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Offshore wind infrastructure modifies benthic habitats, affecting ecosystem services. A natural capital approach allows risks to nature-based assets and ecosystem benefits to be assessed. The UK Natural Capital Committee produced guidance for conducting natural capital assessments to aid decision making processes. Development of an asset register and risk register are key components of this methodology. The former provides an inventory of NC stocks, and the latter considers the likelihood of changes and the scale of their impact on delivery of ecosystem services. In this study, suitability of the methodology in a marine environment context was critically evaluated. Natural capital stocks before and after installation of Greater Gabbard offshore wind farm were compared and risks to delivery of ecosystem services were assessed. It was demonstrated that incorporating an assessment of impacts on natural capital assets in planning and management decisions (as an extension to traditional environmental impact assessment approaches) could further facilitate sustainable use of marine ecosystems. For example, by preventing access to bottom-trawl fisheries activities, wind farms may promote recovery and increase value of seabed natural capital assets. By also introducing aquaculture systems loss of food provision (from reduced fishing activity) could be offset whilst allowing benthic natural capital assets to recover. Natural capital assessment is relevant to the marine context. However, application of the Natural Capital Committee’s methodology was constrained by the limited coverage of standard benthic sampling tools. Given the scale of wind energy plans across the marine environment it is recommended that these shortcomings are appropriately addressed.

Objectives: Dynamic contrast-enhanced MR images can be analyzed through the application of a wide range of kinetic models. This process is prone to variability and a lack of standardization that can affect the measured metrics. There is a need for customized digital reference objects (DROs) for the validation of DCE-MRI software packages that undertake kinetic model analysis. DROs are currently available only for a small subset of the kinetic models commonly applied to DCE-MRI data. This work aimed to address this gap. Methods: Code was written in the MATLAB programming environment to generate customizable DROs. This modular code allows the insertion of a plug-in to describe the kinetic model to be tested. We input our generated DROs into three commercial and open-source analysis packages and assessed the agreement of kinetic model parameter values output with the ‘ground-truth’ values used in the DRO generation. Results: For the five kinetic models tested, the concordance correlation coefficient values were >98%, indicating excellent agreement of the results with ‘ground-truth’. Conclusions: Testing our DROs on three independent software packages produced concordant results, strongly suggesting our DRO generation code is correct. This implies that our DROs can be used to validate other third party software for the kinetic model analysis of DCE-MRI data. Advances in knowledge This work extends published work of others to allow customized generation of test objects for any applied kinetic model and allows the incorporation of B1 mapping into the DRO for application at higher field strengths.

Supplementary Materials (clean)

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.

Supplementary Figure S1. Representative 31P-MRS spectra of EV5 and CA9/1 tumors.

Supplementary Figure Legend. Legend for Supplementary Figure S1.

Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (

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.

Changes to fisheries that result from offshore wind farm (OWF) installations may be considered good or bad depending on various stakeholders’ perspectives. OWFs can act as artificial reefs that may benefit secondary fish production, but such effects may also have ecological consequences. The fisheries exclusion effect that turns some OWFs into no-go areas, hence effectively no-take zones, could provide resource enhancements or redistribution. However, the displacement of fishing effort may have consequences to fisheries elsewhere. Changes in the sensory environment related to sound, as well as electromagnetic fields and physical alterations of current and wind wakes, may have as yet unknown impacts on fisheries resources. Understanding the interactions among effect type, OWF development phase, and spatiotemporal population dynamics of commercial and recreational species remains chal-lenging, exemplified by the commercial fishery lobster genus Homarus in European and North American waters. While knowledge of the interactions between resource species and OWFs is improving, there remain questions on the wider interaction between and consequences of OWFs and fisheries. Studies of this wider relevance should aim to improve understanding of the economic and societal impacts of OWFs linked to ecosystem services that support fisheries. Furthermore, assisting fisheries management and providing advice requires monitoring and survey data collection at appropriate spatiotemporal scales. This information will help to determine whether OWFs have any meaningful impact on regional fisheries, and increased investments will be needed to target scientifically appropriate monitoring of OWFs and fisheries, which is supported by better integrated policy and regulation.

Measurement of particle motion from an offshore piling event in the North was conducted to determine noise levels. For this purpose, a bespoken sensor was developed that was both autonomous and sensitive up to 2 kHz. The measurement was undertaken both for unmitigated and mitigated piling. Three different types of mitigation techniques were employed. The acceleration zero-to-peak values and the acceleration exposure levels were determined. The results show that inferred mitigation techniques reduce the levels significantly as well as decreases the power content of higher frequencies. These results suggest that mitigation has an effect and will reduce the effect ranges of impact on marine species.

Objectives Design and build a portable xenon-129 (129Xe) hyperpolariser for clinically accessible 129Xe lung MRI. Methods The polariser system consists of six main functional components: (i) a laser diode array and optics; (ii) a B0 coil assembly; (iii) an oven containing an optical cell; (iv) NMR and optical spectrometers; (v) a gas-handling manifold; and (vi) a cryostat within a permanent magnet. All components run without external utilities such as compressed air or three-phase electricity, and require just three mains sockets for operation. The system can be manually transported in a lightweight van and rapidly installed on a small estates footprint in a hospital setting. Results The polariser routinely provides polarised 129Xe for routine clinical lung MRI. To test the concept of portability and rapid deployment, it was transported 200 km, installed at a hospital with no previous experience with the technology and 129Xe MR images of a diagnostic quality were acquired the day after system transport and installation. Conclusion This portable 129Xe hyperpolariser system could form the basis of a cost-effective platform for wider clinical dissemination and multicentre evaluation of 129Xe lung MR imaging. Advances in knowledge Our work successfully demonstrates the feasibility of multicentre clinical 129Xe MRI with a portable hyperpolariser system.

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro–Wilk test was used to assess for normality of data and Spearman’s rank-order or Pearson’s correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = −0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

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.

Hyperpolarised magnetic resonance imaging (HP

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.

States in the Northeast United States have the ambitious goal of producing more than 22 GW of offshore wind energy in the coming decades. The infrastructure associated with offshore wind energy development is expected to modify marine habitats and potentially alter the ecosystem services. Species distribution models were constructed for a group of fish and macroinvertebrate taxa resident in the Northeast US Continental Shelf marine ecosystem. These models were analyzed to provide baseline context for impact assessment of lease areas in the Middle Atlantic Bight designated for renewable wind energy installations. Using random forest machine learning, models based on occurrence and biomass were constructed for 93 species providing seasonal depictions of their habitat distributions. We developed a scoring index to characterize lease area habitat use for each species. Subsequently, groups of species were identified that reflect varying levels of lease area habitat use ranging across high, moderate, low, and no reliance on the lease area habitats. Among the species with high to moderate reliance were black sea bass (Centropristis striata), summer flounder (Paralichthys dentatus), and Atlantic menhaden (Brevoortia tyrannus), which are important fisheries species in the region. Potential for impact was characterized by the number of species with habitat dependencies associated with lease areas and these varied with a number of continuous gradients. Habitats that support high biomass were distributed more to the northeast, while high occupancy habitats appeared to be further from the coast. There was no obvious effect of the size of the lease area on the importance of associated habitats. Model results indicated that physical drivers and lower trophic level indicators might strongly control the habitat distribution of ecologically and commercially important species in the wind lease areas. Therefore, physical and biological oceanography on the continental shelf proximate to wind energy infrastructure development should be monitored for changes in water column structure and the productivity of phytoplankton and zooplankton and the effects of these changes on the trophic system.

Radiomic image features are becoming a promising non-invasive method to obtain quantitative measurements for tumour classification and therapy response assessment in oncological research. However, despite its increasingly established application, there is a need for standardisation criteria and further validation of feature robustness with respect to imaging acquisition parameters. In this paper, the robustness of radiomic features extracted from computed tomography (CT) images is evaluated for liver tumour and muscle, comparing the values of the features in images reconstructed with two different slice thicknesses of 2.0 mm and 5.0 mm. Novel approaches are presented to address the intrinsic dependencies of texture radiomic features, choosing the optimal number of grey levels and correcting for the dependency on volume. With the optimal values and corrections, feature values are compared across thicknesses to identify reproducible features. Normalisation using muscle regions is also described as an alternative approach. With either method, a large fraction of features (75–90%) was found to be highly robust (

As offshore wind energy production increases, the number of subsea cables will proliferate along with associated electromagnetic field (EMF) emissions. Understanding how EMF interactions (a potential pressure) affect resource species (receptor) requires an improved knowledge base to aid management decisions. Within the framework of a potential effect on a receptor, we review key aspects of assessing EMF exposure. From the vantage point of the receptor species, we consider how their perception of EMF varies through time as a consequence of species’ sensory biology, life history theory, and movement ecology. We review known effects of EMFs on species and consider EMF interactions with benthic, bentho-pelagic, and migratory species, focusing on functional roles of electro- and magneto-reception at different life stages. We must move our understanding from individual effects to population-level impacts. The present knowledge base has been drawn from a diverse range of laboratory and field approaches, which can be better integrated to address gaps and reach the desired knowledge base. Improving models of future scenarios depends on taking a more systematic and consistent approach to measuring and modeling alternating current and direct current EMFs and accounting for cable properties and local environmental characteristics. We make recommendations to help decipher receptor species’ responses. Acquiring such knowledge will enable us to translate EMFs, and their effects and encounter rates, into impact assessments for resource species to inform appropriate management. Publisher PDF

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.

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

Purpose To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material–enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods In this institutional review board–approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent 13C MRI after injection of hyperpolarized [1–carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The 13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized 13C MRI and the pharmacokinetic parameters transfer constant (Ktrans) and washout parameter (kep) derived from DCE MRI were compared before and after treatment. Results Exchange of the 13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean Ktrans (132%) and mean kep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion Hyperpolarized 13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI. Published under a CC BY 4.0 license.

Significance Carbon-13 MRI was used to assess exchange of hyperpolarized 13C label between injected [1-13C]pyruvate and the endogenous tumor lactate pool in breast cancer patients. Higher levels of 13C label exchange were observed in more-aggressive tumors, including all triple-negative cancers. The 13C label exchange correlated significantly with the expression of the transmembrane transporter mediating uptake of pyruvate into tumor cells and hypoxia inducible factor 1 (HIF1α), but no significant correlation with the expression of lactate dehydrogenase, the enzyme that catalyzes the exchange. The study has shown that 13C MRI can be used for metabolic imaging of breast cancer patients in the clinic, creating possibilities for noninvasive cancer monitoring in this patient group., Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

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 marine environment is a complex system, and with growing human demand, the sustainable use of multiple marine resources is continually challenged. The increasing complexity of overlapping marine activities causes pressures on the environment. Here, we review the fundamental aspects for effective marine management, particularly the role of science and scientific evidence to inform marine policy and decision making. The outcomes of internal expert workshops were used to analyse currently applied marine management practices in the UK using four marine sectors in English waters based on the expertise: environmental impact assessments; dredge and disposal operations; marine protected areas; and offshore renewable energy. Strengths, weaknesses, and commonalities between these sectors were assessed in terms of their effectiveness for marine management. Finally, we make recommendations based on the outputs to better inform effective yet sustainable marine management. The importance of increasing accessibility to data, hypothesis-driven environmental monitoring, streamlining funding opportunities and ensuring effective dissemination of data to ensure scientific outcomes and achieve increased robustness of assessments is emphasised. We also recommend that assessment drivers align with the outputs and approaches should be holistic and engage with the public to ensure a shared understanding and vision.

Cumulative effects assessments are a legal requirement in many jurisdictions and are key to informing marine policy. However, practice does not yet deliver fit-for-purpose assessments relative to sustainable development and environmental protection obligations. The complexity of cumulative effect questions, which are embedded in complex social-ecological systems, makes multiple, methodologically diverse assessments a necessity. Using the expansion of marine renewable energy developments in European Union waters as a case study, this paper explores how social-ecological systems thinking and cumulative effects assessment theory can combine to structure CEAs that better support the management and regulation of maritime activities at regional scales. A general perspective for cumulative effects assessment is proposed to remove ambiguity of intent and to orient assessments towards a common objective. Candidate principles for practice are presented for consideration. These principles are integrated into a stepped assessment approach that seeks to improve cumulative effects assessments of localised activities relative to the information needs of decision-makers implementing the ecosystem approach.

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.