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"Olesen, Jesper"
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What can we learn from a peer review?
2021
The quality assurance of research articles is based on a widespread reliance on peer review, which has gradually become black boxed, as the way to do it. By opening the black box, it turns out that this form of quality assurance varies a great deal. This article looks at the comments offered by peer reviewers and treats them as an important but overlooked element of the methodological circle and science production. Based on an auto-ethnographical study of one manuscript that undergoes peer reviewing in three different journals the article examines how the review comments affect the author and hence promote/inhibit the becoming of a research article. The article offers a transmethodological look at peer review by employing concepts from actor-network theory. This allows for a theoretical move from notions of single authorship to notions of writing as a performance of relations between heterogeneous actors. The analysis aims to identify the connections that are established between the manuscript and other actors such as scientific standards for good research, journals’ aim and scope, universities’ requirements for staff publication, peer reviewer’s personal academic interests etc. which all become part of a peer review network. In conclusion, the article suggests acknowledging the relational and co-productive aspect of peer reviewing as an important part of quality assurance of scientific knowledge.
Journal Article
Coverage rates of the children vaccination programme in Greenland
by
Skovgaard, Nils
,
Pedersen, Michael Lynge
,
Albertsen, Nadja
in
arctic
,
Child
,
Child, Preschool
2020
In order to estimate the current coverage rate among all children in Greenland, we conducted an observational cross-sectional study identifying all children in Greenland eligible for a vaccination between 1 March 2018 and 16 June 2019. we found an overall national coverage of 85.4%. The national coverage for the vaccinations given at birth was 97.1%, dropping to 94.3%, 87.7% and 83.6% at ages 3, 5 and 12 months. Among children eligible for the Measles, Mumps and Rubella-vaccinations, the national coverage was 76.9% for children aged 15 months and 64.1% for children aged 4 years, but dropping to 40.9% in the districts. At preschool, the national coverage was 79.9%. Among the 12-year-old, the national coverages of the two vaccinations against Human Papilloma Virus were 88.4% and 71.6%, respectively, and for the three Hepatitis B-vaccinations 89.8%, 84.1% and 69.6%. A subgroup-analysis and test of an SMS-reminder system in Nuuk improved the coverage from 57.8% to 75.5% locally. Overall, we found a high national coverage rate among the newborn in Greenland. The national coverage rates of the remaining vaccinations were below the WHO-recommendations, however with great regional differences.
Abbreviations: CVP: Children Vaccination Programme; BCG: Bacille Calmette-Guerin; EMR: Electronic medical Record system; DTPHiB: Diphtheria, Tetanus, Pertussis, Polio, Haemophilus influenza B; HBV: Hepatitis B; HPV: Human Papilloma Virus; MMR: Measles, Mumps, Rubella; SMS: Short Text Message; WHO: World Health Organization; GVAP: Global Vaccine Action Plan; EVAP: The WHO European Vaccine Action Plan.
Journal Article
Skeletal Muscle PGC-1α Is Required for Maintaining an Acute LPS-Induced TNFα Response
by
Larsson, Signe
,
Pilegaard, Henriette
,
Iversen, Ninna
in
Animals
,
Anti-inflammatory agents
,
Antiinflammatory agents
2012
Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor γ coactivator (PGC)-1α has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1α in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1α knockout (KO), muscle specific PGC-1α KO (MKO) and muscle-specific PGC-1α overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 µg LPS/g body weight or saline. Basal TNFα mRNA content was lower in skeletal muscle of whole body PGC-1α KO mice and in accordance TG mice showed increased TNFα mRNA and protein level relative to WT, indicating a possible PGC-1α mediated regulation of TNFα. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFα expression in these mice. Systemically, TG mice had reduced basal plasma TNFα levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFα levels as WT and showed more marked induction in plasma TNFα than WT after LPS injection, MKO PGC-1α mice had a reduced plasma TNFα and skeletal muscle TNFα mRNA response to LPS. In conclusion, the present findings suggest that PGC-1α enhances basal TNFα expression in skeletal muscle and indicate that PGC-1α does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1α seems however to impair the acute TNFα response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients.
Journal Article
Gestational diabetes and macrosomia among Greenlanders. Time to change diagnostic strategy?
by
Pedersen, Michael Lynge
,
Abelsen, Trine
,
Lind, Ole
in
Adult
,
Alcohol Drinking - epidemiology
,
Arctic Regions - epidemiology
2018
Gestational diabetes mellitus (GDM) is a serious condition associated to both maternal and offspring complications. Yet, no globally accepted consensus exists on how to test and diagnose GDM. In Greenland, the clinical criteria for testing and diagnosing GDM are adapted from Danish guidelines. The aim of this study was to estimate the prevalence of GDM among Greenlanders using both the current clinical GDM criteria and the recent WHO 2013 criteria and, further, to study the association between GDM, pre-pregnant overweight or obesity and macrosomia. A cross-sectional study of all 450 Greenlandic women who gave birth to a singleton in Nuuk within 1 year was performed. Based on an oral glucose tolerance test measuring capillary whole blood glucose, 119 women were categorised as having clinical GDM, WHO 2013 GDM or not GDM. Macrosomia defined as birth weight above 4,000 g was used as outcome variable. The prevalence of clinical GDM and WHO 2013 GDM was 0.4% (95% CI; 0-1.1) and 6.9% (95% CI; 4.5-9.2). WHO 2013 GDM, fasting blood glucose, pre-pregnant maternal overweight and obesity were associated with macrosomia. WHO 2013 GDM criteria were superior to clinical criteria in predicting macrosomia indicating that it may be time to consider the diagnostic strategy used in Greenland. Pre-pregnant overweight may also need more intensified lifestyle-intervention.
Abbreviations: GDM: Gestational diabetes mellitus; VP: venous plasma; CWB: capillary whole blood; OGTT: oral glucose tolerance test; WHO: World Health Organisation; FIGO: The International Federation of Gynaecology and Obstetrics; BMI: body mass index; GA: gestational age
Journal Article
PGC-1α-mediated adaptations in skeletal muscle
by
Kiilerich, Kristian
,
Pilegaard, Henriette
,
Olesen, Jesper
in
Adaptation
,
Antioxidants
,
Biomedical and Life Sciences
2010
Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each single exercise, but how is this regulated? A potential candidate in this is the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, which has been identified as a master regulator of mitochondrial biogenesis, but also been shown to regulate proteins involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1α transcription and potentially PGC-1α activity through post-translational modifications, and concomitant PGC-1α-mediated gene regulation is suggested to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1α-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise training, and describes functional significance of PGC-1α-mediated effects in skeletal muscle. In addition, regulation of PGC-1α expression and activity in skeletal muscle is described. The impact of changes in PGC-1α expression in mouse skeletal muscle and the ability of PGC-1α to regulate multiple pathways and functions underline the potential importance of PGC-1α in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1α-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle and concomitant impaired metabolism.
Journal Article
Gestational diabetes mellitus in Greenland: a national study of prevalence and testing efficacy
by
Pedersen, Michael Lynge
,
Damm, Peter
,
Jørgensen, Marit Eika
in
Adult
,
Births
,
Cross-Sectional Studies
2016
Within the last 20 years, the prevalence of gestational diabetes mellitus (GDM) has been reported to be increasing worldwide in correlation with ethnic and geographic variations. The actual prevalence of GDM throughout all of Greenland remains unknown.
The aim of this study was to estimate the prevalence of GDM among Greenlanders and non-Greenlanders living in Greenland and to estimate the efficacy of testing for GDM.
This study was performed as an observational, cross-sectional study including all women with permanent address in Greenland who had given birth to a singleton during 2014. The prevalence of GDM was calculated as the proportion of all pregnant women tested with a 75-g 2-h glucose tolerance test who had a 2-h capillary whole-blood glucose value of 8.5 mmol/l or above. Testing efficacy was calculated as the proportion of women who fulfilled the testing criteria who were actually tested in Greenland in 2014.
A total of 794 women (727 Greenlanders and 67 non-Greenlanders) were included in the study. The prevalence of GDM among tested women was 3.3% (confidence interval, CI: 0.9-5.6) among Greenlanders and 12.5% (CI: 0-25.7) among non-Greenlanders, corresponding, respectively, to 1.0% (CI: 0.3-1.3) and 4.5% (CI: 0-9.4) of all singleton pregnancies in Greenland in 2014. The overall testing efficacy was 69.0% among all eligible residents of Greenland and 85.1% among eligible residents in the capital city, Nuuk.
In conclusion, the prevalence of GDM seems quite low in Greenland. Although diagnostic testing activity has improved within the last 6 years, still around one-third of all pregnant women in all Greenland fulfilling the testing criteria were not tested. Universal testing for GDM may be needed to improve testing of GDM in Greenland.
Journal Article
Mechanisms behind the superior effects of interval vs continuous training on glycaemic control in individuals with type 2 diabetes: a randomised controlled trial
by
Scheel, Maria M.
,
Holst, Jens J.
,
Pedersen, Bente K.
in
Biological and medical sciences
,
Blood Glucose - drug effects
,
Diabetes
2014
Aims/hypothesis
By use of a parallel and partly crossover randomised, controlled trial design we sought to elucidate the underlying mechanisms behind the advantageous effects of interval walking training (IWT) compared with continuous walking training (CWT) on glycaemic control in individuals with type 2 diabetes. We hypothesised that IWT, more than CWT, would improve insulin sensitivity including skeletal muscle insulin signalling, insulin secretion and disposition index (DI).
Methods
By simple randomisation (sequentially numbered, opaque sealed envelopes), eligible individuals (diagnosed with type 2 diabetes, no exogenous insulin treatment) were allocated to three groups: a control group (CON,
n
= 8), an IWT group (
n
= 12) and an energy expenditure-matched CWT group (
n
= 12). Training groups were prescribed free-living training, five sessions per week (60 min/session). A three-stage hyperglycaemic clamp, including glucose isotope tracers and skeletal muscle biopsies, was performed before and after a 4 month intervention in a hospitalised setting. No blinding was performed.
Results
The improved glycaemic control, which was only seen in the IWT group, was consistent with IWT-induced increases in insulin sensitivity index (49.8 ± 14.6%;
p
< 0.001), peripheral glucose disposal (14.5 ± 4.9%;
p
< 0.05) and DI (66.2 ± 21.8%;
p
< 0.001), with no changes in the CWT or CON group. Moreover, only IWT improved insulin signalling in skeletal muscle via increased insulin-stimulated phosphorylation of AS160 (29.0 ± 10.8%;
p
< 0.05). No changes were seen in insulin secretion during hyperglycaemia alone, hyperglycaemia + glucagon-like peptide 1 infusion or arginine injection.
Conclusions/interpretation
IWT maintains insulin secretion and improves insulin sensitivity and DI, in contrast to energy expenditure-matched CWT. These results suggest that training with alternating intensity, and not just training volume and mean intensity, is a key determinant of changes in whole body glucose disposal in individuals with type 2 diabetes.
Trial registration:
ClinicalTrials (NCT01234155).
Journal Article
Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise
by
Jørgensen, Marit E.
,
Stinson, Sara E.
,
Grarup, Niels
in
631/443/319/1642
,
692/163/2743
,
82/51
2024
In the Greenlandic Inuit population, 4% are homozygous carriers of a genetic nonsense
TBC1D4
p.Arg684Ter variant leading to loss of the muscle-specific isoform of TBC1D4 and an approximately tenfold increased risk of type 2 diabetes
1
. Here we show the metabolic consequences of this variant in four female and four male homozygous carriers and matched controls. An extended glucose tolerance test reveals prolonged hyperglycaemia followed by reactive hypoglycaemia in the carriers. Whole-body glucose disposal is impaired during euglycaemic-hyperinsulinaemic clamp conditions and associates with severe insulin resistance in skeletal muscle only. Notably, a marked reduction in muscle glucose transporter GLUT4 and associated proteins is observed. While metabolic regulation during exercise remains normal, the insulin-sensitizing effect of a single exercise bout is compromised. Thus, loss of the muscle-specific isoform of TBC1D4 causes severe skeletal muscle insulin resistance without baseline hyperinsulinaemia. However, physical activity can ameliorate this condition. These observations offer avenues for personalized interventions and targeted preventive strategies.
In Greenlandic Inuit, a
TBC1D4
loss-of-function mutation increases type 2 diabetes risk by tenfold. Carriers show severe muscle insulin resistance, impaired glucose disposal and reduced muscle GLUT4, yet exercise mitigates these defects, offering potential for personalized lifestyle interventions.
Journal Article
The impact of exercise training and resveratrol supplementation on gut microbiota composition in high‐fat diet fed mice
by
Pilegaard, Henriette
,
Hansen, Martin
,
Kristensen, Caroline M.
in
Adipose tissue
,
Adipose Tissue and Obesity
,
Amyloid
2018
The aim of this study was to examine the effect of exercise training and dietary supplementation of resveratrol on the composition of gut microbiota and to test the hypothesis that exercise training and resveratrol can prevent high‐fat diet (HFD)‐induced changes in the gut microbiota. Mice fed a HFD supplemented with resveratrol (4 g/kg food) were protected against diet‐induced obesity, while exercise trained HFD‐fed animals (running on average 50 km/week) were not. Dietary resveratrol supplementation induced changes predominantly in the low‐abundant bacteria, while exercise training induced changes in the high‐abundant bacteria in the gut as analyzed by ADONIS test with Weighted UniFrac distances. Interestingly, the two interventions affected the gut microbiome independently of the inflammatory state of the HFD‐fed animals as assessed by the systemic serum amyloid A levels. These results suggest that both resveratrol supplementation and regular physical activity modulate the composition of murine microbiota independently of the systemic inflammatory state. Moreover, the effects of exercise training on the microbiota seem to occur without changes in adiposity, while resveratrol‐mediated alterations may relate to adipose tissue mass. Both resveratrol supplementation and regular physical activity modulate the composition of murine microbiota independently of the systemic inflammatory state. Moreover, the effects on the microbiota with exercise training seem to occur without changes in adiposity, while resveratrol‐mediated alterations may relate to adipose tissue mass.
Journal Article
PGC-1alpha-mediated adaptations in skeletal muscle
by
Kiilerich, Kristian
,
Pilegaard, Henriette
,
Olesen, Jesper
in
Adaptation, Physiological
,
Animals
,
Antioxidants - metabolism
2010
Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each single exercise, but how is this regulated? A potential candidate in this is the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, which has been identified as a master regulator of mitochondrial biogenesis, but also been shown to regulate proteins involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1alpha transcription and potentially PGC-1alpha activity through post-translational modifications, and concomitant PGC-1alpha-mediated gene regulation is suggested to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1alpha-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise training, and describes functional significance of PGC-1alpha-mediated effects in skeletal muscle. In addition, regulation of PGC-1alpha expression and activity in skeletal muscle is described. The impact of changes in PGC-1alpha expression in mouse skeletal muscle and the ability of PGC-1alpha to regulate multiple pathways and functions underline the potential importance of PGC-1alpha in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1alpha-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle and concomitant impaired metabolism.
Journal Article