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Sökning: WFRF:(Andersen Christian) > (2020-2024)

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1.
  • Aslam, Tayyba N., et al. (författare)
  • A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure
  • 2023
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:10, s. 1383-1394
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
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2.
  • Breznau, Nate, et al. (författare)
  • Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
  • Tidskriftsartikel (refereegranskat)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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3.
  • Brieghel, Christian, et al. (författare)
  • The Number of Signaling Pathways Altered by Driver Mutations in Chronic Lymphocytic Leukemia Impacts Disease Outcome
  • 2020
  • Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 26:6, s. 1507-1515
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Investigation of signaling pathways altered by recurrent gene mutations and their clinical impact in a consecutive cohort of patients with newly diagnosed chronic lymphocytic leukemia (CLL). The heterogeneous clinical course and genetic complexity of CLL warrant improved molecular prognostication. However, the prognostic value of recurrent mutations at the time of diagnosis remains unclear. Experimental Design: We sequenced samples from 314 consecutive, newly diagnosed patients with CLL to investigate the clinical impact of 56 recurrently mutated genes assessed by next-generation sequencing. Results: Mutations were identified in 70% of patients with enrichment among IGHV unmutated cases. With 6.5 years of follow-up, 15 mutated genes investigated at the time of diagnosis demonstrated significant impact on time to first treatment (TTFT). Carrying driver mutations was associated with shorter TTFT and poor overall survival. For outcome from CLL diagnosis, the number of signaling pathways altered by driver mutations stratified patients better than the number of driver mutations. Moreover, we demonstrated gradual impact on TTFT with increasing number of altered pathways independent of CLL-IPI risk. Thus, a 25-gene, pathway-based biomarker assessing recurrent mutations refines prognostication in CLL, in particular for CLL-IPI low- and intermediate-risk patients. External validation emphasized that a broad gene panel including low burden mutations was key for the biomarker based on altered pathways. Conclusions: We propose to include the number of pathways altered by driver mutations as a biomarker together with CLL-IPI in prospective studies of CLL from time of diagnosis for incorporation into clinical care and personalized follow-up and treatment.
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4.
  • Christensen, Christian Kolle, et al. (författare)
  • Beam damage in operando X-ray diffraction studies of Li-ion batteries
  • 2023
  • Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 30:Pt 3, s. 561-570
  • Tidskriftsartikel (refereegranskat)abstract
    • Operando powder X-ray diffraction (PXRD) is a widely employed method for the investigation of structural evolution and phase transitions in electrodes for rechargeable batteries. Due to the advantages of high brilliance and high X-ray energies, the experiments are often carried out at synchrotron facilities. It is known that the X-ray exposure can cause beam damage in the battery cell, resulting in hindrance of the electrochemical reaction. This study investigates the extent of X-ray beam damage during operando PXRD synchrotron experiments on battery materials with varying X-ray energies, amount of X-ray exposure and battery cell chemistries. Battery cells were exposed to 15, 25 or 35 keV X-rays (with varying dose) during charge or discharge in a battery test cell specially designed for operando experiments. The observed beam damage was probed by μPXRD mapping of the electrodes recovered from the operando battery cell after charge/discharge. The investigation reveals that the beam damage depends strongly on both the X-ray energy and the amount of exposure, and that it also depends strongly on the cell chemistry, i.e. the chemical composition of the electrode.
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5.
  • Gylling, Anne Theil, et al. (författare)
  • The influence of prolonged strength training upon muscle and fat in healthy and chronically diseased older adults
  • 2020
  • Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 136
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Physical muscle function and brain hippocampus size declines with age, accelerating after the age of 60. Strength training over a few months improves physical function, but less is known about how long-term strength training affects physical function and hippocampus volume. Therefore, we aimed to investigate the effect of 1-year strength training of two different intensities upon muscle mass, function, and hippocampus volume in retirement-age individuals.Methods: In this multidisciplinary randomized controlled trial (clinicaltrials.gov: NCT02123641), participants were allocated to either a) supervised, heavy resistance training (HRT, n = 149, 3/wk), b) moderate intensity resistance training (MIT, n = 154, 3/wk) or c) non-exercise activities (CON, n = 148). 451 participants were randomized (62-70 yrs., women 61%, approximate to 80% with a chronic medical disease) and 419 were included in the intention-to-treat analysis (n = 143, 144 and 132; HRT, MIT and CON). Changes in muscle power (primary outcome), strength and size, physical function, body composition, hippocampus volume and physical/mental well-being were analyzed.Findings: Of the participants (HRT + MIT), 83% completed training at least 2/week. Leg extensor power was unchanged in all groups, but strength training had a positive effect on isometric knee extensor strength in both groups, whereas an increased muscle mass, cross-sectional area of vastus lateralis muscle, a decreased whole-body fat percentage, visceral fat content and an improved mental health (SF-36) occurred in HRT only. Further, chair-stand performance improved in all groups, whereas hippocampus volume decreased in all groups over time with no influence of strength training.Interpretation: Together, the results indicate that leg extensor power did not respond to long-term supervised strength training, but this type of training in a mixed group of healthy and chronically diseased elderly individuals can be implemented with good compliance and induces consistent changes in physiological parameters of muscle strength, muscle mass and abdominal fat.
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6.
  • Munch, Marie W., et al. (författare)
  • Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
  • 2021
  • Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
  • Tidskriftsartikel (refereegranskat)abstract
    • Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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7.
  • Sinding, Mikkel-Holger S., et al. (författare)
  • Arctic-adapted dogs emerged at the Pleistocene-Holocene transition
  • 2020
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 368:6498
  • Tidskriftsartikel (refereegranskat)abstract
    • Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an similar to 9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an similar to 33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog-specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago.
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8.
  • Abele, H., et al. (författare)
  • Particle physics at the European Spallation Source
  • 2023
  • Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
  • Forskningsöversikt (refereegranskat)abstract
    • Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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9.
  • Allentoft, Morten E., et al. (författare)
  • 100 ancient genomes show repeated population turnovers in Neolithic Denmark
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
  • Tidskriftsartikel (refereegranskat)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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10.
  • Allentoft, Morten E., et al. (författare)
  • Population genomics of post-glacial western Eurasia
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
  • Tidskriftsartikel (refereegranskat)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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11.
  • Alshammari, Hatem, et al. (författare)
  • Antimicrobial Potential of Strontium-Functionalized Titanium Against Bacteria Associated With Peri-Implantitis
  • 2024
  • Ingår i: Clinical and Experimental Dental Research. - : John Wiley & Sons. - 2057-4347. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To explore the antimicrobial potential of strontium (Sr)-functionalized wafers against multiple bacteria associated with per-implant infections, in both mono- and multispecies biofilms. Materials and Methods: The bactericidal and bacteriostatic effect of silicon wafers functionalized with a strontium titanium oxygen coating (Sr-Ti-O) or covered only with Ti (controls) against several bacteria, either grown as a mono-species or multispecies biofilms, was assessed using a bacterial viability assay and a plate counting method. Mono-species biofilms were assessed after 2 and 24 h, while the antimicrobial effect on multispecies biofilms was assessed at Days 1, 3, and 6. The impact of Sr functionalization on the total percentage of Porphyromonas gingivalis in the multispecies biofilm, using qPCR, and gingipain activity was also assessed. Results: Sr-functionalized wafers, compared to controls, were associated with statistically significant less viable cells in both mono- and multispecies tests. The number of colony forming units (CFUs) within the biofilm was significantly less in Sr-functionalized wafers, compared to control wafers, for Staphylococcus aureus at all time points of evaluation and for Escherichia coli at Day 1. Gingipain activity was less in Sr-functionalized wafers, compared to control wafers, and the qPCR showed that P. gingivalis remained below detection levels at Sr-functionalized wafers, while it consisted of 15% of the total biofilm on control wafers at Day 6. Conclusion: Sr functionalization displayed promising antimicrobial potential, possessing bactericidal and bacteriostatic ability against bacteria associated with peri-implantitis grown either as mono-species or mixed in a multispecies consortium with several common oral microorganisms.
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12.
  • Andersen, Christian Benjamin (författare)
  • Friend or Foe? Biocontrol interactions of Pythium oligandrum within the potato cropping system
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The potato crop is a valuable but vulnerable food source on a global level. It is under constant pressure from destructive plant diseases such as early and late blight. Traditionally to control these diseases farmers have relied heavily on synthetic fungicide use. It is evident that the use of agrochemicals such as synthetic fungicides can cause unwanted effects on the environment, and human health. Thus, there is a need for a more sustainable approach to control diseases in the potato cropping system. One approach could be to use biological control agents, (BCAs) such as mycoparasitic Pythium species to control the disease. However, to utilize these BCAs in the best way we need to increase our fundamental knowledge about their biology and interactions within potato cropping systems. Therefore, the aim of this thesis is to broaden our fundamental knowledge of the mycoparasitic Pythium species, Pythium oligandrum and Pythium periplocum, and how they differentiate from their phytopathogenic counterparts. Further, the thesis also pinpoints characteristics that determine mycoparasitism in these two Pythiums, and how this relates to their biocontrol abilities, at the molecular level. This was elucidated using comparative genomics, transcriptomics. The result showed that ABC transporters, AVH-like RXLR effectors, and an expanded CAZyme among other things, are conserved and important for mycoparasitism, by P. oligandrum and P. periplocum both when preying on phytopathogens but also in comparison to closely related plant pathogens. This thesis also explores if P. oligandrum can be used as an antagonist against early blight disease on potato plants. The results showed that P. oligandrum did induce disease suppression in potato in controlled greenhouse environments, however in the field trials when the disease pressure was high the effects disappeared. The thesis also explores if and how P. oligandrum interacts with the potato plants. The results showed that P. oligandrum induced biostimulation in potato both in controlled environments and field studies, although the biostimulation was in a plant-genotype dependent manner. Finally, the thesis investigates the impact on the resident rhizosphere microbiome of field grown potato plants when P. oligandrum was applied. The results showed that P. oligandrum has a very limited impact on the diversity and community structure in the rhizosphere of potato. Overall, the work in this thesis has generated a deeper understanding of the fundamental biology of the mycoparasitic Pythium species and how they differ from plant pathogens. An increased understanding of the environmental consequences and how P. oligandrum can be utilized as a BCA in the potato cropping system has been elucidated. This work also contributes with pivotal knowledge about how P. oligandrum can be utilized in an IPM strategy in the potato agricultural cropping system.
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13.
  • Andersen, Christian B., et al. (författare)
  • Pythium oligandrum induces growth promotion in starch potato without significantly altering the rhizosphere microbiome
  • 2024
  • Ingår i: Applied Soil Ecology. - 0929-1393. ; 199
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant health promoting organisms, including microbial biological control agents, are of increasing importance for the development of more sustainable agriculture. To understand the function of these microbes as biological control agents under field conditions and their overall impact on soil and plant health, we need to learn more about the impact of plant beneficial microbes on the rhizosphere microbiome of crops such as potato. The plant beneficial oomycete Pythium oligandrum has previously been reported both as a biocontrol agent and as a plant growth promoter, or biostimulant, in several crop species. To investigate the potential of P. oligandrum as a biostimulant in potato, we performed a series of controlled-environment bioassays in three cultivars. We showed that biostimulation of potato by P. oligandrum is plant genotype-specific. We confirmed the biostimulation by P. oligandrum in the starch potato cultivar Kuras under field conditions. We further investigated the effects of P. oligandrum on the potato rhizosphere microbiome, sampling individual potato plants at three time points over the growing season (representing the vegetative growth phase, flowering, and the onset of senescence). Metabarcoding using ITS and 16S amplicon sequencing revealed no significant overall effect of P. oligandrum application on the bacterial and fungal rhizosphere communities. However, some genera were significantly differentially abundant after P. oligandrum application, including some classified as plant-beneficial microbes. We conclude that P. oligandrum has a cultivar-dependent growth-promoting effect in potato and only minor effects on the rhizosphere microbiome.
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14.
  • Andersen, Christian Benjamin (författare)
  • Transformation systems, gene silencing and gene editing technologies in oomycetes
  • 2022
  • Ingår i: Fungal Biology Reviews. - : Elsevier BV. - 1749-4613 .- 1878-0253. ; 40, s. 37-52
  • Forskningsöversikt (refereegranskat)abstract
    • Oomycetes are spore-forming eukaryotic microbes responsible for infections in animal and plant species worldwide, posing a threat to natural ecosystems, biodiversity and food security. Genomics and transcriptomics approaches, together with host interaction studies, give promising results towards better understanding of the infection mechanisms in oomycetes and their general biology. Significant development and progress in oomycetes genomic studies have been achieved over the past decades but further understanding of molecular processes, gene regulations and infection mechanisms are still needed. The use of molecular tools such as CRISPR/Cas and RNAi helped elucidate some of the molecular processes involved in host invasion and infection both in plant and animal pathogenic oomycetes. These methods provide an opportunity for accurate and detailed functional analysis involving various fields of studies such as genomics, epigenomics, proteomics, and interactomics. Functional gene characterisation is essential for filling the knowledge gaps in dynamic biological processes. However, every method has both advantages and limitations that should be considered before choosing the best method for investigating a particular research question. Here we review transformation systems, gene silencing and gene editing techniques in oomycetes, how they function, in which species and what are their main advantages and disadvantages. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of British Mycological Society.
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15.
  • Andersén, Jim, 1976-, et al. (författare)
  • Can environmentally oriented CEOs and environmentally friendly suppliers boost the growth of small firms?
  • 2020
  • Ingår i: Business Strategy and the Environment. - : John Wiley & Sons. - 0964-4733 .- 1099-0836. ; 29:2, s. 325-334
  • Tidskriftsartikel (refereegranskat)abstract
    • The core question addressed in the natural resource‐based view (NRBV) of the firm is how to develop and exploit resources beneficial for both the natural environment and firm performance. Due to the resource constraints and increased competition facing small manufacturing firms, achieving this is a challenge for such companies. Building on the NRBV and resource orchestration literatures, we examine the relationship between green purchasing capabilities (GPCs), CEO's environmental orientation(EO), and firm growth. Results from 304 Swedish small manufacturing firms indicate a significant relationship between GPC and growth, and this relationship is positively moderated by the EO of the CEO.
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16.
  • Andersén, Jim, et al. (författare)
  • Commitment capital : Bridging the gap between organizational commitment and human capital resources
  • 2024
  • Ingår i: Human Resource Management. - : John Wiley and Sons Inc. - 0090-4848 .- 1099-050X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Even though, the human resource management literature has highlighted the importance of having employees that are committed to the organization, research on strategic human capital has yet to fully consider how commitment is related to human capital resources. In order to overcome the dominant individual-level conceptualization of commitment and to detail how commitment affects human capital resources, we develop the unit-level concept of commitment capital, which we divide into three levels: affiliative commitment capital, affinitive commitment capital, and absolute commitment capital. These conceptualizations are based on a 10-year case study and incorporate commitment into a strategic human capital framework, thus bridging the current gap between organizational commitment and human capital resources. 
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17.
  • Andersen, Jeppe R., et al. (författare)
  • A Positive Resampler for Monte Carlo events with negative weights
  • 2020
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:11
  • Tidskriftsartikel (refereegranskat)abstract
    • We propose the Positive Resampler to solve the problem associated with event samples from state-of-the-art predictions for scattering processes at hadron colliders typically involving a sizeable number of events contributing with negative weight. The proposed method guarantees positive weights for all physical distributions, and a correct description of all observables. A desirable side product of the method is the possibility to reduce the size of event samples produced by General Purpose Event Generators, thus lowering the resource demands for subsequent computing-intensive event processing steps. We demonstrate the viability and efficiency of our approach by considering its application to a next-to-leading order + parton shower merged prediction for the production of a W boson in association with multiple jets.
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18.
  • Andersen, Lars Vabbersgaard, et al. (författare)
  • Influence of furniture on the modal properties of wooden floors
  • 2020
  • Ingår i: Model Validation and Uncertainty Quantification, Volume 3 - Proceedings of the 37th IMAC, A Conference and Exposition on Structural Dynamics 2019. - Cham : Springer International Publishing. - 9783030120740 ; , s. 197-204
  • Konferensbidrag (refereegranskat)abstract
    • Structure-borne vibration and low-frequency re-radiated noise from internal and external sources cause annoyance for inhabitants in dwellings. A key parameter in the prediction of vibration and noise levels is the modal parameters of the floors in a building, since vibration and sound levels increase when natural frequencies of the floor coincide with the excitation frequencies of a source, e.g. monoharmonic vibration of unbalanced rotating machinery and appliances or HVAC system—or traffic induced ground vibration propagating into the building. This paper has focus on wooden floors built as an assembly of particleboard and timber joists. Such floors constitute horizontal divisions in many dwellings—both older, traditional buildings and new lightweight buildings. The analysis concerns the impact of furniture placed on a floor with otherwise known properties. Given the small mass of a traditional wooden floor, the presence of furniture can be expected to change the modal properties of the floor significantly. The finite-element model, developed for the present analyses, accounts for uncertainty in the position of the furniture, and the analysis addresses the importance of the elevation of the mass above the floor regarding the natural frequencies and the related modes of vibration.
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19.
  • Andersen, Patricia, et al. (författare)
  • The impact of peripheral artery disease on major adverse cardiovascular events following myocardial infarction
  • 2021
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 345, s. 131-137
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Peripheral artery disease (PAD) constitute a high-risk with adverse clinical outcomes. We aimed to investigate the cardiovascular outcomes following myocardial infarction (MI). Methods and results: This nationwide, Danish register-based follow-up study includes all patients experiencing an MI between 2000 and 2017. Patients with and without PAD were compared. Multivariable logistic regression was used to derive relative risks of 1-year major adverse cardiovascular events (MACE; all-cause mortality, reinfarction, stroke or heart failure). Individual components, cardiovascular mortality, and bleeding, standardized to age, sex and comorbidity distributions of all patients were assessed. MI patients with PAD (n = 5083, 2.9%) were older and more comorbid compared to patients without PAD (n = 174,673). After standardization, PAD was associated with higher 1-year relative risks of MACE (RR 1.21 [95% CI 1.17;1.25]), all-cause (RR 1.29 [95% CI 1.24;1.35]) and cardiovascular mortality (RR 1.3 [95% CI 1.24;1.36]), reinfarction (RR 1.17 [95% CI 1.11;1.22]), stroke (RR 1.12 [95% CI 0.92;1.32]), heart failure (RR 1.22 [95% CI 1.12;1.32]), and bleeding episodes (RR 1.25 [95% CI 1.04,1.46]). Similar results were seen in 30-day survivors after adjustment for antithrombotic post-discharge medication for MACE (RR 1.25 [95% CI 1.20,1.31]), all-cause mortality (RR 1.47 [95% CI 1.37,1.57], cardiovascular mortality (RR 1.49 [95% CI 1.37,1.61]), reinfarction (RR 1.17 [95% CI 1.08,1.12]) and heart failure (RR 1.22 [95% CI 1.12,1.32]). Conclusion: Comparing to patients without PAD, patients with PAD had increased 1-year relative risk of MACE, all-cause mortality, reinfarction, stroke, heart failure, cardiovascular mortality and bleeding following MI. The low prevalence of PAD is suggestive of considerable under-diagnosing.
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20.
  • Björvang, Richelle D., et al. (författare)
  • Mixtures of persistent organic pollutants are found in vital organs of late gestation human fetuses
  • 2021
  • Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 283
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent organic pollutants (POPs) are industrial chemicals with long half-lives. Early life exposure to POPs has been associated with adverse effects. Fetal exposure is typically estimated based on concentrations in maternal serum or placenta and little is known on the actual fetal exposure. We measured the concentrations of nine organochlorine pesticides (OCPs), ten polychlorinated biphenyl (PCB) congeners, and polybrominated diphenyl ether (PBDE) congeners by gas chromatography – tandem mass spectrometry in maternal serum, placenta, and fetal tissues (adipose tissue, liver, heart, lung and brain) in 20 pregnancies that ended in stillbirth (gestational weeks 36–41). The data were combined with our earlier data on perfluoroalkyl substances (PFASs) in the same cohort (Mamsen et al. 2019). HCB, p,p’-DDE, PCB 138 and PCB 153 were quantified in all samples of maternal serum, placenta and fetal tissues. All 22 POPs were detected in all fetal adipose tissue samples, even in cases where they could not be detected in maternal serum or placenta. Tissue:serum ratios were significantly higher in later gestations, male fetuses, and pregnancies with normal placental function. OCPs showed the highest tissue:serum ratios and PFAS the lowest. The highest chemical burden was found in adipose tissue and lowest in the brain. Overall, all studied human fetuses were intrinsically exposed to mixtures of POPs. Tissue:serum ratios were significantly modified by gestational age, fetal sex and placental function. Importantly, more chemicals were detected in fetal tissues compared to maternal serum and placenta, implying that these proxy samples may provide a misleading picture of actual fetal exposures.
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21.
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22.
  • Bothmann, Enrico, et al. (författare)
  • A standard convention for particle-level Monte Carlo event-variation weights
  • 2023
  • Ingår i: SciPost Physics Core. - 2666-9366. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Streams of event weights in particle-level Monte Carlo event generators are a convenient and immensely CPU-efficient approach to express systematic uncertainties in phenomenology calculations, providing systematic variations on the nominal prediction within a single event sample. But the lack of a common standard for labelling these variation streams across different tools has proven to be a major limitation for event-processing tools and analysers alike. Here we propose a well-defined, extensible community standard for the naming, ordering, and interpretation of weight streams that will serve as the basis for semantically correct parsing and combination of such variations in both theoretical and experimental studies.
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23.
  • Brieghel, Christian, et al. (författare)
  • Identifying patients with chronic lymphocytic leukemia without need of treatment : End of endless watch and wait?
  • 2022
  • Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 108:5, s. 369-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Early-stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow-up.Methods We developed and validated a prognostic index to identify newly diagnosed patients without need of treatment (CLL-WONT) by a training/validation approach using data on 4708 patients. Composite scores derived from weighted hazards by multivariable analysis defined CLL-WONT risk groups.Results Age (>65 years: 1 point), Binet stage (B: 2 points), lactate dehydrogenase (LDH) (>205 U/L: 1 point), absolute lymphocyte count (15-30 x 10(9)/L: 1 point; >30 x 10(9)/L; 2 points), beta 2-microglobulin (>4 mg/L: 1 point), IGHV mutation status (unmutated: 1 point), and 11q or 17p deletion (1 point) were independently associated with shorter time to first treatment (TTFT). Low-risk patients demonstrated 5-year TTFT of 2% by internal validation, but 7-19% by external validation. Including all patients with complete scores, the 5-year TTFT was 10% for the 756 (39%) CLL-WONT low-risk patients, and the 704 (37%) patients who were both CLL-WONT and CLL-IPI low risk demonstrated even lower 5-year TTFT (8%).Conclusion We have adopted the CLL-WONT at an institution covering 1 800 000 individuals to allow patients with both low-risk CLL-WONT and CLL-IPI to be managed by primary healthcare providers, thereby prioritizing specialized hematology services for patients in dire need.
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24.
  • Bruno, Raphael Romano, et al. (författare)
  • Management and outcomes in critically ill nonagenarian versus octogenarian patients
  • 2021
  • Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. Methods: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80-89.9 years) and nonagenarian (>= 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. Results: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 +/- 5 vs. 7 +/- 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90-1.74; p = 0.19)). Conclusion: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered- together with illness severity and pre-existing functional capacity - to effectively guide triage decisions.
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25.
  • Cashman, Kevin D., et al. (författare)
  • Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude
  • 2022
  • Ingår i: European Journal of Nutrition. - : Springer. - 1436-6207 .- 1436-6215. ; 61, s. 1015-1034
  • Tidskriftsartikel (refereegranskat)abstract
    • Context and purpose: There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D.Methods: IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5–86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds.Results: To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies.Conclusions: Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose–response relationship and risk characterisation for health outcomes.
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26.
  • Cashman, Kevin D., et al. (författare)
  • Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D
  • 2021
  • Ingår i: European Journal of Nutrition. - : Springer Berlin/Heidelberg. - 1436-6207 .- 1436-6215. ; 60:2, s. 939-959
  • Tidskriftsartikel (refereegranskat)abstract
    • Context and purpose: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D3-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D.Methods: IPD analysis using data from 1429 participants (ages 2–89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models.Results: Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI).Conclusions: IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population.
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27.
  • Christensen, Sarah Friis, et al. (författare)
  • Healthcare resource utilization in patients with myeloproliferative neoplasms: A Danish nationwide matched cohort study
  • 2022
  • Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609.
  • Tidskriftsartikel (refereegranskat)abstract
    • Few studies have assessed healthcare resource utilization (HRU) in patients with Philadelphia-negative myeloproliferative neoplasms (MPN) using a matched cohort design. Further, no detailed assessment of HRU in the years preceding an MPN diagnosis exists. We conducted a registry-based nationwide Danish cohort study, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, and unclassifiable MPN diagnosed between January 2010 and December 2016. HRU data were summarized annually from 2 years before MPN diagnosis until emigration, death, or end of study (December 2017). We included 3342 MPN patients and 32 737 comparisons without an MPN diagnosis, matched on sex, age, region of residence, and level of education. During the study period, the difference in HRU (rate ratio) between patients and matched comparisons ranged from 1.0 to 1.5 for general practitioner contacts, 0.9 to 2.2 for hospitalizations, 0.9 to 3.8 for inpatient days, 1.0 to 4.0 for outpatient visits, 1.3 to 2.1 for emergency department visits, and 1.0 to 4.1 for treatments/examinations. In conclusion, MPN patients had overall higher HRU than the matched comparisons throughout the follow-up period (maximum 8 years). Further, MPN patients had substantially increased HRU in both the primary and secondary healthcare sector in the 2 years preceding the diagnosis.
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28.
  • Christensen, Sarah Friis, et al. (författare)
  • Labor Market Attachment in Patients with Myeloproliferative Neoplasms: A Nationwide Matched Cohort Study
  • 2021
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 138:Suppl 1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Myeloproliferative neoplasms (MPNs) are characterized by a substantial symptom burden, risk of debilitating complications (e.g., thrombosis), and increased comorbidity. Recently, three comprehensive questionnaire studies (Mesa 2016, Harrison 2017, Jingbo 2018) have reported a high impact of MPNs on patients' ability to work. However, no registry-based studies have assessed labor market attachment (LMA) of MPN patients and matched nonMPN comparisons.AIM: To assess the pre- and post-diagnostic LMA of MPN patients and matched nonMPN comparisons.METHODS: We conducted a descriptive, registry-based nationwide cohort study, using data from the Danish National Chronic Myeloid Neoplasia Registry including all Danish MPN patients diagnosed between January 2010 and December 2016. Population-based cohorts of nonMPN comparisons were constructed by 1:10 matching on age, sex, level of education, and region of residence. Data on LMA were retrieved from the Danish Register for Evaluation of Marginalization, which holds information on all public transfer payments in Denmark. Data were linked using the unique civil registration number, which identifies all Danish citizens. The LMA endpoints were defined for each individual as working (not receiving any type of transfer payment), unemployed, receiving transfer payment for either sick leave, disability pension, age pension, or other health-related benefits (e.g., wage-subsidized employment). We assessed LMA weekly for each individual from two years before diagnosis until death, emigration, or two years after the diagnosis. For each cohort, we presented LMA as proportions with 95% confidence intervals (CIs), as well as the proportion of individuals who died during follow-up.RESULTS: The study included 3,342 MPN patients (1,140 essential thrombocythemia [ET]; 1,109 polycythemia vera [PV]; 533 myelofibrosis [MF]; and 560 unspecified MPN [MPN-U]) and 32,737 nonMPN comparisons (11,181 nonET; 10,873 nonPV; 5,217 nonPMF; and 5,466 nonMPN-U). The median age at time of diagnosis was: ET 67 years (interquartile range [IQR], 55-76); PV, 69 years (IQR, 61-77); PMF, 73 years (IQR, 66-79); and MPN-U, 72 years (IQR, 63-80).At time of MPN diagnosis, the majority of MPN patients and nonMPN comparisons received age pension (range: ET, 52.1% [95% CI, 49.2-55.0] to nonMF, 70.3% [95% CI, 69.1-71.6]). The proportions working were: ET, 35.1% (95% CI, 32.3-37.9) vs. nonET, 37.3% (95% CI, 36.5-38.2); PV, 22.6% (95% CI, 20.2-25.1) vs. nonPV, 30.8% (95% CI, 29.9-31.7); MF, 23.8% (95% CI, 20.2-27.4) vs. nonMF, 23.6% (95% CI, 22.5-24.8); and MPN-U, 22.1% (95% CI,18.7- 25.6) vs. nonMPN-U, 27.8% (95% CI, 26.6-29.0). Across MPN subtypes, a larger proportion of patients than comparisons were on sick leave: ET, 3.5% (95% CI, 2.4-4.6) vs. nonET, 1.3% (95% CI, 1.1-1.5); PV, 5.5% (95% CI, 4.2-6.8) vs. nonPV, 0.9% (95% CI, 0.7-1.1); MF (not applicable due to small numbers) vs. nonMF, 0.6% (95% CI, 0.4-0.8); and MPN-U, 3.0% (95% CI, 1.6- 4.5) vs. nonMPN-U, 1.0% (95% CI, 0.7-1.3). Regarding disability pension, the proportions ranged from 4.1% (95% CI, 2.4-5.8) to 5.0% (95% CI, 3.7-6.3) among patients and from 3.1% (95% CI, 2.6-3.6) to 4.7% (95% CI, 4.3-5.1) among comparisons. For both MPN patients and nonMPN comparisons, few were unemployed (≤3.3%) or received other health-related benefits (≤1.6%).Two years preceding diagnosis, the proportion of PV and MPN-U patients working was slightly lower than the matched comparisons: PV, 31.0% (95% CI, 28.4-33.8) vs. nonPV, 34.3% (95% CI, 33.5-35.2) and MPN-U, 28.2% (95% CI, 24.6-32.1) vs. nonMPN-U, 32.0% (95% CI, 30.7-33.2), while this difference was not observed between ET and MF patients and their respective comparisons.From two years before to two years after diagnosis, we observed slightly larger reductions in the proportion working among MPN patients than among comparisons. Among MPN patients, the proportion on sick leave including other health-related benefits, increased during the study period, while it remained unchanged among comparisons. The proportion of patients and comparisons on disability pension remained stable.CONCLUSION: Overall, our findings showed that Danish patients with ET, PV, MF, and MPN-U had slightly impaired LMA already two years before diagnosis and up to two years after diagnosis. Thus, fewer patients were working and more patients transferred to sick leave compared with matched individuals without MPN.
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29.
  • Christensen, Sarah, et al. (författare)
  • Healthcare resource utilization in patients with myeloproliferative neoplasms: a nationwide matched cohort study
  • 2021
  • Ingår i: HemaSphere. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 5:S2, s. 529-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myeloproliferative neoplasms (MPNs) are associated with severe complications and a substantial symptom burden – frequently emerging several years before diagnosis. Due to the chronic nature ofthe diseases, MPN patients have a lifelong need for treatment and care. However, only few studies have assessed MPN healthcare resource utilization (HRU) compared with matched cohorts, and no detailed assessments of HRU in the years preceding MPN diagnosis exist.Aims: To assess the pre- and post-diagnostic HRU of MPN patients compared with matched cohorts of nonMPN comparisons.Methods: We conducted this descriptive, register-based nationwide cohort study, utilizing data from the Danish National Chronic Myeloid Neoplasia Registry on all MPN patients diagnosed between January 2010 and December 2016, and data on HRU from the Danish National Patient Registry and the Danish National Health Service Registry. Populationbased cohorts of nonMPN comparisons were constructed by 1:10 matchingon age, sex, level of education, and region of residence. Data were linkedusing the unique civil registration number, which identifies all Danish citizens. HRU was summarized over each year for all cohorts from twoyears before date of MPN diagnosis and until emigration, death, or endof study (31 December 2017). HRU was calculated as annual number ofhealthcare contacts (inpatient days, outpatient consultations, treatmentsand examinations, and general practitioner [GP] visits) divided by person-years at risk and compared using rate ratios with 95% CI.Results: The study population included 3,342 MPN patients (1,140 essential thrombocythemia [ET]; 1,109 polycythemia vera [PV]; 533 primary myelofibrosis [PMF]; and 560 unspecified MPN [MPN-U]) and 32,737 nonMPN comparisons (11,181 nonET; 10,873 nonPV; 5,217 nonPMF; and 5,466 nonMPN-U). The median age was 67 (ET), 69 (PV), 73 (PMF), and 72 years (MPN-U), and the mean follow-up was 3.8 (ET), 3.8(PV), 3.1 (PMF), and 3.3 years (MPN-U). A total of 750 (22.4%) MPNpatients and 4,627 (14.1%) nonMPN comparisons died during follow-up.In nearly all years of follow-up, MPN patients had a higher HRU thannonMPN comparisons (Figure, rate ratio>1). Rate ratios for outpatientconsultations were largest at the time of diagnosis: ET, 2.7 (95%CI, 2.6-2.9); PV, 3.4 (95%CI, 3.2-3.6); PMF, 4.0 (95%CI, 3.7-4.4); and MPN-U,3.7 (95%CI, 3.4-4.0). For most MPN subtypes, rate ratios also peaked attime of diagnosis for treatment and examinations. In contrast, the largest rate ratio for PV was in the last year of follow-up: 3.5 (95%CI, 2.8-4.3). Across MPN subtypes, rate ratios for GP visits varied from 1.0 to1.5 during follow-up without any considerable fluctuations. Interestingly, increased rate ratios for inpatients days were evident 2 years before diagnosis: ET, 1.8 (95%CI, 1.7-1.9); PV, 1.3, (95%CI, 1.2-1.3); PMF, 1.4(95%CI, 1.2-1.5); and MPN-U, 1.7 (95%CI, 1.6-1.9). During follow-up,notable increases in rate ratios were observed, e.g., PMF 3.0 (95%CI 2.4-3.6) and PV 3.8 (95%CI 3.0-4.8) in year 5 and 7, respectively.Summary/Conclusion: Overall, compared with matched nonMPN comparisons, MPN patients had a higher HRU throughout the study period. This was consistent across MPN subtypes and HRU measures. Within the limitations of small numbers toward end of follow-up and lack ofmatching on comorbidity, our findings confirmed a consistent HRU burden after MPN diagnosis. Equally important, our study revealed substantial increases in HRU two years before MPN diagnosis, warrantingfurther exploration of the pre-diagnostic period, including the potentialbenefits of early detection.
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30.
  • Dahl, Victor Naestholt, et al. (författare)
  • Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review
  • 2022
  • Ingår i: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 125, s. 120-131
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.Methods: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.Results: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).Conclusion: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.
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31.
  • de Lange, Dylan W., et al. (författare)
  • The association of premorbid conditions with 6-month mortality in acutely admitted ICU patients over 80 years
  • 2024
  • Ingår i: Annals of Intensive Care. - : SPRINGER. - 2110-5820. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. Methods Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients >= 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). Results Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3-6). Frailty (CFS >= 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81-86) than patients dying within the first 6 months (median age 84, IQR 82-87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p < 0.01) and were less dependent based on their Katz activities of daily living measurement (median Katz score 6, IQR 5-6 versus 6 points, IQR 3-6, p < 0.01). Conclusions We found that Clinical Frailty Scale, age, and SOFA at admission were independent prognostic factors for 6 month mortality after ICU admission in patients age 80 and above. Adding other geriatric syndromes and scores did not improve the model. This information can be used in shared-decision making. ClinicalTrials.gov: NCT03370692. Conclusions We found that Clinical Frailty Scale, age, and SOFA at admission were independent prognostic factors for 6 month mortality after ICU admission in patients age 80 and above. Adding other geriatric syndromes and scores did not improve the model. This information can be used in shared-decision making.
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32.
  • Dueholm, Morten Kam Dahl, et al. (författare)
  • MiDAS 5 : Global diversity of bacteria and archaea in anaerobic digesters
  • 2024
  • Ingår i: Nature Communications. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Anaerobic digestion of organic waste into methane and carbon dioxide (biogas) is carried out by complex microbial communities. Here, we use full-length 16S rRNA gene sequencing of 285 full-scale anaerobic digesters (ADs) to expand our knowledge about diversity and function of the bacteria and archaea in ADs worldwide. The sequences are processed into full-length 16S rRNA amplicon sequence variants (FL-ASVs) and are used to expand the MiDAS 4 database for bacteria and archaea in wastewater treatment systems, creating MiDAS 5. The expansion of the MiDAS database increases the coverage for bacteria and archaea in ADs worldwide, leading to improved genus- and species-level classification. Using MiDAS 5, we carry out an amplicon-based, global-scale microbial community profiling of the sampled ADs using three common sets of primers targeting different regions of the 16S rRNA gene in bacteria and/or archaea. We reveal how environmental conditions and biogeography shape the AD microbiota. We also identify core and conditionally rare or abundant taxa, encompassing 692 genera and 1013 species. These represent 84–99% and 18–61% of the accumulated read abundance, respectively, across samples depending on the amplicon primers used. Finally, we examine the global diversity of functional groups with known importance for the anaerobic digestion process.
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33.
  • Eriksson, Axel Christian, et al. (författare)
  • Influence of airborne particles' chemical composition on SVOC uptake from PVC flooring - time resolved analysis with aerosol mass spectrometry
  • 2020
  • Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; , s. 85-91
  • Tidskriftsartikel (refereegranskat)abstract
    • We sampled ammonium sulfate particles and indoor particles of outdoor origin through a small chamber covered with polyvinyl chloride (PVC) flooring. We measured the uptake of semi-volatile organic compounds (SVOC) by the airborne particles in real time. The particles acquired SVOC mass fractions up to 10%. The phthalate ester DEHP (di(2-ethylhexyl)phthalate), a known endocrine disruptor, contributed by approximately half of the sorbed SVOC mass. The indoor particles acquired higher DEHP fraction than laboratory generated ammonium sulfate aerosol. We attribute this increased uptake to absorption by organic matter present in the indoor particles. Using a thermodenuder to remove volatile components, predominantly organics, reduced SVOC uptake. Positive matrix factorization applied to the organic mass spectra suggests that hydrocarbon-like organic aerosol (typically fresh traffic exhaust) sorbs DEHP more efficiently than aged organic aerosol. SVOC uptake is one of the processes that modifies outdoor pollution particles after they penetrate buildings, where the majority of exposure occurs. Particles from indoor sources, typically dominated by organic matter, will undergo such processes as well. Aerosol mass spectrometry improves the time resolution of experimental investigations into these processes, and enables experiments with lower, relevant particle concentrations. Additionally, particle size resolved results are readily obtained.
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34.
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35.
  • Flaatten, Hans, et al. (författare)
  • Consent is a confounding factor in a prospective observational study of critically ill elderly patients
  • 2022
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 17:10
  • Tidskriftsartikel (refereegranskat)abstract
    • During analysis of a prospective multinational observation study of critically ill patients >= 80 years of age, the VIP2 study, we also studied the effects of differences in country consent for study inclusion. This is a post hoc analysis where the ICUs were analyzed according to requirement for study consent. Group A: ICUs in countries with no requirement for consent at admission but with deferred consent in survivors. Group B: ICUs where some form of active consent at admission was necessary either from the patient or surrogates. Patients characteristics, the severity of disease and outcome variables were compared. Totally 3098 patients were included from 21 countries. The median age was 84 years (IQR 81-87). England was not included because of changing criteria for consent during the study period. Group A (7 countries, 1200 patients), and group B (15 countries, 1898 patients) were comparable with age and gender distribution. Cognition was better preserved prior to admission in group B. Group A suffered from more organ dysfunction at admission compared to group B with Sequential Organ Failure Assessment score median 8 and 6 respectively. ICU survival was lower in group A, 66.2% compared to 78.4% in group B (p<0.001). We hence found profound effects on outcomes according to differences in obtaining consent for this study. It seems that the most severely ill elderly patients were less often recruited to the study in group B. Hence the outcome measured as survival was higher in this group. We therefore conclude that consent likely is an important confounding factor for outcome evaluation in international studies focusing on old patients.
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36.
  • Flaatten, Hans, et al. (författare)
  • Reliability of the Clinical Frailty Scale in very elderly ICU patients : a prospective European study
  • 2021
  • Ingår i: Annals of Intensive Care. - : Springer. - 2110-5820. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Frailty is a valuable predictor for outcome in elderly ICU patients, and has been suggested to be used in various decision-making processes prior to and during an ICU admission. There are many instruments developed to assess frailty, but few of them can be used in emergency situations. In this setting the clinical frailty scale (CFS) is frequently used. The present study is a sub-study within a larger outcome study of elderly ICU patients in Europe (the VIP-2 study) in order to document the reliability of the CFS. Materials and methods From the VIP-2 study, 129 ICUs in 20 countries participated in this sub-study. The patients were acute admissions >= 80 years of age and frailty was assessed at admission by two independent observers using the CFS. Information was obtained from the patient, if not feasible, from the family/caregivers or from hospital files. The profession of the rater and source of data were recorded along with the score. Interrater variability was calculated using linear weighted kappa analysis. Results 1923 pairs of assessors were included and background data of patients were similar to the whole cohort (n = 3920). We found a very high inter-rater agreement (weighted kappa 0.86), also in subgroup analyses. The agreement when comparing information from family or hospital records was better than using only direct patient information, and pairs of raters from same profession performed better than from different professions. Conclusions Overall, we documented a high reliability using CFS in this setting. This frailty score could be used more frequently in elderly ICU patients in order to create a more holistic and realistic impression of the patient s condition prior to ICU admission.
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37.
  • Fronczek, Jakub, et al. (författare)
  • Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU : a prospective cohort study
  • 2021
  • Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context.METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score.RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01).CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2).
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38.
  • Fronczek, Jakub, et al. (författare)
  • Short-term mortality or patients >= 80 years old admitted to European intensive care units: an international observational study
  • 2022
  • Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 129:1, s. 58-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Limited evidence suggests variation in mortality of older critically ill adults across Europe. We aimed to investigate regional differences in mortality among very old ICU patients. Methods: Multilevel analysis of two international prospective cohort studies. We included patients >= 80 yr old from 322 ICUs located in 16 European countries. The primary outcome was mortality within 30 days from admission to the ICU. Results are presented as n (%) with 95% confidence intervals and odds ratios (ORs). Results: Of 8457 patients, 2944 (36.9% [35.9-38.0%]) died within 30 days. Crude mortality rates varied widely between participating countries (from 10.1% [6.4-15.6%] to 45.1% [41.1-49.2%] in the ICU and from 21.3% [16.3-28.9%] to 55.3% [51.1-59.5%] within 30 days). After adjustment for confounding variables, the variation in 30-day mortality between countries was substantially smaller than between ICUs (median OR 1.14 vs 1.58). Healthcare expenditure per capita (OR=0.84 per $1000 [0.75-0.94]) and social health insurance framework (OR=1.43 [1.01-2.01]) were associated with ICU mortality, but the direction and magnitude of these relationships was uncertain in 30-day follow-up. Volume of admissions was associated with lower mortality both in the ICU (OR=0.81 per 1000 annual ICU admissions [0.71-0.94]) and in 30-day follow-up (OR=0.86 [0.76-0.97]). Conclusion: The apparent variation in short-term mortality rates of older adults hospitalised in ICUs across Europe can be largely attributed to differences in the clinical profile of patients admitted. The volume-outcome relationship identified in this population requires further investigation.
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39.
  • Gregersen, Henrik, et al. (författare)
  • Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma : A randomised phase 2 trial by the Nordic Myeloma Study Group
  • 2022
  • Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 108:1, s. 34-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma. Methods This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 -> 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86). Results Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections. Conclusion In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity.
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40.
  • Guidet, Bertrand, et al. (författare)
  • The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs : the VIP2 study
  • 2020
  • Ingår i: Intensive Care Medicine. - : Springer-Verlag New York. - 0342-4642 .- 1432-1238. ; 46:1, s. 57-69
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival.METHODS: Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients' characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike's information criterion across imputations was used to evaluate the goodness of fit of our models.RESULTS: We included 3920 patients with a median age of 84 years (IQR: 81-87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83-8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3-6); IQCODE: 3.19 (3-3.69); ADL: 6 (4-6); Comorbidity and Polypharmacy score (CPS): 10 (7-14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.-1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14-1.17, p < 0.0001) and CFS (per point): 1.1 (1.05-1.15, p < 0.001). CFS remained an independent factor after inclusion of life-sustaining treatment limitation in the model.CONCLUSION: We confirm that frailty assessment using the CFS is able to predict short-term mortality in elderly patients admitted to ICU. Other geriatric syndromes do not add improvement to the prediction model. Since CFS is easy to measure, it should be routinely collected for all elderly ICU patients in particular in connection to advance care plans, and should be used in decision making.
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41.
  • Haas, Lenneke E M, et al. (författare)
  • Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old : results from an observational study in 241 European ICUs
  • 2021
  • Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 50:5, s. 1719-1727
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear.OBJECTIVE: To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function.DESIGN: Prospective cohort study.SETTING: 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019.SUBJECTS: Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2.METHODS: Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected.RESULTS: Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09-1.25, P < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14-1.17, P < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18-1.51, P < 0.0001).CONCLUSIONS: There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.
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42.
  • Hærvig, Katia Keglberg, et al. (författare)
  • Fetal exposure to maternal cigarette smoking and male reproductive function in young adulthood
  • 2022
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:5, s. 525-538
  • Tidskriftsartikel (refereegranskat)abstract
    • Maternal smoking during pregnancy constitutes a potential, major risk factor for adult male reproductive function. In the hitherto largest longitudinal cohort, we examined biomarkers of reproductive function according to maternal smoking during the first trimester and investigated whether associations were mitigated by smoking cessation prior to the fetal masculinization programming window. Associations between exposure to maternal smoking and semen characteristics, testicular volume and reproductive hormones were assessed among 984 young men from the Fetal Programming of Semen Quality (FEPOS) cohort. Maternal smoking was assessed through interview data and measured plasma cotinine levels during pregnancy. We applied negative binomial, logistic and linear regression models to estimate differences in outcomes according to levels of maternal smoking. Sons of light smokers (≤ 10 cigarettes/day) had a 19% (95% CI − 29%, − 6%) lower sperm concentration and a 24% (95% CI − 35%, − 11%) lower total sperm count than sons of non-smokers. These estimates were 38% (95% CI − 52%, − 22%) and 33% (95% CI − 51%, − 8%), respectively, for sons of heavy smokers (> 10 cigarettes/day). The latter group also had a 25% (95% CI 1%, 54%) higher follitropin level. Similarly, sons exposed to maternal cotinine levels of > 10 ng/mL had lower sperm concentration and total sperm count. Smoking cessation prior to gestational week seven was not associated with a higher reproductive capacity. We observed substantial and consistent exposure–response associations, providing strong support for the hypothesis that maternal smoking impairs male reproductive function. This association persisted regardless of smoking cessation in early pregnancy.
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43.
  • Hærvig, Katia Keglberg, et al. (författare)
  • Fetal programming of semen quality (Fepos) cohort – a dnbc male-offspring cohort
  • 2020
  • Ingår i: Clinical Epidemiology. - 1179-1349. ; 12, s. 757-770
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prenatal exposures may contribute to male infertility in adult life, but large-scale epidemiological evidence is still lacking. The Fetal Programming of Semen quality (FEPOS) cohort was founded to provide means to examine if fetal exposures can interfere with fetal reproductive development and ultimately lead to reduced semen quality and reproductive hormone imbalances in young adult men. Methods: Young adult men at least 18 years and 9 months of age born to women in the Danish National Birth Cohort living in relative proximity to Copenhagen or Aarhus and for whom a maternal blood sample and two maternal interviews during pregnancy were available were invited to FEPOS. Recruitment began in March 2017 and ended in December 2019. The participants answered a comprehensive questionnaire and underwent a physical examination where they delivered a semen, urine, and hair sample, measured their own testicular volume, and had blood drawn. Results: In total 21,623 sons fulfilled eligibility criteria of whom 5697 were invited and 1058 participated making the response rate 19%. Semen characteristics did not differ between sons from the Copenhagen and Aarhus clinics. When comparing the FEPOS semen parameters to similar cohorts, the median across all semen characteristics was slightly lower for FEPOS participants, although with smaller variation. Conclusion: With its 1058 young adult men, the FEPOS cohort is the largest population-based male-offspring cohort worldwide specifically designed to investigate prenatal determinants of semen quality. Wide-ranging information on maternal health, lifestyle, socioeconomic status, occupation, and serum concentrations of potential reproductive toxicants during pregnancy combined with biological markers of fertility in their sons collected after puberty allow for in-depth investigations of the ‘fetal origins of adult disease hypothesis’.
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44.
  • Hidalgo Migueles, Jairo Hidalgo, et al. (författare)
  • GRANADA consensus on analytical approaches to assess associations with accelerometer-determined physical behaviours (physical activity, sedentary behaviour and sleep) in epidemiological studies
  • 2022
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 56:7, s. 376-384
  • Tidskriftsartikel (refereegranskat)abstract
    • The inter-relationship between physical activity, sedentary behaviour and sleep (collectively defined as physical behaviours) is of interest to researchers from different fields. Each of these physical behaviours has been investigated in epidemiological studies, yet their codependency and interactions need to be further explored and accounted for in data analysis. Modern accelerometers capture continuous movement through the day, which presents the challenge of how to best use the richness of these data. In recent years, analytical approaches first applied in other scientific fields have been applied to physical behaviour epidemiology (eg, isotemporal substitution models, compositional data analysis, multivariate pattern analysis, functional data analysis and machine learning). A comprehensive description, discussion, and consensus on the strengths and limitations of these analytical approaches will help researchers decide which approach to use in different situations. In this context, a scientific workshop and meeting were held in Granada to discuss: (1) analytical approaches currently used in the scientific literature on physical behaviour, highlighting strengths and limitations, providing practical recommendations on their use and including a decision tree for assisting researchers decision-making; and (2) current gaps and future research directions around the analysis and use of accelerometer data. Advances in analytical approaches to accelerometer-determined physical behaviours in epidemiological studies are expected to influence the interpretation of current and future evidence, and ultimately impact on future physical behaviour guidelines.
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45.
  • Holm Andersen, Line, 1988-, et al. (författare)
  • Can reintroduction of beavers improve insect biodiversity?
  • 2023
  • Ingår i: Journal of Environmental Management. - : Elsevier BV. - 0301-4797 .- 1095-8630. ; 337
  • Tidskriftsartikel (refereegranskat)abstract
    • Ecosystem engineering species, such as beavers, may help the restoration of biodiversity. Through the building of dams and lodges and altering the natural hydrology, beavers change the habitat structure and create multiple habitats that facilitate a wide variety of other organisms including terrestrial invertebrate communities. Here we study the effect of beaver reintroduction in Klosterheden in Denmark on biomass of flying invertebrates and diversity of moths. Further, aerial photos were used to assess riparian structure and productivity using the normalized difference vegetation index (NDVI). Our findings show that the presence of beavers affected flying invertebrate biomass, but that this was dependent on time of the year. Further, a strong effect of presence of beavers was found on diversity of moths. The results also show an increase in vegetation productivity and structural heterogeneity at sites with presence of beavers. Overall, our results demonstrate the importance of beavers as important ecosystem engineers that affect invertebrate species composition and abundance, as well as riparian structure and productivity.
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46.
  • Holm, Mona Katrine Alberthe, et al. (författare)
  • Decrease in all-cause 30-day mortality after bacteraemia over a 15-year period : A population-based cohort study in Denmark in 2000–2014
  • 2021
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Bacteraemia is a frequent infectious condition that strongly affects morbidity and mortality. The incidence is increasing worldwide. This study explores all-cause 30-day mortality after bacteraemia in two out of Denmark’s five healthcare regions with approximately 2.4 million inhabitants. Methods: Clinically significant bacteraemia episodes (n = 55,257) were identified from a geographically well-defined background population between 2000 and 2014, drawing on population-based data regarding bacterial species and vital status. All-cause 30-day mortality was assessed in relation to bacteraemia episodes, number of patients with analysed blood cultures and the background population. Results: We observed a decreasing trend of all-cause 30-day mortality between 2000 and 2014, both in relation to the number of bacteraemia episodes and the background population. Mortality decreased from 22.7% of the bacteraemia episodes in 2000 to 17.4% in 2014 (annual IRR [95% CI]: 0.983 [0.979–0.987]). In relation to the background population, there were 41 deaths per 100,000 inhabitants in 2000, decreasing to 39 in 2014 (annual IRR [95% CI]: 0.988 [0.982–0.993]). Numbers of inhabitants, bacteraemia episodes, and analysed persons having BCs increased during the period. Conclusions: All-cause 30-day mortality in patients with bacteraemia decreased significantly over a 15-year period.
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47.
  • Ibarz, Mercedes, et al. (författare)
  • Sepsis at ICU admission does not decrease 30-day survival in very old patients : a post-hoc analysis of the VIP1 multinational cohort study
  • 2020
  • Ingår i: Annals of Intensive Care. - : Springer. - 2110-5820. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival.RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85].CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.
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48.
  • Jensen, Christian Fuglesang S., et al. (författare)
  • Microdissection Testicular Sperm Extraction Versus Multiple Needle-pass Percutaneous Testicular Sperm Aspiration in Men with Nonobstructive Azoospermia : A Randomized Clinical Trial
  • 2022
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 82:4, s. 377-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Surgical extraction of testicular spermatozoa is needed in men with nonobstructive azoospermia (NOA) who wish to become biological fathers. Based on available uncontrolled studies with unspecific patient selection, microdissection testicular sperm extraction (mTESE), having a sperm retrieval rate (SRR) of 50%, is considered the most efficient sperm retrieval procedure. However, no randomized clinical trials for comparison of different sperm retrieval procedures exist. Testicular sperm aspiration (TESA) is simple and commonly used, and we hypothesized that this technique using multiple needle passes would give similar SRRs to mTESE. Objective: To compare mTESE and multiple needle-pass TESA in men with NOA. Design, setting, and participants: A randomized clinical trial was performed between June 2017 and April 2021, with inclusion of 100 men with NOA from four centers in Denmark and Sweden. All participants received treatment at the same institution. Intervention: Participants were randomized to mTESE (n = 49) or multiple needle-pass TESA (n = 51). Patients with failed multiple needle-pass TESA proceeded directly to salvage mTESE. Outcome measurements and statistical analysis: The primary outcome was SRR. Secondary outcomes included complications and changes in reproductive hormones after surgery. Results and limitations: Spermatozoa were retrieved in 21/49 (43%) men after mTESE and in 11/51 (22%) men after multiple needle-pass TESA (rate difference –0.21; 95% confidence interval –0.39 to –0.03; p = 0.02). The combined SRR for multiple needle-pass TESA + salvage mTESE was 15/51 (29%). No complications occurred after multiple needle-pass TESA only, while 5/89 (6%) men having mTESE experienced a complication requiring surgical intervention. Overall, no statistically significant differences in reproductive hormones were observed between groups after 6 mo. Limitations include the low number of patients in secondary outcome data. Conclusions: In direct comparison, SRR was higher in mTESE than in multiple needle-pass TESA. Patient summary: Men with azoospermia need surgical extraction of spermatozoa to become biological fathers. In this randomized trial, we compared two surgeries (microdissection testicular sperm extraction [mTESE] and testicular sperm aspiration [TESA]) and found that mTESE gives a higher sperm retrieval rate than multiple needle-pass TESA.
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49.
  • Jensen, Christian Fuglesang S., et al. (författare)
  • Results from the first autologous grafting of adult human testis tissue : A case report
  • 2024
  • Ingår i: Human Reproduction. - 0268-1161. ; 39:2, s. 303-309
  • Tidskriftsartikel (refereegranskat)abstract
    • Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.
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50.
  • Jensen, Christian Fuglesang Skjødt, et al. (författare)
  • Sertoli and Germ Cells Within Atrophic Seminiferous Tubules of Men With Non-Obstructive Azoospermia
  • 2022
  • Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Infertile men with non-obstructive azoospermia (NOA) have impaired spermatogenesis. Dilated and un-dilated atrophic seminiferous tubules are often present in the testes of these patients, with the highest likelihood of active spermatogenesis in the dilated tubules. Little is known about the un-dilated tubules, which in NOA patients constitute the majority. To advance therapeutic strategies for men with NOA who fail surgical sperm retrieval we aimed to characterize the spermatogonial stem cell microenvironment in atrophic un-dilated tubules. Methods: Testis biopsies approximately 3x3x3 mm3 were obtained from un-dilated areas from 34 patients. They were classified as hypospermatogenesis (HS) (n=5), maturation arrest (MA) (n=14), and Sertoli cell only (SCO) (n= 15). Testis samples from five fertile men were included as controls. Biopsies were used for histological analysis, RT-PCR analysis and immunofluorescence of germ and Sertoli cell markers. Results: Anti-Müllerian hormone mRNA and protein expression was increased in un-dilated tubules in all three NOA subtypes, compared to the control, showing an immature state of Sertoli cells (p<0.05). The GDNF mRNA expression was significantly increased in MA (P=0.0003). The BMP4 mRNA expression showed a significant increase in HS, MA, and SCO (P=0.02, P=0.0005, P=0.02, respectively). The thickness of the tubule wall was increased 2.2-fold in the SCO-NOA compared to the control (p<0.05). In germ cells, we found the DEAD-box helicase 4 (DDX4) and melanoma-associated antigen A4 (MAGE-A4) mRNA and protein expression reduced in NOA (MAGE-A: 46% decrease in HS, 53% decrease in MA, absent in SCO). In HS-NOA, the number of androgen receptor positive Sertoli cells was reduced 30% with a similar pattern in mRNA expression. The γH2AX expression was increased in SCO as compared to HS and MA. However, none of these differences reached statistical significance probably due to low number of samples. Conclusions: Sertoli cells were shown to be immature in un-dilated tubules of three NOA subtypes. The increased DNA damage in Sertoli cells and thicker tubule wall in SCO suggested a different mechanism for the absence of spermatogenesis from SCO to HS and MA. These results expand insight into the differences in un-dilated tubules from the different types of NOA patients.
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