| 1. |
- Kristensen, Frederik Pagh Bredahl, et al.
(author)
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The Prevalence of Polyneuropathy in Type 2 Diabetes Subgroups Based on HOMA2 Indices of b-Cell Function and Insulin Sensitivity
- 2023
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In: Diabetes Care. - 0149-5992. ; 46:8, s. 1546-1555
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Journal article (peer-reviewed)abstract
- OBJECTIVE Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of b-cell function and insulin sensitivity. RESEARCH DESIGN AND METHODS We estimated b-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ‡ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S. RESULTS A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic pa-tients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycer-ides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15–1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S. CONCLUSIONS Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.
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| 2. |
- Zettergren, Henning, et al.
(author)
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Roadmap on dynamics of molecules and clusters in the gas phase
- 2021
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In: European Physical Journal D. - : Springer Science and Business Media LLC. - 1434-6060 .- 1434-6079. ; 75:5
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Journal article (peer-reviewed)abstract
- This roadmap article highlights recent advances, challenges and future prospects in studies of the dynamics of molecules and clusters in the gas phase. It comprises nineteen contributions by scientists with leading expertise in complementary experimental and theoretical techniques to probe the dynamics on timescales spanning twenty order of magnitudes, from attoseconds to minutes and beyond, and for systems ranging in complexity from the smallest (diatomic) molecules to clusters and nanoparticles. Combining some of these techniques opens up new avenues to unravel hitherto unexplored reaction pathways and mechanisms, and to establish their significance in, e.g. radiotherapy and radiation damage on the nanoscale, astrophysics, astrochemistry and atmospheric science.
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| 3. |
- Allentoft, Morten E., et al.
(author)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Journal article (peer-reviewed)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 4. |
- Allentoft, Morten E., et al.
(author)
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Population genomics of post-glacial western Eurasia
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Journal article (peer-reviewed)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 5. |
- Andersen, Julie Swartz, et al.
(author)
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Economic comparison of mass timber and concrete construction in the nordic region
- 2023
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In: 13th World Conference on Timber Engineering, WCTE 2023. ; 7, s. 4360-4369
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Conference paper (peer-reviewed)abstract
- The timber sector has been growing strongly in various regions of the world. Yet, the construction industry is still far from being sustainable. One barrier is the economic concern in planning and construction works of timber constructions. This study aims to provide insights on the cost performance of Cross Laminated Timber (CLT) constructions for stakeholders to make an informed decision. It analysed the production cost of multi-story residential buildings with CLT in comparison to concrete in Norway and Sweden. The production cost data of various construction projects with either CLT or concrete was collected and analysed. Interviews with stakeholders were conducted to complement the interpretation of the cost data. The result showed that each project had its individual conditions in the economic background and requirements by client, and thus it was difficult to formulate a general tendency on the cost performance. The variability of the cost was larger and the average production cost was higher in CLT cases. Yet, there are high incentives of contractors and clients for a more sustainable alternative in general. The incentive is also reinforced by the general experience of contractors that the construction cost is better optimized as the contractor gains more experiences.
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| 6. |
- Blauenfeldt, Rolf Ankerlund, et al.
(author)
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Remote Ischemic Conditioning for Acute Stroke : The RESIST Randomized Clinical Trial
- 2023
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In: JAMA. - 0098-7484. ; 330:13, s. 1236-1246
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Journal article (peer-reviewed)abstract
- Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P =.67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P =.68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.
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| 7. |
- Breznau, Nate, et al.
(author)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
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Journal article (peer-reviewed)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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| 8. |
- Hansted Andersen, Julie, et al.
(author)
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Construction cost of timber buildings
- 2022
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Reports (other academic/artistic)abstract
- There are increasing interests and practices in modern large timber constructions globally for the renewability and carbon storage function of wood. However, many stakeholders with limited knowledge and experience with timber still feel uncertain on how to carry out construction projects with timber. The common notion is that timber constructions would become more costly than a conventional alternative such as concrete. In order to inform wide spectrum of construction stakeholders in Scandinavia, this report presents a study on construction cost of cross laminated timber (CLT) buildings compared with concrete/steel buildings in Denmark, Norway and Sweden. The study investigated the actual cost of 9 recent multi-storey residential buildings, 5 constructed with a load-bearing system in primarily CLT and 4 constructed in primarily concrete in Norway and Sweden. Due to the nature of the chronological and geographical differences of market conditions, the cost data were evaluated separately for Norway and Sweden. In addition to the case building analysis, interviews were conducted with stakeholders from the case building projects as well as those from the industry with experiences with CLT buildings. The interviews contributed to a broader perspective of the cost analysis, with explanations of the projects and experiences of advantages and disadvantages for CLT building and concrete buildings. The results showed a tendency that the construction cost of the Norwegian CLT projects were higher than the Norwegian concrete projects. For the Swedish projects the concrete building had a higher cost compared to the CLT projects, however it can't be concluded as a tendency for the Swedish projects, since investigation only included one concrete project and two CLT projects. The results showed that often the material-related costs were higher for CLT buildings than concrete buildings. Such costs are for example the material cost itself and transportation cost for a long distance. Furthermore, the fire protection and measures for the finalized building according to fire safety resulted in a higher cost in the CLT cases. However, the construction time is often shorter for CLT buildings than concrete buildings, and CLT buildings are lighter and therefore the foundation can be dimensioned smaller. Although such observations were made, throughout the interviews it was stated that one should be careful comparing the cost of two buildings since the cost is very much depended on the specific project. Thus, the results shown in this report must be seen as tendencies and not as a forecast for specific cost difference between CLT building and concrete buildings. This study was an investigation of construction costs and advantages and disadvantages of CLT buildings in relation to the construction cost up till 2022. When there is a major change in the economy and legislations of the construction sector, the cost structure may be substantially affected. One of such factors may be the increasing focus on the reduction of greenhouse gas (GHG) emissions from the construction industry. The availability of resource might be also a key factor for the future cost development for both CLT and concrete.
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| 9. |
- Nilsson, Karin H., et al.
(author)
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RSPO3 is important for trabecular bone and fracture risk in mice and humans
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here, the authors show that RSPO3 exerts an important role for vertebral trabecular bone mass and bone strength in mice and fracture risk in humans. With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.
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| 10. |
- Nøst, Therese Haugdahl, et al.
(author)
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Increased levels of microRNA-320 in blood serum and plasma is associated with imminent and advanced lung cancer
- 2023
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In: Molecular Oncology. - : John Wiley & Sons. - 1574-7891 .- 1878-0261. ; 17:2, s. 312-327
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Journal article (peer-reviewed)abstract
- Lung cancer (LC) incidence is increasing globally and altered levels of microRNAs (miRNAs) in blood may contribute to identification of individuals with LC. We identified miRNAs differentially expressed in peripheral blood at LC diagnosis and evaluated, in pre-diagnostic blood specimens, how long before diagnosis expression changes in such candidate miRNAs could be detected. We identified upregulated candidate miRNAs in plasma specimens from a hospital-based study sample of 128 patients with confirmed LC and 62 individuals with suspected but confirmed negative LC (FalsePos). We then evaluated the expression of candidate miRNAs in pre-diagnostic plasma or serum specimens of 360 future LC cases and 375 matched controls. There were 1663 miRNAs detected in diagnostic specimens, nine of which met our criteria for candidate miRNAs. Higher expression of three candidates, miR-320b, 320c, and 320d, was associated with poor survival, independent of LC stage and subtype. Moreover, miR-320c and miR-320d expression was higher in pre-diagnostic specimens collected within 2 years of LC diagnosis. Our results indicated that elevated levels of miR-320c and miR-320d may be early indications of imminent and advanced LC.
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| 11. |
- Schwartz, Franziska A., et al.
(author)
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Dynamics of a Staphylococcus aureus infective endocarditis simulation model
- 2022
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In: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; 130:8, s. 515-523
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Journal article (peer-reviewed)abstract
- Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a novel in vitro IE model using a simulated IE vegetation (IEV) model produced from whole venous blood, on which we achieved stable bacterial colonization after 24h. The bacteria were organized in biofilm aggregates and displayed increased tolerance towards antibiotics. In this current study, we aimed at further characterizing the time course of biofilm formation and the impact on antibiotic tolerance development. We found that a S. aureus reference strain, as well as three clinical IE isolates formed biofilms on the IEV after 6h. When treatment was initiated immediately after infection, the antibiotic effect was significantly higher than when treatment was started after the biofilm was allowed to mature. We could follow the biofilm development microscopically by visualizing growing bacterial aggregates on the IEV. The findings indicate that mature, antibiotic-tolerant biofilms can be formed in our model already after 6h, accelerating the screening for optimal treatment strategies for IE.
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| 12. |
- Sunnerhagen, Torgny, et al.
(author)
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External validation of the HANDOC score–high sensitivity to identify patients with non-beta-haemolytic streptococcal endocarditis
- 2020
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In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 52:1, s. 54-57
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Journal article (peer-reviewed)abstract
- Background: Invasive infections with non-beta-haemolytic streptococci (NBHS) is quite common and presents the clinicians with difficulties regarding which patients are at risk for infective endocarditis (IE). The HANDOC score was developed to identify patients with NBHS bacteraemia who are at low risk of IE. This study was conducted to validate HANDOC in an external cohort. Methods: Patients with NBHS in blood cultures between March and September 2016 in a Danish centre were included as part of an on-going study. Patient characteristics were collected to classify bacteria according to Dukés criteria and the components of the HANDOC score were collected retrospectively from the patients’ medical records. Results: 68 patients were included in the cohort, of which 16 fulfilled Dukés criteria for IE. All patients with IE (16 of 16) had a HANDOC score above the predefined cut-off. Cases of IE were found in patients with. Streptococcus mitis, Streptococcus bovis, Streptococcus mutans, Streptococcus anginosus, and Streptococcus sanguinis group streptococci. The HANDOC score thus had a sensitivity of 100% and a specificity of 62% in this cohort. Conclusions: HANDOC has a sensitivity of 100% and a relatively high specificity (62%) also in a prospectively enrolled cohort of patients from another country than its origin. This indicates that HANDOC can be implemented in clinical practice to identify patients with a low risk of IE in whom echocardiography can be omitted.
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| 13. |
- Kanai, M, et al.
(author)
-
- 2023
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