in patients’ quality of life. Future work: Future work will focus on attempts to increase efficacy by increasing dose or frequency, the coadministration of a CFTR potentiator, or the use of modified viral vectors capable of repeated administration. Trial registration: ClinicalTrials.gov NCT01621867. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research partnership.

Large predators frequent the open ocean where subsurface light drives visually based trophic interactions. However, we lack knowledge on how predators achieve energy balance in the unproductive open ocean where prey biomass is minimal in well-lit surface waters but high in dim midwaters in the form of scattering layers. We use an interdisciplinary approach to assess how the bioenergetics of scattering layer forays by a model predator vary across biomes. We show that the mean metabolic cost rate of daytime deep foraging dives to scattering layers decreases as much as 26% from coastal to pelagic biomes. The more favorable energetics offshore are enabled by the addition of a shallow scattering layer that, if not present, would otherwise necessitate costlier dives to deeper layers. The unprecedented importance of this shallow scattering layer challenges assumptions that the globally ubiquitous primary deep scattering layer constitutes the only mesopelagic resource regularly targeted by apex predators.

Understanding biological and environmental factors that influence movement behaviors and population connectivity of highly migratory fishes is essential for cooperative international management and conservation of exploited populations, like bluefin tuna. Pacific bluefin tuna Thunnus orientalis (PBT) spawn in the western Pacific Ocean and then juveniles disperse to foraging grounds across the North Pacific. Several techniques have been used to characterize the distribution and movement of PBT, but few methods can provide complete records across ontogeny from larvae to adult in individual fish. Here, otolith biominerals of large PBT collected from the western, eastern, and south Pacific Ocean, were analyzed for a suite of trace elements across calcified/proteinaceous growth zones to investigate patterns across ontogeny. Three element:Ca ratios, Li:Ca, Mg:Ca, and Mn:Ca displayed enrichment in the otolith core, then decreased to low stable levels after age 1-2 years. Thermal and metabolic physiologies, common diets, or ambient water chemistry likely influenced otolith crystallization, protein content, and elemental incorporation in early life. Although similar patterns were also exhibited for otolith Sr:Ca, Ba:Ca and Zn:Ca in the first year, variability in these elements differed significantly after age-2 and in the otolith edges by capture region, suggesting ocean-specific environmental factors or growth-related physiologies affected otolith mineralization across ontogeny., Competing Interests: The authors have declared that no competing interests exist.

Pacific bluefin tuna, Thunnus orientalis, migrates from spawning grounds in the western Pacific Ocean to foraging grounds in the California Current System (CCS), where they are thought to specialize on high energy, surface schooling prey. However, there has been substantial variability in estimates of forage availability in the CCS over the past two decades. To examine the foraging ecology of juvenile T. orientalis in the face this variability, we quantified the diet and prey energetics of 963 individuals collected in the Southern California Bight (SCB) from 2008 to 2016. Using classification and regression tree analysis, we observed three sampling periods characterized by distinct prey. In 2008, T. orientalis diet was dominated by midwater lanternfishes and enoploteuthid squids. During 2009-2014, T. orientalis consumed diverse fishes, cephalopods, and crustaceans. Only in 2015-2016 did T. orientalis specialize on relatively high energy, surface schooling prey (e.g. anchovy, pelagic red crab). Despite containing the smallest prey, stomachs collected in 2009-2014 had the highest number of prey and similar total energetic contents to stomachs collected in 2015-2016. We demonstrate that T. orientalis is an opportunistic predator that can exhibit distinct foraging behaviors to exploit diverse forage. Expanding our understanding of T. orientalis foraging ecology will improve our ability to predict its responses to changes in resource availability as well as potential impacts on the fisheries it supports., Competing Interests: The authors have declared that no competing interests exist.

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements.

Despite their broad distribution across the North Pacific Ocean, the only known spawning grounds for Pacific Bluefin Tuna (Thunnus orientalis) are around coastal Japan and the East China Sea. However, an increase in the prevalence of large bluefin tuna up to 10 years old in the California Current System during exceptionally warm ocean conditions has led to speculation that they may be spawning in this region. To investigate this possibility, we collected samples from 36 females (estimated 3-8 years old) between 2015 and 2019. Histological analyses revealed no signs of imminent, active, or recent spawning. Further examination of historical ichthyoplankton collections showed no records of larval bluefin tuna, but confirmed the presence of the larvae of other tuna species in waters > 24°C. Fishery-dependent records showed that bluefin tuna are rarely recorded in purse seine catches where surface temperatures exceed 23°C. Our study, therefore, provided no evidence of bluefin tuna reproduction in the CCS. However, more comprehensive sampling, in particular off southern Baja California, may be required to confirm the absence of spawning., Competing Interests: The authors have declared that no competing interests exist.

Element:Ca ratios in the otolith cores of young-of-the-year (YOY) swordfish, Xiphias gladius, were used as natural tracers to predict the nursery origin of subadult and adult swordfish from three foraging grounds in the North Pacific Ocean (NPO). First, the chemistry of otolith cores (proxy for nursery origin) was used to develop nursery-specific elemental signatures in YOY swordfish. Sagittal otoliths of YOY swordfish were collected from four regional nurseries in the NPO between 2000 and 2005: (1) Central Equatorial North Pacific Ocean (CENPO), (2) Central North Pacific Ocean (CNPO), (3) Eastern Equatorial North Pacific Ocean (EENPO) and (4) Western North Pacific Ocean (WNPO). Calcium ( 43 Ca), magnesium ( 24 Mg), strontium ( 88 Sr) and barium ( 138 Ba) were quantified in the otolith cores of YOY swordfish using laser ablation inductively coupled plasma mass spectrometry. Univariate tests indicated that three element:Ca ratios (Mg:Ca, Sr:Ca and Ba:Ca) were significantly different among nurseries. Overall classification success of YOY swordfish to their nursery of collection was 72% based on quadratic discriminant analysis. Next, element:Ca ratios in the otolith cores of subadults and adults collected from three foraging grounds where targeted fisheries exist (Hawaii, California and Mexico) were examined to calculate nursery-specific contribution estimates. Mixed-stock analysis indicated that the CENPO nursery contributed the majority of individuals to all three foraging grounds (Hawaii 45.6 ± 13.2%, California 84.6 ± 10.8% and Mexico 64.5 ± 15.9%). The results from this study highlight the importance of the CENPO nursery and provide researchers and fisheries managers with new information on the connectivity of the swordfish population in the NPO., (© 2021 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)

Background & Aims: Nutritional assessment in paediatric inflammatory bowel disease (IBD) is key to supporting growth whilst minimising adiposity. Bedside assessment using bioelectrical impedance spectroscopy (BIS) has previous identified patients with declining cellular and nutritional health. We aimed to assess BIS measures in stable paediatric IBD patient., Methods: Stable IBD patients were recruited at routine hospital visits. All patients underwent BIS, anthropometry and disease activity assessment. Multivariable regression and receiver operator curve (ROC) analyses were undertaken to assess the utility of BIS phase angle 50 KHz (PA-50) and 200/5 KHz impedance ratio (IR) in nutritional assessment., Results: There were 140 study visits from 97 patients, mean age 14.49 years, 62.9% Crohn's disease. Mean BMI Z-score (BMIZ) was 0.31 (range -2.97 to 3.99), 33% of patients were overweight (BMIZ>1) and 13.8% of patients were underweight (BMIZ < -1). Crohn's disease patients had a lower mean BMIZ score 0.14, compared to ulcerative colitis, 0.68, p = 0.007. There was no relationship between PA-50 and BMIZ or disease activity. IR was not related to disease activity but was negatively related to BMIZ in a multivariable regression, accounting for age, sex and disease subtype (beta -0.331, p = 0.001). ROC analyses did not identify a clinically useful cut off for either PA-50 or IR to identify patients with active disease, biologic use or BMIZ>1 or < -1., Conclusion: BIS appears to have limited added value in nutritional assessment of stable paediatric IBD patients. Nearly 1/3 patients were overweight and personalised approach to supplementation is vital to avoid overnutrition., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate the positional mean peak running periods during a field hockey match using a moving average method. The secondary aim was to investigate how the peak periods changed between quarters and playing positions. The moving average method was used to analyse the data because of the nature of field hockey, which has natural fluctuations of high and low intensity periods of play. The time periods included periods from 1 to 10 minutes. The level of significance for results was set at p ≤ 0.05. The study found that forwards had a peak running intensity of 194 ± 24.2 m·min -1 , midfielders 189 ± 11.9 m·min -1 , and defenders 182.6 ± 17.9 m·min -1 . These results showed that forwards had the highest maximum running speed, with defenders having the lowest one (p = 0.0025). Additionally, running output started to plateau after 7/8-min periods for each of the three positions. Forwards did not show any statistically significant changes across the four quarters. Midfielders showed effect sizes ranging from >0.6 to >2.0 (moderate, large and very large) significance when comparing the first three quarters to the fourth one. Defenders showed >0.6 to <2.0 (moderate to large) effect sizes to occur when comparing the first and second quarter to the fourth. There are three main practical implications from the results of this study: 1) the creation of conditioning drills, 2) substitution patterns, and 3) knowledge to be able to plan and train at or above peak match demands., (© 2021 Hamish Dewar, Jenny Clarke, published by Sciendo.)

Geochemical chronologies were constructed from otoliths of adult Pacific bluefin tuna (PBT) to investigate the timing of age-specific egress of juveniles from coastal nurseries in the East China Sea or Sea of Japan to offshore waters of the Pacific Ocean. Element:Ca chronologies were developed for otolith Li, Mg, Mn, Zn, Sr, and Ba, and our assessment focused on the section of the otolith corresponding to the age-0 to age-1 + interval. Next, we applied a common time-series approach to geochemical profiles to identify divergences presumably linked to inshore-offshore migrations. Conspicuous geochemical shifts were detected during the juvenile interval for Mg:Ca, Mn:Ca, and Sr:Ca that were indicative of coastal-offshore transitions or egress generally occurring for individuals approximately 4-6 mo. old, with later departures (6 mo. or older) linked to overwintering being more limited. Changepoints in otolith Ba:Ca profiles were most common in the early age-1 period (ca. 12-16 mo.) and appear associated with entry into upwelling areas such as the California Current Large Marine Ecosystem following trans-Pacific migrations. Natal origin of PBT was also predicted using the early life portion of geochemical profile in relation to a baseline sample comprised of age-0 PBT from the two primary spawning areas in the East China Sea and Sea of Japan. Mixed-stock analysis indicated that the majority (66%) of adult PBT in our sample originated from the East China Sea, but individuals of Sea of Japan origin were also detected in the Ryukyu Archipelago., (© 2021. The Author(s).)

Stable isotope analysis (SIA) measurements from long-term captivity studies provide required parameters for interpretation of consumer SIA data. We raised young-of-the-year (14-19 cm) California yellowtail (Seriola dorsalis) on a low δ 15 N and δ 13 C diet (pellet aquaculture feed) for 525 days, then switched to a high δ 15 N and δ 13 C diet (mackerel and squid) for 753 days. Yellowtail muscle was sequentially sampled from each individual after the diet switch (0 to 753 days) and analyzed for δ 15 N and δ 13 C, allowing for calculation of diet-tissue discrimination factors (DTDFs) from two isotopically different diets (low δ 15 N and δ 13 C: pellets; high δ 15 N and δ 13 C: fish/squid) and turnover rates of 15 N and 13 C. DTDFs were diet dependent: Δ 15 N = 5.1‰, Δ 13 C = 3.6‰ for pellets and Δ 15 N = 2.6‰, Δ 13 C = 1.3‰ for fish/squid. Half-life estimates from 15 N and 13 C turnover rates for pooled yellowtail were 181 days and 341 days, respectively, but varied considerably by individual ( 15 N: 99-239 d; 13 C: 158-899 d). Quantifying DTDFs supports isotopic approaches to field data that assume isotopic steady-state conditions (e.g., mixing models for diet reconstruction). Characterizing and quantifying turnover rates allow for estimates of diet/habitat shifts and "isotopic clock" approaches, and observed inter-individual variability suggests the need for large datasets in field studies. We provide diet-dependent DTDFs and growth effects on turnover rates, and associated error around these parameters, for application to field-collected SIA data from other large teleosts.

Purpose: Peripheral T-cell lymphomas are clinically aggressive and usually fatal, as few complete or durable remissions are achieved with currently available therapies. Recent evidence supports a critical role for lymphoma-associated macrophages during T-cell lymphoma progression, but the specific signals involved in the cross-talk between malignant T cells and their microenvironment are poorly understood. Colony-stimulator factor 1 receptor (CSF1R, CD115) is required for the homeostatic survival of tissue-resident macrophages. Interestingly, its aberrant expression has been reported in a subset of tumors. In this article, we evaluated its expression and oncogenic role in T-cell lymphomas., Experimental Design: Loss-of-function studies, including pharmacologic inhibition with a clinically available tyrosine kinase inhibitor, pexidartinib, were performed in multiple in vitro and in vivo models. In addition, proteomic and genomic screenings were performed to discover signaling pathways that are activated downstream of CSF1R signaling., Results: We observed that CSF1R is aberrantly expressed in many T-cell lymphomas, including a significant number of peripheral and cutaneous T-cell lymphomas. Colony-stimulating factor 1 (CSF1), in an autocrine or paracrine-dependent manner, leads to CSF1R autophosphorylation and activation in malignant T cells. Furthermore, CSF1R signaling was associated with significant changes in gene expression and in the phosphoproteome, implicating PI3K/AKT/mTOR in CSF1R-mediated T-cell lymphoma growth. We also demonstrated that inhibition of CSF1R in vivo and in vitro models is associated with decreased T-cell lymphoma growth., Conclusions: Collectively, these findings implicate CSF1R in T-cell lymphomagenesis and have significant therapeutic implications., (©2019 American Association for Cancer Research.)

Natal origin of subadult (age-1) Pacific bluefin tuna (PBT, Thunnus orientalis ) from the California Current Large Marine Ecosystem (CCLME) was determined using natural tracers in ear stones (otoliths). Age-0 PBT collected from the two known spawning areas in the western Pacific Ocean (East China Sea, Sea of Japan) were used to establish baseline signatures from otolith cores over 4 years (2014-2017) based on a suite of trace elements (Li, Mg, Mn, Sr, Zn and Ba). Distinct chemical signatures existed in the otolith cores of age-0 PBT collected from the two spawning areas, with overall classification accuracy ranging 73-93% by year. Subadult PBT collected in the CCLME over the following 4 years (2015-2018) were then age-class matched to baselines using mixed-stock analysis. Natal origin of trans-Pacific migrants in the CCLME ranged 43-78% from the East China Sea and 22-57% from the Sea of Japan, highlighting the importance of both spawning areas for PBT in the CCLME. This study provides the first estimates on the natal origin of subadult PBT in this ecosystem using otolith chemistry and expands upon the application of these natural tracers for population connectivity studies for this species.

Chemical contaminant profiles are linked to an animal's niche, providing a potential tool by which to assess resource partitioning in pelagic species. As proof of concept, we examined contaminant signatures in three species of sharks (Isurus oxyrinchus, Prionace glauca, and Alopias vulpinus) known to overlap in both space and time. Since these sharks comprise a predatory guild within the Southern California Bight (SCB), we predicted that species may partition spatial and dietary resources to limit the extent of competitive exclusion. Indeed, species were distinguishable by both total contaminant loads and their contaminant fingerprint, as random forest analysis found that species could be correctly classified 96% of the time. Our results demonstrate the utility of chemical analyses for ecological studies, and how contaminant tracers can be used in combination with traditional methods to elucidate how species may undergo niche partitioning to reduce competition for overlapping resources within predatory guilds.

Factors influencing organic contaminant accumulation in sharks, especially across ontogeny, are not well-known. Contaminant concentrations were measured in three species of sharks (Blue, Shortfin Mako, and Common Thresher) across a range of size classes (neonatal to adult) that vary in their ecological and physiological characteristics. Empirical data was compared to a theoretical framework that predicted the shape of lifetime accumulation curves. We found that a one-size-fits-all accumulation model was not appropriate as species-specific characteristics had a significant effect on contaminant accumulation trajectories. Maternal offloading likely has an important effect on determining neonatal shark contaminant starting points, and trophic ecology and physiology may interact to affect the shape of species' contaminant accumulation curves. Makos were found to have the highest accumulation potential and Blues the lowest, with Threshers being intermediate in accumulation potential. Changes in species' ecology and/or physiology were also reflected in contaminant signature changes over ontogeny. If contaminant concentrations are to be used as a proxy for risk, species-specific characteristics need to be taken into account when estimating contaminant exposure and its potential negative effects on shark health and human consumption safety.

As upper-level predators, sharks are important for maintaining marine food web structure, but populations are threatened by fishery exploitation. Sustainable management of shark populations requires improved understanding of migration patterns and population demographics, which has traditionally been sought through physical and/or electronic tagging studies. The application of natural tags such as elemental variations in mineralized band pairs of elasmobranch vertebrae cartilage could also reveal endogenous and exogenous processes experienced by sharks throughout their life histories. Here, elemental profiles were characterized in vertebrae encompassing complete life histories (birth-to-death) of shortfin mako ( Isurus oxyrinchus ), common thresher ( Alopias vulpinus ) and blue shark ( Prionace glauca ) of known tag and recapture locations in the eastern North Pacific Ocean. All sharks were injected with oxytetracycline at initial capture, released and subsequently recaptured, with individual liberty times ranging from 215 days to 6 years. Vertebral band pairs forming over the liberty intervals were verified by counting the number of band pairs deposited since the oxytetracycline band. Regular oscillations in vertebrae manganese (Mn) content corresponded well with the number of validated band pairs, suggesting that Mn variation could be used to age sharks. Increases in vertebrae barium concentration were correlated with times when individuals occupied areas with high coastal upwelling indices, the timing and spatial intensity of which varied from year to year. Interspecific relationships were probably influenced by behavioural differences in horizontal and vertical habitat use, feeding habits and thermoregulatory physiology. These results indicate that vertebral sclerochronology has the potential to advance our knowledge of elasmobranch life history including age and growth estimation and environmental reconstruction., (© 2018 The Authors.)

During their migrations, marine predators experience varying levels of protection and face many threats as they travel through multiple countries' jurisdictions and across ocean basins. Some populations are declining rapidly. Contributing to such declines is a failure of some international agreements to ensure effective cooperation by the stakeholders responsible for managing species throughout their ranges, including in the high seas, a global commons. Here we use biologging data from marine predators to provide quantitative measures with great potential to inform local, national and international management efforts in the Pacific Ocean. We synthesized a large tracking data set to show how the movements and migratory phenology of 1,648 individuals representing 14 species-from leatherback turtles to white sharks-relate to the geopolitical boundaries of the Pacific Ocean throughout species' annual cycles. Cumulatively, these species visited 86% of Pacific Ocean countries and some spent three-quarters of their annual cycles in the high seas. With our results, we offer answers to questions posed when designing international strategies for managing migratory species.

Pelagic ecosystems are changing due to environmental and anthropogenic forces, with uncertain consequences for the ocean's top predators. Epipelagic and mesopelagic prey resources differ in quality and quantity, but their relative contribution to predator diets has been difficult to track. We measured mercury (Hg) stable isotopes in young (<2 years old) Pacific bluefin tuna (PBFT) and their prey species to explore the influence of foraging depth on growth and methylmercury (MeHg) exposure. PBFT total Hg (THg) in muscle ranged from 0.61 to 1.93 μg g -1 dw (1.31 μg g -1 dw ±0.37 SD; 99% ± 6% MeHg) and prey ranged from 0.01 to 1.76 μg g -1 dw (0.13 μg g -1 dw ±0.19 SD; 85% ± 18% MeHg). A systematic decrease in prey δ 202 Hg and Δ 199 Hg with increasing depth of occurrence and discrete isotopic signatures of epipelagic prey (δ 202 Hg: 0.74 to 1.49‰; Δ 199 Hg: 1.76-2.96‰) and mesopelagic prey (δ 202 Hg: 0.09 to 0.90‰; Δ 199 Hg: 0.62-1.95‰) allowed the use of Hg isotopes to track PBFT foraging depth. An isotopic mixing model was used to estimate the dietary proportion of mesopelagic prey in PBFT, which ranged from 17% to 55%. Increased mesopelagic foraging was significantly correlated with slower growth and higher MeHg concentrations in PBFT. The slower observed growth rates suggest that prey availability and quality could reduce the production of PBFT biomass.

Seafood is an essential source of protein for more than 3 billion people worldwide, yet bycatch of threatened species in capture fisheries remains a major impediment to fisheries sustainability. Management measures designed to reduce bycatch often result in significant economic losses and even fisheries closures. Static spatial management approaches can also be rendered ineffective by environmental variability and climate change, as productive habitats shift and introduce new interactions between human activities and protected species. We introduce a new multispecies and dynamic approach that uses daily satellite data to track ocean features and aligns scales of management, species movement, and fisheries. To accomplish this, we create species distribution models for one target species and three bycatch-sensitive species using both satellite telemetry and fisheries observer data. We then integrate species-specific probabilities of occurrence into a single predictive surface, weighing the contribution of each species by management concern. We find that dynamic closures could be 2 to 10 times smaller than existing static closures while still providing adequate protection of endangered nontarget species. Our results highlight the opportunity to implement near real-time management strategies that would both support economically viable fisheries and meet mandated conservation objectives in the face of changing ocean conditions. With recent advances in eco-informatics, dynamic management provides a new climate-ready approach to support sustainable fisheries.

The ocean is a dynamic environment inhabited by a diverse array of highly migratory species, many of which are under direct exploitation in targeted fisheries. The timescales of variability in the marine realm coupled with the extreme mobility of ocean-wandering species such as tuna and billfish complicates fisheries management. Developing eco-informatics solutions that allow for near real-time prediction of the distributions of highly mobile marine species is an important step towards the maturation of dynamic ocean management and ecological forecasting. Using 25 yr (1990-2014) of NOAA fisheries' observer data from the California drift gillnet fishery, we model relative probability of occurrence (presence-absence) and catchability (total catch per gillnet set) of broadbill swordfish Xiphias gladius in the California Current System. Using freely available environmental data sets and open source software, we explore the physical drivers of regional swordfish distribution. Comparing models built upon remotely sensed data sets with those built upon a data-assimilative configuration of the Regional Ocean Modelling System (ROMS), we explore trade-offs in model construction, and address how physical data can affect predictive performance and operational capacity. Swordfish catchability was found to be highest in deeper waters (>1,500 m) with surface temperatures in the 14-20°C range, isothermal layer depth (ILD) of 20-40 m, positive sea surface height (SSH) anomalies, and during the new moon (<20% lunar illumination). We observed a greater influence of mesoscale variability (SSH, wind speed, isothermal layer depth, eddy kinetic energy) in driving swordfish catchability (total catch) than was evident in predicting the relative probability of presence (presence-absence), confirming the utility of generating spatiotemporally dynamic predictions. Data-assimilative ROMS circumvent the limitations of satellite remote sensing in providing physical data fields for species distribution models (e.g., cloud cover, variable resolution, subsurface data), and facilitate broad-scale prediction of dynamic species distributions in near real time., (© 2017 by the Ecological Society of America.)

The 2011 release of Fukushima-derived radionuclides into the Pacific Ocean made migratory sharks, teleosts, and marine mammals a source of speculation and anxiety regarding radiocesium ( 134+137 Cs) contamination, despite a lack of actual radiocesium measurements for these taxa. We measured radiocesium in a diverse suite of large predators from the North Pacific Ocean and report no detectable (i.e., ≥ 0.1 Bq kg -1 dry wt) Fukushima-derived 134 Cs in all samples, except in one olive ridley sea turtle (Lepidochelys olivacea) with trace levels (0.1 Bq kg -1 ). Levels of 137 Cs varied within and across taxa, but were generally consistent with pre-Fukushima levels and were lower than naturally occurring 40 K by one to one to two orders of magnitude. Predator size had a weaker effect on 137 Cs and 40 K levels than tissue lipid content. Predator stable isotope values (δ 13 C and δ 15 N) were used to infer recent migration patterns, and showed that predators in the central, eastern, and western Pacific should not be assumed to accumulate detectable levels of radiocesium a priori. Nondetection of 134 Cs and low levels of 137 Cs in diverse marine megafauna far from Fukushima confirms negligible increases in radiocesium, with levels comparable to those prior to the release from Fukushima. Reported levels can inform recently developed models of cesium transport and bioaccumulation in marine species.

Hypoxia is a global and increasingly important stressor in aquatic ecosystems, with major impacts on biodiversity worldwide. Hypoxic waters are often contaminated with a wide range of chemicals but little is known about the interactions between these stressors. We investigated the effects of hypoxia on the responses of zebrafish (Danio rerio) embryos to copper, a widespread aquatic contaminant. We showed that during continuous exposures copper toxicity was reduced by over 2-fold under hypoxia compared to normoxia. When exposures were conducted during 24 h windows, hypoxia reduced copper toxicity during early development and increased its toxicity in hatched larvae. To investigate the role of the hypoxia signaling pathway on the suppression of copper toxicity during early development, we stabilized the hypoxia inducible factor (HIF) pathway under normoxia using a prolyl-4-hydroxylase inhibitor, dimethyloxalylglycine (DMOG) and demonstrated that HIF activation results in a strong reduction in copper toxicity. We also established that the reduction in copper toxicity during early development was independent of copper uptake, while after hatching, copper uptake was increased under hypoxia, corresponding to an increase in copper toxicity. These findings change our understanding of the current and future impacts of worldwide oxygen depletion on fish communities challenged by anthropogenic toxicants.

In June 2013, a record-breaking female Isurus oxyrinchus (total length 373 cm, mass 600 kg) was captured by rod and reel off Huntington Beach, California, where it was subsequently donated to research and provided a rare opportunity to collect the first data for a female I. oxyrinchus of this size. Counts of vertebral band pairs estimate the shark to have been c. 22 years old, depending upon assumptions of band-pair deposition rates, and the distended uteri and spent ovaries indicated that this shark had recently given birth. The stomach contained a c. 4 year-old female California sea lion Zalophus californianus that confirmed the high trophic position of this large I. oxyrinchus, which was corroborated with the high levels of measured contaminants and tissue isotope analyses., (© 2015 The Fisheries Society of the British Isles.)

Endothermy (the metabolic production and retention of heat to warm body temperature above ambient) enhances physiological function, and whole-body endothermy generally sets mammals and birds apart from other animals. Here, we describe a whole-body form of endothermy in a fish, the opah (Lampris guttatus), that produces heat through the constant "flapping" of wing-like pectoral fins and minimizes heat loss through a series of counter-current heat exchangers within its gills. Unlike other fish, opah distribute warmed blood throughout the body, including to the heart, enhancing physiological performance and buffering internal organ function while foraging in the cold, nutrient-rich waters below the ocean thermocline., (Copyright © 2015, American Association for the Advancement of Science.)