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  • Middeldorp, Christel M., et al. (author)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Journal article (peer-reviewed)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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4.
  • Muysoms, F. E., et al. (author)
  • European Hernia Society guidelines on the closure of abdominal wall incisions
  • 2015
  • In: Hernia. - : Springer Science and Business Media LLC. - 1265-4906 .- 1248-9204. ; 19:1, s. 1-24
  • Research review (peer-reviewed)abstract
    • Background The material and the surgical technique used to close an abdominal wall incision are important determinants of the risk of developing an incisional hernia. Optimising closure of abdominal wall incisions holds a potential to prevent patients suffering from incisional hernias and for important costs savings in health care. Methods The European Hernia Society formed a Guidelines Development Group to provide guidelines for all surgical specialists who perform abdominal incisions in adult patients on the materials and methods used to close the abdominal wall. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and methodological guidance was taken from Scottish Intercollegiate Guidelines Network (SIGN). The literature search included publications up to April 2014. The guidelines were written using the AGREE II instrument. An update of these guidelines is planned for 2017. Results For many of the Key Questions that were studied no high quality data was detected. Therefore, some strong recommendations could be made but, for many Key Questions only weak recommendations or no recommendation could be made due to lack of sufficient evidence. Recommendations To decrease the incidence of incisional hernias it is strongly recommended to utilise a non-midline approach to a laparotomy whenever possible. For elective midline incisions, it is strongly recommended to perform a continuous suturing technique and to avoid the use of rapidly absorbable sutures. It is suggested using a slowly absorbable monofilament suture in a single layer aponeurotic closure technique without separate closure of the peritoneum. A small bites technique with a suture to wound length (SL/WL) ratio at least 4/1 is the current recommended method of fascial closure. Currently, no recommendations can be given on the optimal technique to close emergency laparotomy incisions. Prophylactic mesh augmentation appears effective and safe and can be suggested in high-risk patients, like aortic aneurysm surgery and obese patients. For laparoscopic surgery, it is suggested using the smallest trocar size adequate for the procedure and closure of the fascial defect if trocars larger or equal to 10 mm are used. For single incision laparoscopic surgery, we suggest meticulous closure of the fascial incision to avoid an increased risk of incisional hernias.
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  • Allentoft, Morten E., et al. (author)
  • Population genomics of post-glacial western Eurasia
  • 2024
  • In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
  • Journal article (peer-reviewed)abstract
    • Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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  • Bärebring, Linnea, et al. (author)
  • Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer– a validation study
  • 2020
  • In: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 40, s. 201-207
  • Journal article (peer-reviewed)abstract
    • Background & aims: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC). Methods: A total of 136 women and men (50–80 years) with stage I-III CRC and a wide range of baseline FFM (35.7–73.5 kg) were included in the study. Body composition was measured at study baseline within 2–9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFMBIA) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFMDXA). Results: Correlation between changes in FFMBIA and FFMDXA was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFMBIA was significant compared to FFMDXA, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFMBIA to detect a smaller loss of FFM (60–76%) or a gain in FFM of ≥5% (33–62%) was poor. Conclusion: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis. © 2020 The Author(s)
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  • Flachenecker, P, et al. (author)
  • Multiple sclerosis registries in Europe - results of a systematic survey
  • 2014
  • In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:11, s. 1523-1532
  • Journal article (peer-reviewed)abstract
    • Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. Methods: National MS registries or databases were identified by literature search, from the results of the MS Barometer 2011 and by asking 33 national MS societies. A standardized questionnaire was developed and sent to the registries’ leaders, followed by telephone interviews with them. Results: Twenty registries were identified, with 13 completing the questionnaire and seven being interviewed by telephone. These registries differed widely for objectives, structure, collected data, and for patients and centres included. Despite this heterogeneity, common objectives of the registries were epidemiology ( n=10), long-term therapy outcome ( n=8), healthcare research ( n=9) and support/basis for clinical trials ( n=8). While physician-based outcome measures (EDSS) are used in all registries, data from patients’ perspectives were only collected in six registries. Conclusions: The detailed information on a large number of national MS registries in Europe is a prerequisite to facilitating harmonized integration of existing data from MS registries and databases, as well as comprehensive analyses and comparison across European populations.
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  • Henriksen, N. A., et al. (author)
  • EHS and AHS guidelines for treatment of primary ventral hernias in rare locations or special circumstances
  • 2020
  • In: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 4:2, s. 342-353
  • Research review (peer-reviewed)abstract
    • BACKGROUND: Rare locations of hernias, as well as primary ventral hernias under certain circumstances (cirrhosis, dialysis, rectus diastasis, subsequent pregnancy), might be technically challenging. The aim was to identify situations where the treatment strategy might deviate from routine management. METHODS: The guideline group consisted of surgeons from the European and Americas Hernia Societies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used in formulating the recommendations. The Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists were used to evaluate the quality of full-text papers. A systematic literature search was performed on 1 May 2018 and updated 1 February 2019. The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was followed. RESULTS: Literature was limited in quantity and quality. A majority of the recommendations were graded as weak, based on low quality of evidence. In patients with cirrhosis or on dialysis, a preperitoneal mesh repair is suggested. Subsequent pregnancy is a risk factor for recurrence. Repair should be postponed until after the last pregnancy. For patients with a concomitant rectus diastasis or those with a Spigelian or lumbar hernia, no recommendation could be made for treatment strategy owing to lack of evidence. CONCLUSION: This is the first European and American guideline on the treatment of umbilical and epigastric hernias in patients with special conditions, including Spigelian and lumbar hernias. All recommendations were weak owing to a lack of evidence. Further studies are needed on patients with rectus diastasis, Spigelian and lumbar hernias.
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  • Henriksen, N. A., et al. (author)
  • Guidelines for treatment of umbilical and epigastric hernias from the European Hernia Society and Americas Hernia Society
  • 2020
  • In: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 107:3, s. 171-190
  • Research review (peer-reviewed)abstract
    • Background: Umbilical and epigastric hernia repairs are frequently performed surgical procedures with an expected low complication rate. Nevertheless, the optimal method of repair with best short- and long-term outcomes remains debatable. The aim was to develop guidelines for the treatment of umbilical and epigastric hernias. Methods: The guideline group consisted of surgeons from Europe and North America including members from the European Hernia Society and the Americas Hernia Society. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, the Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists, and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were used. A systematic literature search was done on 1 May 2018, and updated on 1 February 2019. Results: Literature reporting specifically on umbilical and epigastric hernias was limited in quantity and quality, resulting in a majority of the recommendations being graded as weak, based on low-quality evidence. The main recommendation was to use mesh for repair of umbilical and epigastric hernias to reduce the recurrence rate. Most umbilical and epigastric hernias may be repaired by an open approach with a preperitoneal flat mesh. A laparoscopic approach may be considered if the hernia defect is large, or if the patient has an increased risk of wound morbidity. Conclusion: This is the first European and American guideline on the treatment of umbilical and epigastric hernias. It is recommended that symptomatic umbilical and epigastric hernias are repaired by an open approach with a preperitoneal flat mesh.
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  • Katri, A., et al. (author)
  • A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model
  • 2019
  • In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:9, s. 1339-1346
  • Journal article (peer-reviewed)abstract
    • Objectives: Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor agonist with antiresorptive and chondroprotective properties. In this study we investigated the effect of KBP in a rat model of osteoarthritis. Methods: Medial meniscectomy (MNX) was performed in 39 rats, while 10 underwent sham surgery. Rats were treated with KBP and/or naproxen. Nociception was assessed by mechanical and cold allodynia, weight bearing asymmetry, and burrowing behavior. Blood samples were collected for biomarker measurements, and knees for histology. Cartilage histopathology was evaluated according to the advanced Osteoarthritis Research International (OARSI) score and KBPs in vitro antiresorptive effects were assessed using human osteoclasts cultured on bone. Results: The MNX animals displayed an increased nociceptive behavior. Treatment with KBP attenuated the MNX-induced osteoarthritis-associated joint pain. The cartilage histopathology was significantly lower in rats treated with KBP than in MNX animals. Bone and cartilage degradation, assessed by CTX-I and CTX-II plasma levels, were decreased in all KBP-treated groups and KBP potently inhibited bone resorption in vitro. Conclusions: Our study demonstrates the effectiveness of KBP in ameliorating osteoarthritis-associated joint pain and in protecting the articular cartilage, suggesting KBP as a potential drug candidate for osteoarthritis.
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  • Oskarsson, T., et al. (author)
  • Osteoporotic Fractures in Childhood Cancer Survivors - ALICCS Cohort Study
  • 2018
  • In: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:Suppl.2, s. S693-S694
  • Journal article (other academic/artistic)abstract
    • Background/Objectives: Children and adolescents undergoing treatment for cancer are exposed to multiple factors that impact the development of peak bone mass and bone quality. The aims of this study were to examine the risks and cumulative incidence of osteoporotic fractures in childhood cancer survivors and identify subgroups at higher risk.Design/Methods: In the national cancer registries of Denmark, Finland, Iceland and Sweden we identified patients diagnosed with cancer before 20 years of age from the start of registration in the 1940s and 1950s through 2008. We compared 26.334 one‐year survivors with a cohort of 162.372 age‐ and sex‐matched population comparison subjects selected from the national population registries. With data derived from national hospital registries we estimated the standardized hospitalization rate ratios (SHRR) and the mean cumulative count (MCC) of hospital admissions for osteoporotic fractures. To identify subgroups at risk we used Cox regression models to generate hazard ratios (HR) for osteoporotic fractures. Death and new cancer were treated as competing risks.Results: The estimated SHRR for the first osteoporotic fracture was 1.41 (95% CI; 1.27‐1.58) but the MCC for recurrent osteoporotic fractures did not differ between the survivors and the comparison group. The SHRR for isolated hip fractures was 2.90 (2.32‐3.63). The adjusted HR for osteoporotic fracture as the first event was 1.53 (1.09‐2.16) if cancer was diagnosed 15‐19 years and 2.10 (1.48‐2.98) for long‐term survivors of CNS tumors. Survivors 15‐19 years at cancer diagnosis and long‐term survivors of CNS tumors were also at higher risk of experiencing a second fracture, HR 3.29 (1.65‐6.55) and HR 2.71 (1.45‐5.05), respectively.Conclusions: Childhood cancer survivors are at higher risk of being hospitalized for osteoporotic fractures but the burden of recurrent fractures is not higher. For subgroups at risk, surveillance of bone health and measures to increase bone strength and prevent fractures should be encouraged.
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  • Rizos, A., et al. (author)
  • A European multicentre survey of impulse control behaviours in Parkinson's disease patients treated with short- and long-acting dopamine agonists
  • 2016
  • In: European Journal of Neurology. - : Wiley. - 1351-5101. ; 23:8, s. 1255-1261
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated primarily with dopamine agonist (DA) use. Comparative surveys of clinical occurrence of impulse control behaviours on longer acting/transdermal DA therapy across age ranges are lacking. The aim of this study was to assess the occurrence of ICDs in PD patients across several European centres treated with short- or long-acting [ropinirole (ROP); pramipexole (PPX)] and transdermal [rotigotine skin patch (RTG)] DAs, based on clinical survey as part of routine clinical care. Methods: A survey based on medical records and clinical interviews of patients initiating or initiated on DA treatment (both short- and long-acting, and transdermal) across a broad range of disease stages and age groups was performed. Results: Four hundred and twenty-five cases were included [mean age 68.3 years (range 37-90), mean duration of disease 7.5 years (range 0-37)]. ICD frequencies (as assessed by clinical interview) were significantly lower with RTG (4.9%; P <0.05) compared with any other assessed DAs except for prolonged release PPX (PPX-PR). The rate of ICDs for PPX-PR (6.6%) was significantly lower than for immediate release PPX (PPX-IR) (19.0%; P <0.05). Discontinuation rates of DA therapy due to ICDs were low. Conclusion: Our data suggest a relatively low rate of ICDs with long-acting or transdermal DAs, however these preliminary observational data need to be confirmed with prospective studies controlling for possible confounding factors.
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  • Rizos, A., et al. (author)
  • Tolerability of non-ergot oral and transdermal dopamine agonists in younger and older Parkinson’s disease patients : an European multicentre survey
  • 2020
  • In: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 127:6, s. 875-879
  • Journal article (peer-reviewed)abstract
    • In older patients with Parkinson’s disease (PD), the use of dopamine agonists (DA) has been limited due to uncertainties related to their tolerability in spite of potential gains with the advent of longer acting or transdermal therapies. Comparative real-life data addressing the tolerability of DA therapy across age ranges are currently sparse. This study addressed the tolerability (Shulman criteria, continued intake of DA therapy for at least 6 months) in PD patients across several European centres treated with long-acting and transdermal DA (Rotigotine skin patch, Ropinirole extended release, or Pramipexole prolonged release) as part of routine clinical care in younger and older PD patients. A medical record-based retrospective data capture and clinical interview-based follow-up survey of patients initiating or initiated on DA treatment (short and long acting) in a real-life setting. 425 cases were included [mean age 68.3 years (range 37–90), mean duration of disease 7.5 years (range 0–37), 31.5% older age (≥ 75 years of age)]. Tolerability was above 90% irrespective of age, with no significant differences between younger and older patients. Based on our findings, we suggest that long-acting/transdermal DA are tolerated in non-demented older patients, as well as in younger patients, however, with lower daily dose in older patients.
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  • Svendsen, JI, et al. (author)
  • Late quaternary ice sheet history of northern Eurasia
  • 2004
  • In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 23:11-13, s. 1229-1271
  • Research review (peer-reviewed)abstract
    • The maximum limits of the Eurasian ice sheets during four glaciations have been reconstructed: (1) the Late Saalian (> 140 ka), (2) the Early Weichselian (100-80 ka), (3) the Middle Weichselian (60-50 ka) and (4) the Late Weichselian (25-15 ka). The reconstructed ice limits are based on satellite data and aerial photographs combined with geological field investigations in Russia and Siberia, and with marine seismic- and sediment core data. The Barents-Kara Ice Sheet got progressively smaller during each glaciation, whereas the dimensions of the Scandinavian Ice Sheet increased. During the last Ice Age the Barents-Kara Ice Sheet attained its maximum size as early as 90-80,000 years ago when the ice front reached far onto the continent. A regrowth of the ice sheets occurred during the early Middle Weichselian, culminating about 60-50,000 years ago. During the Late Weichselian the Barents-Kara Ice Sheet did not reach the mainland east of the Kanin Peninsula, with the exception of the NW fringe of Taimyr. A numerical ice-sheet model, forced by global sea level and solar changes, was run through the full Weichselian glacial cycle. The modeling results are roughly compatible with the geological record of ice growth, but the model underpredicts the glaciations in the Eurasian Arctic during the Early and Middle Weichselian. One reason for this is that the climate in the Eurasian Arctic was not as dry then as during the Late Weichselian glacial maximum.
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  • Toft, A., et al. (author)
  • Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation
  • 2023
  • In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
  • Journal article (peer-reviewed)abstract
    • IntroductionIncreasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by CHMP2B mutation. MethodsCombining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish CHMP2B-FTD family. ResultsCompared with family controls, mutation carriers had significantly higher levels of complement C9, lysozyme and transcobalamin II, and lower levels of ubiquitin, cathepsin B, and amyloid precursor protein. DiscussionLower CSF ubiquitin concentrations in CHMP2B mutation carriers indicate that ubiquitin levels relate to the specific disease pathology, rather than all-cause neurodegeneration. Increased lysozyme and complement proteins may indicate innate immune activation. Altered levels of amyloid precursor protein and cathepsins have previously been associated with impaired lysosomal proteolysis in FTD. HighlightsCSF markers of proteostasis were explored in CHMP2B-mediated frontotemporal dementia (FTD).31 members of the Danish CHMP2B-FTD family were included.We used solid-phase extraction and parallel reaction monitoring mass spectrometry.Six protein levels were significantly altered in CHMP2B-FTD compared with controls.Lower CSF ubiquitin levels in patients suggest association with disease mechanisms.
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  • Barregård, Lars, 1948, et al. (author)
  • Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
  • 2013
  • In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
  • Journal article (peer-reviewed)abstract
    • Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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  • Davegårdh, Cajsa, et al. (author)
  • Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects
  • 2017
  • In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15:1, s. 1-27
  • Journal article (peer-reviewed)abstract
    • Background: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. Methods: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals. Functional follow-up experiments were performed using siRNA mediated gene silencing in primary human myoblasts and a transgenic mouse model. Results: We observed genome-wide changes in DNA methylation and expression patterns during differentiation of primary human muscle stem cells (myoblasts). We identified epigenetic and transcriptional changes of myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6, PAX7, MEF2A, MEF2C, and MEF2D), cell cycle regulators, metabolic enzymes and genes previously not linked to myogenesis, including IL32, metallothioneins, and pregnancy-specific beta-1-glycoproteins. Functional studies demonstrated IL-32 as a novel target that regulates human myogenesis, insulin sensitivity and ATP levels in muscle cells. Furthermore, IL32 transgenic mice had reduced insulin response and muscle weight. Remarkably, approximately 3.7 times more methylation changes (147,161 versus 39,572) were observed during differentiation of myoblasts from obese versus non-obese subjects. In accordance, DNMT1 expression increased during myogenesis only in obese subjects. Interestingly, numerous genes implicated in metabolic diseases and epigenetic regulation showed differential methylation and expression during differentiation only in obese subjects. Conclusions: Our study identifies IL-32 as a novel myogenic regulator, provides a comprehensive map of the dynamic epigenome during differentiation of human muscle stem cells and reveals abnormal epigenetic changes in obesity.
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21.
  • Hernández-Granados, P., et al. (author)
  • European Hernia Society guidelines on management of rectus diastasis
  • 2021
  • In: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 108:10, s. 1189-1191
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The definition, classification and management of rectus diastasis (RD) are controversial in the literature and a variety of different surgical treatments have been described. This article reports on the European Hernia Society (EHS) Clinical Practice Guideline for RD. METHOD: The Guideline group consisted of eight surgeons. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were used. A systematic literature search was done in November 2018 and updated in November 2019 and October 2020. Nine Key Questions (KQs) were formulated. RESULTS: Literature reporting on the definition, classification, symptoms, outcomes and treatments was limited in quality, leading to weak recommendations for the majority of the KQs. The main recommendation is to define RD as a separation between rectus muscles wider than 2 cm. A new classification system is suggested based on the width of muscle separation, postpregnancy status and whether or not there is a concomitant hernia. Impaired body image and core instability appear to be the most relevant symptoms. Physiotherapy may be considered before surgical management. It is suggested to use linea alba plication in patients without concomitant hernia and a mesh-based repair of RD with concomitant midline hernias. CONCLUSION: RD should be defined as a separation of rectus muscles wider than 2 cm and a new classification system is suggested.
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  • Hubberten, HW, et al. (author)
  • The periglacial climate and environment in northern Eurasia during the Last Glaciation
  • 2004
  • In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 23:11-13, s. 1333-1357
  • Research review (peer-reviewed)abstract
    • This paper summarizes the results of studies of the Late Weichselian periglacial environments carried out in key areas of northern Eurasia by several QUEEN teams (European Science Foundation (ESF) programme: "Quaternary Environment of the Eurasian North"). The palaeoglaciological boundary conditions are defined by geological data on timing and extent of the last glaciation obtained in the course of the EU funded project "Eurasian Ice Sheets". These data prove beyond any doubt, that with the exception of the northwestern fringe of the Taymyr Peninsula, the rest of the Eurasian mainland and Severnaya Zemlya were not affected by the Barents-Kara Sea fee Sheet during the Last Glacial Maximum (LGM). Inversed modelling based on these results shows that a progressive cooling which started around 30 ka BP, caused ice growth in Scandinavia and the northwestern areas of the Barents-Kara Sea shelf, due to a maritime climate with relatively high precipitation along the western flank of the developing ice sheets. In the rest of the Eurasian Arctic extremely low precipitation rates (less than 50 mm yr(-1)), did not allow ice sheet growth in spite of the very cold temperatures. Palaeoclimatic and palaeoenvironmental conditions for the time prior to, during, and after the LGM have been reconstructed for the non-glaciated areas around the LGM ice sheet with the use of faunal and vegetation records, permafrost, eolian sediments, alluvial deposits and other evidences. The changing environment, from interstadial conditions around 30 ka BP to a much colder and drier environment at the culmination of the LGM at 20-15 ka BP, and the beginning of warming around 15 ka BP have been elaborated from the field data, which fits well with the modelling results. (C) 2003 Elsevier Ltd. All rights reserved.
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23.
  • Jorgensen, A. A., et al. (author)
  • Petabit-per-second data transmission using a chip-scale microcomb ring resonator source
  • 2022
  • In: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 16:11, s. 798-802
  • Journal article (peer-reviewed)abstract
    • Optical fibre communication is the backbone of the internet. As essential core technologies are approaching their limits of size, speed and energy-efficiency, there is a need for new technologies that offer further scaling of data transmission capacity. Here we show that a single optical frequency-comb source based on a silicon nitride ring resonator supports data capacities in the petabit-per-second regime. We experimentally demonstrate transmission of 1.84 Pbit s–1 over a 37-core, 7.9-km-long fibre using 223 wavelength channels derived from a single microcomb ring resonator producing a stabilized dark-pulse Kerr frequency comb. We also present a theoretical analysis that indicates that a single, chip-scale light source should be able to support 100 Pbit s–1 in massively parallel space-and-wavelength multiplexed data transmission systems. Our findings could mark a shift in the design of future communication systems, targeting device-efficient transmitters and receivers.
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24.
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25.
  • Kong, D., et al. (author)
  • Single Dark-Pulse Kerr Comb Supporting 1.84 Pbit/s Transmission over 37-Core Fiber
  • 2020
  • In: Conference Proceedings - Lasers and Electro-Optics Society Annual Meeting-LEOS. - 1092-8081. ; 2020-May
  • Conference paper (peer-reviewed)abstract
    • We show that a single dark-pulse Kerr comb can generate high enough OSNR to carry 1.84 Pbit/s data, achieved by 223 WDM spectral lines modulated with 32-Gbaud, SNR-adapted probabilistically shaped DP-QAM, over a 37-core fiber.
  •  
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