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Ventilation heterogeneity is frequent in bronchial asthma and can be assessed using multiple breath wash-out testing (MBW). Most data is available in paediatric patients and using nitrogen as a tracer gas. We aimed to evaluate sulphur hexafluoride (SF 6 ) MBW in adult asthmatics. Spirometry, whole-body plethysmography, impulse oscillometry and SF 6 -MBW were prospectively performed. MBW parameters reflecting global (lung clearance index, LCI), acinar (S acin ) and conductive (S cond ) ventilation heterogeneity were derived from three consecutive wash-outs. LCI was calculated for the traditional 2.5% and an earlier 5% stopping point that has the potential to reduce wash-out times. 91 asthmatics (66%) and 47 non-asthmatic controls (34%) were included in final analysis. LCI 2.5 and LCI 5 were higher in asthmatics (p < 0.001). Likewise, S acin and S cond were elevated (p < 0.001 and p < 0.01). Coefficient of variation was 3.4% for LCI 2.5 and 3.5% for LCI 5 in asthmatics. Forty-one asthmatic patients had normal spirometry. ROC analysis revealed an AUC of 0.906 for the differentiation from non-asthmatic controls exceeding diagnostic performance of individual and conventional parameters (AUC = 0.819, p < 0.05). SF 6 -MBW is feasible and reproducible in adult asthmatics. Ventilation heterogeneity is increased as compared to non-asthmatic controls persisting in asthmatic patients with normal spirometry. Diagnostic performance is not affected using an earlier LCI stopping point while reducing wash-out duration considerably.

Introduction Arterial spin labeling (ASL) is a functional neuroimaging technique that has been frequently used to investigate acute pain states. A major advantage of ASL as opposed to blood‐oxygen‐level‐dependent functional neuroimaging is its applicability for low‐frequency designs. As such, ASL represents an interesting option for studies in which repeating an experimental event would reduce its ecological validity. Whereas most ASL pain studies so far have used thermal stimuli, to our knowledge, no ASL study so far has investigated pain responses to sharp mechanical pain. Methods As a proof of concept, we investigated whether ASL has the sensitivity to detect brain activation within core areas of the nociceptive network in healthy controls following a single stimulation block based on 96 s of mechanical painful stimulation using a blunt blade. Results We found significant increases in perfusion across many regions of the nociceptive network such as primary and secondary somatosensory cortices, premotor cortex, posterior insula, inferior parietal cortex, parietal operculum, temporal gyrus, temporo‐occipital lobe, putamen, and the cerebellum. Contrary to our hypothesis, we did not find any significant increase within ACC, thalamus, or PFC. Moreover, we were able to detect a significant positive correlation between pain intensity ratings and pain‐induced perfusion increase in the posterior insula. Conclusion We demonstrate that ASL is suited to investigate acute pain in a single event paradigm, although to detect activation within some regions of the nociceptive network, the sensitivity of our paradigm seemed to be limited. Regarding the posterior insula, our paradigm was sensitive enough to detect a correlation between pain intensity ratings and pain‐induced perfusion increase. Previous experimental pain studies have proposed that intensity coding in this region may be restricted to thermal stimulation. Our result demonstrates that the posterior insula encodes intensity information for mechanical stimuli as well. Using arterial spin labeling (ASL), one single block of sharp mechanical pain stimulation (96 s) induced perfusion increase in many areas of the nociceptive network. Moreover, a positive correlation between pain intensity ratings and perfusion increase in the posterior insula could be detected. Our results demonstrate that ASL constitutes a powerful alternative to BOLD fMRI for low‐frequency designs and that pain intensity coding in the posterior insula is not restricted to thermal stimulation.

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries ( www.covidclinical.net ). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

Submitted manuscript version, licensed Natureresearch Preprint Policy . Published version available at: http://dx.doi.org/10.1038/s41396-019-0368-1

Subglacial upwelling of nutrient-rich bottom water is known to sustain elevated summer primary production in tidewater-glacier-influenced fjord systems. However, the importance of subglacial upwelling during the early spring season has not been considered yet. We hypothesized that subglacial discharge under sea ice is present in early spring and that its flux is sufficient to increase phytoplankton primary productivity. We evaluated the effects of the submarine discharge on primary production in a seasonally fast-ice covered Svalbard fjord (Billefjorden) influenced by a tidewater outlet glacier in April and May 2019. We found clear evidence for subglacial discharge and upwelling. Although the estimated bottom-water entrainment factor (1.6) and total fluxes were lower than in summer studies, we still observed substantial impact on the fjord ecosystem and primary production at this time of the year. The subglacial discharge leads to a salinity-stratified surface water layer and sea ice formation with low bulk salinity and permeability. The combination of the stratified surface layer, a 2-fold higher under-ice irradiance due to thinner snow cover, and higher N and Si concentrations at the glacier front supported phytoplankton primary production 2 orders of magnitude higher (42.6 mg C m−2 d−1) compared to a marine reference site at the fast-ice edge. Reciprocal transplant experiments showed that nutrient supply increased phytoplankton primary production by approximately 30 %. The brackish-water sea ice at the glacier front with its low bulk salinity contained a reduced brine volume, limiting the inhabitable brine channel space and nutrient exchange with the underlying seawater compared to full marine sea ice. Microbial and algal communities were substantially different in subglacial-influenced water and sea ice compared to the marine reference site, sharing taxa with the subglacial outflow water. We suggest that with climate change, the retreat of tidewater glaciers in early spring could lead to decreased under-ice phytoplankton primary production. In contrast, sea ice algae production and biomass may become increasingly important, unless sea ice disappears first, in which case spring phytoplankton primary production may increase.

Phyto- and zooplankton in Arctic and sub-Arctic seas show very strong seasonal changes in diversity and biomass. Here we document the seasonal variability in the mesozooplankton community structure in a sub-Arctic fjord in Northern Norway based on monthly sampling between November 2018 and February 2020. We combined traditional morphological zooplankton identification with DNA metabarcoding of a 313 base pair fragment of the COI gene. This approach allowed us to provide the most detailed mesozooplankton species list known for this region across an entire year, including both holo- and meroplankton. The zooplankton community was dominated by small copepods throughout the sampling period both in terms of abundance and relative sequence counts. However, meroplankton was the most diverse group, especially within the phylum polychaeta. We identified four distinct periods based on the seasonal analysis of the zooplankton community composition. The pre-spring bloom period (February–March) was characterized by low abundance and biomass of zooplankton. The spring bloom (April) was characterized by the presence of Calanus young stages, cirripedia and krill eggs. The spring-summer period (May–August) was characterized by a succession of meroplankton and a relatively high abundance of copepods of the genus Calanus spp. Finally, the autumn-winter period (September–December) was characterized by a high copepod diversity and a peak in abundance of small copepods (e.g., Oithona similis, Acartia longiremis, Pseudocalanus acuspes, Pseudocalanus elongatus, Pseudocalanus moultoni, Pseudocalanus minutus). During this period, we also observed an influx of boreal warm-water species which were notably absent during the rest of the year. Both the traditional community analysis and metabarcoding were highly complementary and with a few exceptions showed similar trends in the seasonal changes of the zooplankton community structure.

Arctic coastal ecosystems are rapidly changing due to climate warming. This makes modeling their productivity crucially important to better understand future changes. System primary production in these systems is highest during the pronounced spring bloom, typically dominated by diatoms. Eventually the spring blooms terminate due to silicon or nitrogen limitation. Bacteria can play an important role for extending bloom duration and total CO2 fixation through ammonium regeneration. Current ecosystem models often simplify the effects of nutrient co-limitations on algal physiology and cellular ratios and simplify nutrient regeneration. These simplifications may lead to underestimations of primary production. Detailed biochemistry- and cell-based models can represent these dynamics but are difficult to tune in the environment. We performed a cultivation experiment that showed typical spring bloom dynamics, such as extended algal growth via bacterial ammonium remineralization, reduced algal growth and inhibited chlorophyll synthesis under silicate limitation, and gradually reduced nitrogen assimilation and chlorophyll synthesis under nitrogen limitation. We developed a simplified dynamic model to represent these processes. Overall, model complexity in terms of the number of parameters is comparable to the phytoplankton growth and nutrient biogeochemistry formulations in common ecosystem models used in the Arctic while improving the representation of nutrient-co-limitation-related processes. Such model enhancements that now incorporate increased nutrient inputs and higher mineralization rates in a warmer climate will improve future predictions in this vulnerable system.

Arctic coastal ecosystems are rapidly changing due to climate warming. This makes modeling their productivity crucially important to better understand future changes. System primary production in these systems is highest during the pronounced spring bloom, typically dominated by diatoms. Eventually the spring blooms terminate due to silicon or nitrogen limitation. Bacteria can play an important role for extending bloom duration and total CO2 fixation through ammonium regeneration. Current ecosystem models often simplify the effects of nutrient co-limitations on algal physiology and cellular ratios and simplify nutrient regeneration. These simplifications may lead to underestimations of primary production. Detailed biochemistry- and cell-based models can represent these dynamics but are difficult to tune in the environment. We performed a cultivation experiment that showed typical spring bloom dynamics, such as extended algal growth via bacterial ammonium remineralization, reduced algal growth and inhibited chlorophyll synthesis under silicate limitation, and gradually reduced nitrogen assimilation and chlorophyll synthesis under nitrogen limitation. We developed a simplified dynamic model to represent these processes. Overall, model complexity in terms of the number of parameters is comparable to the phytoplankton growth and nutrient biogeochemistry formulations in common ecosystem models used in the Arctic while improving the representation of nutrient-co-limitation-related processes. Such model enhancements that now incorporate increased nutrient inputs and higher mineralization rates in a warmer climate will improve future predictions in this vulnerable system.

The polar night has recently received increased attention as a surprisingly active biological season. Yet, polar night microbial ecology is a vastly understudied field. To identify the physical and biogeochemical parameters driving microbial activity over the dark season, we studied a sub-Arctic fjord system in northern Norway from autumn to early spring with detailed monthly sampling. We focused on the impact of mixing, terrestrial organic matter input and light on microbial ecosystem dynamics. Our study highlights strong differences in the key drivers between spring, autumn, and winter. The spring bloom started in March in a fully mixed water column, opposing the traditional critical depth hypothesis. Incident solar radiation was the key driver maximum Chlorophyll was reached in April. The onset of the autumn phytoplankton bloom was controlled by vertical mixing, causing nutrient upwelling and dilution of zooplankton grazers, which had their highest biomass during this time. According to the dilution-recoupling hypothesis grazer dilution reduced grazing stress and allowed the fall bloom formation. Mixing at that time was initiated by strong winds and reduced stratification as a consequence of freezing temperatures and lower freshwater runoff. During the light-limited polar night, the primary production was extremely low but bacteria continued growing on decaying algae, their exudates and also allochthonous organic matter. A melting event in January could have increased input of organic matter from land, supporting a mid-winter bacterial bloom. In conclusion, polar night biogeochemistry and microbial ecology was not only driven by light availability, but strongly affected by variability in reshwater discharge and allochthonous carbon input. With climate change freshwater discharge will increase in the Arctic, which will likely increase importance of the dynamics described in this study.

Subglacial upwelling of nutrient-rich bottom water is known to sustain elevated summer primary production in tidewater-glacier-influenced fjord systems. However, the importance of subglacial upwelling during the early spring season has not been considered yet. We hypothesized that subglacial discharge under sea ice is present in early spring and that its flux is sufficient to increase phytoplankton primary productivity. We evaluated the effects of the submarine discharge on primary production in a seasonally fast-ice covered Svalbard fjord (Billefjorden) influenced by a tidewater outlet glacier in April and May 2019. We found clear evidence for subglacial discharge and upwelling. Although the estimated bottom-water entrainment factor (1.6) and total fluxes were lower than in summer studies, we still observed substantial impact on the fjord ecosystem and primary production at this time of the year. The subglacial discharge leads to a salinity-stratified surface water layer and sea ice formation with low bulk salinity and permeability. The combination of the stratified surface layer, a 2-fold higher under-ice irradiance due to thinner snow cover, and higher N and Si concentrations at the glacier front supported phytoplankton primary production 2 orders of magnitude higher (42.6 mg C m−2 d−1) compared to a marine reference site at the fast-ice edge. Reciprocal transplant experiments showed that nutrient supply increased phytoplankton primary production by approximately 30 %. The brackish-water sea ice at the glacier front with its low bulk salinity contained a reduced brine volume, limiting the inhabitable brine channel space and nutrient exchange with the underlying seawater compared to full marine sea ice. Microbial and algal communities were substantially different in subglacial-influenced water and sea ice compared to the marine reference site, sharing taxa with the subglacial outflow water. We suggest that with climate change, the retreat of tidewater glaciers in early spring could lead to decreased under-ice phytoplankton primary production. In contrast, sea ice algae production and biomass may become increasingly important, unless sea ice disappears first, in which case spring phytoplankton primary production may increase.