Safety and efficacy of mTOR inhibitor treatment in patients with tuberous sclerosis complex under 2 years of age – a multicenter retrospective study

Background: Tuberous sclerosis complex (TSC) is a multisystem disease with prominent neurologic manifestations such as epilepsy, cognitive impairment and autism spectrum disorder. mTOR inhibitors have successfully been used to treat TSC-related manifestations in older children and adults. However, data on their safety and efficacy in infants and young children are scarce. The objective of this study is to assess the utility and safety of mTOR inhibitor treatment in TSC patients under the age of 2 years. Results: A total of 17 children (median age at study inclusion 2.4 years, range 0–6; 12 males, 5 females) with TSC who received early mTOR inhibitor therapy were studied. mTOR inhibitor treatment was started at a median age of 5 months (range 0–19 months). Reasons for initiation of treatment were cardiac rhabdomyomas (6 cases), subependymal giant cell astrocytomas (SEGA, 5 cases), combination of cardiac rhabdomyomas and SEGA (1 case), refractory epilepsy (4 cases) and disabling congenital focal lymphedema (1 case). In all cases everolimus was used. Everolimus therapy was overall well tolerated. Adverse events were classified according to the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0). Grade 1–2 adverse events occurred in 12 patients and included mild transient stomatitis (2 cases), worsening of infantile acne (1 case), increases of serum cholesterol and triglycerides (4 cases), changes in serum phosphate levels (2 cases), increase of cholinesterase (2 cases), transient neutropenia (2 cases), transient anemia (1 case), transient lymphopenia (1 case) and recurrent infections (7 cases). No grade 3–4 adverse events were reported. Treatment is currently continued in 13/17 patients. Benefits were reported in 14/17 patients and included decrease of cardiac rhabdomyoma size and improvement of arrhythmia, decrease of SEGA size, reduction of seizure frequency and regression of congenital focal lymphedema. Despite everolimus therapy, two patients treated for intractable epilepsy are still experiencing seizures and another one treated for SEGA showed no volume reduction. Conclusion: This retrospective multicenter study demonstrates that mTOR inhibitor treatment with everolimus is safe in TSC patients under the age of 2 years and shows beneficial effects on cardiac manifestations, SEGA size and early epilepsy

Raw physical oceanography and current meter data from mooring F5-18 in the Fram Strait, September 2018 - July 2020

Time series data of physical oceanography (seawater conductivity, temperature, pressure, salinity), ocean current velocities, hydroacoustics and multi-frequency acoustic backscatter were obtained from mooring F5-18 in the Fram Strait in September 2018 - July 2020 as part of the Helmholtz infrastructure program Frontiers in Arctic Marine Monitoring (FRAM) and the long-term monitoring program at AWI HAUSGARTEN. The mooring was deployed during RV MARIA S. MERIAN expedition MSM76 and recovered during MSM93. The attached archive contains raw data files of three Seabird SBE37 microcats (nominal depths: 46m, 247m, 731m; sampling interval 20 min), one RDI 600kHz ADCP (nominal depth: 34m; sampling interval 30min), one RDI Longranger ADCP (nominal depth: 403m; sampling interval 1h) and one AADI RCM11 current meter (nominal depth: 730m; sampling interval 2h). The 600kHz ADCP wasn't aligned correctly in the water column due to issues with the attached flotations. Therefore, the data is likely not usable. The mooring also included one ASL Acoustic Zooplankton Fish Profiler (nominal depth: 135m; data archived elsewhere) and one Develogic Sonovault (nominal depth: 790m; data also archived elsewhere). Auxiliary information such as sensor calibration sheets, mooring diagrams and schedule files are also provided, if applicable

Metadata of mooring F4-OZA in the Fram Strait, September 2018 - July 2020

Time series data of hydroacoustics and multi-frequency acoustic backscatter were obtained from mooring F4-OZA in the Fram Strait in September 2018 - July 2020 as part of the Helmholtz infrastructure program Frontiers in Arctic Marine Monitoring (FRAM) and the long-term monitoring program at AWI HAUSGARTEN. The mooring was deployed during RV MARIA S. MERIAN expedition MSM76 and recovered during MSM93. The mooring included one ASL Acoustic Zooplankton Fish Profiler (nominal depth: 155m; data archived elsewhere) and one Develogic Sonovault (nominal depth: 836m; data also archived elsewhere). The attached .zip file only contains the mooring diagrams

Raw physical oceanography and ocean current velocity data from mooring F4-19 in the Fram Strait, August 2019 - June 2021

Time-series data of physical oceanography, ocean current velocities and hydroacoustics were obtained from mooring F4-19 in the Fram Strait in August 2019 - June 2021 as part of the Helmholtz infrastructure program Frontiers in Arctic Marine Monitoring (FRAM) and the long-term monitoring program at AWI HAUSGARTEN. The mooring was deployed during RV POLARSTERN expedition PS121, and recovered during PS126. The attached archive contains raw data files of 7 Seabird SBE37 microcats (nominal depths: 76m, 153m, 253m, 402m, 502m,731m, 1204m; sampling interval 1h), four Seabird SBE56 temperature loggers (nominal depths: 53m, 102m, 203m, 323m; sampling interval 30s), one upward-looking RDI Workhorse 300kHz ADCP (nominal depth: 53m; sampling interval 1h), one upward-looking RDI Workhorse Longranger ADCP (depth: 382m; sampling interval 1h) and two Nortek Aquadopp current meters (nominal depths: 730m, 1205m; sampling interval 20min). The 300 kHz ADCP stopped recording after 3 months due to a battery failure. The mooring also included an ASL Acoustic Zooplankton Fish Profiler (nominal depth: 103m; data archived elsewhere) and a Develogic Sonovault (nominal depth: 800m; data archived elsewhere). Auxiliary information such as sensor calibration sheets, mooring diagrams and schedule files are also provided, if applicable

Raw data of physical oceanography and current velocity data from mooring F4-18 in the Fram Strait, July 2018 - August 2019

Time series data of physical oceanography (seawater conductivity, temperature, pressure, salinity), ocean current velocities and hydroacoustics were obtained from mooring F4-18 in the Fram Strait in July 2018 - August 2019 as part of the Helmholtz infrastructure program Frontiers in Arctic Marine Monitoring (FRAM) and the long-term monitoring program at AWI HAUSGARTEN. The mooring was deployed during Polarstern expedition PS114, and recovered during PS121. The attached archive contains raw data files of 6 Seabird SBE37 microcats (nominal depths: 63m, 150m, 250m, 500m, 731m, 1202m; sampling interval 1h), one RDI Workhorse Longranger ADCP (depth: 380m; sampling interval: 1h) and two AADI RCM11 current meters (depths: 730m, 1208m; sampling interval: 2h). The mooring also included a Develogic Sonovault (nominal depth: 800m; data archived elsewhere). Auxiliary information such as sensor calibration sheets, mooring diagrams and schedule files are also provided, if applicable

Millennial-scale terrestrial ecosystem responses to Upper Pleistocene climatic changes: 4D-reconstruction of the Schwalbenberg Loess-Palaeosol-Sequence (Middle Rhine Valley, Germany)

International audienc

Sea-ice derived meltwater stratification slows the biological carbon pump: results from continuous observations

The ocean moderates the world's climate through absorption of heat and carbon, but how much carbon the ocean will continue to absorb remains unknown. The North Atlantic Ocean west (Baffin Bay/Labrador Sea) and east (Fram Strait/Greenland Sea) of Greenland features the most intense absorption of anthropogenic carbon globally; the biological carbon pump (BCP) contributes substantially. As Arctic sea-ice melts, the BCP changes, impacting global climate and other critical ocean attributes (e.g. biodiversity). Full understanding requires year-round observations across a range of ice conditions. Here we present such observations: autonomously collected Eulerian continuous 24-month time-series in Fram Strait. We show that, compared to ice-unaffected conditions, sea-ice derived meltwater stratification slows the BCP by 4 months, a shift from an export to a retention system, with measurable impacts on benthic communities. This has implications for ecosystem dynamics in the future warmer Arctic where the seasonal ice zone is expected to expand

Supplement 1: Space-borne frequency comb metrology

supplemental document Originally published in Optica on 20 December 2016 (optica-3-12-1381