Same space, different standards : a review of cumulative effects assessment practice for marine mammals

The lead author is a PhD student, whose stipend during the undertaking of this work was provided by a James Watt scholarship (Heriot-Watt University). Financial support enabling the open access publication of this research was provided by Natural England - the government’s adviser for the natural environment in England.Marine mammals are vulnerable to a variety of acute and chronic anthropogenic stressors, potentially experiencing these in isolation, successively and/or simultaneously. Formal assessment of the likely impact(s) of the cumulative effects of multiple stressors on a defined population is carried out through a Cumulative Effects Assessment (CEA), which is a mandatory component of the Environmental Impact Assessment (EIA) process in many countries. However, for marine mammals, the information required to feed into CEA, such as thresholds for disturbance, frequency of multiple (and simultaneous) exposures, interactions between stressors, and individual variation in response, is extremely limited, though our understanding is slowly improving. The gaps in knowledge make it challenging to effectively quantify and subsequently assess the risk of individual and population consequences of multiple disturbances in the form of a CEA. To assess the current state of practice for assessing cumulative effects on marine mammals within UK waters, 93 CEAs were reviewed across eleven maritime industries. An objective framework of thirteen evaluative criteria was used to score each assessment on a scale of 13-52 (weak - strong). Scores varied significantly by industry. On average, the aquaculture industry produced the lowest scoring CEAs, whilst the large offshore windfarm industry (≥ 20 turbines) scored highest, according to the scoring criteria used. There was a significant increase in scores over the sample period (2009-2019), though this was mostly attributed to five industries (cable, large and small offshore wind farms, tidal and wave energy). There was inconsistency in the language used to define and describe cumulative effects and a lack of routinely applied methodology. We use the findings presented here, along with a wider review of the literature, to provide recommendations and discussion points aimed at supporting the standardisation and improvement of CEA practice. Although this research focused on how marine mammals were considered within UK CEAs, recommendations made are broadly applicable to assessments conducted for other receptors, countries and/or environments. Adoption of these proposals would help to ensure a more consistent approach, and would aid decision-makers and practitioners in mitigating any potential impacts, to ensure conservation objectives of marine mammal populations are not compromised.Publisher PDFPeer reviewe

"Give me some space" : exploring youth to parent aggression and violence

A small scale qualitative project, undertaken by an interdisciplinary domestic violence research group involving academic researchers and research assistants, with colleagues from Independent Domestic Abuse Services (IDAS), investigated youth aggression and violence against parents. Following the literature review, data was generated through several research conversations with young people (n = 2), through semi-structured interviews with mothers (n = 3) and practitioners (n = 5), and through a practitioner focus group (n = 8). Thematic analysis and triangulation of the data from parents, practitioners and young people, elicited interconnected and complex overarching themes. Young people could be both victim and perpetrator. The witnessing or experiencing of domestic aggression and violence raised the concept of ‘bystander children’. The impact of young people experiencing familial violence was underestimated by parents. For practitioners, the effects of working with domestic violence was shown to be significant - both positively and negatively

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

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

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Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)