Therapeutic drug monitoring in adolescents with anorexia nervosa for safe treatment with adjunct olanzapine

Objective: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best-evidenced substance used off-label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP-guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age- and disorder-specific therapeutic reference range. Method: Sixty-five adolescents with AN (aged 10-18) treated with OLZ (98% female; 97.5% AN-restricting-type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. Results: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. Conclusions: OLZ in the hands of specialists is a well-tolerated and safe treatment adjunct for adolescents with AN

Miocene to present oceanographic variability in the Scotia Sea and Antarctic Ice Sheet dynamics: Insight from revised seismic-stratigraphy following IODP Expedition 382

Scotia Sea and the Drake Passage is key towards understanding the development of modern oceanic circulation patterns and their implications for ice sheet growth and decay. The sedimentary record of the southern Scotia Sea basins documents the regional tectonic, oceanographic and climatic evolution since the Eocene. However, a lack of accurate age estimations has prevented the calibration of the reconstructed history. The upper sedimentary record of the Scotia Sea was scientifically drilled for the first time in 2019 during International Ocean Discovery Program (IODP) Expedition 382, recovering sediments down to ∼643 and 676 m below sea floor in the Dove and Pirie basins respectively. Here, we report newly acquired high resolution physical properties data and the first accurate age constraints for the seismic sequences of the upper sedimentary record of the Scotia Sea to the late Miocene. The drilled record contains four basin-wide reflectors – Reflector-c, -b, -a and -a' previously estimated to be ∼12.6 Ma, ∼6.4 Ma, ∼3.8 Ma and ∼2.6 Ma, respectively. By extrapolating our new Scotia Sea age model to previous morpho-structural and seismic-stratigraphic analyses of the wider region we found, however, that the four discontinuities drilled are much younger than previously thought. Reflector-c actually formed before 8.4 Ma, Reflector-b at ∼4.5/3.7 Ma, Reflector-a at ∼1.7 Ma, and Reflector-a' at ∼0.4 Ma. Our updated age model of these discontinuities has major implications for their correlation with regional tectonic, oceanographic and cryospheric events. According to our results, the outflow of Antarctic Bottom Water to northern latitudes controlled the Antarctic Circumpolar Current flow from late Miocene. Subsequent variability of the Antarctic ice sheets has influenced the oceanic circulation pattern linked to major global climatic changes during early Pliocene, Mid-Pleistocene and the Marine Isotope Stage 11

Ancient marine sediment DNA reveals diatom transition in Antarctica

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: The following databases were used in this study: SILVA small (version 132Ref-nr) and large (version 132Ref) subunit ribosomal RNA database (https://www.arb-silva.de/), and psbO55 (https://www.ebi.ac.uk/biostudies/studies/S-BSST659?query=S-BSST659). Detailed Supplementary Information on methods and analysis is provided with this submission. The demultiplexed raw sequencing data generated and analysed during this study have been deposited in the NCBI Sequence Read Archive database (https://www.ncbi.nlm.nih.gov/sra) under Accession code/BioProject PRJNA861836 (BioSamples SAMN29928044 - SAMN29928123)59, and includes metadata for each sediment and control sample. For further requests please contact the corresponding author. Source data are provided with this paper.Code availability: The bioinformatic pipeline used in this study was previously published in ref. 8 and additional information is provided with the Supplementary Information Notes 1–3.Antarctica is one of the most vulnerable regions to climate change on Earth and studying the past and present responses of this polar marine ecosystem to environmental change is a matter of urgency. Sedimentary ancient DNA (sedaDNA) analysis can provide such insights into past ecosystem-wide changes. Here we present authenticated (through extensive contamination control and sedaDNA damage analysis) metagenomic marine eukaryote sedaDNA from the Scotia Sea region acquired during IODP Expedition 382. We also provide a marine eukaryote sedaDNA record of ~1 Mio. years and diatom and chlorophyte sedaDNA dating back to ~540 ka (using taxonomic marker genes SSU, LSU, psbO). We find evidence of warm phases being associated with high relative diatom abundance, and a marked transition from diatoms comprising <10% of all eukaryotes prior to ~14.5 ka, to ~50% after this time, i.e., following Meltwater Pulse 1A, alongside a composition change from sea-ice to open-ocean species. Our study demonstrates that sedaDNA tools can be expanded to hundreds of thousands of years, opening the pathway to the study of ecosystem-wide marine shifts and paleo-productivity phases throughout multiple glacial-interglacial cycles.Australian and New Zealand International Ocean Discovery Program Consortium (ANZIC)University of AdelaideAustralian Research Council (ARC)Deutsche Forschungsgemeinschaft (DFG)NASANational Science Foundation (NSF)Dutch Research Council (NWO)European Union Horizon 202

Expedition 382 summary

This is the final version. Available on open access from IODP Publications via the DOI in this recordInternational Ocean Discovery Program Expedition 382, Iceberg Alley and Subantarctic Ice and Ocean Dynamics, investigated the long-term climate history of Antarctica, seeking to understand how polar ice sheets responded to changes in insolation and atmospheric CO2 in the past and how ice sheet evolution influenced global sea level and vice versa. Five sites (U1534–U1538) were drilled east of the Drake Passage: two sites at 53.2°S at the northern edge of the Scotia Sea and three sites at 57.4°–59.4°S in the southern Scotia Sea. We recovered continuously deposited late Neogene sediments to reconstruct the past history and variability in Antarctic Ice Sheet (AIS) mass loss and associated changes in oceanic and atmospheric circulation. The sites from the southern Scotia Sea (Sites U1536–U1538) will be used to study the Neogene flux of icebergs through “Iceberg Alley,” the main pathway along which icebergs calved from the margin of the AIS travel as they move equatorward into the warmer waters of the Antarctic Circumpolar Current (ACC). In particular, sediments from this area will allow us to assess the magnitude of iceberg flux during key times of AIS evolution, including the following: The middle Miocene glacial intensification of the East Antarctic Ice Sheet, The mid-Pliocene warm period, The late Pliocene glacial expansion of the West Antarctic Ice Sheet, The mid-Pleistocene transition (MPT), and The “warm interglacials” and glacial terminations of the last 800 ky. We will use the geochemical provenance of iceberg-rafted detritus and other glacially eroded material to determine regional sources of AIS mass loss. We will also address interhemispheric phasing of ice sheet growth and decay, study the distribution and history of land-based versus marine-based ice sheets around the continent over time, and explore the links between AIS variability and global sea level. By comparing north–south variations across the Scotia Sea between the Pirie Basin (Site U1538) and the Dove Basin (Sites U1536 and U1537), Expedition 382 will also deliver critical information on how climate changes in the Southern Ocean affect ocean circulation through the Drake Passage, meridional overturning in the region, water mass production, ocean–atmosphere CO2 transfer by wind-induced upwelling, sea ice variability, bottom water outflow from the Weddell Sea, Antarctic weathering inputs, and changes in oceanic and atmospheric fronts in the vicinity of the ACC. Comparing changes in dust proxy records between the Scotia Sea and Antarctic ice cores will also provide a detailed reconstruction of changes in the Southern Hemisphere westerlies on millennial and orbital timescales for the last 800 ky. Extending the ocean dust record beyond the last 800 ky will help to evaluate dust-climate couplings since the Pliocene, the potential role of dust in iron fertilization and atmospheric CO2 drawdown during glacials, and whether dust input to Antarctica played a role in the MPT. The principal scientific objective of Subantarctic Front Sites U1534 and U1535 at the northern limit of the Scotia Sea is to reconstruct and understand how intermediate water formation in the southwest Atlantic responds to changes in connectivity between the Atlantic and Pacific basins, the “cold water route.” The Subantarctic Front contourite drift, deposited between 400 and 2000 m water depth on the northern flank of an east–west trending trough off the Chilean continental shelf, is ideally situated to monitor millennial- to orbital-scale variability in the export of Antarctic Intermediate Water beneath the Subantarctic Front. During Expedition 382, we recovered continuously deposited sediments from this drift spanning the late Pleistocene (from ~0.78 Ma to recent) and from the late Pliocene (~3.1–2.6 Ma). These sites are expected to yield a wide array of paleoceanographic records that can be used to interpret past changes in the density structure of the Atlantic sector of the Southern Ocean, track migrations of the Subantarctic Front, and give insights into the role and evolution of the cold water route over significant climate episodes, including the following: The most recent warm interglacials of the late Pleistocene and The intensification of Northern Hemisphere glaciation.Natural Environment Research Council (NERC

Ancient marine sediment DNA reveals diatom transition in Antarctica

Antarctica is one of the most vulnerable regions to climate change on Earth and studying the past and present responses of this polar marine ecosystem to environmental change is a matter of urgency. Sedimentary ancient DNA (sedaDNA) analysis can provide such insights into past ecosystem-wide changes. Here we present authenticated (through extensive contamination control and sedaDNA damage analysis) metagenomic marine eukaryote sedaDNA from the Scotia Sea region acquired during IODP Expedition 382. We also provide a marine eukaryote sedaDNA record of ~1 Mio. years and diatom and chlorophyte sedaDNA dating back to ~540 ka (using taxonomic marker genes SSU, LSU, psbO). We find evidence of warm phases being associated with high relative diatom abundance, and a marked transition from diatoms comprising <10% of all eukaryotes prior to ~14.5 ka, to ~50% after this time, i.e., following Meltwater Pulse 1A, alongside a composition change from sea-ice to open-ocean species. Our study demonstrates that sedaDNA tools can be expanded to hundreds of thousands of years, opening the pathway to the study of ecosystem-wide marine shifts and paleo-productivity phases throughout multiple glacial-interglacial cycles

Antiphased dust deposition and productivity in the Antarctic Zone over 1.5 million years

The Southern Ocean paleoceanography provides key insights into how iron fertilization and oceanic productivity developed through Pleistocene ice-ages and their role in influencing the carbon cycle. We report a high-resolution record of dust deposition and ocean productivity for the Antarctic Zone, close to the main dust source, Patagonia. Our deep-ocean records cover the last 1.5 Ma, thus doubling that from Antarctic ice-cores. We find a 5 to 15-fold increase in dust deposition during glacials and a 2 to 5-fold increase in biogenic silica deposition, reflecting higher ocean productivity during interglacials. This antiphasing persisted throughout the last 25 glacial cycles. Dust deposition became more pronounced across the Mid-Pleistocene Transition (MPT) in the Southern Hemisphere, with an abrupt shift suggesting more severe glaciations since ~0.9 Ma. Productivity was intermediate pre-MPT, lowest during the MPT and highest since 0.4 Ma. Generally, glacials experienced extended sea-ice cover, reduced bottom-water export and Weddell Gyre dynamics, which helped lower atmospheric CO2 levels

Ancient marine sediment DNA reveals diatom transition in Antarctica

Antarctica is one of the most vulnerable regions to climate change on Earth and studying the past and present responses of this polar marine ecosystem to environmental change is a matter of urgency. Sedimentary ancient DNA (sedaDNA) analysis can provide such insights into past ecosystem-wide changes. Here we present authenticated (through extensive contamination control and sedaDNA damage analysis) metagenomic marine eukaryote sedaDNA from the Scotia Sea region acquired during IODP Expedition 382. We also provide a marine eukaryote sedaDNA record of ~1 Mio. years and diatom and chlorophyte sedaDNA dating back to ~540 ka (using taxonomic marker genes SSU, LSU, psbO). We find evidence of warm phases being associated with high relative diatom abundance, and a marked transition from diatoms comprising <10% of all eukaryotes prior to ~14.5 ka, to ~50% after this time, i.e., following Meltwater Pulse 1A, alongside a composition change from sea-ice to open-ocean species. Our study demonstrates that sedaDNA tools can be expanded to hundreds of thousands of years, opening the pathway to the study of ecosystem-wide marine shifts and paleo-productivity phases throughout multiple glacial-interglacial cycles.ISSN:2041-172

Latitudinal variance in the drivers and pacing of warmth during mid‐Pleistocene MIS 31 in the Antarctic Zone of the Southern Ocean

Early Pleistocene Marine Isotope Stage (MIS)-31 (1.081 to 1.062 Ma) is a unique interval of extreme global warming, including evidence of a West Antarctic Ice Sheet (WAIS) collapse. Here we present a new 1000-year resolution, spanning 1.110-1.030 Ma, diatom-based reconstruction of primary productivity, relative sea surface temperature changes, sea-ice proximity/open ocean conditions and diatom species absolute abundances during MIS-31, from the Scotia Sea (59° S) using deep-sea sediments collected during International Ocean Discovery Program (IODP) Expedition 382. The lower Jaramillo magnetic reversal (base of C1r.1n, 1.071 Ma) provides a robust and independent time-stratigraphic marker to correlate records from other drill cores in the Antarctic Zone of the Southern Ocean (AZSO). An increase in open ocean species Fragilariopsis kerguelensis in early MIS-31 at 53° S (Ocean Drilling Program Site 1094) correlates with increased obliquity forcing, whereas at 59° S (IODP Site U1537; this study) three progressively increasing, successive peaks in the relative abundance of F. kerguelensis correlate with Southern Hemisphere-phased precession pacing. These observations reveal a complex pattern of ocean temperature change and sustained sea surface temperature increase lasting longer than a precession cycle within the Atlantic sector of the AZSO. Timing of an inferred WAIS collapse is consistent with delayed warmth (possibly driven by sea-ice dynamics) in the southern AZSO, supporting models that indicate WAIS sensitivity to local sub-ice shelf melting. Anthropogenically enhanced impingement of relatively warm water beneath the ice shelves today highlights the importance of understanding dynamic responses of the WAIS during MIS-31, a warmer than Holocene interglacial

Antiphased dust deposition and productivity in the Antarctic Zone over 1.5 million years.

The Southern Ocean paleoceanography provides key insights into how iron fertilization and oceanic productivity developed through Pleistocene ice-ages and their role in influencing the carbon cycle. We report a high-resolution record of dust deposition and ocean productivity for the Antarctic Zone, close to the main dust source, Patagonia. Our deep-ocean records cover the last 1.5 Ma, thus doubling that from Antarctic ice-cores. We find a 5 to 15-fold increase in dust deposition during glacials and a 2 to 5-fold increase in biogenic silica deposition, reflecting higher ocean productivity during interglacials. This antiphasing persisted throughout the last 25 glacial cycles. Dust deposition became more pronounced across the Mid-Pleistocene Transition (MPT) in the Southern Hemisphere, with an abrupt shift suggesting more severe glaciations since ~0.9 Ma. Productivity was intermediate pre-MPT, lowest during the MPT and highest since 0.4 Ma. Generally, glacials experienced extended sea-ice cover, reduced bottom-water export and Weddell Gyre dynamics, which helped lower atmospheric CO2 levels