Research in association with New Seal Licensing System : Research on the population structure of harbour seals

The population structure of harbour seals (Phoca vitulina) around Scotland was investigated using different genetic markers and approaches. This allowed discrete population units or metapopulations to be identified. The population genetic structure is compared to the recently defined harbour seal management regions (SCOS, 2011), ensuring Scottish Government’s regional management procedures and plans for harbour seals are based on genetic data as well as the currently employed ecological haulout and pupping site data. Analysis of DNA samples from a total of 453 individuals around Scotland including samples from comparative regions in the UK and Europe (including an out-group of Pacific harbour seals) was carried out. Following some initial trials the most appropriate population differentiation analysis comprised 10 putative populations across all the samples analysed. Focusing on Scotland, Bayesian clustering analysis clearly separated Scotland from England, France and the Dutch Wadden Sea. In this scenario 3 clusters were generally identified: a) Norway, b)West Coast of Scotland/Northern Ireland and c) Pentland Firth / Orkney / Shetland / Moray Firth / Tay and Eden with some degree of shared individuals between them. Examining the Scottish populations alone indicated there might be some additional separation between the Tay and Eden compared to the other north and east coast groups. Within the Scottish populations a number of harbour seal Management Areas have been assigned based on haul outs and breeding sites (SCOS, 2011). The result of the genetic analyses reported here clearly supports the designation and definition of these Areas. Allelic diversity and heterozygosity are standard measures that assess the level of inbreeding which populations display as a reflection of their ‘genetic health’. The populations with relatively good sample sizes and low levels of genetic diversity were Shetland (n=2.545, HO=0.363) and the Outer Hebrides (2.467, HO= 0.331). It has been widely shown that inbreeding, translated as very low levels of genetic diversity in wild populations is correlated with disease such as cancer (Acevedo-Whitehouse et al. 2003) and with susceptibility to pathogens such as parasites (Rijks et al. 2008) among others.Publisher PDFPublisher PD

Not just fat : investigating the proteome of cetacean blubber tissue

Mammalian adipose tissue is increasingly being recognized as an endocrine organ involved in the regulation of a number of metabolic processes and pathways. It responds to signals from different hormone systems and the central nervous system, and expresses a variety of protein factors with important paracrine and endocrine functions. This study presents a first step towards the systematic analysis of the protein content of cetacean adipose tissue, the blubber, in order to investigate the kinds of proteins present and their relative abundance. Full depth blubber subsamples were collected from dead-stranded harbour porpoises (Phocoena phocoena) (n = 21). Three total protein extraction methods were trialled, and the highest total protein yields with the lowest extraction variability were achieved using a RIPA cell lysis and extraction buffer based protocol. Extracted proteins were separated using 1D Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE), and identified using nanoflow Liquid Chromatography Electrospray Ionization in tandem with Mass Spectrometry (nLC-ESI–MS/MS). A range of proteins were identified (n = 295) and classed into eight functional groups, the most abundant of which were involved in cell function and metabolism (45%), immune response and inflammation (15%) and lipid metabolism (11%). These proteins likely originate both from the various cell types within the blubber tissue itself, and from the circulation. They therefore have the potential to capture information on the cellular and physiological stresses experienced by individuals at the time of sampling. The importance of this proteomic approach is two-fold: Firstly, it could help to assign novel functions to marine mammal blubber in keeping with current understanding of the multi-functional role of adipose tissue in other mammals. Secondly, it could lead to the development of a suite of biomarkers to better monitor the physiological state and health of live individuals though remote blubber biopsy sampling.Publisher PDFPeer reviewe

The measurement and normalisation of dielectric dissipation factor for diagnostics of transformer insulation

This article describes additional features of the method of Dielectric Dissipation Factor (DDF)/Tangent Delta (tgδ) measurement for a more accurate diagnosis of the condition of the transformer solid insulation. The proposed method is based on determining the DDF weight of solid insulation and oil in the measured value of DDF for the proper insulation zone of the transformer. The article proposes normalisation of DDF values according to the rated voltage of the transformer, and the analysis of the impact of design combining insulation and its condition on recalculation of DDF measurement results at a given temperature to the base temperature

PRIMJENA LINEARNOG PROGRAMIRANJA NA DRUŠTVENIM POLJOPRIVREDNIM GOSPODARSTVIMA

In recent years there has been significant interest in modelling cumulative effects and the population consequences of individual changes in cetacean behaviour and physiology due to disturbance. One potential source of disturbance that has garnered particular interest is whale-watching. Though perceived as 'green' or eco-friendly tourism, there is evidence that whale-watching can result in statistically significant and biologically meaningful changes in cetacean behaviour, raising the question whether whale-watching is in fact a long term sustainable activity. However, an assessment of the impacts of whale-watching on cetaceans requires an understanding of the potential behavioural and physiological effects, data to effectively address the question and suitable modelling techniques. Here, we review the current state of knowledge on the viability of long-term whale-watching, as well as logistical limitations and potential opportunities. We conclude that an integrated, coordinated approach will be needed to further understanding of the possible effects of whale-watching on cetaceans.Publisher PDFPeer reviewe

Understanding the combined effects of multiple stressors : a new perspective on a longstanding challenge

This work was supported by the Office of Naval Research [grant numbers N000142012697, N000142112096]; and the Strategic Environmental Research and Development Program [grant numbers RC20-1097, RC20-7188, RC21-3091].Wildlife populations and their habitats are exposed to an expanding diversity and intensity of stressors caused by human activities, within the broader context of natural processes and increasing pressure from climate change. Estimating how these multiple stressors affect individuals, populations, and ecosystems is thus of growing importance. However, their combined effects often cannot be predicted reliably from the individual effects of each stressor, and we lack the mechanistic understanding and analytical tools to predict their joint outcomes. We review the science of multiple stressors and present a conceptual framework that captures and reconciles the variety of existing approaches for assessing combined effects. Specifically, we show that all approaches lie along a spectrum, reflecting increasing assumptions about the mechanisms that regulate the action of single stressors and their combined effects. An emphasis on mechanisms improves analytical precision and predictive power but could introduce bias if the underlying assumptions are incorrect. A purely empirical approach has less risk of bias but requires adequate data on the effects of the full range of anticipated combinations of stressor types and magnitudes. We illustrate how this spectrum can be formalised into specific analytical methods, using an example of North Atlantic right whales feeding on limited prey resources while simultaneously being affected by entanglement in fishing gear. In practice, case-specific management needs and data availability will guide the exploration of the stressor combinations of interest and the selection of a suitable trade-off between precision and bias. We argue that the primary goal for adaptive management should be to identify the most practical and effective ways to remove or reduce specific combinations of stressors, bringing the risk of adverse impacts on populations and ecosystems below acceptable thresholds.Publisher PDFPeer reviewe

In-situ observations using tagged animals

Marine mammals help gather information on some of the harshest environments on the planet, through the use of miniaturized ocean sensors glued on their fur. Since 2004, hundreds of diving marine animals, mainly Antarctic and Arctic seals, have been fitted with a new generation of Argos tags developed by the Sea Mammal Research Unit of the University of St Andrews in Scotland, UK. These tags investigate the at-sea ecology of these animals while simultaneously collecting valuable oceanographic data. Some of the study species travel thousands of kilometres continuously diving to great depths (up to 2100 m). The resulting data are now freely available to the global scientific community at http://www.meop.net. Despite great progress in their reliability and data accuracy, the current generation of loggers while approaching standard ARGO quality specifications have yet to match them. Yet, improvements are underway; they involve updating the technology, implementing a more systematic phase of calibration and taking benefit of the recently acquired knowledge on the dynamical response of sensors. Together these efforts are rapidly transforming animal tagging into one of the most important sources of oceanographic data in polar regions and in many coastal areas.Publisher PDFNon peer reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes