Family history of cancer and the risk of childhood brain tumors: a pooled analysis of the ESCALE and ESTELLE studies (SFCE)

PURPOSE: Although some specific genetic syndromes such as neurofibromatosis (NF) have been identified as risk factor of childhood brain tumors (CBT), the potential role of inherited susceptibility in CBT has yet to be elucidated. METHODS: To further investigate this, we conducted a pooled analysis of two nationwide case-control studies ESCALE and ESTELLE. The mothers of 509 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, responded to a telephone interview conducted by trained interviewers. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. RESULTS: CBT was significantly associated with the family history of cancer in relatives (OR 1.2, 95% CI 1.0-1.5). The OR was slightly higher for maternal relatives than for paternal relatives, and when at least two relatives had a history of cancer. CBT was significantly associated with a family history of brain tumor (OR 2.1, 95% CI 1.3-3.7). This association seemed stronger for first-degree relatives (mother, father, and siblings), for whom, by contrast, no association was seen for cancers other than CBT. No specificity by CBT subtypes or by age of the children were found for any of these findings. CONCLUSION: Our findings support the hypothesis of a familial susceptibility of CBT, not due to being a known NF carrier

A CT-based radiomics classification model for the prediction of histological type and tumour grade in retroperitoneal sarcoma (RADSARC-R): a retrospective multicohort analysis.

BACKGROUND: Retroperitoneal sarcomas are tumours with a poor prognosis. Upfront characterisation of the tumour is difficult, and under-grading is common. Radiomics has the potential to non-invasively characterise the so-called radiological phenotype of tumours. We aimed to develop and independently validate a CT-based radiomics classification model for the prediction of histological type and grade in retroperitoneal leiomyosarcoma and liposarcoma. METHODS: A retrospective discovery cohort was collated at our centre (Royal Marsden Hospital, London, UK) and an independent validation cohort comprising patients recruited in the phase 3 STRASS study of neoadjuvant radiotherapy in retroperitoneal sarcoma. Patients aged older than 18 years with confirmed primary leiomyosarcoma or liposarcoma proceeding to surgical resection with available contrast-enhanced CT scans were included. Using the discovery dataset, a CT-based radiomics workflow was developed, including manual delineation, sub-segmentation, feature extraction, and predictive model building. Separate probabilistic classifiers for the prediction of histological type and low versus intermediate or high grade tumour types were built and tested. Independent validation was then performed. The primary objective of the study was to develop radiomic classification models for the prediction of retroperitoneal leiomyosarcoma and liposarcoma type and histological grade. FINDINGS: 170 patients recruited between Oct 30, 2016, and Dec 23, 2020, were eligible in the discovery cohort and 89 patients recruited between Jan 18, 2012, and April 10, 2017, were eligible in the validation cohort. In the discovery cohort, the median age was 63 years (range 27-89), with 83 (49%) female and 87 (51%) male patients. In the validation cohort, median age was 59 years (range 33-77), with 46 (52%) female and 43 (48%) male patients. The highest performing model for the prediction of histological type had an area under the receiver operator curve (AUROC) of 0·928 on validation, based on a feature set of radiomics and approximate radiomic volume fraction. The highest performing model for the prediction of histological grade had an AUROC of 0·882 on validation, based on a radiomics feature set. INTERPRETATION: Our validated radiomics model can predict the histological type and grade of retroperitoneal sarcomas with excellent performance. This could have important implications for improving diagnosis and risk stratification in retroperitoneal sarcomas. FUNDING: Wellcome Trust, European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group, the National Institutes for Health, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research

A reference time scale for Site U1385 (Shackleton Site) on the SW Iberian Margin

We produced a composite depth scale and chronology for Site U1385 on the SW Iberian Margin. Using log(Ca/Ti) measured by core scanning XRF at 1-cm resolution in all holes, a composite section was constructed to 166.5 meters composite depth (mcd) that corrects for stretching and squeezing in each core. Oxygen isotopes of benthic foraminifera were correlated to a stacked δ^18O reference signal (LR04) to produce an oxygen isotope stratigraphy and age model. Variations in sediment color contain very strong precession signals at Site U1385, and the amplitude modulation of these cycles provides a powerful tool for developing an orbitally-tuned age model. We tuned the U1385 record by correlating peaks in L* to the local summer insolation maxima at 37^oN. The benthic δ^18O record of Site U1385, when placed on the tuned age model, generally agrees with other time scales within their respective chronologic uncertainties. The age model is transferred to down-core data to produce a continuous time series of log(Ca/Ti) that reflect relative changes of biogenic carbonate and detrital sediment. Biogenic carbonate increases during interglacial and interstadial climate states and decreases during glacial and stadial periods. Much of the variance in the log(Ca/Ti) is explained by a linear combination of orbital frequencies (precession, tilt and eccentricity), whereas the residual signal reflects suborbital climate variability. The strong correlation between suborbital log(Ca/Ti) variability and Greenland temperature over the last glacial cycle at Site U1385 suggests that this signal can be used as a proxy for millennial-scale climate variability over the past 1.5 Ma. Millennial climate variability, as expressed by log(Ca/Ti) at Site U1385, was a persistent feature of glacial climates over the past 1.5 Ma, including glacial periods of the early Pleistocene (‘41-kyr world’) when boundary conditions differed significantly from those of the late Pleistocene (‘100-kyr world’). Suborbital variability was suppressed during interglacial stages and enhanced during glacial periods, especially when benthic δ^18O surpassed ~ 3.3-3.5‰. Each glacial inception was marked by appearance of strong millennial variability and each deglaciation was preceded by a terminal stadial event. Suborbital variability may be a symptomatic feature of glacial climate or, alternatively, may play a more active role in the inception and/or termination of glacial cycles.This research was supported by the Natural Environmental Research Council Grant NE/K005804/1 to DH and LS and NE/J017922/1 to DH.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.gloplacha.2015.07.00

A reference time scale for Site U1385 (Shackleton Site) on the SW Iberian Margin

Variations in sediment color contain very strong precession signals at Site U1385, and the amplitude modulation of these cycles provides a powerful tool for developing an orbitally-tuned age model. We tuned the U1385 record by correlating peaks in L* to the local summer insolation maxima at 37°N. The benthic δ18O record of Site U1385, when placed on the tuned age model, generally agrees with other time scales within their respective chronologic uncertainties. The age model is transferred to down-core data to produce a continuous time series of log(Ca/Ti) that reflect relative changes of biogenic carbonate and detrital sediment. Biogenic carbonate increases during interglacial and interstadial climate states and decreases during glacial and stadial periods. Much of the variance in the log(Ca/Ti) is explained by a linear combination of orbital frequencies (precession, tilt and eccentricity), whereas the residual signal reflects suborbital climate variability. The strong correlation between suborbital log(Ca/Ti) variability and Greenland temperature over the last glacial cycle at Site U1385 suggests that this signal can be used as a proxy for millennial-scale climate variability over the past 1.5 Ma. Millennial climate variability, as expressed by log(Ca/Ti) at Site U1385, was a persistent feature of glacial climates over the past 1.5 Ma, including glacial periods of the early Pleistocene (‘41-kyr world’) when boundary conditions differed significantly from those of the late Pleistocene (‘100-kyr world’). Suborbital variability was suppressed during interglacial stages and enhanced during glacial periods, especially when benthic δ18O surpassed ~ 3.3–3.5‰. Each glacial inception was marked by appearance of strong millennial variability and each deglaciation was preceded by a terminal stadial event. Suborbital variability may be a symptomatic feature of glacial climate or, alternatively, may play a more active role in the inception and/or termination of glacial cycles

Late Miocene onset of the modern Antarctic Circumpolar Current

The Antarctic Circumpolar Current plays a pivotal role in global climate through its strong influence on the global overturning circulation, ocean heat and CO uptake. However, when and how the Antarctic Circumpolar Current reached its modern-like characteristics remains disputed. Here we present neodymium isotope and sortable silt records from sediment cores in the Southwest Pacific and South Indian oceans spanning the past 31 million years. Our data indicate that a circumpolar current like that of today did not exist before the late Miocene cooling. These findings suggest that the emergence of a homogeneous and deep-reaching strong Antarctic Circumpolar Current was not linked solely to the opening and deepening of Southern Ocean Gateways triggering continental-scale Antarctic Ice Sheet expansion during the Eocene–Oligocene Transition (∼34 Ma). Instead, we find that besides tectonic pre-conditioning, the expansion of the Antarctic Ice Sheet and sea ice since the middle Miocene Climate Transition (∼14 Ma) played a crucial role. This led to stronger density contrast and intensified Southern Westerly Winds across the Southern Ocean, establishing a vigorous deep-reaching circumpolar flow and an enhanced global overturning circulation, which amplified the late Cenozoic global cooling.This research used samples provided by the International Ocean Discovery Program (IODP). We acknowledge the staff and shipboard party from Leg 28 and Leg 119. We thank the staff at the Gulf Coast core repository (GCR) for curating these cores and for assistance in core handling and shipping. Funding for this research is provided by the Spanish Ministry of Economy, Industry and Competitivity (grant CTM2017-89711-C2-1/2-P; PID2021-126495NB-C31), co-funded by the European Union through FEDER funds. D.E. was funded by the Alexander S. Onassis Public Benefit Foundation PhD research grant (F ZL 016-1/2015-2016), by MOPGA postdoctoral visiting fellowship programme funded by the French Ministry of Europe and Foreign Affairs (grant MOPGA postdoc-3–5669831615), by the Juan de la Cierva-formation postdoctoral research grant (FJC2020-043650-I) funded by MCIN/AEI/ 10.13039/501100011033 and the ‘European Union NextGenerationEU/PRTR’ and by the UK Research and Innovation Engineering and Physical Sciences Research Council (grant number EP/X02623X/1). D.E. received additional funding from an ECORD research grant and IODP-France. I.S. and A.K. were supported by the Australian Research Council Special Research Initiative for Antarctic Gateway Partnership (project ID SR140300001) and the Australian Research Council’s Discovery Project 180102280. Model runs were undertaken with the assistance of resources from the National Computational Infrastructure (NCI), which is supported by the Australian Government. We thank the Paleomagnetic Laboratory CCiTUB-Geo3Bcn CSIC for the support on palaeomagnetic analysis. The GRC Geociències Marines thanks the Generalitat de Catalunya for the Grups de Recerca Consolidats grant 2021SGR01195 and for the ICREA-Academia award to I.C. This paper is a contribution to the SCAR INSTANT Programme.Peer reviewe

Latest Miocene restriction of the Mediterranean Outflow Water:a perspective from the Gulf of Cádiz

The Mediterranean-Atlantic water mass exchange provides the ideal setting for deciphering the role of gateway evolution in ocean circulation. However, the dynamics of Mediterranean Outflow Water (MOW) during the closure of the Late Miocene Mediterranean-Atlantic gateways are poorly understood. Here, we define the sedimentary evolution of Neogene basins from the Gulf of Cádiz to the West Iberian margin to investigate MOW circulation during the latest Miocene. Seismic interpretation highlights a middle to upper Messinian seismic unit of transparent facies, whose base predates the onset of the Messinian salinity crisis (MSC). Its facies and distribution imply a predominantly hemipelagic environment along the Atlantic margins, suggesting an absence or intermittence of MOW preceding evaporite precipitation in the Mediterranean, simultaneous to progressive gateway restriction. The removal of MOW from the Mediterranean-Atlantic water mass exchange reorganized the Atlantic water masses and is correlated to a severe weakening of the Atlantic Meridional Overturning Circulation (AMOC) and a period of further cooling in the North Atlantic during the latest Miocene