A method for measuring meaningful physiological variables in fish blood without surgical cannulation.

Gaining meaningful blood samples from water-breathing fish is a significant challenge. Two main methods typically used are grab 'n' stab and surgical cannulation. Both methods have benefits, but also significant limitations under various scenarios. Here we present a method of blood sampling laboratory fish involving gradual induction of anaesthesia within their home tank, avoiding physical struggling associated with capture, followed by rapid transfer to a gill irrigation system to maintain artificial ventilation via adequate gill water flow and then followed by sampling the caudal vasculature. This method negates many blood chemistry disturbances associated with grab 'n' stab (i.e., low pH and oxygen, elevated lactate, CO2 and stress hormones) and generates results that are directly comparable to cannulated fish under a wide range of experimentally-induced acid-base scenarios (acidosis and alkalosis). Crucially this method was successful in achieving accurate acid-base blood measurements from fish ten times smaller than are typically suitable for cannulation. This opens opportunities not previously possible for studies that relate to basic physiology, sustainable aquaculture, ecotoxicology, conservation, and climate change.

Diverse Microvirus Genomes Identified in the Stomach of a Sharp-Spined Notothen (Trematomus pennellii) from the Ross Sea (East Antarctica).

Sharp-spined notothen (Trematomus pennellii) is an icefish endemic to the southern ocean. From the stomach of an individual, we identified the genomes of 51 microviruses (family Microviridae). The major capsid proteins of most of these share the closest similarities to those identified in other marine organisms.

Fish feeds supplemented with calcium-based buffering minerals decrease stomach acidity, increase the blood alkaline tide and cost more to digest.

Predatory fish in the wild consume whole prey including hard skeletal parts like shell and bone. Shell and bone are made up of the buffering minerals calcium carbonate (CaCO3) and calcium phosphate (Ca3(PO4)2). These minerals resist changes in pH, meaning they could have physiological consequences for gastric acidity, digestion and metabolism in fish. Using isocaloric diets supplemented with either CaCO3, Ca3(PO4)2 or CaCl2 as non-buffering control, we investigated the impacts of dietary buffering on the energetic cost of digestion (i.e. specific dynamic action or SDA), gastric pH, the postprandial blood alkalosis (the "alkaline tide") and growth in juvenile rainbow trout (Oncorhynchus mykiss). Increases in dietary buffering were significantly associated with increased stomach chyme pH, postprandial blood HCO3-, net base excretion, the total SDA and peak SDA but did not influence growth efficiency in a 21 day trial. This result shows that aspects of a meal that have no nutritional value can influence the physiological and energetic costs associated with digestion in fish, but that a reduction in the SDA will not always lead to improvements in growth efficiency. We discuss the broader implications of these findings for the gastrointestinal physiology of fishes, trade-offs in prey choice in the wild, anthropogenic warming and feed formulation in aquaculture.

Rapid blood acid-base regulation by European sea bass (Dicentrarchus labrax) in response to sudden exposure to high environmental CO2.

Fish in coastal ecosystems can be exposed to acute variations in CO2 of between 0.2 and 1 kPa CO2 (2000-10,000 µatm). Coping with this environmental challenge will depend on the ability to rapidly compensate for the internal acid-base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon sudden exposure to ∼1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ∼40 min, thus restoring haemoglobin-O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ∼2 h, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3- in blood, which increased from ∼4 to ∼22 mmol l-1. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3- and pH, probably because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments.

Discovery of novel fish papillomaviruses: From the Antarctic to the commercial fish market.

Fish papillomaviruses form a newly discovered group broadly recognized as the Secondpapillomavirinae subfamily. This study expands the documented genomes of the fish papillomaviruses from six to 16, including one from the Antarctic emerald notothen, seven from commercial market fishes, one from data mining of sea bream sequence data, and one from a western gull cloacal swab that is likely diet derived. The genomes of secondpapillomaviruses are ∼6 kilobasepairs (kb), which is substantially smaller than the ∼8 kb of terrestrial vertebrate papillomaviruses. Each genome encodes a clear homolog of the four canonical papillomavirus genes, E1, E2, L1, and L2. In addition, we identified open reading frames (ORFs) with short linear peptide motifs reminiscent of E6/E7 oncoproteins. Fish papillomaviruses are extremely diverse and phylogenetically distant from other papillomaviruses suggesting a model in which terrestrial vertebrate-infecting papillomaviruses arose after an evolutionary bottleneck event, possibly during the water-to-land transition.

Increasing Blood Pressure Variability Predicts Poor Functional Outcome Following Acute Stroke.

INTRODUCTION: Increasing blood pressure variability has been reported following acute stroke, but there is uncertainty about how best to measure it and about the impact on prognosis following acute ischaemic stroke and transient ischaemic attack. METHODS: Enhanced casual blood pressure and ambulatory blood pressure monitoring were completed at baseline (≤48 h post symptom onset). Blood pressure variability was defined by standard deviation and coefficient of variation of systolic, diastolic, mean arterial pressure, and pulse pressure. Modified Rankin scale score ≥3 described poor functional outcome assessed at 1- and 12-months post-stroke. Multivariable logistic regression models incorporating blood pressure variability measurement and other factors were performed, and odds ratio and 95% confidence intervals reported. RESULTS: 232 patients were recruited; 45 were dependent at 1-month, and 37 at 12-months. Dependent patients were more likely to be older, with a higher burden of pre-morbid conditions, and with increased blood pressure variability. Enhanced casual standard deviations of diastolic blood pressure [1.19 (1.02 to 1.39)] and mean arterial pressure [1.20 (1.00 to 1.43)] predicted dependency at 1-month. Predictors of 12-month dependency included: enhanced casual standard deviation of mean arterial pressure [1.21 (1.0-1.46)]; 24 h ambulatory monitor standard deviations of diastolic blood pressure [2.30 (1.08-4.90)] and mean arterial pressure [1.72 (1.09-2.72)], and the coefficient of variation of mean arterial pressure [1.76 (1.05-2.94)]; day-time ambulatory monitor coefficient of variation of systolic blood pressure [1.44 (1.02-2.03)] and mean arterial pressure [1.46 (1.02-2.08)]; and night-time ambulatory standard deviation of diastolic blood pressure [1.65 (1.03 -2.63)], and the coefficient of variation of mean arterial pressure and [1.38 (1.00- 1.90)] and pulse pressure [1.29 (1.00-1.65)]. CONCLUSION: Increasing blood pressure variability is independently and modestly associated with poor functional outcome at 1- and 12-months following acute stroke.

Advances in Understanding Mobilization Processes of Trace Metals in Marine Sediments.

Different mobilization mechanisms control the metal distribution in surface sediments of the Belgium coastal zone (BCZ) and the anoxic Gotland basin (GB). This mobilization was studied using DGT (diffusive gradients in thin films): vertical one-dimensional (1D) profiles of Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn were measured at 5 mm intervals, while two-dimensional (2D) high-resolution (100 µm) images of smaller zones of the sediment profile were obtained on separate DGT probes. Removal of dissolved Cd, Cu, and Pb in BCZ sediments caused steep vertical gradients at the sediment-water interface that were well replicated in 1D profiles and 2D images. While 1D profiles showed apparent coincident maxima of Co, Mn, and Fe, 2D images revealed mutually exclusive Co and Fe mobilization. Correlation analysis supported this observation and showed a consistent linkage between Co and Mn. Sharp maxima of some metals in the vertical 1D profiles of GB sediment were attributed to localized mobilization in microniches. Examination of an ∼1 mm diameter Cu and Ni maximum in 2D, defined by ∼300 data points, showed that the metals were supplied from localized decomposition of reactive organic material, rather than from reductively dissolving Fe or Mn oxides, and that they were removed as their sulfides.

Can cardiovascular risk management be improved by shared care with general practice to prevent cognitive decline following stroke/TIA? A feasibility randomised controlled trial (SERVED memory).

BACKGROUND: Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care. METHODS: In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months. RESULTS: Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups. CONCLUSIONS: Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline. TRIAL REGISTRATION: ISRCTN, ISRCTN42688361 . Registered 16 April 2015.

A calcium channel or angiotensin converting enzyme inhibitor/angiotensin receptor blocker regime to reduced blood pressure variability in acute ischaemic stroke (CAARBS): A feasibility trial.

BACKGROUND: Trials of lowering blood pressure in patients with acute ischaemic stroke not undergoing thrombolysis have not demonstrated improved outcomes with intervention. Rather than absolute levels, it may be that blood pressure variability is important. However, there are no prospective randomised trials investigating the benefit of reducing blood pressure variability in this patient group. AIMS: The primary aim of this trial was to determine the feasibility of recruitment to a randomised trial investigating the effect of different antihypertensive medications on blood pressure variability. METHODS: CAARBS was a multi-centre, open-label, randomised parallel group controlled feasibility trial. Adults with a first mild-moderate ischaemic stroke or transient ischaemic attack, requiring antihypertensive therapy for secondary prevention, were randomised to a calcium channel blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Blood pressure and variability were measured at baseline, three weeks, and three months. Compliance with measurements and treatment was monitored. RESULTS: Fourteen patients were recruited to the trial (0.6% of those screened), nine of whom completed follow-up. The majority of patients screened (98.1%) were ineligible. Compliance with the intervention was good, as were measurement completion rates (88.9% or higher in all cases except ambulatory measurements). No major adverse events were recorded. CONCLUSIONS: Recruitment to the trial was difficult due to patient ineligibility, suggesting that the current protocol is unlikely to be successful if scaled for a definitive trial. However, the intervention was safe, and compliance was good, suggesting a future trial with modified eligibility criteria could be successful. TRIAL REGISTRATION: ISRCTN10853487.

Self-Monitoring and Management of Blood Pressure in Patients with Stroke or TIA: An Economic Evaluation of TEST-BP, A Randomised Controlled Trial.

BACKGROUND: Prevention of secondary stroke following initial ictus is an important focus of after-stroke care. Blood pressure (BP) is a key risk factor, so usual care following stroke or transient ischaemic attack includes regular BP checks and monitoring of anti-hypertensive medication. This is traditionally carried out in primary care, but the evidence supporting self-monitoring and self-guided management of BP in the general population with hypertension is growing. OBJECTIVE: Our objective was to estimate the cost effectiveness of treatment as usual (TAU) versus (1) self-monitoring of BP (S-MON) and (2) self-monitoring and guided self-management of anti-hypertensive medication (S-MAN). METHODS: This was a within-trial economic evaluation of a randomised controlled trial estimating the incremental cost per 1 mmHg BP reduction and per quality-adjusted life-year (QALY) gained over a 6-month time horizon from the perspective of the UK National Health Service (NHS). RESULTS: Data were evaluable for 140 participants. Costs per patient were £473, £853 and £1035; mean reduction in systolic BP (SBP) was 3.6, 6.7 and 6.1 mmHg, and QALYs accrued were 0.427, 0.422 and 0.423 for TAU, S-MON and S-MAN, respectively. No statistically significant differences in incremental costs or outcomes were detected. On average, S-MAN was dominated or extended dominated. The incremental cost per 1 mmHg BP reduction from S-MON versus TAU was £137. CONCLUSION: On average, S-MAN is an inefficient intervention. S-MON may be cost effective, depending on the willingness to pay for a 1 mmHg BP reduction, although it yielded fewer QALYs over the within-trial time horizon. Decision modelling is required to explore the longer-term costs and outcomes.

Understanding the gastrointestinal physiology and responses to feeding in air-breathing Anabantiform fishes.

The Mekong Delta is host to a large number of freshwater species, including a unique group of facultative air-breathing Anabantiforms. Of these, the striped snakehead (Channa striata), the climbing perch (Anabas testudineus), the giant gourami (Osphronemus goramy) and the snakeskin gourami (Trichogaster pectoralis) are major contributors to aquaculture production in Vietnam. The gastrointestinal responses to feeding in these four species are detailed here. Relative intestinal length was lowest in the snakehead, indicating carnivory, and 5.5-fold greater in the snakeskin, indicating herbivory; climbing perch and giant gourami were intermediate, indicating omnivory. N-waste excretion (ammonia-N + urea-N) was greatest in the carnivorous snakehead and least in the herbivorous snakeskin, whereas the opposite trend was observed for net K+ excretion. Similarly, the more carnivorous species had a greater stomach acidity than the more herbivorous species. Measurements of acid-base flux to water indicated that the greatest postprandial alkaline tide occurred in the snakehead and a potential acidic tide in the snakeskin. Additional findings of interest were high levels of both PCO2 (up to 40 mmHg) and HCO3 - (up to 33 mM) in the intestinal chyme of all four of these air-breathing species. Using in vitro gut sac preparations of the climbing perch, it was shown that the intestinal net absorption of fluid, Na+ and HCO3 - was upregulated by feeding but not net Cl- uptake, glucose uptake or K+ secretion. Upregulated net absorption of HCO3 - suggests that the high chyme (HCO3 - ) does not result from secretion by the intestinal epithelium. The possibility of ventilatory control of PCO2 to regulate postprandial acid-base balance in these air-breathing fish is discussed.

The effect of temperature and meal size on the aerobic scope and specific dynamic action of two temperate New Zealand finfish Chrysophrys auratus and Aldrichetta forsteri.

Shallow coastal and estuarine habitats function as nurseries for many juvenile fish. In this comparative study, metabolic profiles of two New Zealand finfish, snapper (Chrysophrys auratus) and yellow-eyed mullet-YEM (Aldrichetta forsteri) that as juveniles share the same temperate coastal environments, were examined. Metabolic parameters (routine and maximum metabolic rates, and specific dynamic action-SDA) were investigated at a set of temperatures (13, 17, 21 °C) within the range juveniles both species experience annually. SDA was also determined for a range of different feed rations to investigate the effects of meal size on postprandial metabolic response. Temperature was a strong modulator of snapper and YEM metabolic profile (routine and maximum metabolic rates, and absolute and factorial aerobic scope). Metabolic rates increased with temperature in both species as did absolute scope in YEM, though for snapper, it was only greater at the highest temperature. Factorial scope behaved in the same fashion for the two species, being greatest at 13 °C. Both absolute and factorial scope were ~ twofold greater in YEM than in snapper across the entire temperature range. Temperature also affected SDA response in snapper, while in YEM, SDA parameters were largely unaffected when temperature increased from 17 to 21 °C. Snapper were able to consume a large range of meal sizes (0.5-3.0% body mass-BM) with meal sizes > 1% BM having a pronounced effect on numerous SDA parameters, whereas mullet appeared to consume more limited ration sizes (≤ 1.0% BM). In both species, rations ≤ 1% BM produced similar changes in SDA parameters identifying comparable digestive bio-energetics. Overall, our metabolic characterisations demonstrate that both species can adjust to the variable temperate environmental temperatures and manage the energetic costs of digestion and feed assimilation. Yet, despite these general similarities, YEM's greater aerobic scope may point to better physiological adaptation to the highly variable temperate coastal environment than were observed in snapper.

Randomised controlled trial of a Calcium Channel or Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Regime to Reduce Blood Pressure Variability following Ischaemic Stroke (CAARBS): a protocol for a feasibility study.

INTRODUCTION: Raised blood pressure (BP) is common after stroke and is associated with a poor prognosis, yet trials of BP lowering in the immediate poststroke period have not demonstrated a benefit. One possible explanation for this may be that BP variability (BPV) rather than absolute levels predicts outcome, as BPV is increased after stroke and is associated with poor outcomes. Furthermore, there is evidence of distinct antihypertensive class effects on BPV despite similar BP-lowering effects. However, whether BPV in the immediate poststroke period is a therapeutic target has not been prospectively investigated.The objectives of this trial are to assess the feasibility and safety of recruiting patients following an acute ischaemic stroke or transient ischaemic attack (TIA) to an interventional randomised controlled trial comparing the effects of two different antihypertensive drug classes on BPV. Secondary exploratory objectives are to assess if different therapeutic strategies have diverse effects on levels of BPV and if this has an impact on outcomes. METHODS: 150 adult patients with first-ever ischaemic stroke or TIA who require antihypertensive therapy for secondary prevention will be recruited within 7 days of the event from stroke services across three sites. After baseline assessments they will be randomly assigned to treatment with a calcium channel blocker or ACE inhibitor/angiotensin receptor blocker-based regimen and followed up for a period of three months. ETHICS AND DISSEMINATION: Ethical and regulatory approvals have been granted. Dissemination is planned via publication in peer-reviewed medical journals and presentation at relevant conferences. TRIAL REGISTRATION NUMBER: ISRCTN10853487.

Blood pressure differences between home monitoring and daytime ambulatory values and their reproducibility in treated hypertensive stroke and TIA patients.

BACKGROUND: Guidelines recommend ambulatory or home blood pressure monitoring to improve hypertension diagnosis and monitoring. Both these methods are ascribed the same threshold values, but whether they produce similar results has not been established in certain patient groups. METHODS: Adults with mild/moderate stroke or transient ischemic attack (N = 80) completed 2 sets of ambulatory and home blood pressure monitoring. Systolic and diastolic blood pressure values from contemporaneous measurements were compared, and the limits of agreement were assessed. Exploratory analyses for predictive factors of any difference were conducted. RESULTS: Daytime ambulatory blood pressure values were consistently lower than home values, the mean difference in systolic blood pressure for initial ambulatory versus first home monitoring was -6.6 ± 13.5 mm Hg (P≤.001), and final ambulatory versus second home monitoring was -7.1 ± 11.0mm Hg (P≤.001). Mean diastolic blood pressure differences were -2.1 ± 8.5mm Hg (P=.03) and -2.0 ± 7.2mm Hg (P=.02). Limits of agreement for systolic blood pressure were -33.0 to 19.9mm Hg and -28.7 to 14.5mm Hg for the 2 comparisons and for DBP were -18.8 to 14.5mm Hg and -16.1 to 12.2mm Hg, respectively. The individual mean change in systolic blood pressure difference was 11.0 ± 8.3mm Hg across the 2 comparisons. No predictive factors for these differences were identified. CONCLUSIONS: Daytime ambulatory systolic and diastolic blood pressure values were significantly lower than home monitored values at both time points. Differences between the 2 methods were not reproducible for individuals. Using the same threshold value for both out-of-office measurement methods may not be appropriate in patients with cerebrovascular disease.

In situ measurements of micronutrient dynamics in open seawater show that complex dissociation rates may limit diatom growth.

In this first in situ study of the dynamic availability of phytoplankton micronutrients, a SeaExplorer glider was combined with Diffusive Gradients in Thin Films and deployed in the Mediterranean Sea. On the basis of their labile metal complex pools, we discovered that Fe and Co can be potentially limiting and Cu co-limiting to diatom growth, contrary to the generally accepted view that phosphorus (phosphate) is the growth limiting element in the Mediterranean Sea. For flagellates and picoplankton, phosphorus remains the main element limiting growth. Our in situ measurements showed that organic complexes of Fe and Cu (>98% of total dissolved concentration), dissociate slower than inorganic complexes of Co, Cd and Ni (>99% of total dissolved concentration being free ions and inorganic complexes). This strengthens the potential growth limiting effect of Fe and Cu versus phosphate, which is present as a free ion and, thus, directly available for plankton.

Does self-monitoring and self-management of blood pressure after stroke or transient ischemic attack improve control? TEST-BP, a randomized controlled trial.

The therapeutic benefit of self-monitoring blood pressure in stroke patients is uncertain. We investigated the effect of self-monitoring with or without guided antihypertensive management compared with usual care in patients with a recent cerebrovascular event. No between-group differences in blood pressure at outcome were found, but blood pressure self-monitoring and management was well tolerated.

In situ measurement of perfluoroalkyl substances in aquatic systems using diffusive gradients in thin-films technique.

To better understand the environmental impact of ubiquitous perfluoroalkyl substances (PFASs) in waters, reliable and robust measurement techniques are needed. As one of the most widely used passive sampling approaches, diffusive gradients in thin-films (DGT) is not only easy to handle but also provides time-weighted analyte concentrations. Based on DGT with XAD18 as a binding agent, we developed a new methodology to measure two frequently detected PFASs in surface waters and wastewaters, i.e. perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Their diffusion coefficients in the diffusive gel, measured using an independent diffusion cell, were 4.37 × 10-6 and 5.08 × 10-6 cm2 s-1 at 25 °C, respectively. DGT had a high capacity for PFOA and PFOS at 196 and 246 µg per gel disk, suggesting the DGT sampler was suitable for deployment of several weeks. Time-integrated concentrations of PFOA and PFOS in a natural lake and river, and a municipal wastewater treatment plant effluent using DGT samplers deployed in situ for 12-33 d were comparable to those measured by a solid-phase extraction method coupled with high-frequency grab sampling. This study demonstrates that DGT is an effective tool for in situ monitoring of PFASs in natural waters and wastewaters.

Plant Induced Changes to Rhizosphere Characteristics Affecting Supply of Cd to Noccaea caerulescens and Ni to Thlaspi goesingense.

Changes in soil rhizosphere properties after growing the Cd hyperaccumulator Noccaea caerulescens and the Ni hyperaccumulator Thlaspi goesingense were investigated. Dissolved organic carbon content increased in the rhizosphere, but there were no significant changes in the solution concentrations of Cd and Ni. Concentrations of these metals extracted by NH4Cl and EDTA decreased in the rhizosphere, as did DGT-measured concentrations, indicating a depletion of labile metal in the solid phase. The results could be explained by the increased DOC in the rhizosphere maintaining a higher proportion of the labile metal in solution through complexation, with the overall depletion of metals only manifest in the solid phase. The DGT induced fluxes in soils and sediments (DIFS) model was used to provide key kinetic information on soil processes and labile pool size. These data showed that the more limited metal supply in the rhizosphere after the growth of hyperaccumulators was due to both depletion of the solid phase pool and a lower rate constant of supply from solid phase to solution. The effect on the rate constant, which could be rationalized by the plant sequentially accessing and consuming the more labile pools of metal, was most marked for Cd, which had the highest accumulation factors.

Fish polyomaviruses belong to two distinct evolutionary lineages.

The Polyomaviridae is a diverse family of circular double-stranded DNA viruses. Polyomaviruses have been isolated from a wide array of animal hosts. An understanding of the evolutionary and ecological dynamics of these viruses is essential to understanding the pathogenicity of polyomaviruses. Using a high throughput sequencing approach, we identified a novel polyomavirus in an emerald notothen (Trematomus bernacchii) sampled in the Ross sea (Antarctica), expanding the known number of fish-associated polyomaviruses. Our analysis suggests that polyomaviruses belong to three main evolutionary clades; the first clade is made up of all recognized terrestrial polyomaviruses. The fish-associated polyomaviruses are not monophyletic, and belong to two divergent evolutionary lineages. The fish viruses provide evidence that the evolution of the key viral large T protein involves gain and loss of distinct domains.

Protocol for a feasibility randomised controlled trial of Screening and Enhanced Risk management for Vascular Event-related Decline in Memory (SERVED Memory).

INTRODUCTION: Stroke is a leading cause of death and disability. The development of dementia after stroke is common. Vascular risk factors (VRF) which contribute to stroke risk can also contribute to cognitive decline, especially in vascular dementia (VaD). There is no established treatment for VaD, therefore strategies for prevention could have major health resource implications. This study was designed to assess whether patients with early cognitive decline after stroke/transient ischaemic attack (TIA) can be easily identified and whether target-driven VRF management can prevent progression to dementia. OBJECTIVES: The primary objective is to establish the feasibility of recruitment and retention of patients with early cognitive decline to a randomised controlled trial of enhanced VRF management. Secondary objectives include: (a) to determine the potential clinical benefit of the intervention; (b) to estimate the sample size for a future definitive multicentre randomised controlled trial; (c) to inform a future economic evaluation; (d) to explore the link between VRF control and the incidence of cognitive impairment on longitudinal follow-up in a UK population after stroke/TIA with current routine management. METHODS: 100 patients with cognitive decline poststroke/TIA will be recruited from stroke services at the Norfolk and Norwich University Hospital. After collection of baseline data, they will be randomised to intervention (3 monthly follow-up with enhanced management) or control (treatment as usual by the general practitioner). At 12 months outcomes (repeat cognitive testing, VRF assessment) will be assessed. A further 100 patients without cognitive decline will be recruited to a parallel observational group from the same site. At 12 months they will have repeat cognitive testing. ETHICS AND DISSEMINATION: Ethical approval has been granted in England. Dissemination is planned via publication in peer-reviewed medical journals and presentation at relevant conferences. TRIAL REGISTRATION NUMBER: 42688361; Pre-results.