Underexplored continental shelf gateways: timing, mechanisms and role of SW Barents Sea Gateway, Norwegian Arctic

Abstract of presentation given at the OCEANIC GATEWAYS: MODERN AND ANCIENT ANALOGUES AND THEIR CONCEPTUAL AND ECONOMIC IMPLICATIONS Conference, organised by The Geological Society of London, London, 23-25 November 2022.Ocean gateways connecting ocean basins are crucial for water and heat circulation, which influence global temperature, climate evolution and sediment distribution. While deep-water gateways have been a major research focus by the community, very little attention has been drawn to shallower gateways located on the continental shelves, where such circulation also takes place. In this study, we investigate the evolution of a shallow gateway in SW Barents Sea that presently connects NE Atlantic and Arctic oceans. This gateway contributes to about half of the Atlantic–Arctic water exchange, whereas the other half is occurring through the deeper Fram Strait Gateway. When and how this SW Barents Sea Gateway formed are debated and still poorly understood. Outcomes from this study will thus be relevant for regional and global models of ocean circulation. Moreover, this study will contribute to climate evolution models over longer timescale in a climate sensitive region where an Arctic amplification of warming is presently seen

Paleobathymetric reconstructions of the SW Barents Seaway and their implications for Atlantic–Arctic ocean circulation

Unravelling past, large-scale ocean circulation patterns is crucial for deciphering the longterm global paleoclimate. Here we apply numerical modelling to reconstruct the detailed paleobathymetry-topography of the southwestern inlet of the Barents Seaway that presently connects the Atlantic and Arctic oceans. Subaerial topography was likely enough to block Atlantic Water from entering the Barents Seaway in the earliest Eocene (c. 55 Ma). The water may have entered in the middle Eocene (c. 47 Ma) as observed from major basin subsidence, but paleotopographic highs to the east may have hindered connections between the two oceans. From the Oligocene (c. 33 Ma) until the onset of the Quaternary (c. 2.7 Ma), basin shallowing and regional shelf uplift blocked Atlantic Water from entering the Barents Seaway. Our results imply that the Fram Strait remained the sole gateway for Atlantic Water into the Arctic Ocean since its opening in the Miocene until the Quaternary

Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need

Radiographic read paradigms and the roles of the central imaging laboratory in neuro-oncology clinical trials

Determination of therapeutic benefit in intracranial tumors is intimately dependent on serial assessment of radiographic images. The Response Assessment in Neuro-Oncology (RANO) criteria were established in 2010 to provide an updated framework to better characterize tumor response to contemporary treatments. Since this initial update a number of RANO criteria have provided some basic principles for the interpretation of changes on MR images; however, the details of how to operationalize RANO and other criteria for use in clinical trials are ambiguous and not standardized. In this review article designed for the neuro-oncologist or treating clinician, we outline essential steps for performing radiographic assessments by highlighting primary features of the Imaging Charter (referred to as the Charter for the remainder of this article), a document that describes the clinical trial imaging methodology and methods to ensure operationalization of the Charter into the workings of a clinical trial. Lastly, we provide recommendations for specific changes to optimize this methodology for neuro-oncology, including image registration, requirement of growing tumor for eligibility in trials of recurrent tumor, standardized image acquisition guidelines, and hybrid reader paradigms that allow for both unbiased measurements and more comprehensive interpretation

Radiographic read paradigms and the roles of the central imaging laboratory in neuro-oncology clinical trials

Determination of therapeutic benefit in intracranial tumors is intimately dependent on serial assessment of radiographic images. The Response Assessment in Neuro-Oncology (RANO) criteria were established in 2010 to provide an updated framework to better characterize tumor response to contemporary treatments. Since this initial update a number of RANO criteria have provided some basic principles for the interpretation of changes on MR images; however, the details of how to operationalize RANO and other criteria for use in clinical trials are ambiguous and not standardized. In this review article designed for the neuro-oncologist or treating clinician, we outline essential steps for performing radiographic assessments by highlighting primary features of the Imaging Charter (referred to as the Charter for the remainder of this article), a document that describes the clinical trial imaging methodology and methods to ensure operationalization of the Charter into the workings of a clinical trial. Lastly, we provide recommendations for specific changes to optimize this methodology for neuro-oncology, including image registration, requirement of growing tumor for eligibility in trials of recurrent tumor, standardized image acquisition guidelines, and hybrid reader paradigms that allow for both unbiased measurements and more comprehensive interpretation

Hypothetical generalized framework for a new imaging endpoint of therapeutic activity in early phase clinical trials in brain tumors

Imaging response assessment is a cornerstone of patient care and drug development in oncology. Clinicians/clinical researchers rely on tumor imaging to estimate the impact of new treatments and guide decision making for patients and candidate therapies. This is important in brain cancer, where associations between tumor size/growth and emerging neurological deficits are strong. Accurately measuring the impact of a new therapy on tumor growth early in clinical development, where patient numbers are small, would be valuable for decision making regarding late-stage development activation. Current attempts to measure the impact of a new therapy have limited influence on clinical development, as determination of progression, stability or response does not currently account for individual tumor growth kinetics prior to the initiation of experimental therapies. Therefore, we posit that imaging-based response assessment, often used as a tool for estimating clinical effect, is incomplete as it does not adequately account for growth trajectories or biological characteristics of tumors prior to the introduction of an investigational agent. Here, we propose modifications to the existing framework for evaluating imaging assessment in primary brain tumors that will provide a more reliable understanding of treatment effects. Measuring tumor growth trajectories prior to a given intervention may allow us to more confidently conclude whether there is an anti-tumor effect. This updated approach to imaging-based tumor response assessment is intended to improve our ability to select candidate therapies for later-stage development, including those that may not meet currently sought thresholds for "response"and ultimately lead to identification of effective treatments.</p