| 1. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 2. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 3. |
- Reulen, RC, et al.
(författare)
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Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1520-1528
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Tidskriftsartikel (refereegranskat)abstract
- Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide.MethodsThe PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence.Results427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN—comparable to the risk among members of the general population with at least two first-degree relatives affected.ConclusionsColonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.
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| 4. |
- Sloot, Frea, et al.
(författare)
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Inventory of current EU paediatric vision and hearing screening programmes
- 2015
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 22:2, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the diversity in paediatric vision and hearing screening programmes in Europe. Methods: Themes for comparison of screening programmes derived from literature were used to compile three questionnaires on vision, hearing, and public health screening. Tests used, professions involved, age, and frequency of testing seem to influence sensitivity, specificity, and costs most. Questionnaires were sent to ophthalmologists, orthoptists, otolaryngologists, and audiologists involved in paediatric screening in all EU full-member, candidate, and associate states. Answers were cross-checked. Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35 countries, in 71% of these more than once. First measurement of VA varies from three to seven years of age, but is usually before age five. At age three and four, picture charts, including Lea Hyvarinen, are used most; in children over four, Tumbling-E and Snellen. As first hearing screening test, otoacoustic emission is used most in healthy neonates, and auditory brainstem response in premature newborns. The majority of hearing testing programmes are staged; children are referred after 1–4 abnormal tests. Vision screening is performed mostly by paediatricians, ophthalmologists, or nurses. Funding is mostly by health insurance or state. Coverage was reported as >95% in half of countries, but reporting was often not first-hand. Conclusion: Largest differences were found in VA charts used (12), professions involved in vision screening (10), number of hearing screening tests before referral (1–4), and funding sources (8).
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| 5. |
- van den Besselaar, A. M. H. P., et al.
(författare)
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International collaborative study for the calibration of proposed International Standards for thromboplastin, rabbit, plain, and for thromboplastin, recombinant, human, plain
- 2018
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Ingår i: Journal of Thrombosis and Haemostasis. - : WILEY. - 1538-7933 .- 1538-7836. ; 16:1, s. 142-149
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Tidskriftsartikel (refereegranskat)abstract
- Background: The availability of International Standards for thromboplastin is essential for the calibration of routine reagents and hence the calculation of the International Normalized Ratio (INR). Stocks of the current Fourth International Standards are running low. Candidate replacement materials have been prepared. This article describes the calibration of the proposed Fifth International Standards for thromboplastin, rabbit, plain (coded RBT/16) and for thromboplastin, recombinant, human, plain (coded rTF/16). Methods: An international collaborative study was carried out for the assignment of International Sensitivity Indexes (ISIs) to the candidate materials, according to the World Health Organization (WHO) guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists. Results: Results were obtained from 20 laboratories. In several cases, deviations from the ISI calibration model were observed, but the average INR deviation attributabled to the model was not greater than 10%. Only valid ISI assessments were used to calculate the mean ISI for each candidate. The mean ISI for RBT/16 was 1.21 (between-laboratory coefficient of variation [CV]: 4.6%), and the mean ISI for rTF/16 was 1.11 (between-laboratory CV: 5.7%). Conclusions: The between-laboratory variation of the ISI for candidate material RBT/16 was similar to that of the Fourth International Standard (RBT/05), and the between-laboratory variation of the ISI for candidate material rTF/16 was slightly higher than that of the Fourth International Standard (rTF/09). The candidate materials have been accepted by WHO as the Fifth International Standards for thromboplastin, rabbit plain, and thromboplastin, recombinant, human, plain.
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| 6. |
- Carlsen, O. C. L., et al.
(författare)
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Physical activity in pregnancy: a Norwegian-Swedish mother-child birth cohort study
- 2021
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Ingår i: AJOG Global Reports. - : Elsevier BV. - 2666-5778. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Physical activity during pregnancy is important for maternal and offspring health. Optimal conditions during pregnancy may help reduce the burden of noncommunicable diseases. National and international guidelines recommend at least 150 minutes of physical activity of at least moderate intensity per week. To optimize physical activity in pregnant women, it is important to identify factors associated with higher levels of physical activity. OBJECTIVE: This study aimed to explore types and levels of physical activity in midpregnancy in Norway and Sweden and to identify factors associated with higher levels of physical activity. MATERIALS AND METHODS: From the population-based mother-child cohort Preventing Atopic Dermatitis and Allergies in Children study recruiting 2697 women in Norway and Sweden from 2014 to 2016, we included 2349 women who answered an electronic questionnaire at enrollment in midpregnancy. Women were asked about regular physical activity in the last 2 weeks of pregnancy and afterward for types and levels of physical activity in pregnancy and before pregnancy and socioeconomic status, lifestyle, and maternal health. Logistic regression analyses were used to identify factors associated with higher levels of physical activity in pregnancy, defined as >30 minutes per session of ≥2 times per week of moderate- or high-intensity brisk walking, strength training, jogging, and bicycling. RESULTS: No regular physical activity during the last 2 weeks before answering the questionnaire at midpregnancy was reported by 689 women (29%). In this study, 1787 women (76%) reported weekly strolling during pregnancy. Regular physical activity at least twice weekly in the first half of pregnancy was reported as brisk walking by 839 women (36%), bicycling by 361 women (15%), strength training by 322 women (14%), and other activities by <10% of women. Among the 1430 women with regular moderate- or high-intensity physical activity, the estimated median duration per week was 120 minutes. Higher physical activity levels were achieved in 553 women (23.5%) by brisk walking, 287 women (12.2%) by strength training, 263 women (11.2%) by bicycling, and 114 women (4.9%) by jogging. Higher physical activity levels were positively associated with regular physical activity before pregnancy, dog ownership, and atopic dermatitis and negatively associated with higher body mass index, study location in Østfold, previous pregnancy or pregnancies, non-Nordic origin, suburban living, and sick leave. CONCLUSION: At midpregnancy, 29% of women were inactive, and less than 50% of women had at least 2 hours of moderate-intensity physical activity weekly. Awareness of physical activity in pregnancy should be discussed at pregnancy follow-up visits, particularly among women with higher body mass index, sick leave, previous pregnancy or pregnancies, and non-Nordic origin.
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| 7. |
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| 8. |
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| 9. |
- Gudmundsdottir, J. A., et al.
(författare)
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Normal neonatal TREC and KREC levels in early onset juvenile idiopathic arthritis
- 2023
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 249
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dysregulated central tolerance predisposes to autoimmune diseases. Reduced thymic output as well as compromised central B cell tolerance checkpoints have been proposed in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate neonatal levels of T-cell receptor excision circles (TRECs) and kappa-deleting element excision circles (KRECs), as markers of T-and B-cell output at birth, in patients with early onset JIA.Methods: TRECs and KRECs were quantitated by multiplex qPCR from dried blood spots (DBS), collected 2-5 days after birth, in 156 children with early onset JIA and in 312 matched controls.Results: When analysed from neonatal dried blood spots, the median TREC level was 78 (IQR 55-113) in JIA cases and 88 (IQR 57-117) copies/well in controls. The median KREC level was 51 (IQR 35-69) and 53 (IQR 35-74) copies/well, in JIA cases and controls, respectively. Stratification by sex and age at disease onset did not reveal any difference in the levels of TRECs and KRECs.Conclusion: T-and B-cell output at birth, as measured by TREC and KREC levels in neonatal dried blood spots, does not differ in children with early onset JIA compared to controls.
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| 10. |
- Halldórsson, Sæmundur A., et al.
(författare)
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Petrology and geochemistry of the 2014–2015 Holuhraun eruption, central Iceland : compositional and mineralogical characteristics, temporal variability and magma storage
- 2018
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Ingår i: Contributions to Mineralogy and Petrology. - : Springer Science and Business Media LLC. - 0010-7999 .- 1432-0967. ; 173:8
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Tidskriftsartikel (refereegranskat)abstract
- The 2014–2015 Holuhraun fissure eruption provided a rare opportunity to study in detail the magmatic processes and magma plumbing system dynamics during a 6-month-long, moderate- to large-volume basaltic fissure eruption. In this contribution, we present a comprehensive dataset, including major and trace elements of whole-rock and glassy tephra samples, mineral chemistry, and radiogenic and oxygen isotope analyses from an extensive set of samples (n = 62) that were collected systematically in several field campaigns throughout the entire eruptive period. We also present the first detailed chemical and isotopic characterization of magmatic sulfides from Iceland. In conjunction with a unique set of geophysical data, our approach provides a detailed temporal and spatial resolution of magmatic processes before and during this eruption. The 2014–2015 Holuhraun magma is compositionally indistinguishable from recent basalts erupted from the Bárðarbunga volcanic system, consistent with seismic observations for magma ascent close to the Bárðarbunga central volcano, followed by dyke propagation to the Holuhraun eruption site. Whole-rock elemental and isotopic compositions are remarkably constant throughout the eruption. Moreover, the inferred depth of the magma reservoir tapped during the eruption is consistently 8 ± 5 km, in agreement with geodetic observations and melt inclusion entrapment pressures, but inconsistent with vertically extensive multi-tiered magma storage prior to eruption. The near constancy in the chemical and isotopic composition of the lava is consistent with the efficient homogenization of mantle-derived compositional variability. In contrast, occurrence of different mineral populations, including sulfide globules, which display significant compositional variability, requires a more complex earlier magmatic history. This may include sampling of heterogeneous mantle melts that mixed, crystallized and finally homogenized at mid- to lower-crustal conditions.
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| 11. |
- Hilde, K., et al.
(författare)
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Fetal Thoracic Circumference and Lung Volume and Their Relation to Fetal Size and Pulmonary Artery Blood Flow
- 2022
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Ingår i: Journal of Ultrasound in Medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 41:4, s. 985-993
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Tidskriftsartikel (refereegranskat)abstract
- Objective Research on early origins of lung disease suggests the need for studying the relationships of thoracic and lung size with fetal size and pulmonary circulation. The primary aim of this study is therefore to explore the associations between fetal thoracic circumference, lung volume, and fetal size. We also aim to assess if lung volume and thoracic circumference are associated with fetal pulmonary artery blood flow velocity measures. Methods Cross-sectional assessment of singleton pregnancies from the general population (n = 447) at 30 gestational weeks (GW) was performed using ultrasound measurement of fetal thoracic circumference, lung volume, head and abdominal circumference, and femur length. We obtained Doppler blood flow velocity measures from the proximal branches of the fetal pulmonary artery. Associations between variables were studied using Pearson's correlation and multiple linear regression analyses. Results Both thoracic circumference and lung volume correlated with fetal size measures, ranging from r = 0.64 between thoracic circumference and abdominal circumference, to r = 0.28 between lung volume and femur length. Adjustment for gestational age, maternal nicotine use, pre-pregnancy body mass index, and fetal sex marginally influenced the associations with abdominal circumference. The correlations of thoracic circumference and lung volume with pulmonary artery blood flow velocity measures were weak (r <= 0.17). Conclusion We found moderate to low correlation between thoracic circumference, lung volume, and fetal size at 30 GW. The closest relationship was with the abdominal circumference. We found low correlations of thoracic circumference and lung volume with pulmonary artery blood flow velocity measures.
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| 12. |
- Saevarsdottir, KS, et al.
(författare)
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Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:7, s. e049967-
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Tidskriftsartikel (refereegranskat)abstract
- To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.DesignPopulation-based cross-sectional study.SettingIceland.ParticipantsA total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measuresSymptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.ResultsCompared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).ConclusionsSevere disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.
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| 13. |
- Skjerven, H. O., et al.
(författare)
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Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial
- 2020
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Ingår i: The Lancet. - 0140-6736. ; 395:10228, s. 951-961
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Tidskriftsartikel (refereegranskat)abstract
- Background: Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. Methods: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. Findings: 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI –0·3 to 6·5) for skin intervention and 1·0% (–2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. Interpretation: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. Funding: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council—the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare—FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust. © 2020 Elsevier Ltd
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| 14. |
- Alsos, Inger Greve, et al.
(författare)
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Ancient sedimentary DNA shows rapid post-glacial colonisation of Iceland followed by relatively stable vegetation until the Norse settlement (Landnam) AD 870
- 2021
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Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 259
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Tidskriftsartikel (refereegranskat)abstract
- Understanding patterns of colonisation is important for explaining both the distribution of single species and anticipating how ecosystems may respond to global warming. Insular flora may be especially vulnerable because oceans represent severe dispersal barriers. Here we analyse two lake sediment cores from Iceland for ancient sedimentary DNA to infer patterns of colonisation and Holocene vegetation development. Our cores from lakes Torfdalsvatn and Nykurvatn span the last c. 12,000 cal yr BP and c. 8600 cal yr BP, respectively. With near-centennial resolution, we identified a total of 191 plant taxa, with 152 taxa identified in the sedimentary record of Torfdalsvatn and 172 plant taxa in the sedimentary record of Nykurvatn. The terrestrial vegetation at Torfdalsvatn was initially dominated by bryophytes, arctic herbs such as Saxifraga spp. and grasses. Around 10,100 cal yr BP, a massive immigration of new taxa was observed, and shrubs and dwarf shrubs became common whereas aquatic macrophytes became dominant. At Nykurvatn, the dominant taxa were all present in the earliest samples; shrubs and dwarf shrubs were more abundant at this site than at Torfdalsvatn. There was an overall steep increase both in the local accumulated richness and regional species pool until 8000 cal yr BP, by which time 3/4 of all taxa identified had arrived. The period 4500-1000 cal yr BP witnessed the appearance of a a small number of bryophytes, graminoids and forbs that were not recorded in earlier samples. The last millennium, after human settlement of the island (Landnam), is characterised by a sudden disappearance of Juniperus communis, but also reappearance of some high arctic forbs and dwarf shrubs. Notable immigration during the Holocene coincides with periods of increased incidence of sea ice, and we hypothesise that this may have acted as a dispersal vector. Thus, although ongoing climate change might provide a suitable habitat in Iceland for a large range of species only found in the neighbouring regions today, the reduction of sea ice may in fact limit the natural colonisation of new plant species.
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| 15. |
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| 16. |
- Bains, KES, et al.
(författare)
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Infant lung function: criteria for selecting tidal flow-volume loops
- 2022
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Tidal flow–volume (TFV) loops are commonly recorded in infants during sleep, due to the more regular breathing patterns compared to the awake state. Standardised deselection of loops outside pre-specified ranges are based on periods of regular breathing, while criteria and available software for visual evaluation of TFV loops are lacking. We aimed to determine the reliability of standardised criteria for manual selection of infant TFV loops.MethodsUsing a pre-defined set of criteria, three independent raters manually evaluated TFV loops among 57 randomly selected awake healthy 3-month-old infants with available TFV measurements in the Scandinavian Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) study. The TFV loops were sampled using the Eco Medics Exhalyzer D. Criteria for selecting TFV loops included reproducible shape and volume with only one peak in tidal expiratory flow (PTEF), excluding loops with no clear or uneven flow towards PTEF. By intraclass coefficient (ICC), the reliability of agreement between raters was determined for the time to PTEF (tPTEF) to expiratory time (tE) and other TFV loop parameters.ResultsFive infants had unsuccessful tests. Among the remaining 52 infants, the raters selected a median of 25, 26 and 15 loops per test. The ICCs (95% CI) were 0.97 (0.92–0.98) fortPTEF/tE, 0.99 (0.99–1.00) for respiratory rate, 0.98 (0.97–0.99) for tidal volume per kg and 0.98 (0.97–0.99) for expiratory volume, reflecting excellent agreement in all categories.ConclusionManual TFV loop selection using standardised criteria provides a reliable alternative for lung function measures in awake infants with interrupted breathing cycles in a real-life setting.
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| 17. |
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| 18. |
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| 19. |
- Bains, KES, et al.
(författare)
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Infant tidal flow-volume parameters and arousal state
- 2022
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Infant lung function can be assessed with tidal flow–volume (TFV) loops. While TFV loops can be measured in both awake and sleeping infants, the influence of arousal state in early infancy is not established. The aim of the present study was to determine whether TFV loop parameters in healthy infants differed while awake compared to the sleeping state at 3 months of age.MethodsFrom the population-based Scandinavian Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) birth cohort, 91 infants had reproducible TFV loops measured with Exhalyzer®D in both the awake and sleeping state at 3 months of age. The TFV loops were manually selected according to a standardised procedure. The ratio of time to peak tidal expiratory flow (tPTEF) to expiratory time (tE) and the corresponding volume ratio (VPTEF/VE), as well as tidal volume (VT) and respiratory rate were compared using nonparametric tests.ResultsThe mean (95% CI)tPTEF/tEwas significantly higher while awake compared to the sleeping state: 0.39 (0.37–0.41)versus0.28 (0.27–0.29); with the correspondingVPTEF/VEof 0.38 (0.36–0.40)versus0.29 (0.28–0.30). TheVTwas similar, while the respiratory rate was higher while awake compared to the sleeping state: 53 (51–56) breaths·min−1versus38 (36–40) breaths·min−1.ConclusionHighertPTEF/tE,VPTEF/VEand respiratory rate, but similarVTwhile awake compared to the sleeping state suggests that separate normative TFV loop values according to arousal state may be required in early infancy.
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| 20. |
- Berntorp, Karolina, et al.
(författare)
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Instantaneous wave-free ratio compared with fractional flow reserve in PCI : A cost-minimization analysis
- 2021
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Ingår i: International Journal of Cardiology. - : Hindawi Publishing Corporation. - 0167-5273 .- 1874-1754. ; 344, s. 54-59
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary physiology is a routine diagnostic tool when assessing whether coronary revascularization is indicated. The iFR-SWEDEHEART trial demonstrated similar clinical outcomes when using instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) to guide revascularization. The objective of this analysis was to assess a cost-minimization analysis of iFR-guided compared with FFR-guided revascularization.METHODS: In this cost-minimization analysis we used a decision-tree model from a healthcare perspective with a time-horizon of one year to estimate the cost difference between iFR and FFR in a Nordic setting and a United States (US) setting. Treatment pathways and health care utilizations were constructed from the iFR-SWEDEHEART trial. Unit cost for revascularization and myocardial infarction in the Nordic setting and US setting were derived from the Nordic diagnosis-related group versus Medicare cost data. Unit cost of intravenous adenosine administration and cost per stent placed were based on the average costs from the enrolled centers in the iFR-SWEDEHEART trial. Deterministic and probabilistic sensitivity analyses were carried out to test the robustness of the result.RESULTS: The cost-minimization analysis demonstrated a cost saving per patient of $681 (95% CI: $641 - $723) in the Nordic setting and $1024 (95% CI: $934 - $1114) in the US setting, when using iFR-guided compared with FFR-guided revascularization. The results were not sensitive to changes in uncertain parameters or assumptions.CONCLUSIONS: IFR-guided revascularization is associated with significant savings in cost compared with FFR-guided revascularization.
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| 21. |
- Escaned, Javier, et al.
(författare)
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Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes
- 2018
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Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 11:15, s. 1437-1449
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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| 23. |
- Fardig, M, et al.
(författare)
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Skin Barrier Function and Infant Tidal Flow-Volume Loops-A Population-Based Observational Study
- 2023
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Ingår i: Children (Basel, Switzerland). - : MDPI AG. - 2227-9067. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between the skin barrier- and lung function in infancy is largely unexplored. We aimed to explore if reduced skin barrier function by high transepidermal water loss (TEWL), or manifestations of eczema or Filaggrin (FLG) mutations, were associated with lower lung function in three-month-old infants. Methods: From the population-based PreventADALL cohort, 899 infants with lung function measurements and information on either TEWL, eczema at three months of age and/or FLG mutations were included. Lower lung function by tidal flow-volume loops was defined as a ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE) <0.25 and a tPTEF <0.17 s (<25th percentile). A high TEWL >8.83 g/m2/h (>75th percentile) denoted reduced skin barrier function, and DNA was genotyped for FLG mutations (R501X, 2282del4 and R2447X). Results: Neither a high TEWL, nor eczema or FLG mutations, were associated with a lower tPTEF/tE. While a high TEWL was associated with a lower tPTEF; adjusted OR (95% CI) 1.61 (1.08, 2.42), the presence of eczema or FLG mutations were not. Conclusions: Overall, a high TEWL, eczema or FLG mutations were not associated with lower lung function in healthy three-month-old infants. However, an inverse association between high TEWL and tPTEF was observed, indicating a possible link between the skin barrier- and lung function in early infancy.
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