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Funding: Bureau of Ocean Energy Management (contract number M14PC00009), representing an integrated analysis drawn from the work fully reported in OCS Study Report Number BOEM 2018-003. Many marine animals have evolved sensory abilities to use electric and magnetic cues in essential aspects of life history, such as to detect prey, predators and mates as well as to orientate and migrate. Potential disruption of vital cues by human activities must be understood in order to mitigate potential negative influences. Cable deployments in coastal waters are increasing worldwide, in capacity and number, owing to growing demands for electrical power and telecommunications. Increasingly, the local electromagnetic environment used by electro- and magneto-sensitive species will be altered. We quantified biologically relevant behavioural responses of the presumed, magneto-receptive American lobster and the electro-sensitive Little skate to electromagnetic field (EMF) emissions of a subsea high voltage direct current (HVDC) transmission cable for domestic electricity supply. We demonstrate a striking increase in exploratory/foraging behaviour in skates in response to EMF and a more subtle exploratory response in lobsters. In addition, by directly measuring both the magnetic and electric field components of the EMF emitted by HVDC cables we found that there were DC and unexpectedly AC components. Modelling, restricted to the DC component, showed good agreement with measured results. Our cross-disciplinary study highlights the need to integrate an understanding of the natural and anthropogenic EMF environment together with the responses of sensitive animals when planning future cable deployments and predicting their environmental effects. Publisher PDF

1. Connectivity of marine populations and ecosystems is crucial to maintaining and enhancing their structure, distribution, persistence, resilience and productivity. Artificial hard substrate, such as that associated with oil and gas platforms, provides settlement opportunities for species adapted to hard substrates in areas of soft sediment. The contribution of artificial hard substrate and the consequences of its removal (e.g. through decommissioning) to marine connectivity is not clear, yet such information is vital to inform marine spatial planning and future policy decisions on the use and protection of marine resources. 2. This study demonstrates the application of a social network analysis approach to quantify and describe the ecological connectivity, informed by particle tracking model outputs, of hard substrate marine communities in the North Sea. Through comparison of networks with and without artificial hard substrate, and based on hypothetical decommissioning scenarios, this study provides insight into the contribution of artificial hard substrate, and the consequence of decommissioning, to the structure and function of marine community connectivity. 3. This study highlights that artificial hard substrate, despite providing only a small proportion of the total area of hard substrate, increases the geographic extent and connectivity of the hard substrate network, bridging gaps, thereby providing ‘stepping stones’ between otherwise disconnected areas of natural hard substrate. Compared to the baseline scenario, a decommissioning scenario with full removal of oil and gas platforms results in a nearly 60% reduction in connectivity. Such reduction in connectivity may have negative implications for species’ distribution, gene flow and resilience following disturbance or exploitation of marine hard substrate communities. 4. Synthesis and applications. Social network analysis can provide valuable insight into connectivity between marine communities and enable the evaluation of impacts associated with changes to the marine environment. Providing standardized, transparent and robust outputs, such a tool is useful to facilitate understanding across different disciplines, including marine science, marine spatial planning and marine policy. Social network analysis therefore has great potential to address current knowledge gaps with respect to marine connectivity and crucially facilitate assessment of the impacts of changes in offshore substrate as part of the marine spatial planning process, thereby informing policy and marine management decisions.

Part of this work was supported by the Bureau of Ocean Energy Management (contract number M14PC00009). The expanding marine renewable energy industry will increase the prevalence of electromagnetic fields (EMFs) from power cables in coastal waters. Assessments of environmental impacts are required within licensing/permitting processes and increased prevalence of cables will increase questions concerning EMF emissions and potential cumulative impacts. It is presumed that protecting a cable by burial, may also mitigate EMF emissions and potential impacts on species. Focussing on a bundled high voltage direct current (HVDC) transmission cable, we use computational and interpretive models to explore the influence of cable properties and burial depth on the DC magnetic field (DC-MF) potentially encountered by receptive species. Greater cable pair separation increased the deviations from the geomagnetic field and while deeper burial reduced the deviations, the DC-MF was present at intensities perceivable by receptive species. An animal moving along a cable route may be exposed to variable EMFs due to varied burial depth and that combined with an animal’s position in the water column determines the distance from source and EMF exposure. Modelling contextually realistic scenarios would improve assessments of potential effects. We suggest developers and cable industries make cable properties and energy transmission data available, enabling realistic modelling and environmental assessment supporting future developments. Postprint

BackgroundImmune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI.MethodsFifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year.ResultsDifferential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (papp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (pConclusionsMultiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma.

The aim of this study was to assess the feasibility of rapid sodium MRI (23Na-MRI) for the imaging of peritoneal cancer deposits in high grade serous ovarian cancer (HGSOC) and to evaluate the relationship of 23Na-MRI with tumour cellularity. 23Na-MRI was performed at 3 T on twelve HGSOC patients using a 3D-cones acquisition technique. Tumour biopsies specimens were collected after imaging and cellularity was measured from histology. Total 23Na-MRI scan time for each patient was approximately 11 min. At an isotropic resolution of 5.6 mm, signal-to-noise ratios (SNRs) of 82.2 ± 15.3 and 15.1 ± 7.1 (mean ± standard deviation) were achieved for imaging of tumour tissue sodium concentration (TSC) and intracellular weighted sodium concentration (IWS) respectively. Tumour TSC and IWS concentrations were: 56.8 ± 19.1 mM and 30.8 ± 9.2 mM respectively and skeletal muscle TSC and IWS concentrations were 33.2 ± 16.3 mM and 20.5 ± 9.9 mM respectively. There were significant sodium concentration differences between cancer and skeletal muscle, Wilcoxon signed-rank test, P

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1–13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7–11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5–6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. Significance: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7–11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

PURPOSE Spatial heterogeneity of tumors is a major challenge in precision oncology. The relationship between molecular and imaging heterogeneity is still poorly understood because it relies on the accurate coregistration of medical images and tissue biopsies. Tumor molds can guide the localization of biopsies, but their creation is time consuming, technologically challenging, and difficult to interface with routine clinical practice. These hurdles have so far hindered the progress in the area of multiscale integration of tumor heterogeneity data. METHODS We have developed an open-source computational framework to automatically produce patient-specific 3-dimensional–printed molds that can be used in the clinical setting. Our approach achieves accurate coregistration of sampling location between tissue and imaging, and integrates seamlessly with clinical, imaging, and pathology workflows. RESULTS We applied our framework to patients with renal cancer undergoing radical nephrectomy. We created personalized molds for 6 patients, obtaining Dice similarity coefficients between imaging and tissue sections ranging from 0.86 to 0.96 for tumor regions and between 0.70 and 0.76 for healthy kidneys. The framework required minimal manual intervention, producing the final mold design in just minutes, while automatically taking into account clinical considerations such as a preference for specific cutting planes. CONCLUSION Our work provides a robust and automated interface between imaging and tissue samples, enabling the development of clinical studies to probe tumor heterogeneity on multiple spatial scales.

As the EU's commitment to renewable energy is projected to grow to 20% of energy generation by 2020, the use of marine renewable energy from wind, wave and tidal resources is increasing. This literature review (233 studies) (i) summarizes knowledge on how marine renewable energy devices affect benthic environments, (ii) explains how these effects could alter ecosystem processes that support major ecosystem services and (iii) provides an approach to determine urgent research needs. Conceptual diagrams were set up to structure hypothesized cause-effect relationships (i.e. paths). Paths were scored for (i) temporal and spatial scale of the effect, (ii) benthic sensitivity to these effects, (iii) the effect consistency and iv) scoring confidence, and consecutively ranked. This approach identified prominent knowledge gaps and research needs about (a) hydrodynamic changes possibly resulting in altered primary production with potential consequences for filter feeders, (b) the introduction and range expansion of non-native species (through stepping stone effects) and, (c) noise and vibration effects on benthic organisms. Our results further provide evidence that benthic sensitivity to offshore renewable effects is higher than previously indicated. Knowledge on changes of ecological functioning through cascading effects is limited and requires distinct hypothesis-driven research combined with integrative ecological modelling.

Background The accuracy of any radiation therapy delivery is limited by target organ translocation and distortion. Bladder filling is one of the recognised factors affecting prostate translocation and distortion. The purpose of our study was to evaluate the effect of bladder volume on prostate translocation and distortion by using detailed three-dimensional prostate delineation on MRI. Patients and methods Fifteen healthy male volunteers were recruited in this prospective, institutional review board-approved study. Each volunteer underwent 4 different drinking preparations prior to imaging, with MR images acquired pre- and post-void. MR images were co-registered by using bony landmarks and three-dimensional contouring was performed in order to assess the degree of prostate translocation and distortion. According to changes in bladder or rectum distention, subdivisions were made into bladder and rectal groups. Studies with concomitant change in both bladder and rectal volume were excluded. Results Forty studies were included in the bladder volume study group and 8 in the rectal volume study group. The differences in rectal volumes yielded higher levels of translocation (p < 0.01) and distortion (p = 0.02) than differences in bladder volume. Moderate correlation of prostate translocation with bladder filling was shown (r = 0.64, p < 0.01). There was no important prostate translocation when bladder volume change was < 2-fold (p < 0.01). Moderate correlation of prostate distortion with bladder filling was shown (r = 0.61, p < 0.01). Conclusions Bladder volume has a minimal effect on prostate translocation and effect on prostate distortion is negligible. Prostate translocation may be minimalised if there is < 2-fold increase in the bladder volume.

The growing awareness of climate change and the recognised need to secure energy production has been a driving force behind the expansion of the offshore wind industry across the world. Benefits from offshore wind farms (OWFs) may extend further than low CO2 energy production. Wind turbine substructures introduce hard surfaces that are rapidly colonised by epibenthic marine organisms, altering biomass and biodiversity within the local ecosystem. Biodiversity plays a critical role in supporting ecosystem processes and functions that maintain ecosystem services. As offshore wind development continues to grow and modify marine habitats, changes in biodiversity could affect the provision of ecosystem services. In this context, this review sets out to capture the current understanding of epibenthic biodiversity change following the installation of OWFs and attempt to link these changes in biodiversity with marine ecosystem services through the associated processes and functions.

A computational algorithm was designed to produce a measure of DW image distortion across the prostate. This algorithm was tested and validated on virtual phantoms incorporating known degrees and distributions of distortion. A study was then carried out on DW image volumes from three sets of 10 patients who had been imaged previously. These volumes had been radiologically assessed to have, respectively, ‘no distortion’ or ‘significant distortion’ or the potential for ‘significant distortion’ due to susceptibility effects from hip prostheses. Prostate outlines were drawn on a T2-weighted (T2W) image ‘gold-standard’ volume and on an ADC image volume derived from DW images acquired over the same region. The algorithm was then applied to these outlines to quantify and map image distortion. The proposed method correctly reproduced known distortion values and distributions in virtual phantoms. It also successfully distinguished between the three groups of patients: mean distortion in ‘non-distorted’ image volumes, 1.942 ± 0.582 mm; ‘distorted’, 4.402 ± 1.098 mm; and ‘hip patients’ 8.083 ± 4.653 mm; P

Marine renewable energy developments (MREDs) are rapidly expanding in size and number as society strives to maintain electricity generation whilst simultaneously reducing climate-change linked CO2 emissions. MREDs are part of an ongoing large-scale modification of coastal waters that also includes activities such as commercial fishing, shipping, aggregate extraction, aquaculture, dredging, spoil-dumping and oil and gas exploitation. It is increasingly accepted that developments, of any kind, should only proceed if they are ecologically sustainable and will not reduce current or future delivery of ecosystem services. The benthos underpins crucial marine ecosystem services yet, in relation to MREDs, is currently poorly monitored: current monitoring programmes are extensive and costly yet provide little useful data in relation to ecosystem-scale-related changes, a situation called ‘data-rich, information-poor’ (DRIP). MRED –benthic interactions may cause changes that are of a sufficient scale to change ecosystem services provision, particularly in terms of fisheries and biodiversity and, via trophic linkages, change the distribution of fish, birds and mammals. The production of DRIPy data should be eliminated and the resources used instead to address relevant questions that are logically bounded in time and space. Efforts should target identifying metrics of change that can be linked to ecosystem function or service provision, particularly where those metrics show strongly non-linear effects in relation to the stressor. Future monitoring should also be designed to contribute towards predictive ecosystem models and be sufficiently robust and understandable to facilitate transparent, auditable and timely decision-making.

Introduction: More than a quarter of tumors are missed by magnetic resonance imaging/ultrasound (MRI/US) fusion-guided biopsy, the majority due to software-based misregistration. Transrectal approaches to biopsy are typically performed in the lateral decubitus position; conversely, diagnostic MRI is performed with the patient lying supine. Any position-related difference in prostate location or gland deformation could potentially exacerbate misregistration at subsequent biopsy. Methods: Fifteen healthy male volunteers (mean age 35.9 years, range 27–53) were included in this prospective, institutional review board-approved study. Each volunteer had an MRI performed in the supine position, followed by the second in the lateral decubitus position (mimicking a typical biopsy position). MRI images were co-registered and analyzed in order to assess prostate translocation and distortion. Results: Whole prostate translocation of ≥5 mm was observed in 20% of patients and ≥3 mm in 60% of patients. When dividing the prostate into prostatic sectors, the prostatic base demonstrated the largest positional difference. When plotting the translocation directions with relative volume difference, there was a moderate negative correlation trend in the latero-lateral direction. Only minimal distortion was observed, with similar distortion among all prostatic sectors. Conclusions: Positional change affects the prostate translocation, however, the effect on prostate distortion appears to be negligible. Prostate translocation in latero-lateral direction can be minimized with larger bladder volumes. Thereby, prostate translocation needs to be considered alongside software misregistration error; however, positional change should not affect software registration of MRI/US fusion-guided prostate biopsy.

This study assessed the feasibility of using diffusion kurtosis imaging (DKI) as a measure of tissue heterogeneity and proliferation to predict the response of high grade serous ovarian cancer (HGSOC) to neoadjuvant chemotherapy (NACT). Seventeen patients with HGSOC were imaged at 3 T and had biopsy samples taken prior to any treatment. The patients were divided into two groups: responders and non-responders based on Response Evaluation Criteria In Solid Tumours (RECIST) criteria. The following imaging metrics were calculated: apparent diffusion coefficient (ADC), apparent diffusion (Dapp) and apparent kurtosis (Kapp). Tumour cellularity and proliferation were quantified using histology and Ki-67 immunohistochemistry. Mean Kapp before therapy was higher in responders compared to non-responders: 0.69 ± 0.13 versus 0.51 ± 0.11 respectively, P = 0.02. Tumour cellularity correlated positively with Kapp (rho = 0.50, P = 0.04) and negatively with both ADC (rho = −0.72, P = 0.001) and Dapp (rho = −0.80, P app (rho = 0.53, P = 0.03) but not with ADC or Dapp. In conclusion, Kapp was found to be a potential predictive biomarker of NACT response in HGSOC, which suggests that DKI is a promising clinical tool for use oncology and radiology that should be evaluated further in future larger studies.

PURPOSESpatial heterogeneity of tumours is a major challenge in precision oncology. The relationship between molecular and imaging heterogeneity is still poorly understood, as it relies on the accurate co-registration of medical images and tissue biopsies. tumour moulds can guide the localization of biopsies, but their creation is time consuming, technologically challenging, and difficult to interface with routine clinical practice. These hurdles have so far hindered the progress in the area of multiscale integration of tumour heterogeneity data.METHODSWe have developed an open source computational framework to automatically produce patient-specific 3D-printed moulds that can be used in the clinical setting. Our approach achieves accurate co-registration of sampling location between tissue and imaging, and integrates seamlessly with clinical, imaging and pathology workflows.RESULTSWe applied our framework to patients with renal cancer undergoing radical nephrectomy. We created personalised moulds for five patients, obtaining Dice similarity coefficients between imaging and tissue sections ranging from 0.86 to 0.93 for tumour regions, and between 0.70 and 0.76 for healthy kidney. The framework required minimal manual intervention, producing the final mould design in just minutes, while automatically taking into account clinical considerations such as a preference for specific cutting planes.CONCLUSIONOur work provides a robust and automated interface between imaging and tissue samples, enabling the development of clinical studies to probe tumour heterogeneity on multiple spatial scales.

© The Ecological Society of America The removal of thousands of structures associated with oil and gas development from the world's oceans is well underway, yet the environmental impacts of this decommissioning practice remain unknown. Similar impacts will be associated with the eventual removal of offshore wind turbines. We conducted a global survey of environmental experts to guide best decommissioning practices in the North Sea, a region with a substantial removal burden. In contrast to current regulations, 94.7% of experts (36 out of 38) agreed that a more flexible case-by-case approach to decommissioning could benefit the North Sea environment. Partial removal options were considered to deliver better environmental outcomes than complete removal for platforms, but both approaches were equally supported for wind turbines. Key considerations identified for decommissioning were biodiversity enhancement, provision of reef habitat, and protection from bottom trawling, all of which are negatively affected by complete removal. We provide recommendations to guide the revision of offshore decommissioning policy, including a temporary suspension of obligatory removal.

OBJECTIVE: To compare image quality, artefact, and distortion in standard echo-planar imaging (EPI) with periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) for prostate magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in patients with previous total hip replacement (THR). METHODS: 21 male subjects with a clinical suspicion for, or known prostate cancer and previous THR were scanned at 1.5 T using a phased-array body coil. DWI was obtained using single-shot EPI and PROPELLER techniques using fat saturation (PROPELLER-DWI-FS), and without (PROPELLER-DWI-NFS). Image quality (the overall impression of diagnostic quality) was compared to T2-weighted (T2WI) imaging using a 5-point Likert scale, with diffusion sequences additionally scored for artefact and distortion according to a 4-point scale, with artefact defined as the amount of prostate affected and distortion as the degree of warping of the organ. The T2W and DW image volumes were compared to produce quantitative distortion maps. A two-sample Wilcoxon test compared the qualitative scores, with inter-reader variability calculated using Cohen's kappa. RESULTS: 21 patients were included in the study, with an average age of 70.4 years and PSA 9.2 ng/ml. Hip metalwork was present bilaterally in 3 patients, left-sided in 9, and right-sided in 9. PROPELLER-DWI-FS significantly improved image quality (p < 0.01) and reduced distortion (p < 0.01) when compared to standard EP-DWI. Artefact was not shown to be significantly improved. The last 5 patients in the study were additionally imaged with PROPELLER-DWI-NFS, which resulted in a significant reduction in artefact compared to EP-DWI (p < 0.05). Quantitative distortion was significantly lower compared to EP-DWI for both PROPELLER with fat saturation (p < 0.01) and without fat saturation (p < 0.01). CONCLUSION: PROPELLER-DWI demonstrates better image quality and decreases both artefact and distortion compared to conventional echo planar sequences in patients with hip metalwork.

IntroductionAcquired brain injury (ABI) is a major cause of morbidity and mortality in childhood. Specialist rehabilitation services are often situated far from families and local services may be non-standardised and fragmented. A strategic level of understanding is needed to improve patient care and outcomes. Roadmapping techniques are commonly used in industry settings to discover and present a systematic understanding of structures; however, they are rarely used in the healthcare setting. With continuing pressures on healthcare systems worldwide, they provide an effective method for examining services.MethodsThe Institute for Manufacturing (IfM) strategic roadmapping method was used to identify areas of difficulty and opportunities in paediatric neurorehabilitation. Participants included stakeholders from a wide range of professions and sectors who have input with children after ABI.ResultsDelegates identified a range of ‘layers’ covering trends, drivers, current experience and unmet needs. From these layers, four priorities were identified and further expanded.These included: ‘access to medical and therapy expertise close(r) to home’, ‘shared understanding across family, school and health’, ‘family and professional awareness of resources and support’ and ‘establishing a centre for rehabilitation technology evaluation, advice and co-ordination of services and research’.ConclusionThe IfM strategic roadmapping method identified and developed key areas for development in the field of paediatric neurological rehabilitation. Healthcare professionals looking at strategic level difficulties should strongly consider the use of such systematic tools when evaluating areas of practice.

Proponents of marine renewable energy worldwide highlight that regulatory and consenting procedures are a significant barrier to the upscaling of infrastructure required to transform the energy generation sector. Uncertainties about the cumulative effects of marine renewable energy developments cause substantial delays during the consenting process, which are exacerbated by the lack of clarity about how to assess cumulative effects. These obstacles have contributed to perceptions that this essential emerging industry receives disproportionate scrutiny relative to established maritime activities. However, alongside legislated targets to reduce carbon emissions, there are legal obligations to protect, maintain and improve the condition of the marine environment. As the imperative to halt the decline in the condition of the environment increases, so expectations of cumulative impact assessments grow and the risk of consenting delays persists. To investigate how robust current cumulative impact assessment practise is, a novel evaluation framework was developed and applied to Environmental Statements of the world's largest offshore wind farms, currently in United Kingdom waters. The framework was designed to evaluate cumulative impact assessments relative to the information needs of decision-makers tasked with managing cumulative effects. We found that current practise does not meet those needs, that there is dissonance between science and practise, and problematic variability between assessments was observed. Straightforward recommendations for improved practise are provided, which if implemented may ease the perceived regulatory burden by clarifying practise. We also highlight additional steps that could enable project-led cumulative impact assessments to better support regional marine management. The results and recommendations will be of interest to countries worldwide where marine renewable energy is emerging alongside ecosystem-approach and marine spatial planning aspirations.

Objective To prospectively investigate the longitudinal effect of ejaculatory abstinence on MRI-measured seminal vesicle (SV) volume and whole-prostate ADC over consecutive days. Methods 15 healthy male volunteers (mean 35.9 years, range 27–53) underwent 3-T MRI at baseline and 1, 2 and 3 days post-ejaculation. Prostate and SV volumes were derived by volume segmentation and whole-gland apparent diffusion coefficient (ADC) values calculated. A mixed-effects linear regression compared ADC values and prostate/seminal vesicle volumes in each volunteer between studies in a pairwise manner. Results All subjects completed the four MRIs. Mean prostate volume was 22.45 cm3 (range 13.04–31.21 cm3), with no change between the four studies (p = 0.89–0.99). 13/15 subjects showed SV volume reduction from baseline to day 1, with group-mean decreasing from 6.45 to 4.80 cm3 (−25.6%, p

Concurrent with the development of wind energy, research activity on wind energy generation and wildlife has evolved significantly during the last decade. This chapter presents an overview of remaining key knowledge gaps, consequent future research directions and their significance for management and planning for wind energy generation. The impacts of wind farms on wildlife are generally site-, species- and season-specific and related management strategies and practices may differ considerably between countries. These differences acknowledge the need to consider potential wildlife impacts for each wind farm project. Still, the ecological mechanisms guiding species’ responses and potential vulnerability to wind farms can be expected to be fundamental in nature. A more cohesive understanding of the causes, patterns, mechanisms, and consequences of animal movement decisions will thereby facilitate successful mitigation of impacts. This requires planning approaches that implement the mitigation hierarchy effectively to reduce risks to species of concern. At larger geographical scales, population-level and cumulative impacts of multiple wind farms (and other anthropogenic activity) need to be addressed. This requires longitudinal and multiple-site studies to identify species-specific traits that influence risk of mortality, notably from collision with wind turbines, disturbance or barrier effects. In addition, appropriate pre- and post-construction monitoring techniques must be utilized. Predictive modelling to forecast risk, while tackling spatio-temporal variability, can guide the mitigation of wildlife impacts at wind farms.

This study investigated the effect of temporal resolution on the dual-input pharmacokinetic (PK) modelling of dynamic contrast-enhanced MRI (DCE-MRI) data from normal volunteer livers and from patients with hepatocellular carcinoma. Eleven volunteers and five patients were examined at 3 T. Two sections, one optimized for the vascular input functions (VIF) and one for the tissue, were imaged within a single heart-beat (HB) using a saturation-recovery fast gradient echo sequence. The data was analysed using a dual-input single-compartment PK model. The VIFs and/or uptake curves were then temporally sub-sampled (at interval ▵t = [2-20] s) before being subject to the same PK analysis. Statistical comparisons of tumour and normal tissue PK parameter values using a 5% significance level gave rise to the same study results when temporally sub-sampling the VIFs to HB▵t4 s. However, sub-sampling to ▵t4 s did adversely affect the statistical comparisons. Temporal sub-sampling of just the liver/tumour tissue uptake curves at ▵t ≤ 20 s, whilst using high temporal resolution VIFs, did not substantially affect PK parameter statistical comparisons. In conclusion, there is no practical advantage to be gained from acquiring very high temporal resolution hepatic DCE-MRI data. Instead the high temporal resolution could be usefully traded for increased spatial resolution or SNR.

Marine renewable energy promises to assist in the effort to reduce carbon emissions worldwide. As with any large-scale development in the marine environment, however, it comes with uncertainty about potential environmental impacts, most of which have not been adequately evaluated—in part because many of the devices have yet to be deployed and tested. We review the nature of environmental and, more specifically, ecological effects of the development of diverse types of marine renewable energy—covering marine wind, wave, tidal, ocean current, and thermal gradient—and discuss the current state of knowledge or uncertainty on how these effects may be manifested. Many of the projected effects are common with other types of development in the marine environment; for example, additional structures lead to concerns for entanglement, habitat change, and community change. Other effects are relatively unique to marine energy conversion, and specific to the type of energy being harnessed, the individual device type, or the reduction in energy in marine systems. While many potential impacts are unavoidable but measurable, we would argue it is possible (and necessary) to minimize others through careful device development and site selection; the scale of development, however, will lead to cumulative effects that we must understand to avoid environmental impacts. Renewable energy developers, regulators, scientists, engineers, and ocean stakeholders must work together to achieve the common dual objectives of clean renewable energy and a healthy marine environment.

A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T(1)-weighted data from the descending aorta and hepatic portal vein, and on T*(2)-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

the uk government's strategy for reducing greenhouse gas emissions to meet carbon mitigation obligations and the wider aims on sustainable development has provided the impetus for a rapid growth in activity associated with offshore renewable energy, particularly offshore wind farms. recently, consents for offshore renewable energy development (ored) were approved in three strategic areas—the outer thames estuary, the greater wash and the eastern irish sea. the scale of the planned developments means that each will have a large environmental footprint and multiple ored will have a cumulative effect on the environment. here we discuss current understanding of ored construction, operation and decommissioning with regard to the potential interaction with elasmobranchs because of the worrying status of elasmobranch populations within the uk coastal zone. based on the likely interactions between elasmobranchs and ored a framework is proposed which aims to promote cooperative initiatives between elasmobranch conservation management and the offshore renewables industry.

Summary 1Global-scale environmental degradation and its links with non-renewable fossil fuels have led to an increasing interest in generating electricity from renewable energy resources. Much of this interest centres on offshore renewable energy developments (ORED). The large scale of proposed ORED will add to the existing human pressures on coastal ecosystems, therefore any ecological costs and benefits must be determined. 2The current pressures on coastal ecology set the context within which the potential impacts (both positive and negative) of offshore renewable energy generation are discussed. 3The number of published peer-review articles relating to renewable energy has increased dramatically since 1991. Significantly, only a small proportion of these articles relate to environmental impacts and none considers coastal ecology. 4Actual or potential environmental impact can occur during construction, operation and/or decommissioning of ORED. 5Construction and decommissioning are likely to cause significant physical disturbance to the local environment. There are both short- and long-term implications for the local biological communities. The significance of any effects is likely to depend on the natural disturbance regime and the stability and resilience of the communities. 6During day-to-day operation, underwater noise, emission of electromagnetic fields and collision or avoidance with the energy structures represent further potential impacts on coastal species, particularly large predators. The wider ecological implications of any direct and indirect effects are discussed. 7Synthesis and applications. This review demonstrates that offshore renewable energy developments will have direct and, potentially, indirect consequences for coastal ecology, with these effects occurring at different scales. Ecologists should be involved throughout all the phases of an ORED to ensure that appropriate assessments of the interaction of single and multiple developments with the coastal environment are undertaken.

To aid the extraction of the portal venous input function (PVIF) from axial dynamic contrast-enhanced CT images of the liver, eliminating the need for full manual outlining of the vessel across time points.A cohort of 20 patients undergoing perfusion CT imaging of the liver was examined. Dynamic images of the liver were reformatted into contiguous thin slices. A region of interest was defined within a transverse section of the portal vein on a single contrast-enhanced image. This region of interest was then computationally projected across all thin slices for all time points to yield a semi-automated PVIF curve. This was compared against the "gold-standard" PVIF curve obtained by conventional manual outlining.Bland-Altman plots of curve characteristics indicated no substantial difference between automated and manual PVIF curves [concordance correlation coefficient in the range (0.66, 0.98)]. No substantial differences were shown by Bland-Altman plots of derived pharmacokinetic parameters when a suitable kinetic model was applied in each case [concordance correlation coefficient in range (0.92, 0.95)].This semi-automated method of extracting the PVIF performed equivalently to a "gold-standard" manual method for assessing liver function. Advances in knowledge: This technique provides a quick, simple and effective solution to the problems incurred by respiration motion and partial volume factors in the determination of the PVIF in liver dynamic contrast-enhanced CT.

e21032 Background: Circulating tumour DNA (ctDNA) is released by cancer cells into the bloodstream and can be analysed via liquid biopsy, providing a real-time snapshot of tumour burden. After treatment, ctDNA concentrations may be low, making detection challenging, and collecting larger sample volumes may be impractical. Our study aims to achieve high-sensitivity monitoring of melanoma patients melanoma on therapy, maximising the number of mutations targeted per patient by individualised sequencing. Methods: 72 patients with stage 3 or 4 melanoma have so far been recruited to MelResist, a translational research study. 235 plasma, urine, tumour and buffy coat samples have been analysed for 10 BRAF mutant metastatic melanoma patients receiving systemic therapies, and 30 matched CT scans were analysed for RECIST response. Exome or targeted sequencing were carried out on tumour samples and plasma at baseline and progression and mutations identified were used to design individualised amplicon and hybrid-capture sequencing panels targeting hundreds to thousands of mutations per patient. Results: Baseline ctDNA allele fraction predicted for overall survival ( r = -0.56, p < 0.05). Longitudinal analysis of ctDNA showed that mutant allele fractions significantly correlated with tumour burden from CT imaging ( r = 0.79, p < 0.0001) and ctDNA changes were concordant with 20/22 (90%) of RECIST response events. ctDNA allele fractions increased with a lead time of 70 days relative to serum lactate dehydrogenase, a standard measure of disease burden (IQR = 42-142 days). Targeting multiple mutations per patient enabled detection of less than one mutant genome copy per sample and allowed comprehensive monitoring of clonal evolution on therapy, even using limited sample volumes. Conclusions: Analysis of an initial cohort of BRAF mutant metastatic melanoma patients has confirmed feasibility to apply an individualised targeted sequencing panel on both plasma and urine DNA. For a given sample volume, monitoring multiple mutations improves detection sensitivity compared to targeting individual loci, has predictive value and can be applied to all melanoma patients, irrespective of BRAF mutation status.

In the marine environment there are natural magnetic and electric fields associated with both physical and biological sources, and there are anthropogenic electromagnetic fields (EMFs) that permeate it. Many marine animals can detect electric and magnetic fields and utilize them in such important life processes as movement, orientation and foraging. Here, these EMFs are explored and discussed in terms of how they arise, their properties (particularly those that are measurable) and the animals that have the ability to detect them. Then the evidence base for whether anthropogenic EMFs can affect sensitive receptor animals is explored. As marine renewable energy developments (MREDs) expand rapidly worldwide, with multiple devices and networks of subsea cables that emit EMFs into the marine environment, it is necessary to focus on their interaction with marine animals. The MRED industry has to take EMFs into account, so the industry perspective is also covered. Finally, suggestions are made on how research on EMFs associated with MREDs (and other sources) and its interaction with marine animals should advance in future.

The race for a timely combat of climate change through the reduction of greenhouse gasses such as carbon dioxide has pushed renewable energy developments to a higher echelon. At present, wind is one of the most profitable sources of exploitable renewable energy. Wind farms are popping up at many places worldwide. Their expansion on land, however is constrained, because sites where wind farms do not conflict with the high-quality environmental standards of the local community are limited. Being uninhabited, the marine environment offers a vast area for wind farm development. Being uninhabited, however, does not equal not being subject to impact. The sea and oceans host rich ecosystems, many of which have and continue to deliver priceless and indispensable goods and services to mankind. Offshore wind farm development is hence subject to environmental impact assessment and residual impacts should be carefully monitored. Most, if not all, current offshore wind farms are accompanied by an environmental monitoring programme. These programmes should be considered the ‘finger on the pulse’ to avoid surpassing critical impact levels. They further ensure the achievement of the knowledge base needed to adjust new developments in a scientifically and environmentally sensitive and sound manner. On 26–28 November 2013, the Royal Belgian Institute of Natural Sciences organised the international scientific WinMon.BE 2013 conference on ‘‘Environmental impacts of offshorewind farms: learning from the past to optimise future monitoring programmes’’ (http:// odnature.naturalsciences.be/winmonbe2013).During the Guest editors: Steven Degraer, Jennifer Dannheim, Andrew B. Gill, Han Lindeboom & Dan Wilhelmsson / Environmental impacts of offshore wind farms

To investigate the role of multiparametric magnetic resonance (MR) imaging in the evaluation of response to platinum-based neoadjuvant chemotherapy in advanced ovarian cancer and to compare imaging parameters between primary ovarian mass and metastatic disease.Evaluable patients suspected of having advanced ovarian carcinoma were enrolled in a prospective protocol-driven study. Research ethics committee approval and written informed consent were obtained. Multiparametric MR imaging (diffusion-weighted MR imaging, dynamic contrast material-enhanced [DCE] MR imaging, and hydrogen 1 MR spectroscopy) was performed with a 3.0-T wholebody MR imaging system. Three marker lesions-primary ovarian mass, omental cake, and peritoneal deposit-were outlined by a radiologist on apparent diffusion coefficient (ADC) and vascular signal fraction (VSF) maps and on DCE MR images. Comparisons of mean ADC, mean VSF, DCE MR imaging parameters, and choline concentration between responders and nonresponders were based on Response Evaluation Criteria in Solid Tumors and CA-125 criteria.Twenty-two patients were evaluable. The mean ADC for peritoneal metastases was lower than that for ovarian (P = .015) and omental (P = .006) sites. There were no differences in pretreatment DCE MR imaging parameters between tumor sites. After treatment, responders showed a significantly larger increase in ADC (P = .021) and fractional volume of the extravascular extracellular space (v(e)) (P = .025) of ovarian lesions compared with nonresponders, but there was no change in ADC at other sites. Pre- and posttreatment values of choline concentration of ovarian lesions were lower in responders (P = .025) than in nonresponders (P = .010).The significant differences in baseline ADCs among primary ovarian cancer, omental cake, and peritoneal deposits indicate that diffusivity profiles may be tumor-site dependent, suggesting biologic heterogeneity of disease. ADC and v(e) parameters correlated with the cytotoxic effects of platinum-based therapy and may be useful response markers, while choline concentration predicted but did not reflect response.

Androgen deprivation therapy (ADT) is a key primary treatment for advanced and metastatic prostate cancer and is an important neoadjuvant before radiotherapy. We evaluated 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI in monitoring ADT response. Twenty-three consecutive patients with prostate cancer treated by primary ADT were included. Imaging was performed at baseline and 3 months posttreatment with ADT. After 3 months therapy there was a significant reduction in all dynamic contrast-enhanced MRI parameters measured in tumor regions of interest (K(trans), k(ep), v(p), IAUGC-90); P < 0.001. Areas of normal-appearing peripheral zone showed no significant change; P = 0.285-0.879. Post-ADT, there was no significant change in apparent diffusion coefficient values in tumors, whilst apparent diffusion coefficient values significantly decreased in areas of normal-appearing peripheral zone, from 1.786 × 10(-3) mm(2) /s to 1.561 × 10(-3) mm(2) /s; P = 0.007. As expected the median Prostate-Specific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL posttreatment, and median prostate volume dropped from 47.6 cm(3) to 24.9 cm(3) ; P < 0.001. These results suggest that dynamic contrast-enhanced MRI and diffusion-weighted MRI offer different information but that both could prove useful adjuncts to the anatomical information provided by T2-weighted imaging. dynamic contrast-enhanced as a marker of angiogenesis may help demonstrate ADT resistance and diffusion-weighted imaging may be more accurate in determining presence of tumor cell death versus residual tumor.

The aim of this study was to develop and demonstrate a methodology for dynamic contrast-enhanced MRI at 3 T in patients with advanced ovarian cancer and to report the results from pharmacokinetic modeling of the data. Nineteen patients with suspected advanced ovarian carcinoma (FIGO stage 3 or higher) were enrolled in this prospective study. Up to three marker lesions were identified: primary ovarian mass, omental ''cake'', and peritoneal deposits. Dynamic contrast-enhanced MRI was performed using a three-dimensional T(1)-weighted gradient-echo acquisition with a temporal resolution of 1.6 sec, following intravenous administration of 0.1 mmol/kg gadobutrol. Precontrast T(1) mapping, using an inversion-recovery fast gradient-echo sequence, was also performed. Imaging was completed in 18/19 patients, although two were subsequently excluded based on pathology results. Pharmacokinetic modeling of the data was performed according to the extended Kety model, using an arterial input function formed by concatenation of the Fritz-Hansen and Weinmann curves. No statistically significant differences were found between the results for the three marker lesions. In the future, this work will allow kinetic modeling results from ovarian dynamic contrast-enhanced MRI to be correlated with response to treatment. The high temporal resolution allows good characterization of the rapid contrast agent uptake in these vascular tumors.

TPS155 Background: In recent years rationally designed targeted molecules have improved progression free survival in selected tumour types. These agents are primarily cytostatic and it is increasin...

Sympathetic nervous system activity was assessed in experimental and control subjects who were exposed to graded orthostatic and isometric stress during monthly hospital visits. After the first session, the experimental subjects practiced a technique that elicited the relaxation response. Their concentrations of plasma norepinephrine during subsequent graded stresses were significantly higher. No such changes were noted in the control group. These results were than replicated in the control group in a crossover experiment. The groups did not differ in their heart rate and blood pressure responses. These observations are consistent with reduced norepinephrine end-organ responsivity after regular elicitation of the relaxation response.