Medulloblastomas with ELP1 pathogenic variants: A weakly penetrant syndrome with a restricted spectrum in a limited age window

Background: ELP1 pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are still lacking for genetic counseling in this new syndrome. Methods: We retrospectively reviewed clinical and genetic data of a French series of 29 ELP1-mutated MB. Results: All patients developed SHH-MB, with a biallelic inactivation of PTCH1 found in 24 tumors. Other recurrent alterations encompassed the TP53 pathway and activation of MYCN/MYCL signaling. The median age at diagnosis was 7.3 years (range: 3-14). ELP1-mutated MB behave as sporadic cases, with similar distribution within clinical and molecular risk groups and similar outcomes (5 y - OS=86%); no unusual side effect of treatments was noticed. Remarkably, a germline ELP1 PV was identified in all patients with available constitutional DNA (n=26); moreover, all tested familial trio (n=11) revealed that the PVs were inherited. Two of the 26 index cases from the French series had a family history of MB; pedigrees from these patients and from 1 additional Dutch family suggested a weak penetrance. Apart from MB, no cancer was associated with ELP1 PVs; second tumors reported in 4 patients occurred within the irradiation fields, in the usual time-lapse for expected radiotherapy-induced neoplasms. Conclusions: The low penetrance, the "at risk' age window limited to childhood and the narrow tumor spectrum, question the actual benefit of genetic screening in these patients and their family. Our results suggest restricting ELP1 germline sequencing to patients with SHH-MB, depending on the parents"request

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Small Wins through Inducement Prizes: Introducing Challenge-Oriented Regional Prizes (CORP)

There is an emerging consensus that innovation policies must be geared towards solving societal challenges. The policy complexity of the third generation of innovation policy (TGIP), however, puts less-developed European regions at risk of being left behind from this novel policy paradigm due to lower institutional and governance capacities. Building on the concept of a small wins strategy that focuses on small-scale and bottom-up initiatives that are guided by a shared mission to address wicked problems, the article’s methodology uses expert interviews, examples of challenge prizes, and desk research to explore whether inducement prizes can potentially engage less-developed regions (LDRs) in TGIP to address place-based societal challenges through a small wins strategy. The article introduces the concept of a challenge-oriented regional prize (CORP) as a stepping-stone policy tool to engage LDRs in TGIP through a small wins strategy, namely regarding issues of directionality, legitimacy, responsibility, and strategic orientation. CORPs are, however, not a silver bullet policy tool for LDRs to engage in TGIPs due to their design and implementation constraints.</jats:p

Small Wins through Inducement Prizes: Introducing Challenge-Oriented Regional Prizes (CORP)

There is an emerging consensus that innovation policies must be geared towards solving societal challenges. The policy complexity of the third generation of innovation policy (TGIP), however, puts less-developed European regions at risk of being left behind from this novel policy paradigm due to lower institutional and governance capacities. Building on the concept of a small wins strategy that focuses on small-scale and bottom-up initiatives that are guided by a shared mission to address wicked problems, the article&rsquo;s methodology uses expert interviews, examples of challenge prizes, and desk research to explore whether inducement prizes can potentially engage less-developed regions (LDRs) in TGIP to address place-based societal challenges through a small wins strategy. The article introduces the concept of a challenge-oriented regional prize (CORP) as a stepping-stone policy tool to engage LDRs in TGIP through a small wins strategy, namely regarding issues of directionality, legitimacy, responsibility, and strategic orientation. CORPs are, however, not a silver bullet policy tool for LDRs to engage in TGIPs due to their design and implementation constraints

Small Wins through Inducement Prizes: Introducing Challenge-Oriented Regional Prizes (CORP)

International audienceThere is an emerging consensus that innovation policies must be geared towards solving societal challenges. The policy complexity of the third generation of innovation policy (TGIP), however, puts less-developed European regions at risk of being left behind from this novel policy paradigm due to lower institutional and governance capacities. Building on the concept of a small wins strategy that focuses on small-scale and bottom-up initiatives that are guided by a shared mission to address wicked problems, the article’s methodology uses expert interviews, examples of challenge prizes, and desk research to explore whether inducement prizes can potentially engage less-developed regions (LDRs) in TGIP to address place-based societal challenges through a small wins strategy. The article introduces the concept of a challenge-oriented regional prize (CORP) as a stepping-stone policy tool to engage LDRs in TGIP through a small wins strategy, namely regarding issues of directionality, legitimacy, responsibility, and strategic orientation. CORPs are, however, not a silver bullet policy tool for LDRs to engage in TGIPs due to their design and implementation constraints

La thrombo-embolie aortique chez le chat

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Conduite à tenir devant une thrombo-embolie aortique

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Quand la géodiversité guide la biodiversité : apport de l’Inventaire National du Patrimoine Géologique: Actes Chambéry, 15-17 octobre 2018

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