Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure.

Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM's.

Managing offshore multi-use settings: Use of conceptual mapping to reduce uncertainty of co-locating seaweed aquaculture and wind farms.

The offshore Multi-use Setting (MUS) is a concept that aims to co-locate marine industrial activities, including wind farms and aquaculture. MUS is considered an innovative approach to promoting efficiency in space and resource use whilst contributing global policy priorities. However, the impacts of MUS development across social, economic, and environmental domains are uncertain, hindering the commercialisation of the concept. In this study, we initially demonstrate the potential consequences of co-locating seaweed aquaculture and a wind farm as a step towards MUS. Using a hypothetical case study and modified Delphi methodology, 14 subject matter experts predicted potential outcomes across social and environmental objectives. Five Cognitive maps and impact tables of 58 potential consequences were generated based on experts' perspective on co-locating seaweed aquaculture and a wind farm. The findings highlight the potential to exasperate pressures in the area, including those already attributed to wind farm operations, such as species mortality and stakeholder conflict. However, it may also enhance social-ecological conditions, such as resource provisioning and promoting habitat functionality in the region, through the addition of seaweed aquaculture. The cognitive maps demonstrate the complexity of managing MUS implementation, where high degree of variability and uncertainty about the outcomes is present. The findings of this study provide the vital entry point to performing further integrative assessment and modelling approaches, such as probabilistic analysis and simulations, in support of MUS decision-making. The research also strongly recommends alternative strategies in the pursuit of combining seaweed production and wind farms to avoid significant financial (among many other) trade-offs and risks. More broadly, we have found that our approach's ability to visually represent a complex situation while considering multiple objectives could be immensely valuable for other bioeconomy innovations or nature-based solutions. It helps mitigate the potential for expensive investments without a comprehensive evaluation of the associated risks and negative impacts, as necessitated by the principles of sustainability in decision-making.

Analysis of Retrospective Versus Prospective Peer Review in a Multisite Academic Radiation Department.

Purpose: Our multisite academic radiation department reviewed our experience with transitioning from weekly primarily retrospective to daily primarily prospective peer review to improve plan quality and decrease the rate of plan revisions after treatment start. Methods and Materials: This study was an institutional review board-approved prospective comparison of radiation treatment plan review outcomes of plans reviewed weekly (majority within 1 week after treatment start) versus plans reviewed daily (majority before treatment start, except brachytherapy, frame-based radiosurgery, and some emergent plans). Deviations were based on peer comments and considered major if plan revisions were recommended before the next fraction and minor if modifications were suggested but not required. Categorical variables were compared using χ2 distribution tests of independence; means were compared using independent t tests. Results: In all, 798 patients with 1124 plans were reviewed: 611 plans weekly and 513 plans daily. Overall, 76 deviations (6.8%) were noted. Rates of any deviation were increased in the daily era (8.6% vs 5.2%; P = .026), with higher rates of major deviations in the daily era (4.1% vs 1.6%; P = .012). Median working days between initial simulation and treatment was the same across eras (8 days). Deviations led to a plan revision at a higher rate in the daily era (84.1% vs 31.3%; P < .001). Conclusions: Daily prospective peer review is feasible in a multisite academic setting. Daily peer review with emphasis on prospective plan evaluation increased constructive plan feedback, plan revisions, and plan revisions being implemented before treatment start.

Can the global marine aquarium trade (MAT) be a model for sustainable coral reef fisheries?

Globally, 6 million coral reef fishers provide ~25% of emergent countries' catch, but species have low value. The marine aquarium trade (MAT) targets high-value biodiversity, but missing data amplify draconian governance and demand for international prohibition. To stimulate sustainability and reef conservation investment, we generate a fiscal baseline using the first global analysis of numbers, diversity, and biomass of MAT-traded organisms. Each year, ~55 million organisms worth US$2.15 billion at retail are traded comparable with major fisheries, e.g., tuna. A sustainable MAT also requires overexploitation assessments. We identify 25 species/genera with "Extremely High" risk ratios and place the Indonesian and Sulu-Celebes Seas in the highest exploitation category. Despite predicted hobbyist number increases, unabated reef degradation and low governance will transform the MAT into an aquaculture-dominated industry decoupled from communities (i.e., culture located in importing countries). A "MAT-positive" future requires evidence-based management/governance, consumer education, and sustainable practice incentivization but can address the biodiversity and social and economic inequality crises.

Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge.

Stereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.

A global horizon scan of issues impacting marine and coastal biodiversity conservation.

The biodiversity of marine and coastal habitats is experiencing unprecedented change. While there are well-known drivers of these changes, such as overexploitation, climate change and pollution, there are also relatively unknown emerging issues that are poorly understood or recognized that have potentially positive or negative impacts on marine and coastal ecosystems. In this inaugural Marine and Coastal Horizon Scan, we brought together 30 scientists, policymakers and practitioners with transdisciplinary expertise in marine and coastal systems to identify new issues that are likely to have a significant impact on the functioning and conservation of marine and coastal biodiversity over the next 5-10 years. Based on a modified Delphi voting process, the final 15 issues presented were distilled from a list of 75 submitted by participants at the start of the process. These issues are grouped into three categories: ecosystem impacts, for example the impact of wildfires and the effect of poleward migration on equatorial biodiversity; resource exploitation, including an increase in the trade of fish swim bladders and increased exploitation of marine collagens; and new technologies, such as soft robotics and new biodegradable products. Our early identification of these issues and their potential impacts on marine and coastal biodiversity will support scientists, conservationists, resource managers and policymakers to address the challenges facing marine ecosystems.

Inclusion of condition in natural capital assessments is critical to the implementation of marine nature-based solutions.

Current approaches to measure ecosystem services (ES) within natural capital (NC) and nature-based solutions (NbS) assessments are generally coarse, often using a single figure for ecosystem services (e.g., nutrient remediation or blue carbon sequestration) applied to the local or national habitat stock, which fails to take account of local ecosystem conditions and regional variability. As such, there is a need for improved understanding of the link between habitat condition and ES provision, using comparable indicators in order to take more informed management decisions. Here the UK, Solent Marine Sites (SEMS) is used as a case study system to demonstrate how Water Framework Directive (WFD) 'ecological status' and other indicators of ecosystem condition (state or quality) can be coupled with habitat extent information to deliver a more precise locally-tailored NC approach for active coastal and marine habitat restoration. Habitat extent and condition data are collected for seven NbS relevant coastal habitats (littoral sediment, mat-forming green macroalgae, subtidal sediment, saltmarsh, seagrass, reedbeds and native oyster beds). The workflow includes: 1) biophysical assessment of regulatory ES; 2) monetary valuation; and 3) compilation of future scenarios of habitat restoration and creation. The results indicate that incorporating classifications by condition indices into local NC extent accounts improved ES benefits by 11-67%. This suggests that omitting condition from NC assessments could lead to undervaluation of ES benefits. Future scenarios of restoration in the SEMS also show that the additional regulatory benefits of reaching 'Good' ecological status are £376 million annually, but could be as much as £1.218 billion if 'High'status and all habitat creation targets were met. This evidence of the potential value of restoration and importance of including condition indices in assessments is highly relevant to consider when investing in water ecosystems conservation and restoration as called for by the UN Decade on Ecosystem Restoration (2021-2030), and more generally in global nutrient neutrality and blue carbon policy strategies.

Literature review of management of brain metastases from germ cell tumors.

OBJECTIVE: In this review article, we discuss the role of chemotherapy, surgery, and radiation therapy in the treatment of brain metastases from germ cell tumors (GCT). BACKGROUND: GCT rarely metastasize to the brain and there is limited data to guide management. Most instances of brain metastases occur in patients with non-seminomatous germ cell tumors (NSGCT). METHODS: We searched PubMed using the terms 'central nervous system (CNS) metastases' or 'brain metastases' and 'germ cell' from 2011 through August 2021. Review articles and prospective trials related to the treatment of brain metastases in GCT were included in addition to articles obtained by hand search of the references and clinical practice guidelines. CONCLUSIONS: We highlight the importance of using chemotherapy as first-line therapy in most situations. We discuss the very minimal data regarding surgery and its primary role when there is significant mass effect or brain shift. We also compare whole brain radiation therapy (WBRT) with the use of radiosurgery. We then provide overall recommendations based on the reviewed data and our experience as a referral center for GCT.

Cost benefit analysis of survey methods for assessing intertidal sediment disturbance: A bait collection case study.

Coastal management requires cost-effective, yet accurate, assessments of habitat condition, especially in areas protected by statutory conservation measures. Unmanned Aerial Vehicles (UAVs) provide alternatives to manned aircraft and walk-over (WO) surveys. To support coastal managers with method selection, we compare the costs and benefits of the three techniques using the extent of bait collection (sediment scarring from manual digging) on intertidal mudflats from three UK sites. UAV and WO surveys were conducted in parallel and aerial photography was downloaded from the Channel Coastal Observatory (CCO). Digging was digitised from estimations on foot (WO) or by manually labelling imagery with confidence assigned (UAV/CCO). Method efficacy is compared with respect to spatial coverage, control over survey time/location, spatial resolution, positioning accuracy, and area of digging detected. Personnel hours and up-front costs (e.g. training/equipment), costs for personnel time standardised by shore area, personnel risk, and environmental impact are also compared. Regarding efficacy, CCO imagery had extensive shore coverage compared to UAV and WO, however, assessments are restricted to times/locations with available imagery. Each method's resolution was sufficient to detect digging. WO achieved the highest resolution (on foot), but the lowest positioning accuracy, in contrast to accurate feature delineation on aerial imagery. An additive two-way ANOVA revealed a significantly higher percent area of 'dug' sediment (all confidence levels) recorded by UAV than WO. CCO was the most cost-effective with no fieldwork/equipment costs. UAV had the highest up-front costs, but WO was more costly for personnel hours/km2 for survey time and digitisation. For all methods, digitisation was the most time-consuming aspect. Compared to WO, UAV achieved rapid shore surveys and the CCO and UAV methods minimise personnel risks. UAV and WO both cause wildlife disturbance, with trampling an additional WO impact. With each method suited to sediment disturbance assessment, selection will depend on resources and objectives and will be aided by this holistic cost-benefit analysis. Cost-effectiveness will improve with evolving regulations that facilitate UAV use and technological developments (e.g. machine learning for disturbance detection) that could significantly expedite imagery analysis and enable broadscale assessments from CCO or satellite imagery.

Discovery of increased number or interval growth of brain metastases on same-day GammaKnife™ planning MRI: Predicting factors and patient outcomes.

Purpose: To determine factors associated with increased risk of finding new and/or enlarged brain metastases (BM) on GammaKnife™ (GK) MRI and their impact on patient outcomes. Results: 43.9% of patients showed BM growth, 32.9% had additional brain metastases (aBM), and 18.1 % had both. Initial brain metastasis velocity (iBMV) was associated with finding aBM. Time between diagnostic MRI (dMRI) and GK MRI was associated with interval growth and each day increased this risk by 2%. Prior brain metastasectomy and greater time between either dMRI or latest extracranial RT and GK MRI predicted both aBM and BM growth. aBM and/or BM growth led to management change in 1.8% of cases and were not associated with OS or incidence of distant intracranial failure. Conclusions: Number of metastases seen on dMRI and iBMV predicted both aBM and/or BM growth, however, these factors did not significantly affect survival or incidence of distant intracranial failure.

GammaTile for Gliomas: A Single-Center Case Series.

GammaTile® (GT Medical Technologies, Tempe, Arizona) is a surgically targeted radiation source, approved by FDA for brachytherapy in primary and secondary brain neoplasms. Each GammaTile is composed of a collagen sponge with four seeds of cesium 131 and is particularly useful in recurrent tumors. We report our early experience in seven patients with recurrent gliomas to assess this type of brachytherapy with particular attention to ease of use, complication, and surgical planning. This study represents a retrospective chart review of surgical use and early clinical outcomes of GammaTile in recurrent gliomas. The number of tiles was planned using pre-operative imaging and dosimetry was planned based on post-operative imaging. Patients were followed during their hospital stay and were followed up after discharge. Parameters such as case length, resection extent, complication, ICU length of stay (LOS), hospital LOS, pre-operative Glasgow Coma Scale (GCS), immediate post-operative GCS, post-operative imaging findings, recurrence at follow-up, length of follow-up, and dosimetry were collected in a retrospective manner. Seven patients were identified that met the inclusion criteria. Two patients were diagnosed with recurrent glioblastoma multiforme (GBM), one lower-grade glioma that recurred as a GBM, one GBM that recurred as a gliosarcoma, and two recurrent oligodendrogliomas. We found that operation time, ICU LOS, hospital LOS, pre- and post-operative GCS, and post-operative complications were within the expected ranges for tumor resection patients. Further, dosimetry data suggests that six out of seven patients received adequate radiation coverage, with the seventh having implantation limitations due to nearby organs at risk. We report no postoperative complications that can be attributed to the GammaTiles themselves. In our cohort, we report seven cases where GammaTiles were implanted in recurrent gliomas. No implant-related post-operative complications were identified. This early data suggests that GammaTile can be a safe form of brachytherapy in recurrent gliomas.

Safety and efficacy of GammaTile intracranial brachytherapy implanted during awake craniotomy.

INTRODUCTION: GammaTile intracranial brachytherapy (cesium-131 seeds) has demonstrated encouraging safety and local control results, and recently received Food and Drug Administration clearance for newly diagnosed and recurrent brain tumors. The authors present the first reported case of GammaTile intraoperative brachytherapy performed during an awake craniotomy. METHODS: A 50-year-old man had a biopsy-proven, 2.8 cm left lateral frontal glioblastoma lesion nearing Broca's area on MRI. Despite several interventions (craniotomy, adjuvant chemoradiation, tumor treating fields) tumor progression occurred near the left parietal resection cavity. Re-resection was planned with awake craniotomy and language mapping. A preoperative planning session involving Radiation Oncology and Neurosurgery identified the area of the expected postoperative bed, and consequently five GammaTiles were ordered, each containing 4 cesium-131 3.5 U seeds. RESULTS: During surgery, tumor mapping and bipolar stimulation were performed while the patient spoke in complete sentences. Speech arrest occurred upon stimulation at the posterior edge of the gyrus, indicative of language cortex. Microsurgical maximal safe resection subsequently occurred, and areas at risk for residual/recurrence disease were determined in consultation with Radiation Oncology. Subsequently, Neurosurgery placed all five GammaTiles (20 cesium-131 seeds total) after which closure was completed and radioactive surveys of the room remained within state statue. Postoperative dosimetry yielded excellent coverage. CONCLUSIONS: The first reported case of GammaTile intraoperative brachytherapy during awake craniotomy supports the safety and feasibility of this treatment strategy. This case indicates that for patients with tumors adjacent to eloquent cortex, awake craniotomy can allow for custom implantation of intraoperative brachytherapy following maximum safe resection.

Analysis of Virtual Versus In-Person Prospective Peer Review Workflow in a Multisite Academic Radiation Oncology Department.

PURPOSE: In radiation oncology, peer review is a process where subjective treatment planning decisions are assessed by those independent of the prescribing physician. Before March 2020, all peer review sessions occurred in person; however due to the COVID-19 pandemic, the peer-review workflow was transitioned from in-person to virtual. We sought to assess any differences between virtual versus in-person prospective peer review. METHODS AND MATERIALS: Patients scheduled to receive nonemergent nonprocedural radiation therapy (RT) were presented daily at prospective peer-review before the start of RT administration. Planning software was used, with critical evaluation of several variables including treatment intent, contour definition, treatment target coverage, and risk to critical structures. A deviation was defined as any suggested plan revision. RESULTS: In the study, 274 treatment plans evaluated in-person in 2017 to 2018 were compared with 195 plans evaluated virtually in 2021. There were significant differences in palliative intent (36% vs 22%; P = .002), but not in total time between simulation and the start of treatment (9.2 vs 10.0 days; P = .10). Overall deviations (8.0% in-person vs 2.6% virtual; P = .015) were significantly reduced in virtual peer review. CONCLUSIONS: Prospective daily peer review of radiation oncology treatment plans can be performed virtually with similar timeliness of patient care compared with in-person peer review. A decrease in deviation rate in the virtual peer review setting will need to be further investigated to determine whether virtual workflow can be considered a standard of care.

Evidence for self-sustaining populations of Arcuatula senhousia in the UK and a review of this species' potential impacts within Europe.

The invasive Asian date mussel (Arcuatula senhousia) inhabits diverse global coastal environments, in some circumstances posing significant ecological and economic risks. Recently recorded in the Greater North Sea ecoregion, an established population has not previously been confirmed. Combining historical and field data, we provided baseline information from the UK and recorded colonisation in a variety of habitats. Gonadal development was assessed using the gonadosomatic index (GSI) to determine if an intertidal soft-sediment population is self-sustaining. Arcuatula senhousia records from subtidal muddy/mixed-sediment within a major estuarine system from 2007 to 2016 were also analysed. First detected in 2011, spatial distribution was variable across the years within the subtidal, with individuals found at 4-9 out of 25 sites, and densities per site varying from 10 to 290 individuals per m2. The intertidal population was, in part, associated with seagrass (Zostera spp.) and attached to bivalves. In marinas, individuals were attached to concrete tiles, associated with live Mytilus edulis, and to dead Ostrea edulis. Mean GSI from the intertidal population differed across months, peaking in July before declining in September/October, but with high inter-individual variability. Arcuatula senhousia is reproducing and maintaining viable populations. Using a natural capital approach, we identify the potential impacts on Europe's functionally important habitats, fisheries and aquaculture if its spread continues.

Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome.

Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare metabolic disorder caused by inactivating mutations in sphingosine-1-phosphate lyase 1 (SGPL1), which is required for the final step of sphingolipid metabolism. SPLIS features include steroid-resistant nephrotic syndrome and impairment of neurological, endocrine, and hematopoietic systems. Many affected individuals die within the first 2 years. No targeted therapy for SPLIS is available. We hypothesized that SGPL1 gene replacement would address the root cause of SPLIS, thereby serving as a universal treatment for the condition. As proof of concept, we evaluated the efficacy of adeno-associated virus 9-mediated transfer of human SGPL1 (AAV-SPL) given to newborn Sgpl1-KO mice that model SPLIS and die in the first weeks of life. Treatment dramatically prolonged survival and prevented nephrosis, neurodevelopmental delay, anemia, and hypercholesterolemia. STAT3 pathway activation and elevated proinflammatory and profibrogenic cytokines observed in KO kidneys were attenuated by treatment. Plasma and tissue sphingolipids were reduced in treated compared with untreated KO pups. SGPL1 expression and activity were measurable for at least 40 weeks. In summary, early AAV-SPL treatment prevents nephrosis, lipidosis, and neurological impairment in a mouse model of SPLIS. Our results suggest that SGPL1 gene replacement holds promise as a durable and universal targeted treatment for SPLIS.

Data on elemental concentrations in marine sediments from the South and South West of England.

The present Data In Brief methodological paper details the acquisition, mining and pre-processing of elemental concentration data in marine sediments (coastal and open sea) of Southern England, presented and discussed in the co-submitted Environment International paper entitled: "Three decades of trace element sediment contamination: the mining of governmental databases and the need to address hidden sources for clean and healthy seas" [1]. Elemental sediment concentration data were obtained from the two main UK environmental sources, i.e. the Environment Agency (EA) and the Marine Environment Monitoring and Assessment National (MERMAN) database managed by the British Oceanographic Data Centre (BODC). The merged database is the result of a rigorous data selection-validation process and provides spatially and temporally extensive records of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), nickel (Ni), lead (Pb) and zinc (Zn) concentrations for hundreds of sites over 31 years (1983-2013). Additional records of manganese (Mn), aluminium (Al), lithium (Li), tin (Sn) [and tributyltin (TBT)], barium (Ba), antimony (Sb), boron (B), calcium (Ca), molybdenum (Mo), cobalt (Co), selenium (Se), potassium (K), magnesium (Mg), beryllium (Be), vanadium (V), titanium (Ti), sodium (Na), silver (Ag), thallium (Tl) and strontium (Sr) are also included. The full secondary database is hosted in the Mendeley Data repository and the geo-spatial information to map sites is given in supplementary files to the paper. To provide end-users with the relevant context on spatial and temporal coverage, monitoring statistics are given for the nine trace elements (TEs). Site-specific statistics include: the first and last year of sediment monitoring, the number of years monitored, and minimum, maximum, mean and median numbers of years monitored. Also given are summary data on the number of sites monitored each year, from the first records from 1983 to 2013. For the nine TEs (total and strong acid digestion techniques are considered separately for Cr and Fe), monitoring statistics are presented separately for coastal and open sea sites. Data are relevant to diverse end-users to assess the local and regional contaminant loads and to contextualize anthropogenic threats to benthic systems in multiple locations from the French/English Channel, southern North and Celtic Seas.