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| 13. |
- Munch, Marie W., et al.
(författare)
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Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
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Tidskriftsartikel (refereegranskat)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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| 14. |
- Steen-Larsen, H. C., et al.
(författare)
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Continuous monitoring of summer surface water vapor isotopic composition above the Greenland Ice Sheet
- 2013
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 13:9, s. 4815-4828
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Tidskriftsartikel (refereegranskat)abstract
- We present here surface water vapor isotopic measurements conducted from June to August 2010 at the NEEM (North Greenland Eemian Drilling Project) camp, NW Greenland (77.45 degrees N, 51.05 degrees W, 2484 m a.s.l.). Measurements were conducted at 9 different heights from 0.1m to 13.5m above the snow surface using two different types of cavity-enhanced near-infrared absorption spectroscopy analyzers. For each instrument specific protocols were developed for calibration and drift corrections. The inter-comparison of corrected results from different instruments reveals excellent reproducibility, stability, and precision with a standard deviations of similar to 0.23 parts per thousand for delta O-18 and similar to 1.4 parts per thousand for delta D. Diurnal and intraseasonal variations show strong relationships between changes in local surface humidity and water vapor isotopic composition, and with local and synoptic weather conditions. This variability probably results from the interplay between local moisture fluxes, linked with firn-air exchanges, boundary layer dynamics, and large-scale moisture advection. Particularly remarkable are several episodes characterized by high (> 40 parts per thousand) surface water vapor deuterium excess. Air mass back-trajectory calculations from atmospheric analyses and water tagging in the LMDZiso (Laboratory of Meteorology Dynamics Zoom-isotopic) atmospheric model reveal that these events are associated with predominant Arctic air mass origin. The analysis suggests that high deuterium excess levels are a result of strong kinetic fractionation during evaporation at the sea-ice margin.
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| 15. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 16. |
- Clausen, Niels, et al.
(författare)
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Similar bleeding phenotype in young children with haemophilia A or B : A cohort study
- 2014
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:6, s. 747-755
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Tidskriftsartikel (refereegranskat)abstract
- The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL-1 respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A.
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| 17. |
- Fan, Y., et al.
(författare)
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The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice
- 2023
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Ingår i: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 8, s. 787-802
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Tidskriftsartikel (refereegranskat)abstract
- Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis. Faecal metagenomics and serum metabolomics reveal compositional and functional alterations in the gut microbiota of women with anorexia nervosa, and faecal transplants could transfer an anorexia-associated phenotype to germ-free mice.
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| 18. |
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| 19. |
- Hietala, H., et al.
(författare)
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Supermagnetosonic subsolar magnetosheath jets and their effects : from the solar wind to the ionospheric convection
- 2012
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 30:1, s. 33-48
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Tidskriftsartikel (refereegranskat)abstract
- It has recently been proposed that ripples inherent to the bow shock during radial interplanetary magnetic field (IMF) may produce local high speed flows in the magnetosheath. These jets can have a dynamic pressure much larger than the dynamic pressure of the solar wind. On 17 March 2007, several jets of this type were observed by the Cluster spacecraft. We study in detail these jets and their effects on the magnetopause, the magnetosphere, and the ionospheric convection. We find that (1) the jets could have a scale size of up to a few RE but less than similar to 6 R-E transverse to the XGSE axis; (2) the jets caused significant local magnetopause perturbations due to their high dynamic pressure; (3) during the period when the jets were observed, irregular pulsations at the geostationary orbit and localised flow enhancements in the ionosphere were detected. We suggest that these inner magnetospheric phenomena were caused by the magnetosheath jets.
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| 20. |
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