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Sökning: WFRF:(Hansen Mette)

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1.
  • Bjørnsbo, Kirsten Schroll, et al. (författare)
  • Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort
  • 2024
  • Ingår i: BMJ Open. - 2044-6055. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50–80 years old Inter99 participants. Methods and analysis The Inter99 cohort comprises individuals aged 30–60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. Ethics and dissemination The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark’s registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers.
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2.
  • Hansen, Aleksander L., et al. (författare)
  • Birthweight is associated with clinical characteristics in people with recently diagnosed type 2 diabetes
  • 2023
  • Ingår i: Diabetologia. - 0012-186X. ; 66:9, s. 1680-1692
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes but it is unknown whether low birthweight is associated with distinct clinical characteristics at disease onset. We examined whether a lower or higher birthweight in type 2 diabetes is associated with clinically relevant characteristics at disease onset. Methods: Midwife records were traced for 6866 individuals with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Using a cross-sectional design, we assessed age at diagnosis, anthropomorphic measures, comorbidities, medications, metabolic variables and family history of type 2 diabetes in individuals with the lowest 25% of birthweight (<3000 g) and highest 25% of birthweight (>3700 g), compared with a birthweight of 3000–3700 g as reference, using log-binomial and Poisson regression. Continuous relationships across the entire birthweight spectrum were assessed with linear and restricted cubic spline regression. Weighted polygenic scores (PS) for type 2 diabetes and birthweight were calculated to assess the impact of genetic predispositions. Results: Each 1000 g decrease in birthweight was associated with a 3.3 year (95% CI 2.9, 3.8) younger age of diabetes onset, 1.5 kg/m2 (95% CI 1.2, 1.7) lower BMI and 3.9 cm (95% CI 3.3, 4.5) smaller waist circumference. Compared with the reference birthweight, a birthweight of <3000 g was associated with more overall comorbidity (prevalence ratio [PR] for Charlson Comorbidity Index Score ≥3 was 1.36 [95% CI 1.07, 1.73]), having a systolic BP ≥155 mmHg (PR 1.26 [95% CI 0.99, 1.59]), lower prevalence of diabetes-associated neurological disease, less likelihood of family history of type 2 diabetes, use of three or more glucose-lowering drugs (PR 1.33 [95% CI 1.06, 1.65]) and use of three or more antihypertensive drugs (PR 1.09 [95% CI 0.99, 1.20]). Clinically defined low birthweight (<2500 g) yielded stronger associations. Most associations between birthweight and clinical characteristics appeared linear, and a higher birthweight was associated with characteristics mirroring lower birthweight in opposite directions. Results were robust to adjustments for PS representing weighted genetic predisposition for type 2 diabetes and birthweight. Conclusion/interpretation: Despite younger age at diagnosis, and fewer individuals with obesity and family history of type 2 diabetes, a birthweight <3000 g was associated with more comorbidities, including a higher systolic BP, as well as with greater use of glucose-lowering and antihypertensive medications, in individuals with recently diagnosed type 2 diabetes.
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3.
  • Hansen, Aleksander L., et al. (författare)
  • Low birthweight in patients with type 2 diabetes is associated with elevated risk of cardiovascular events and mortality
  • Ingår i: Diabetologia. - 0012-186X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes and CVD. This prospective cohort study investigated whether lower birthweight increases CVD risk after diagnosis of type 2 diabetes. Methods: Original midwife records were evaluated for 8417 participants recently diagnosed with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Patients were followed for the first occurrence of a composite CVD endpoint (myocardial infarction, coronary revascularisation, peripheral arterial disease, stroke, unstable angina, heart failure or CVD death), a three-component endpoint comprising major adverse cardiovascular events (MACE), and all-cause mortality. Ten-year risks were estimated using the Aalen–Johansen estimator considering non-CVD death as a competing risk. HRs were determined by Cox regression. Models were controlled for sex, age, calendar year at birth, family history of diabetes and born-at-term status. Results: A total of 1187 composite CVD endpoints, 931 MACE, and 1094 deaths occurred during a median follow-up period of 8.5 years. The 10-year standardised composite CVD risk was 19.8% in participants with a birthweight <3000 g compared with 16.9% in participants with a birthweight of 3000–3700 g, yielding a risk difference (RD) of 2.9% (95% CI 0.4, 5.4) and an adjusted HR of 1.20 (95% CI 1.03, 1.40). The 10-year MACE risk for birthweight <3000 g was similarly elevated (RD 2.4%; 95% CI 0.1, 4.7; HR 1.22; 95% CI 1.01, 1.46). The elevated CVD risk was primarily driven by stroke, peripheral arterial disease and CVD death. All-cause mortality showed no substantial difference. Conclusions/interpretation: Having a birthweight <3000 g is associated with higher CVD risk among patients with type 2 diabetes, driven primarily by risk of stroke and CVD death. Graphical Abstract: (Figure presented.)
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5.
  • Hansen, Mette, et al. (författare)
  • The female handball player
  • 2018. - 1
  • Ingår i: Handball Sports Medicine. - : Springer. - 9783662558911 - 9783662558928 ; , s. 553-570
  • Bokkapitel (refereegranskat)
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6.
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7.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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8.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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9.
  • Ostergaard, Henrik, et al. (författare)
  • Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide
  • 2011
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:8, s. 2333-2341
  • Tidskriftsartikel (refereegranskat)abstract
    • Current management of hemophilia B entails multiple weekly infusions of factor IX (FIX) to prevent bleeding episodes. In an attempt to make a longer acting recombinant FIX (rFIX), we have explored a new releasable protraction concept using the native N-glycans in the activation peptide as sites for attachment of polyethylene glycol (PEG). Release of the activation peptide by physiologic activators converted glycoPEGylated rFIX (N9-GP) to native rFIXa and proceeded with normal kinetics for FXIa, while the Km for activation by FVIIa-tissue factor (TF) was increased by 2-fold. Consistent with minimal perturbation of rFIX by the attached PEG, N9-GP retained 73%-100% specific activity in plasma and whole-blood-based assays and showed efficacy comparable with rFIX in stopping acute bleeds in hemophilia B mice. In animal models N9-GP exhibited up to 2-fold increased in vivo recovery and a markedly prolonged half-life in mini-pig (76 hours) and hemophilia B dog (113 hours) compared with rFIX (16 hours). The extended circulation time of N9-GP was reflected in prolonged correction of coagulation parameters in hemophilia B dog and duration of effect in hemophilia B mice. Collectively, these results suggest that N9-GP has the potential to offer efficacious prophylactic and acute treatment of hemophilia B patients at a reduced dosing frequency. (Blood. 2011; 118(8): 2333-2341)
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10.
  • Wedge, Eileen, et al. (författare)
  • Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia : Clinical and Molecular Genetic Prognostic Factors in a Nordic Population
  • 2021
  • Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:12, s. 991.e1-991.e9
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic myelomonocytic leukemia (CMML) is an aggressive disease in which survival after allogeneic hematopoietic stem cell transplantation (HCT) remains relatively poor. An assessment of prognostic factors is an important part of treatment decision making and has the potential to be greatly improved by the inclusion of molecular genetics. However, there is a significant knowledge gap in the interpretation of mutational patterns. This study aimed to describe outcomes of allogeneic HCT in patients with CMML in relation to clinical and molecular genetic risk factors. This retrospective study included 64 patients with CMML who underwent allogeneic HCT between 2008 and 2018, with a median follow-up of 5.4 years. Next-generation sequencing using targeted myeloid panels was carried out on saved material from 51 patients from the time of transplantation. Kaplan-Meier and Cox regression were used for analysis of overall survival (OS), and cumulative incidence with competing risks and Fine and Gray models were used for analysis of relapse and nonrelapse mortality (NRM). Mutations were detected in 48 patients (94%), indicating high levels of minimal residual disease (MRD) positivity at transplantation, even among those in complete remission (CR) (n = 14), 86% of whom had detectable mutations. The most frequently mutated genes were ASXL1 (37%), TET2 (37%), RUNX1 (33%), SRSF2 (26%), and NRAS (20%). Risk stratification using the CMML-specific Prognostic Scoring System molecular score (CPSS-Mol) resulted in 45% of patients moving to a higher risk-group compared with risk stratification using the CPSS. High leucocyte count (>= 13 x 10(9)/L), transfusion requirement, and previous intensive chemotherapy were associated with higher incidence of relapse. Being in CR was not linked to better outcomes. Neither ASXL1 nor RUNX1 mutation was associated with a difference in OS, relapse, or NRM, despite being high risk in the nontransplantation setting. TET2 mutations were associated with a significantly higher 3-year OS (73% versus 40%; P =.039). Achieving MRD-negative CR was rare in this CMML cohort, which may explain why we did not observe better outcomes for those in CR. This merits further investigation. Our analyses suggest that the negative impact of ASXL1 and RUNX1 mutations can be overcome by allogeneic HCT; however, risk stratification is complex in CMML and requires larger cohorts and multivariate models, presenting an ongoing challenge in this rare disease.
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11.
  • Ahmad, Shafqat, et al. (författare)
  • Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. : combined analysis of 111,421 individuals of European ancestry
  • 2013
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 9:7, s. 1003607-1003607
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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12.
  • Ahmad, Shafqat, et al. (författare)
  • Gene x physical activity interactions in obesity : combined analysis of 111,421 individuals of European ancestry
  • 2013
  • Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 9:7, s. e1003607-
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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13.
  • Anthonsen, Mette, 1972, et al. (författare)
  • Social democrats, unions and corporatism: Denmark and Sweden compared
  • 2011
  • Ingår i: Party Politics. - 1354-0688. ; 17:1, s. 118-134
  • Tidskriftsartikel (refereegranskat)abstract
    • A number of recent studies have documented weakening ties between social democratic parties and trade unions. This article is concerned with the effects of weakening party–union ties on policymaking. In many classic studies of corporatism it has been argued that this mode of policymaking depends on strong ties between social democratic parties and trade unions. In this article, we argue, in contrast, that strong party–union ties are potentially detrimental to corporatism, because in a polarized political environment unions may be tempted to exert political influence via political allies instead of bargaining with their counterparts. In order to evaluate this argument empirically, we present a detailed analysis of two countries with strong corporatist traditions (Denmark and Sweden) from the 1970s to the 1990s.
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14.
  • Anthonsen, Mette, et al. (författare)
  • Unions, Social Democrats, and Corporatism. Denmark and Sweden Compared
  • 2011
  • Ingår i: Party Politics. - : SAGE Publications. - 1460-3683 .- 1354-0688. ; 17:1, s. 118-134
  • Tidskriftsartikel (refereegranskat)abstract
    • A number of recent studies have documented weakening ties between social democratic parties and trade unions. This article is concerned with the effects of weakening party— union ties on policymaking. In many classic studies of corporatism it has been argued that this mode of policymaking depends on strong ties between social democratic parties and trade unions. In this article, we argue, in contrast, that strong party—union ties are potentially detrimental to corporatism, because in a polarized political environment unions may be tempted to exert political influence via political allies instead of bargaining with their counterparts. In order to evaluate this argument empirically, we present a detailed analysis of two countries with strong corporatist traditions (Denmark and Sweden) from the 1970s to the 1990s.
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15.
  • Bayona-Valderrama, Ángela, et al. (författare)
  • Water quality for citizen confidence: The implementation process of 2020 EU Drinking Water Directive in Nordic countries
  • Ingår i: Water Policy. - 1366-7017.
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Union Drinking Water Directive aims to protect human health and promote safe water consumption. The 2020 revision, Article 17 in particular, directed member states to provide public access to information on drinking water. This update was a response to citizen initiatives calling for the active participation of end-users in water services and greater transparency from water utilities. Difficulties implementing previous versions of the directive have highlighted divergences between policy purposes, local capacity to implement, and public response. These divergences are explored within eight case studies in Nordic countries and analysed using the policy implementation framework. We employed a mixed-method, multi-stage approach. Policy formulation was characterized through a literature review, policy design by the synthesis of legislative instruments, and policy implementation via an analysis of delivery behaviour based on interviews. We identified the main drivers of the directive’s update and contrast these with the ongoing implementation process in the countries of study. Our results point to a differential and highly contextual implementation, which differs from the primary drivers of the policy update, namely, the establishment of public confidence in water services.
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16.
  • Beaumont, Robin N, et al. (författare)
  • Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
  • 2023
  • Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
  • Tidskriftsartikel (refereegranskat)abstract
    • A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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17.
  • Bekoe, Samuel Oppong, et al. (författare)
  • Detection and quantification of antibiotic residues in urine samples of healthy individuals from rural and urban communities in Ghana using a validated SPE-LC-MS/MS method
  • 2020
  • Ingår i: SN APPLIED SCIENCES. - 2523-3963. ; 2:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of unregulated and inappropriate dispensing, and use of antibiotics remains significant in the development of antimicrobial resistance in infectious disease endemic regions of developing countries. The exposure to antibiotics from unfamiliar and unsuspecting sources such as drinking water and food, and adulterated herbal medicines remains a cause for concern. A sensitive SPE-LC-MS/MS method was developed and validated for the quantification and qualification of 12 antibiotics, including amoxicillin, clavulanic acid, metronidazole, ampicillin, cefuroxime, tetracycline, ceftriaxone, sulphamethoxazole, trimethoprim, ciprofloxacin, benzylpenicillin, and erythromycin, in the urine of healthy volunteers. The method was linear (r(2) > 0.98) within the concentration range 50-5000 ngmL(-1) for all the analytes. Instrument precision of 8-27% and 4-21% at 100 and 1000 ngmL(-1) levels were demonstrated. High mean recoveries between 71 and 125% with minimal variations were obtained for all compounds in the accuracy study. Limits of detection and quantification ranged between 70.3-271.0 ngmL(-1) and 213-821 ngmL(-1) respectively. The validated method successfully detected and quantified 9 of the 12 analytes, with the exception of clavulanic acid, cefuroxime, and benzylpenicillin. Most of the samples contained one analyte (52, 86.7%), with a handful containing two (7, 11.7%) and three analytes (1, 1.7%). Ciprofloxacin was the modal analyte detected (17, 24.6%), with amoxicillin and trimethoprim recording the average lowest (22.76 x 10(3) ngmL(-1)) and highest concentrations (255.47 x 10(3) ngmL(-1)) respectively. The developed method is a useful tool for non-invasive monitoring of consumption and the irrational use of antibiotics in microbial resistant-prone regions of the world.
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18.
  • Bekoe, Samuel Oppong, et al. (författare)
  • Detection and quantification of antibiotic residues in urine samples of healthy individuals from rural and urban communities in Ghana using a validated SPE-LC-MS/MS method
  • 2020
  • Ingår i: SN APPLIED SCIENCES. - : Springer Science and Business Media LLC. - 2523-3963 .- 2523-3971. ; 2:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of unregulated and inappropriate dispensing, and use of antibiotics remains significant in the development of antimicrobial resistance in infectious disease endemic regions of developing countries. The exposure to antibiotics from unfamiliar and unsuspecting sources such as drinking water and food, and adulterated herbal medicines remains a cause for concern. A sensitive SPE-LC-MS/MS method was developed and validated for the quantification and qualification of 12 antibiotics, including amoxicillin, clavulanic acid, metronidazole, ampicillin, cefuroxime, tetracycline, ceftriaxone, sulphamethoxazole, trimethoprim, ciprofloxacin, benzylpenicillin, and erythromycin, in the urine of healthy volunteers. The method was linear (r(2) > 0.98) within the concentration range 50-5000 ngmL(-1) for all the analytes. Instrument precision of 8-27% and 4-21% at 100 and 1000 ngmL(-1) levels were demonstrated. High mean recoveries between 71 and 125% with minimal variations were obtained for all compounds in the accuracy study. Limits of detection and quantification ranged between 70.3-271.0 ngmL(-1) and 213-821 ngmL(-1) respectively. The validated method successfully detected and quantified 9 of the 12 analytes, with the exception of clavulanic acid, cefuroxime, and benzylpenicillin. Most of the samples contained one analyte (52, 86.7%), with a handful containing two (7, 11.7%) and three analytes (1, 1.7%). Ciprofloxacin was the modal analyte detected (17, 24.6%), with amoxicillin and trimethoprim recording the average lowest (22.76 x 10(3) ngmL(-1)) and highest concentrations (255.47 x 10(3) ngmL(-1)) respectively. The developed method is a useful tool for non-invasive monitoring of consumption and the irrational use of antibiotics in microbial resistant-prone regions of the world.
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19.
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20.
  • Blomqvist, Jerker, et al. (författare)
  • Om ordbildning och ordbildningar
  • 1996
  • Ingår i: Hvad tales her om? 46 artikler om græsk-romersk kultur. Festskrift till Johnny Christensen i anledning af hans afsked som professor ved Københavns Universitet. - 8772894156 ; , s. 11-26
  • Bokkapitel (populärvet., debatt m.m.)
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21.
  • Cruz-Paredes, Carla, et al. (författare)
  • Wood ash application in a managed Norway spruce plantation did not affect ectomycorrhizal diversity or N retention capacity
  • 2019
  • Ingår i: Fungal Ecology. - : Elsevier BV. - 1754-5048. ; 39, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Ectomycorrhizal (ECM) fungi are key players in N cycling in coniferous forests, and forest management such as application of wood ash can affect their functionality. The aim of this study was to determine the effects of wood ash application on ECM fungal mycelial production, capacity to retain N, diversity and community composition. In-growth mesh bags were installed in control and treated plots. After 6 months, 15N labeled ammonium and nitrate were applied into the mesh bags, and 24 h later extramatrical mycelium (EMM) was extracted and analyzed. Wood ash had no effects on EMM in-growth, N retention capacity, diversity or community composition. In contrast, there were significant seasonal differences in the amount of EMM produced. These results demonstrate that applying up to 6 t ha−1 of wood ash in this type of plantation forest is a safe management practice that does not increase N leaching or negatively affect ECM fungi.
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22.
  • Daaland Wormdahl, Espen, et al. (författare)
  • Brannsikkerhet i bygg med massivtre
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • I dette prosjektet er det gjennomført et litteraturstudie på brannsikkerhet ved bruk av massivtre i bygninger.   Problemstillingene det ble jobbet med var temperaturforløp i en naturlig brann, selvslokking og forkullingshastighet. Ut fra litteraturstudiet konkluderer vi med at kunnskapen om brannsikkerhet i forbindelse med massivtre i bygninger er mangelfull.  Det er spesielt rundt problemstillinger knyttet til ubeskyttet massivtre, forkullingshastigheter, delaminering og selvslokking det er flere ubesvarte spørsmål, og dette er forhold som kan ha stor innvirkning på brannsikkerheten i bygninger.   Vi anbefaler at det utarbeides retningslinjer for hvordan anvendelse av massivtre skal håndteres i prosjektering og risikoanalyse for nye bygg
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23.
  • Dahl, Olav, et al. (författare)
  • Evaluation of the stage classification of anal cancer by the TNM 8th version versus the TNM 7th version
  • 2020
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 59:9, s. 1016-1023
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The UICC TNM 7th edition introduced stage groups for anal cancer which in 2019 has not yet come into general use. The new TNM 8th edition from 2016 defines 7 sub-stages. Background data for these changes are lacking. We aimed to investigate whether the new classification for anal cancer reliably predict the prognosis in the different stages.Patients and methods: The Nordic Anal Cancer Group (NOAC) conducted a large retrospective study of all anal cancers in Norway, Sweden and most of Denmark in 2000–2007. From the Nordic cohort 1151 anal cancer patients with follow-up data were classified by the TNM 4th edition which has identical T, N and M definitions as the TNM 7th edition, and therefore also can be classified by the TNM 7th stage groups. We used the Nordic cohort to translate the T, N and M stages into the TNM 8th stages and sub-stages. Overall survival for each stage was assessed.Results: Although the summary stage groups for TNM 8th edition discriminates patients with different prognosis reasonably well, the analyses of the seven sub-stages show overlapping overall survival: HR for stage IIA 1.30 (95%CI 0.80–2.12) is not significantly different from stage I (p = .30) and HR for stage IIB 2.35 (95%CI 1.40–3.95) and IIIA 2.48 (95%CI 1.43–4.31) are also similar as were HRs for stage IIIB 3.41 (95%CI 1.99–5.85) and IIIC 3.22 (95%CI 1.99–5.20). Similar overlapping was shown for local recurrence and distant spread.Conclusion: The results for the sub-stages calls for a revision of the staging system. We propose a modification of the TNM 8th edition for staging of anal cancer into four stages based on the T, N and M definitions of the TNM 8th classification.
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24.
  • Dam, Tine Vrist, et al. (författare)
  • Muscle Performance during the Menstrual Cycle Correlates with Psychological Well-Being, but Not Fluctuations in Sex Hormones
  • 2022
  • Ingår i: Medicine and Science in Sports and Exercise. - 0195-9131. ; 54, s. 1678-1689
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We aimed to study variations in strength and power performance during the menstrual cycle (MC) in eumenorrheic young women and during the pill cycle in oral contraceptives (OC) users. Methods: Forty healthy, normal-weight women between 18 and 35 yr (n = 30 eumenorrheic women; n = 10 OC users) completed this prospective cohort study. Seven to nine times during the MC/pill-cycle, the participants completed a physical performance test series, a questionnaire about psychological well-being, blood sampling, and determination of body mass. The physical tests included isometric handgrip strength, elbow flexor strength, countermovement jump (CMJ) height, and a 10-s Wingate bike test. Results: No direct correlation was observed between the variations in sex hormones and physical performance parameters. However, positive correlations were observed between physical performance outcomes and self-reported motivation, perception of own physical performance level, pleasure level, and arousal level. CMJ was 6% lower in the late luteal phase (LL) compared with the midluteal phase (ML) (P = 0.04). Wingate peak power was 3% lower in early follicular (EF) compared with the ML (P = 0.04). Furthermore, Wingate average power was 2%-5% lower in LL compared with all other MC phases. In line with these observations, physical pain was higher in EF and LL, and the pleasure level was lower in EF compared with the other MC phases. In OC users, we observed no variation in performance and self-reported parameters between the placebo-pill phase and the OC-pill phase. Conclusions: Impairments in CMJ and Wingate performance were observed at the end and start of MC compared with other MC phases, which were associated with lower psychological well-being, but not the sex hormone fluctuations.
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25.
  • de Valk, Harold W., et al. (författare)
  • Switching to Degludec is Associated with Reduced Hypoglycaemia, Irrespective of Definition Used or Patient Characteristics : Secondary Analysis of the ReFLeCT Prospective, Observational Study
  • 2020
  • Ingår i: Diabetes Therapy. - : Springer. - 1869-6953 .- 1869-6961. ; 11:9, s. 2159-2167
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Hypoglycaemia is a common side effect of insulin therapy; low or high glycated haemoglobin (HbA(1c)) levels, history of hypoglycaemia or long diabetes duration are known modifiers of hypoglycaemia risk. In randomised clinical trials, lower rates of hypoglycaemia have been observed with the new-generation insulin analogue, long-acting insulin degludec, compared with other basal insulins.Methods: The ReFLeCT study was a prospective observational study over 12 months. Patient-reported diary data on hypoglycaemia were collected from patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) who were switching from other basal insulins to insulin degludec (degludec) at their physician's discretion in routine clinical care. Two secondary analyses were undertaken to investigate the change in number of hypoglycaemic events: a post hoc analysis using the updated American Diabetes Association (ADA) level 1, 2 and 3 hypoglycaemia definitions, and a pre-specified analysis using patient characteristics (baseline HbA(1c), diabetes duration, and physician's rationale for initiating degludec).Results: Switching to degludec was associated with significantly fewer hypoglycaemic events for all definitions in T1D, and level 1 and 2 in T2D (too few level 3 events for statistical comparison). Moreover, patient characteristics did not influence the observed reduction in hypoglycaemia in T1D and T2D.Conclusion: These results demonstrate that switching to degludec from other basal insulins was associated with reduced rates of hypoglycaemia, irrespective of the definition used or baseline patient characteristics.Plain Language Summary: Low blood sugar levels (hypoglycaemia) are a common, and sometimes serious, side effect of treatment with insulin in people with diabetes. In the ReFleCT study, adults with type 1 (T1D) and type 2 diabetes (T2D) were asked to complete a diary for 12 months when their doctor changed their previous long-acting insulin treatment to insulin degludec (degludec). The key outcome of the study was whether the frequency of hypoglycaemia changed when a patient's insulin treatment was switched. Here, we used the diary information from the ReFLeCT study to investigate whether the change in the rate of hypoglycaemia was related to the way hypoglycaemia was defined, or to patients' characteristics at the time their insulin was switched. These characteristics included the length of time that patients had had diabetes, their blood sugar control, and their doctor's reason for changing their medication. Our findings showed that the way hypoglycaemia was defined, and patients' characteristics, did not generally influence the frequency of hypoglycaemia for patients with T1D or T2D. However, the most severe hypoglycaemia in patients with T2D occurred too infrequently to be assessed. Patients in all groups had less hypoglycaemia overall after switching compared with their previous treatment, suggesting that degludec may be a treatment option for a broad range of patients with diabetes.
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26.
  • Domazet, Sidsel L., et al. (författare)
  • Low-grade inflammation in persons with recently diagnosed type 2 diabetes : The role of abdominal adiposity and putative mediators
  • Ingår i: Diabetes, Obesity and Metabolism. - 1462-8902.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. Materials and Methods: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. Results: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%–25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%–7%) and high triglyceride levels (2%–6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%–2%). Conclusions: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%–40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.
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27.
  • Eriksen, Anne Kirstine, et al. (författare)
  • A lifestyle intervention among elderly men on active surveillance for non-aggressive prostate cancer: a randomised feasibility study with whole-grain rye and exercise.
  • 2017
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215 .- 1745-6215. ; 18:1, s. 20-
  • Tidskriftsartikel (refereegranskat)abstract
    • The prognosis for men with non-aggressive prostate cancer is good, and several studies have investigated the impact of lifestyle changes including physical activity and diet on the prognosis. Despite positive results in animal studies and a few human interventions with whole-grain rye on markers of prostate cancer progression, the feasibility of trials investigating such dietary changes in combination with physical activity remains largely unstudied. The primary aim was to investigate the feasibility of an intervention with high whole-grain rye intake and vigorous physical activity for 6 months in men diagnosed with prostate cancer.
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28.
  • Eskelund, Christian W., et al. (författare)
  • TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy
  • 2017
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
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29.
  • Fadini, Gian Paolo, et al. (författare)
  • Switching to Degludec from Other Basal Insulins is Associated with Reduced Hypoglycemia Rates : a Prospective Study
  • 2019
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 104:12, s. 5977-5990
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Observational studies of insulin degludec (degludec) with hypoglycemia events prospectively recorded are lacking.OBJECTIVE: To evaluate the safety and effectiveness of degludec in patients with type 1 (T1D) or type 2 diabetes (T2D) switching from other basal insulins in routine care.DESIGN: ReFLeCT was a multinational, multicenter, prospective, observational, single-arm study comprising a 4-week baseline period (pre-switch basal insulin) and 12-month follow-up (degludec).SETTING: Routine clinical practice. Patients or Other Participants: Insulin-treated patients (≥18 years) with T1D (n=556) or T2D (n=611) with treatment plans to initiate degludec.INTERVENTIONS: Switching to degludec from other basal insulins.MAIN OUTCOME MEASURE(S): Change from baseline in number of overall hypoglycemic events recorded in patient diaries.RESULTS: In T1D, the 12-month follow-up/baseline rate ratios [95% CI] of overall (0.80 [0.74;0.88]), non-severe (0.83 [0.76;0.91]), severe (0.28 [0.14;0.56]) and nocturnal (0.61 [0.50;0.73]) hypoglycemia suggested significantly reduced hypoglycemia rates with degludec (all P<0.001). At 12 months, HbA1c, fasting plasma glucose (FPG) and basal insulin dose decreased significantly. Body weight increased and treatment satisfaction improved significantly. In T2D, the hypoglycemia rate ratios were: overall (0.46 [0.38;0.56]), non-severe (0.53 [0.44;0.64]) and nocturnal (0.35 [0.20;0.62]) (all P<0.001; too few events for analysis of severe). At 12 months, HbA1c and FPG decreased significantly. Body weight and insulin doses remained unchanged, and treatment satisfaction was significantly improved.CONCLUSIONS: In a routine clinical care setting, switching to degludec from other basal insulins was associated with significantly reduced rates of hypoglycemia, improved glycemic control, and treatment satisfaction in patients with T1D or T2D.
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30.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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31.
  • Flentie, Kelly, et al. (författare)
  • Chemical disarming of isoniazid resistance in Mycobacterium tuberculosis
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : The National Academy of Scionces of the United States of America. - 0027-8424 .- 1091-6490. ; 116:21, s. 10510-10517
  • Tidskriftsartikel (refereegranskat)abstract
    • Mycobacterium tuberculosis (Mtb) killed more people in 2017 than any other single infectious agent. This dangerous pathogen is able to withstand stresses imposed by the immune system and tolerate exposure to antibiotics, resulting in persistent infection. The global tuberculosis (TB) epidemic has been exacerbated by the emergence of mutant strains of Mtb that are resistant to frontline antibiotics. Thus, both phenotypic drug tolerance and genetic drug resistance are major obstacles to successful TB therapy. Using a chemical approach to identify compounds that block stress and drug tolerance, as opposed to traditional screens for compounds that kill Mtb, we identified a small molecule, C10, that blocks tolerance to oxidative stress, acid stress, and the frontline antibiotic isoniazid (INH). In addition, we found that C10 prevents the selection for INH-resistant mutants and restores INH sensitivity in otherwise INH-resistant Mtb strains harboring mutations in the katG gene, which encodes the enzyme that converts the prodrug INH to its active form. Through mechanistic studies, we discovered that C10 inhibits Mtb respiration, revealing a link between respiration homeostasis and INH sensitivity. Therefore, by using C10 to dissect Mtb persistence, we discovered that INH resistance is not absolute and can be reversed.
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32.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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33.
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34.
  • Gedebjerg, Anne, et al. (författare)
  • CRP, C-Peptide, and Risk of First-Time Cardiovascular Events and Mortality in Early Type 2 Diabetes : A Danish Cohort Study
  • 2023
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:5, s. 1037-1045
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the relationship between hs-CRP, a marker of low-grade inflam-mation, alone or in combination with C-peptide, a marker of hyperinsulinemia/ insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-peptide (n = 5,765) in the prospective Danish Centre for Strategic Research in Type 2 Diabetes cohort study. Patients with no prior CVE (n = 6,407) were followed until first myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and all patients (n = 7,301) were followed for all-cause mortality. We com-puted adjusted hazard ratios (aHRs) by Cox regression and tested for the interaction between hs-CRP and C-peptide. RESULTS During follow-up (median 4.8 years), high (>3 mg/L) versus low (<1 mg/L) hs-CRP was associated with increased CVE risk (aHR 1.45 [95% CI 1.07–1.96]) and with even greater risk of all-cause mortality (2.47 [1.88–3.25]). Compared with patients with low hs-CRP (£3 mg/L) and low C-peptide (<1,470 pmol/L), those with high lev-els of both biomarkers had the highest CVE (1.61 [1.10–2.34]) and all-cause mortality risk (2.36 [1.73–3.21]). Among patients with high C-peptide, risk of CVEs did not differ by low or high hs-CRP, whereas risk of all-cause mortality did. CONCLUSIONS The finding of high hs-CRP as a stronger prognostic biomarker of all-cause mortality than of CVEs may facilitate improved early detection and prevention of deadly diseases besides CVEs. Conversely, elevated C-peptide as a strong CVE biomarker sup-ports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention.
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35.
  • Geelen, Inge G. P., et al. (författare)
  • Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response : clinical and immunological effects
  • 2023
  • Ingår i: Annals of Hematology. - : Springer. - 0939-5555 .- 1432-0584. ; 102:6, s. 1395-1408
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile.
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36.
  • Gejl, Kasper D., et al. (författare)
  • Changes in metabolism but not myocellular signaling by training with CHO-restriction in endurance athletes
  • 2018
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:17
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbohydrate (CHO) restricted training has been shown to increase the acute training response, whereas less is known about the acute effects after repeated CHO restricted training. On two occasions, the acute responses to CHO restriction were examined in endurance athletes. Study 1 examined cellular signaling and metabolic responses after seven training-days including CHO manipulation (n = 16). The protocol consisted of 1 h high-intensity cycling, followed by 7 h recovery, and 2 h of moderate-intensity exercise (120SS). Athletes were randomly assigned to low (LCHO: 80 g) or high (HCHO: 415 g) CHO during recovery and the 120SS. Study 2 examined unaccustomed exposure to the same training protocol (n = 12). In Study 1, muscle biopsies were obtained at rest and 1 h after 120SS, and blood samples drawn during the 120SS. In Study 2, substrate oxidation and plasma glucagon were determined. In Study 1, plasma insulin and proinsulin C-peptide were higher during the 120SS in HCHO compared to LCHO (insulin: 0 min: +37%; 60 min: +135%; 120 min: +357%, P = 0.05; proinsulin C-peptide: 0 min: +32%; 60 min: +52%; 120 min: +79%, P = 0.02), whereas plasma cholesterol was higher in LCHO (+15-17%, P = 0.03). Myocellular signaling did not differ between groups. p-AMPK and p-ACC were increased after 120SS (+35%, P = 0.03; +59%, P = 0.0004, respectively), with no alterations in p-p38, p-53, or p-CREB. In Study 2, glucagon and fat oxidation were higher in LCHO compared to HCHO during the 120SS (+26-40%, P = 0.03; +44-76%, P = 0.01 respectively). In conclusion, the clear respiratory and hematological effects of CHO restricted training were not translated into superior myocellular signaling after accustomization to CHO restriction.
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37.
  • Gejl, Kasper Degn, et al. (författare)
  • No Superior Adaptations to Carbohydrate Periodization in Elite Endurance Athletes
  • 2017
  • Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 49:12, s. 2486-2497
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The present study investigated the effects of periodic carbohydrate (CHO) restriction on endurance performance and metabolic markers in elite endurance athletes. Methods Twenty-six male elite endurance athletes (maximal oxygen consumption (VO2max), 65.0 mL O(2)kg(-1)min(-1)) completed 4 wk of regular endurance training while being matched and randomized into two groups training with (low) or without (high) CHO manipulation 3 dwk(-1). The CHO manipulation days consisted of a 1-h high-intensity bike session in the morning, recovery for 7 h while consuming isocaloric diets containing either high CHO (414 2.4 g) or low CHO (79.5 1.0 g), and a 2-h moderate bike session in the afternoon with or without CHO. VO2max, maximal fat oxidation, and power output during a 30-min time trial (TT) were determined before and after the training period. The TT was undertaken after 90 min of intermittent exercise with CHO provision before the training period and both CHO and placebo after the training period. Muscle biopsies were analyzed for glycogen, citrate synthase (CS) and -hydroxyacyl-coenzyme A dehydrogenase (HAD) activity, carnitine palmitoyltransferase (CPT1b), and phosphorylated acetyl-CoA carboxylase (pACC). Results The training effects were similar in both groups for all parameters. On average, VO2max and power output during the 30-min TT increased by 5% +/- 1% (P < 0.05) and TT performance was similar after CHO and placebo during the preload phase. Training promoted overall increases in glycogen content (18% +/- 5%), CS activity (11% +/- 5%), and pACC (38% +/- 19%; P < 0.05) with no differences between groups. HAD activity and CPT1b protein content remained unchanged. Conclusions Superimposing periodic CHO restriction to 4 wk of regular endurance training had no superior effects on performance and muscle adaptations in elite endurance athletes.
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38.
  • Gunnarsdottir, Maria J., et al. (författare)
  • Implementing risk-based approaches to improve drinking water quality in small water supplies in the Nordic region – barriers and solutions
  • 2023
  • Ingår i: Journal of Water and Health. - 1477-8920. ; 21:12, s. 1747-1760
  • Tidskriftsartikel (refereegranskat)abstract
    • Small water supplies face similar problems worldwide, regardless of ownership or management type. Non-compliance with water quality regulations is more frequent in small supplies than in large ones, as are waterborne disease outbreaks. The new EU Drinking Water Directive requires risk-based approach (RBA) to secure water safety as is recommended in the WHO's Guidelines for drinking water quality through ‘water safety plans’. This is already in regulation in the Nordic countries, although less used in small supplies. In this research, we explore the challenges, barriers and possible solutions to implementing RBA and improving compliance in small supplies. This was achieved by conducting and analysing interviews with 53 stakeholders from all 8 Nordic countries to produce recommendations for action by the different implicated actors. Our findings suggest the centrality of governmental policy, including support for continuous training, provision of simple RBA guidelines and increasing cooperation in the water sector. The Nordic experience reflects global challenges with small water supplies and the trend towards systematic preventive management epitomized in the framework for drinking water safety advocated by the World Health Organization since 2004.
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39.
  • Gunnarsdottir, Maria J., et al. (författare)
  • Status of risk-based approach and national framework for safe drinking water in small water supplies of the Nordic water sector
  • 2020
  • Ingår i: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1438-4639. ; 230
  • Tidskriftsartikel (refereegranskat)abstract
    • Reliable safe water supply is a pillar of society and a key to public health. The Nordic countries have an abundance of clean fresh water as a source for drinking water supplies. They have followed developments in safeguarding water, both the recommendations of the World Health Organization framework for safe drinking water and European legislation. Worldwide, including the Nordic countries, small water supplies are less compliant with water safety regulation. The forthcoming EU directive on drinking water require risk-based approaches and improved transparency on water quality. This research looks at the Nordic frameworks for safe water supply, with emphasis on risk-based approaches and smaller systems. We analyzed the legal frameworks for safe water, the structure of the water sector across the Nordic countries and explored how prepared these countries are to meet these requirements. Our findings show that, while legal requirements are mostly in place, delivery of information to the public needs to be improved. Most Nordic countries are in the process of implementing risk-based management in large and medium size water supplies, whereas small supplies are lagging. We conclude that a key to success is increased training and support for small supplies. We suggest wider adoption of the Nordic model of cooperation with benchmarking of safe water for all to transfer knowledge between the countries. This work provides insights into challenges and opportunities for the Nordic countries and provides insights relevant to countries worldwide in their effort towards realization of SDG Target 6.1.
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40.
  • Hærvig, Katia Keglberg, et al. (författare)
  • Paternal pre-conceptional smoking and semen quality in the adult son
  • Ingår i: Andrology. - 2047-2919.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Growing evidence suggests intergenerational effects of paternal pre-conceptional smoking through the germ line, but its specific impact on offspring semen quality remains uncertain because of challenges in isolating paternal exposure from maternal passive smoking or underreporting. Methods: We reran previous analyses estimating differences in semen parameters and testicular size according to paternal smoking in 867 young adult men, adding first-trimester maternal plasma cotinine to the original adjustment for maternal self-reported smoking. We also estimated differences in sperm DNA fragmentation. Paternal smoking was reported by the pregnant women around gestational week 16. Analyses were additionally adjusted for household occupational status, parental ages at birth, maternal pre-pregnancy body mass index and alcohol consumption, and abstinence time, and accounted for spillage, minutes from ejaculation to analysis, and son's own smoking. Results: We found no association between paternal preconceptional smoking and any of the semen parameters or testicular size. Adjustment for son's own smoking did not change results. Discussion: While maternal plasma cotinine offers an objective measure of tobacco exposure and allows for a more thorough adjustment of maternal smoking, the high correlation between paternal pre-conceptional smoking and maternal cotinine exposure may, have resulted in overadjustment removing some paternal effect. Inability to distinguish between paternal never smokers and former smokers, may have led to misclassification of paternal pre-conceptional smoking and underestimation of associations. Conclusion: We found no support for an independent association between paternal pre-conceptional smoking and semen quality in young adult sons, but studies with more detailed paternal smoking history are needed before firm conclusions can be drawn.
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41.
  • Hansen, Karoline Kærgaard, et al. (författare)
  • Exposure levels of dust, endotoxin, and microorganisms in the Danish recycling industry
  • 2023
  • Ingår i: Annals of Work Exposures and Health. - 2398-7308 .- 2398-7316. ; 67:7, s. 816-830
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Recycling of domestic waste and a number of employees in the recycling industry is expected to increase. This study aims to quantify current exposure levels of inhalable dust, endotoxin, and microorganisms and to identify determinants of exposure among recycling workers. Methods: This cross-sectional study included 170 full-shift measurements from 88 production workers and 14 administrative workers from 12 recycling companies in Denmark. The companies recycle domestic waste (sorting, shredding, and extracting materials from waste). We collected inhalable dust with personal samplers that were analysed for endotoxin (n = 170) and microorganisms (n = 101). Exposure levels of inhalable dust, endotoxin, and microorganisms and potential determinants of exposure were explored by mixed-effects models. Results: The production workers were 7-fold or higher exposed to inhalable dust, endotoxin, bacteria, and fungi than the administrative workers. Among production workers recycling domestic waste, the geometric mean exposure level was 0.6 mg/m3 for inhalable dust, 10.7 endotoxin unit (EU)/m3 for endotoxin, 1.6 × 104 colony forming units (CFU)/m³ of bacteria, 4.4 × 104 CFU/m³ of fungi (25 °C), and 1.0 × 103 CFU/m³ of fungi (37 °C). Workers handling paper or cardboard had higher exposure levels than workers handling other waste fractions. The temperature did not affect exposure levels, although there was a tendency toward increased exposure to bacteria and fungi with higher temperatures. For inhalable dust and endotoxin, exposure levels during outdoor work were low compared to indoor work. For bacteria and fungi, indoor ventilation decreased exposure. The work task, waste fraction, temperature, location, mechanical ventilation, and the company size explained around half of the variance of levels of inhalable dust, endotoxin, bacteria, and fungi. Conclusion: The production workers of the Danish recycling industry participating in this study had higher exposure levels of inhalable dust, endotoxin, bacteria, and fungi than the administrative workers. Exposure levels of inhalable dust and endotoxin among recycling workers in Denmark were generally below established or suggested occupational exposure limits (OEL). However, 43% to 58% of the individual measurements of bacteria and fungi were above the suggested OEL. The waste fraction was the most influential determinant for exposure, and the highest exposure levels were seen during handling paper or cardboard. Future studies should examine the relationship between exposure levels and health effects among workers recycling domestic waste.
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42.
  • Hansen, Mette, et al. (författare)
  • Effect of Whey Protein Hydrolysate on Performance and Recovery of Top-Class Orienteering Runners.
  • 2015
  • Ingår i: International Journal of Sport Nutrition & Exercise Metabolism. - : Human Kinetics. - 1526-484X .- 1543-2742. ; 25:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This trial aimed to examine the effect of whey protein hydrolysate intake before and after exercise sessions on endurance performance and recovery in elite orienteers during a training camp. Eighteen elite orienteers participated in a randomized controlled intervention trial during a 1-week training camp (13 exercise sessions). Half of the runners (PRO-CHO) ingested a protein drink before (0.3 g kg−1) and a protein-carbohydrate drink after (0.3 g protein kg−1 and 1 g carbohydrate kg−1) each exercise session. The others ingested energy and timematched carbohydrate drinks (CHO). A 4-km run-test with 20 control points was performed before and on the last day of the intervention. Blood and saliva were obtained in the mornings, before and after run-tests, and after the last training session. During the intervention, questionnaires were fulfilled regarding psychological sense of performance capacity and motivation. PRO-CHO and not CHO improved performance in the 4-km run-test (interaction p < .05). An increase in serum creatine kinase was observed during the week, which was greater in CHO than PRO-CHO (interactionp < .01). Lactate dehydrogenase (p < .001) and cortisol (p = .057) increased during the week, but the change did not differ between groups. Reduction in sense of performance capacity during the intervention was greater in CHO (p < .05) than PRO-CHO. In conclusion, ingestion of whey protein hydrolysate before and after each exercise session improves performance and reduces markers of muscle damage during a strenuous 1-week training camp. The results indicate that protein supplementation in conjunction with each exercise session facilitates the recovery from strenuous training in elite orienteers.
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43.
  • Hedberg Nyqvist, Kerstin, et al. (författare)
  • Expansion of the Ten Steps to Successful Breastfeeding into Neonatal Intensive Care: Expert Group Recommendations for Three Guiding Principles
  • 2012
  • Ingår i: Journal of Human Lactation. - : SAGE Publications. - 0890-3344 .- 1552-5732. ; 28:3, s. 289-296
  • Tidskriftsartikel (refereegranskat)abstract
    • The World Health Organization/United Nations Children's Fund Baby-Friendly Hospital Initiative: Revised, Updated, and Expanded for Integrated Care (2009) identifies the need for expanding the guidelines originally developed for maternity units to include neonatal intensive care. For this purpose, an expert group from the Nordic countries and Quebec, Canada, prepared a draft proposal, which was discussed at an international workshop in Uppsala, Sweden, in September 2011. The expert group suggests the addition of 3 "Guiding Principles" to the Ten Steps to support this vulnerable population of mothers and infants: 1. The staff attitude to the mother must focus on the individual mother and her situation. 2. The facility must provide family-centered care, supported by the environment. 3. The health care system must ensure continuity of care, that is, continuity of pre-, peri-, and postnatal care and post-discharge care. The goal of the expert group is to create a final document, the Baby Friendly Hospital Initiative for Neonatal Units, including standards and criteria for each of the 3 Guiding Principles, Ten Steps, and the Code; to develop tools for self-appraisal and monitoring compliance with the guidelines; and for external assessment to decide whether neonatal intensive/intermediate care units meet the conditions required to be designated as Baby-Friendly. The documents will be finalized after consultation with the World Health Organization/United Nations Children's Fund, and the goal is to offer these documents to international health care, professional, and other nongovernmental organizations involved in lactation and breastfeeding support for mothers of infants who require special neonatal care.
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44.
  • Hesselkilde, Eva Zander, et al. (författare)
  • Longitudinal study of electrical, functional and structural remodelling in an equine model of atrial fibrillation
  • 2019
  • Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model. Method: Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups. Results: AFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed. Conclusion: Horses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.
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45.
  • Huuhtanen, Jani, et al. (författare)
  • IFN-alfa with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia
  • 2022
  • Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 132:17
  • Tidskriftsartikel (refereegranskat)abstract
    • In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-alpha is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-alpha in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR beta sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8(+) recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-alpha reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-alpha had costimulatory effects on TCR signaling. Our work supports the combination of IFN-alpha with TKI therapy, as IFN-alpha broadens the immune repertoire and restores immunological function.
  •  
46.
  • Huuhtanen, Jani, et al. (författare)
  • Single-cell analysis of immune recognition in chronic myeloid leukemia patients following tyrosine kinase inhibitor discontinuation
  • 2024
  • Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 38, s. 109-125
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 single-cell RNA and T cell receptor (TCR) sequenced samples (scRNA+TCRαβ-seq) from patients with CML (n = 13, N = 25), other cancers (n = 28), and healthy (n = 7). The high number and active phenotype of natural killer (NK) cells in CML separated them from healthy and other cancers. Most NK cells in CML belonged to the active CD56dim cluster with high expression of GZMA/B, PRF1, CCL3/4, and IFNG, with interactions with leukemic cells via inhibitory LGALS9-TIM3 and PVR-TIGIT interactions. Accordingly, upregulation of LGALS9 was observed in CML target cells and TIM3 in NK cells when co-cultured together. Additionally, we created a classifier to identify TCRs targeting leukemia-associated antigen PR1 and quantified anti-PR1 T cells in 90 CML and 786 healthy TCRβ-sequenced samples. Anti-PR1 T cells were more prevalent in CML, enriched in bone marrow samples, and enriched in the mature, cytotoxic CD8+TEMRA cluster, especially in a patient maintaining TFR. Our results highlight the role of NK cells and anti-PR1 T cells in anti-leukemic immune responses in CML.
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47.
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48.
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49.
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50.
  • Jacobsen, Carsten Suhr, et al. (författare)
  • Inter-laboratory testing of the effect of DNA blocking reagent G2 on DNA extraction from low-biomass clay samples
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we show that a commercial blocking reagent (G2) based on modified eukaryotic DNA significantly improved DNA extraction efficiency. We subjected G2 to an inter-laboratory testing, where DNA was extracted from the same clay subsoil using the same batch of kits. The inter-laboratory extraction campaign revealed large variation among the participating laboratories, but the reagent increased the number of PCR-amplified16S rRNA genes recovered from biomass naturally present in the soils by one log unit. An extensive sequencing approach demonstrated that the blocking reagent was free of contaminating DNA, and may therefore also be used in metagenomics studies that require direct sequencing.
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