| 1. |
- Kurilshikov, Alexander, et al.
(författare)
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Large-scale association analyses identify host factors influencing human gut microbiome composition
- 2021
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
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Tidskriftsartikel (refereegranskat)abstract
- To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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| 2. |
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| 3. |
- André, Lars, et al.
(författare)
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The prevalence of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants is very low: a retrospective cohort register study
- 2024
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - 1757-7241. ; 32, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCurrent guidelines from Scandinavian Neuro Committee mandate a 24-hour observation for head trauma patients on anticoagulants, even with normal initial head CT scans, as a means not to miss delayed intracranial hemorrhages. This study aimed to assess the prevalence, and time to diagnosis, of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants.MethodUtilizing comprehensive two-year data from Region Skåne’s emergency departments, which serve a population of 1.3 million inhabitants, this study focused on adult head trauma patients prescribed oral anticoagulants. We identified those with intracranial hemorrhage within 30 days, defining delayed intracranial hemorrhage as a bleeding not apparent on their initial CT head scan. These cases were further defined as clinically relevant if associated with mortality, any intensive care unit admission, or neurosurgery.ResultsOut of the included 2,362 head injury cases (median age 84, 56% on a direct acting oral anticoagulant), five developed delayed intracranial hemorrhages. None of these five cases underwent neurosurgery nor were admitted to an intensive care unit. Only two cases (0.08%, 95% confidence interval [0.01–0.3%]) were classified as clinically relevant, involving subdural hematomas in patients aged 82 and 87 years, who both subsequently died. The diagnosis of these delayed intracranial hemorrhages was made at 4 and 7 days following initial presentation to the emergency department.ConclusionIn patients with head trauma, on oral anticoagulation, the incidence of clinically relevant delayed intracranial hemorrhage was found to be less than one in a thousand, with detection occurring four days or later after initial presentation. This challenges the effectiveness of the 24-hour observation period recommended by the Scandinavian Neurotrauma Committee guidelines, suggesting a need to reassess these guidelines to optimise care and resource allocation.
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| 4. |
- Johansson, André, et al.
(författare)
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Development of outcomes for evaluating emergency care triage : a Delphi approach
- 2023
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Triage is used as standard of care for prioritization and identification of time-critical patients in the emergency department (ED) globally, but it is unclear what outcomes should be used to evaluate triage. Currently used outcomes do not include important time-critical diagnoses and conditions.METHOD: We used 18 Swedish triage experts to collect and assess outcomes for the evaluation of 5-level triage systems. The experts suggested 68 outcomes which were then tested through a modified Delphi approach in three rounds. The outcomes aimed to identify correctly prioritized red patients (in need of a resuscitation team), and orange patients (other time critical conditions). Consensus was pre-defined as 70% dichotomized (positive/negative) concordance.RESULTS: Diagnoses, interventions, mortality, level of care and lab results were included in the outcomes. Positive consensus was reached for 49 outcomes and negative consensus for 7 outcomes, with an 83% response rate. The five most approved outcomes were the interventions Percutaneous coronary intervention, Surgical airway and Massive transfusion together with the diagnoses Tension pneumothorax and Intracerebral hemorrhage that received specific interventions. The outcomes with the clearest disapproval included Admittance to a ward, Treatment with antihistamines and The ordering of a head computed tomography scan. The outcomes were considered valid only if occurring in or from the ED.CONCLUSION: This study proposes a standard of 49 outcomes divided into two sets tied to red and orange priority respectively, to be used when evaluating 5-level priority triage systems; Lund Outcome Set for Evaluation of Triage (LOSET). The proposed outcomes include diagnoses, interventions and laboratory results. Before widespread implementation of LOSET, prospective testing is needed, preferably at multiple sites.
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| 5. |
- Niklasson, Emily, et al.
(författare)
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Higher risk of traumatic intracranial hemorrhage with antiplatelet therapy compared to oral anticoagulation—a single-center experience
- 2024
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Ingår i: European Journal of Trauma and Emergency Surgery. - 1863-9933.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Traumatic brain injury is the main reason for the emergency department visit of up to 3% of the patients and a major worldwide cause for morbidity and mortality. Current emergency management guidelines recommend close attention to patients taking oral anticoagulation but not patients on antiplatelet therapy. Recent studies have begun to challenge this. The aim of this study was to determine the impact of antiplatelet therapy and oral anticoagulation on traumatic intracranial hemorrhage. Methods: Medical records of adult patients triaged with “head injury” as the main reason for emergency care were retrospectively reviewed from January 1, 2017, to December 31, 2017, and January 1, 2020, to December 31, 2021. Patients ≥ 18 years with head trauma were included. Odds ratio was calculated, and multiple logistic regression was performed. Results: A total of 4850 patients with a median age of 70 years were included. Traumatic intracranial hemorrhage was found in 6.2% of the patients. The risk ratio for traumatic intracranial hemorrhage in patients on antiplatelet therapy was 2.25 (p < 0.001, 95% confidence interval 1.73–2.94) and 1.38 (p = 0.002, 95% confidence interval 1.05–1.84) in patients on oral anticoagulation compared to patients without mediations that affect coagulation. In binary multiple regression, antiplatelet therapy was associated with intracranial hemorrhage, but oral anticoagulation was not. Conclusion: This study shows that antiplatelet therapy is associated with a higher risk of traumatic intracranial hemorrhage compared to oral anticoagulation. Antiplatelet therapy should be given equal or greater consideration in the guidelines compared to anticoagulation therapy. Further studies on antiplatelet subtypes within the context of head trauma are recommended to improve the guidelines’ diagnostic accuracy.
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| 6. |
- Olsen, Hanne T., et al.
(författare)
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Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients
- 2020
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 382:12, s. 1103-1111
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Tidskriftsartikel (refereegranskat)abstract
- Background In critically ill, mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the intensive care unit (ICU). Data on whether a plan of no sedation, as compared with a plan of light sedation, has an effect on mortality are lacking. Methods In a multicenter, randomized, controlled trial, we assigned, in a 1:1 ratio, mechanically ventilated ICU patients to a plan of no sedation (nonsedation group) or to a plan of light sedation (i.e., to a level at which the patient was arousable, defined as a score of -2 to -3 on the Richmond Agitation and Sedation Scale [RASS], on which scores range from -5 [unresponsive] to +4 [combative]) (sedation group) with daily interruption. The primary outcome was mortality at 90 days. Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days. Between-group differences were calculated as the value in the nonsedation group minus the value in the sedation group. Results A total of 710 patients underwent randomization, and 700 were included in the modified intention-to-treat analysis. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group than in the sedation group, indicating a greater chance of in-hospital death. The mean RASS score in the nonsedation group increased from -1.3 on day 1 to -0.8 on day 7 and, in the sedation group, from -2.3 on day 1 to -1.8 on day 7. Mortality at 90 days was 42.4% in the nonsedation group and 37.0% in the sedated group (difference, 5.4 percentage points; 95% confidence interval [CI], -2.2 to 12.2; P=0.65). The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the nonsedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 1 patient (0.3%) in the nonsedation group and in 10 patients (2.8%) in the sedation group (difference, -2.5 percentage points; 95% CI, -4.8 to -0.7 [unadjusted for multiple comparisons]). Conclusions Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. (Funded by the Danish Medical Research Council and others; NONSEDA ClinicalTrials.gov number, NCT01967680.)
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| 7. |
- Pei, Yifan, et al.
(författare)
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Occasional paternal inheritance of the germline-restricted chromosome in songbirds
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
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Tidskriftsartikel (refereegranskat)abstract
- Songbirds have one special accessory chromosome, the so-called germline-restricted chromosome (GRC), which is only present in germline cells and absent from all somatic tissues. Earlier work on the zebra finch (Taeniopygia guttata castanotis) showed that the GRC is inherited only through the female line-like the mitochondria-and is eliminated from the sperm during spermatogenesis. Here, we show that the GRC has the potential to be paternally inherited. Confocal microscopy using GRC-specific fluorescent in situ hybridization probes indicated that a considerable fraction of sperm heads (1 to 19%) in zebra finch ejaculates still contained the GRC. In line with these cytogenetic data, sequencing of ejaculates revealed that individual males from two families differed strongly and consistently in the number of GRCs in their ejaculates. Examining a captive-bred male hybrid of the two zebra finch subspecies (T. g. guttata and T. g. castanotis) revealed that the mitochondria originated from a castanotis mother, whereas the GRC came from a guttata father. Moreover, analyzing GRC haplotypes across nine castanotis matrilines, estimated to have diverged for up to 250,000 y, showed surprisingly little variability among GRCs. This suggests that a single GRC haplotype has spread relatively recently across all examined matrilines. A few diagnostic GRC mutations that arose since this inferred spreading suggest that the GRC has continued to jump across matriline boundaries. Our findings raise the possibility that certain GRC haplotypes could selfishly spread through the population via occasional paternal transmission, thereby out-competing other GRC haplotypes that were limited to strict maternal inheritance, even if this was partly detrimental to organismal fitness.
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| 8. |
- Petäjä, Tuukka, et al.
(författare)
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Overview : Integrative and Comprehensive Understanding on Polar Environments (iCUPE) - concept and initial results
- 2020
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:14, s. 8551-8592
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Tidskriftsartikel (refereegranskat)abstract
- The role of polar regions is increasing in terms of megatrends such as globalization, new transport routes, demography, and the use of natural resources with consequent effects on regional and transported pollutant concentrations. We set up the ERA-PLANET Strand 4 project iCUPE - integrative and Comprehensive Understanding on Polar Environments to provide novel insights and observational data on global grand challenges with an Arctic focus. We utilize an integrated approach combining in situ observations, satellite remote sensing Earth observations (EOs), and multi-scale modeling to synthesize data from comprehensive long-term measurements, intensive campaigns, and satellites to deliver data products, metrics, and indicators to stakeholders concerning the environmental status, availability, and extraction of natural resources in the polar areas. The iCUPE work consists of thematic state-of-the-art research and the provision of novel data in atmospheric pollution, local sources and transboundary transport, the characterization of arctic surfaces and their changes, an assessment of the concentrations and impacts of heavy metals and persistent organic pollutants and their cycling, the quantification of emissions from natural resource extraction, and the validation and optimization of satellite Earth observation (EO) data streams. In this paper we introduce the iCUPE project and summarize initial results arising out of the integration of comprehensive in situ observations, satellite remote sensing, and multi-scale modeling in the Arctic context.
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| 9. |
- Richter, Steffen, et al.
(författare)
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Ultrafast dynamics of hot charge carriers in an oxide semiconductor probed by femtosecond spectroscopic ellipsometry
- 2020
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Ingår i: New Journal of Physics. - : IOP PUBLISHING LTD. - 1367-2630. ; 22:8
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Tidskriftsartikel (refereegranskat)abstract
- Many linked processes occur concurrently in strongly excited semiconductors, such as interband and intraband absorption, scattering of electrons and holes by the heated lattice, Pauli blocking, bandgap renormalization and the formation of Mahan excitons. In this work, we disentangle their dynamics and contributions to the optical response of a ZnO thin film. Using broadband pump-probe ellipsometry, we can directly and unambiguously obtain the real and imaginary part of the transient dielectric function which we compare with first-principles simulations. We find interband and excitonic absorption partially blocked and screened by the photo-excited electron occupation of the conduction band and hole occupation of the valence band (absorption bleaching). Exciton absorption turns spectrally narrower upon pumping and sustains the Mott transition, indicating Mahan excitons. Simultaneously, intra-valence-band transitions occur at sub-picosecond time scales after holes scatter to the edge of the Brillouin zone. Our results pave new ways for the understanding of non-equilibrium charge-carrier dynamics in materials by reliably distinguishing between changes in absorption coefficient and refractive index, thereby separating competing processes. This information will help to overcome the limitations of materials for high-power optical devices that owe their properties from dynamics in the ultrafast regime.
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| 10. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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| 11. |
- Zeiger, Emilie, et al.
(författare)
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Evaluation of the diagnostic and prognostic potential of optical coherence tomography (OCT) of the pulmonary arteries during standardised right heart catheterisation in patients with pulmonary hypertension : a cross-sectional single-centre experience
- 2023
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Ingår i: Cardiovascular Diagnosis and Therapy. - 2223-3652. ; 13:3, s. 453-464
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pulmonary hypertension (PH) is diagnosed based on an invasive evaluation of the mean pulmonary artery (PA) pressure. The morphological assessment of the pulmonary arteries was only recently not feasible. With the advent of optical coherence tomography (OCT)-imaging, an accessible tool allows to study PA morphology longitudinally. The primary hypothesis was that OCT distincts the PA structure of PH patients from control subjects. The secondary hypothesis was that PA wall thickness (WT) correlates with the progression of PH. Methods: This is a retrospective monocentric study of 28 paediatric patients with (PH group) and without PH (control group) who had undergone cardiac catheterisation including OCT imaging of the PA branches. OCT parameters analysed were WT and the quotient of WT and diameter (WT/DM) and those were compared between the PH group and the control group. In addition, the OCT parameters were aligned with the haemodynamic parameters to evaluate the potential of OCT as a risk factor for patients with PH. Results: WT and WT/DM in the PH group were significantly higher compared to the control group {WT: 0.150 [0.230, range (R): 0.100–0.330] vs. 0.100 [0.050, R: 0.080–0.130] mm, P<0.001; WT/DM: 0.06 [0.05] vs. 0.03 [0.01], P=0.006}. There were highly significant correlations between WT and WT/DM with the haemodynamic parameters mean pulmonary arterial pressure (mPAP) [Spearman correlation coefficient (rs) =0.702, P<0.001; rs=0.621, P<0.001], systolic pulmonary arterial pressure (sPAP) (rs=0.668, P<0.001; rs=0.658, P<0.001) and WT and pulmonary vascular resistance (PVR) (rs=0.590, P=0.02). Also, there was a significant correlation between WT and WT/DM and the risk factors quotient of mPAP and mean systemic arterial pressure (mSAP) (mPAP/mSAP) (rs=0.686, P<0.001; rs=0.644, P<0.001) and pulmonary vascular resistance index (PVRI) (rs=0.758, P=0.002; rs=0.594, P=0.02). Conclusions: OCT can detect significant differences in WT of the PA in patients with PH. Furthermore, the OCT parameters correlate significantly with haemodynamic parameters and risk factors for patients with PH. More investigations are required to evaluate to what extent the impact of OCT can contribute to the clinical care of children with PH.
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