| 1. |
- Hansson, L-A, et al.
(author)
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A synthesis of animal movement across scales
- 2014
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In: Animal Movement Across Scales. - : Oxford University Press. - 9780199677184 ; , s. 259-267
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Book chapter (peer-reviewed)abstract
- This chapter aims at synthesizing the knowledge presented in the chapters of the book’s three sections by addressing evolutionary compromises, dispersal, gene flow, and assisted movements. How climate change and other environmental changes at different scales may affect animal movement, migration, and dispersal in the future are also summarized here. Moreover, how the different senses are utilized for navigation and orientation and how these may lead to different movement and migration patterns are also discussed. Finally, how the recent technical revolution has affected animal movement research is addressed and the view on future perspectives of animal movement research is also provided.
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| 2. |
- Andersson, Carl-Henrik, et al.
(author)
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A Genetic Variant of the Sortilin 1 Gene isAssociated with Reduced Risk ofAlzheimer's Disease
- 2016
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 53:4, s. 1353-1363
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Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder represented by the accumulation of intracellular tau protein and extracellular deposits of amyloid-β (Aβ) in the brain. The gene sortilin 1 (SORT1) has previously been associated with cardiovascular disease in gene association studies. It has also been proposed to be involved in AD pathogenesis through facilitating Aβ clearance by binding apoE/Aβ complexes prior to cellular uptake. However, the neuropathological role of SORT1 in AD is not fully understood. To evaluate the associations between gene variants of SORT1 and risk of AD, we performed genetic analyses in a Swedish case-control cohort. Ten single nucleotide polymorphisms (SNPs), covering the whole SORT1 gene, were selected and genotyped in 620 AD patients and 1107 controls. The SNP rs17646665, located in a non-coding region of the SORT1 gene, remained significantly associated with decreased risk of AD after multiple testing (pc=0.0061). In addition, other SNPs were found to be nominally associated with risk of AD, as well as altered cognitive function and the CSF biomarker Aβ42, but these associations did not survive correction for multiple testing. The fact that SORT1 has been strongly associated with risk of cardiovascular disease is intriguing as cardiovascular disease is also regarded as a risk factor for AD. Finally, increased knowledge about SORT1 function has a potential to increase our understanding of APOE, the strongest risk factor for AD.
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| 3. |
- Auråen, Henrik, et al.
(author)
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Urgent lung allocation system in the Scandiatransplant countries
- 2018
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In: Journal of Heart and Lung Transplantation. - 1053-2498. ; 37:12, s. 1403-1409
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Journal article (peer-reviewed)abstract
- BACKGROUND: Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill patients, the Scandiatransplant urgent lung allocation system (ScULAS) was introduced in 2009, giving supranational priority to patients considered urgent. There were no pre-defined criteria for listing a patient as urgent, but each center was granted only 3 urgent calls per year. This study aims to explore the characteristics and outcome of patients listed as urgent, assess changes associated with the implementation of ScULAS, and describe how the system was utilized by the member centers. METHODS: All patients listed for lung transplantation at the 5 Scandiatransplant centers 5 years before and after implementation of ScULAS were included. RESULTS: After implementation, 8.3% of all listed patients received urgent status, of whom 81% were transplanted within 4 weeks. Patients listed as urgent were younger, more commonly had suppurative lung disease, and were more often on life support compared with patients without urgent status. For patients listed as urgent, post-transplant graft survival was inferior at 30 and 90 days. Although there were no pre-defined criteria for urgent listing, the system was not utilized at its maximum. CONCLUSIONS: ScULAS rapidly allocated organs to patients considered urgent. These patients were younger and more often had suppurative lung disease. Patients with urgent status had inferior short-term outcome, plausibly due to the higher proportion on life support before transplantation.
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| 4. |
- Berg Hansen, Kristoffer, et al.
(author)
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Myocardial efficiency in patients with different aetiologies and stages of heart failure
- 2022
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In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 23:3, s. 328-337
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Journal article (peer-reviewed)abstract
- Aims: Myocardial external efficiency (MEE) is the ratio of cardiac work in relation with energy expenditure. We studied MEE in patients with different aetiologies and stages of heart failure (HF) to discover the role and causes of deranged MEE. In addition, we explored the impact of patient characteristics such as sex, body mass index (BMI), and age on myocardial energetics.Methods and results: Cardiac energetic profiles were assessed with C-11-acetate positron emission tomography (PET) and left ventricular ejection fraction (LVEF) was acquired with echocardiography. MEE was studied in 121 participants: healthy controls (n = 20); HF patients with reduced (HFrEF; n = 25) and mildly reduced (HFmrEF; n = 23) LVEF; and patients with asymptomatic (AS-asymp; n = 38) and symptomatic (AS-symp; n = 15) aortic stenosis (AS). Reduced MEE coincided with symptoms of HF irrespective of aetiology and declined in tandem with deteriorating LVEF. Patients with AS-symp and HFmrEF had reduced MEE as compared with controls (22.2 +/- 4.9%, P = 0.041 and 20.0 +/- 4.2%, P < 0.001 vs. 26.1 +/- 5.8% in controls) and a further decline was observed in patients with HFrEF (14.7 +/- 6.3%, P < 0.001). Disproportionate left ventricular hypertrophy was a major cause of reduced MEE. Female sex (P < 0.001), a lower BMI (P = 0.001), and advanced age (P = 0.03) were associated with a lower MEE.Conclusion: MEE was reduced in patients with HFrEF, HFmrEF, and HF due to pressure overload and MEE may therefore constitute a treatment target in HF. Patients with LVH, advanced age, female sex, and low BMI had more pronounced reduction in MEE and personalized treatment within these patient subgroups could be relevant.
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| 5. |
- Boy, M., et al.
(author)
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Interactions between the atmosphere, cryosphere, and ecosystems at northern high latitudes
- 2019
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:3, s. 2015-2061
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Journal article (peer-reviewed)abstract
- The Nordic Centre of Excellence CRAICC (Cryosphere-Atmosphere Interactions in a Changing Arctic Climate), funded by NordForsk in the years 2011-2016, is the largest joint Nordic research and innovation initiative to date, aiming to strengthen research and innovation regarding climate change issues in the Nordic region. CRAICC gathered more than 100 scientists from all Nordic countries in a virtual centre with the objectives of identifying and quantifying the major processes controlling Arctic warming and related feedback mechanisms, outlining strategies to mitigate Arctic warming, and developing Nordic Earth system modelling with a focus on short-lived climate forcers (SLCFs), including natural and anthropogenic aerosols. The outcome of CRAICC is reflected in more than 150 peer-reviewed scientific publications, most of which are in the CRAICC special issue of the journal Atmospheric Chemistry and Physics. This paper presents an overview of the main scientific topics investigated in the centre and provides the reader with a state-of-the-art comprehensive summary of what has been achieved in CRAICC with links to the particular publications for further detail. Faced with a vast amount of scientific discovery, we do not claim to completely summarize the results from CRAICC within this paper, but rather concentrate here on the main results which are related to feedback loops in climate change-cryosphere interactions that affect Arctic amplification.
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| 6. |
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| 7. |
- Glimelius, Bengt, et al.
(author)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Journal article (peer-reviewed)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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| 8. |
- Golman, Klaes, et al.
(author)
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13C-angiography.
- 2002
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In: Academic Radiology. - 1878-4046. ; 9:Suppl 2, s. 507-510
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Journal article (peer-reviewed)
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| 9. |
- Gregersen, Henrik, et al.
(author)
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Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma : A randomised phase 2 trial by the Nordic Myeloma Study Group
- 2022
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In: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 108:1, s. 34-44
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Journal article (peer-reviewed)abstract
- Objective We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma. Methods This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 -> 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86). Results Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections. Conclusion In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity.
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| 10. |
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| 11. |
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| 12. |
- Hansson, Karl, 1985, et al.
(author)
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Use of the tau protein-to-peptide ratio in CSF to improve diagnostic classification of Alzheimer's disease
- 2019
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In: Clinical Mass Spectrometry. - : Elsevier BV. - 2376-9998. ; 14, s. 74-82
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) tau and phospho-tau are well established biomarkers of Alzheimer's disease. While these measures are conventionally referred to as 'total tau' (T-tau) and 'phospho-tau' (P-tau), several truncated and modified tau forms exist that may relay additional diagnostic information. We evaluated the diagnostic performance of an endogenous tau peptide in CSF, tau 175-190, in the phosphorylated and non-phosphorylated state. A liquid chromatography-mass spectrometry (LC-MS) method was established to measure these peptides in CSF and was used to analyze two independent clinical cohorts; the first cohort included patients with Alzheimer's disease (AD, n = 15), Parkinson's disease (PD, n = 15), progressive supranuclear palsy (PSP, n = 15), and healthy controls (n = 15), the second cohort included AD patients (n = 16), and healthy controls (n = 24). In both cohorts T-tau and P-tau concentrations were determined by immunoassay. While tau 175-190 and P-tau 175-190 did not differentiate the study groups, the separation of AD and controls by T-tau (area under the ROC Curve (AUC) = 95%) and P-tau (AUC = 92%) was improved when normalizing the ELISA measurements to the concentrations of the endogenous peptides: T-tau/tau 175-190 (AUC = 100%), P-tau/P-tau 175-190 (AUC = 95%). The separation between patients and controls by T-tau (AUC = 88%) and P-tau (AUC = 82%) was similarly improved in the second cohort by taking the ratios of T-tau/tau 175-190 (AUC = 97%) and P-tau/P-tau 175-190 (AUC = 98%). In conclusion, our results suggest that the performance of the AD biomarkers T-tau and P-tau could be improved by normalizing their measurements to the endogenous peptides tau 175-190 and P-tau 175-190, possibly because these endogenous tau peptides serve to normalize for physiological, and disease-independent, secretion of tau from neurons to the extracellular space and the CSF. Finally, the observations made here add to the general applicability of mass spectrometry as a tool for rapid identification and accurate quantification of biomarker candidates. (C) 2019 The Association for Mass Spectrometry: Applications to the Clinical Lab (MSACL). Published by Elsevier B.V. All rights reserved.
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| 13. |
- Hansson, Nils Henrik, et al.
(author)
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Evaluation of ECG-gated [(11)C]acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency
- 2016
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In: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 23:4, s. 670-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Noninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [(11)C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [(11)C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [(11)C]acetate PET.METHODS: Thirty-five subjects with aortic valve stenosis underwent ECG-gated [(11)C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE.RESULTS: LV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias -3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness.CONCLUSIONS: Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [(11)C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.
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| 14. |
- Hansson, Sara Lina, et al.
(author)
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Experienced consequences of being diagnosed with ADHD as an adult - a qualitative study
- 2015
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In: Bmc Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 15:31
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Journal article (peer-reviewed)abstract
- Background: Despite increasing knowledge of attention deficit hyperactivity disorder (ADHD) across the life span, there is still little research on adults' own experiences of being diagnosed with ADHD. The aim of the present study was to explore and describe patients' experiences and perceptions of being diagnosed with ADHD in adulthood. The study can be seen as an attempt to validate the diagnosis from a patient perspective. Methods: Twenty-one adults diagnosed with ADHD were individually interviewed. The interviews were open-ended and exploratory, analysed with a qualitative phenomenographical approach, and the results were described in categories. Results: Positive experiences were dominant, but there was a complex intra-and inter-individual variation of experiences. Descriptions focused on the diagnosis, on identity, and on life. The diagnosis was described as explaining a previously inexplicable life history, but was also questioned, both as a phenomenon and in relation to the individual (the diagnosis in focus). It was experienced as providing self-knowledge and increased value, but could also cause devaluation and concern about identity (identity in focus). It meant help to achieve a better life, but was also perceived to restrict possibilities and cause disappointment over lack of professional help. It could lead to a wish for an earlier diagnosis that could have spared suffering, as well as to a changed view of the participants' relatives (life in focus). All but one of the interviewees expressed important positive consequences of being diagnosed with ADHD. About half of them acknowledged negative aspects of being diagnosed, but none regretted going through the neuropsychiatric evaluation. Conclusions: From a patient perspective, there are major positive consequences of being diagnosed with ADHD, compared to the undiagnosed situation. Knowledge of the individual's combination of experiences is important for professionals, as these experiences can affect well-being and interfere with treatment. Negative experiences in particular might need to be addressed in the treatment work.
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| 15. |
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| 16. |
- Harms, Hendrik J, et al.
(author)
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Automatic calculation of myocardial external efficiency using a single 11C-acetate PET scan.
- 2018
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In: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 25:6, s. 1937-1944
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Journal article (peer-reviewed)abstract
- BACKGROUND: Myocardial external efficiency (MEE) is defined as the ratio of kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean systemic pressure] and the chemical energy from oxygen consumed (MVO2) by the left ventricular mass (LVM). We developed a fully automated method for estimating MEE based on a single 11C-acetate PET scan without ECG-gating.METHODS AND RESULTS: Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and 20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center study. MVO2 was calculated using washout of 11C -acetate activity. FCO and LVM were calculated automatically using dynamic PET and parametric image formation. FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all subjects. The correlation between MEEPET-CMR and MEEPET was high (r = 0.85, P < 0.001) without significant bias. MEEPET was 23.6 ± 4.2% for controls and was lowered in AVS (17.2 ± 4.3%, P < 0.001) and in MVR (18.0 ± 5.2%, P = 0.004). MEEPET was strongly associated with both NYHA class (P < 0.001) and the magnitude of valvular dysfunction (mean aortic gradient: P < 0.001, regurgitant fraction: P = 0.009).CONCLUSION: A single 11C-acetate PET yields accurate and automated MEE results on different scanners. MEE might provide an unbiased measurement of the phenotypic response to valvular disease.
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| 17. |
- Harms, Hendrik Johannes, et al.
(author)
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Automatic extraction of forward stroke volume using dynamic PET/CT : a dual-tracer and dual-scanner validation in patients with heart valve disease.
- 2015
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In: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to develop and validate an automated method for extracting forward stroke volume (FSV) using indicator dilution theory directly from dynamic positron emission tomography (PET) studies for two different tracers and scanners.METHODS: 35 subjects underwent a dynamic (11)C-acetate PET scan on a Siemens Biograph TruePoint-64 PET/CT (scanner I). In addition, 10 subjects underwent both dynamic (15)O-water PET and (11)C-acetate PET scans on a GE Discovery-ST PET/CT (scanner II). The left ventricular (LV)-aortic time-activity curve (TAC) was extracted automatically from PET data using cluster analysis. The first-pass peak was isolated by automatic extrapolation of the downslope of the TAC. FSV was calculated as the injected dose divided by the product of heart rate and the area under the curve of the first-pass peak. Gold standard FSV was measured using phase-contrast cardiovascular magnetic resonance (CMR).RESULTS: FSVPET correlated highly with FSVCMR (r = 0.87, slope = 0.90 for scanner I, r = 0.87, slope = 1.65, and r = 0.85, slope = 1.69 for scanner II for (15)O-water and (11)C-acetate, respectively) although a systematic bias was observed for both scanners (p < 0.001 for all). FSV based on (11)C-acetate and (15)O-water correlated highly (r = 0.99, slope = 1.03) with no significant difference between FSV estimates (p = 0.14).CONCLUSIONS: FSV can be obtained automatically using dynamic PET/CT and cluster analysis. Results are almost identical for (11)C-acetate and (15)O-water. A scanner-dependent bias was observed, and a scanner calibration factor is required for multi-scanner studies. Generalization of the method to other tracers and scanners requires further validation.
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| 18. |
- Harms, Hendrik Johannes, et al.
(author)
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Automatic Extraction of Myocardial Mass and Volume Using Parametric Images from Dynamic Nongated PET
- 2016
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 57:9, s. 1382-1387
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Journal article (peer-reviewed)abstract
- Dynamic cardiac PET is used to quantify molecular processes in vivo. However, measurements of left ventricular (LV) mass and volume require electrocardiogram-gated PET data. The aim of this study was to explore the feasibility of measuring LV geometry using nongated dynamic cardiac PET. Methods: Thirty-five patients with aortic-valve stenosis and 10 healthy controls underwent a 27-min C-11-acetate PET/CT scan and cardiac MRI (CMR). The controls were scanned twice to assess repeatability. Parametric images of uptake rate K-1 and the blood pool were generated from nongated dynamic data. Using software-based structure recognition, the LV wall was automatically segmented from K-1 images to derive functional assessments of LV mass (m(LV)) and wall thickness. End systolic and end-diastolic volumes were calculated using blood pool images and applied to obtain stroke volume and LV ejection fraction (LVEF). PET measurements were compared with CMR. Results: High, linear correlations were found for LV mass (r = 0.95), end-systolic volume (r = 0.93), and end-diastolic volume (r = 0.90), and slightly lower correlations were found for stroke volume (r = 0.74), LVEF (r = 0.81), and thickness (r = 0.78). Bland Altman analyses showed significant differences for m(LV) and thickness only and an overestimation for LVEF at lower values. Intra- and interobserver correlations were greater than 0.95 for all PET measurements. PET repeatability accuracy in the controls was comparable to CMR. Conclusion: LV mass and volume are accurately and automatically generated from dynamic C-11-acetate PET without electrocardiogram gating. This method can be incorporated in a standard routine without any additional workload and can, in theory, be extended to other PET tracers.
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| 19. |
- Kindlund, Bert, 1969, et al.
(author)
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FOXP3-expressing CD4(+) T-cell numbers increase in areas of duodenal gastric metaplasia and are associated to CD4(+) T-cell aggregates in the duodenum of Helicobacter pylori-infected duodenal ulcer patients.
- 2009
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In: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 14:3, s. 192-201
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Journal article (peer-reviewed)abstract
- BACKGROUND: We have previously demonstrated that Helicobacter pylori infection is associated with an increased number of CD4(+)CD25(high) regulatory T cells in the gastric and duodenal mucosa. In this study, we determined the number and localization of CD4(+) cells expressing the regulatory T-cell-specific transcription factor FOXP3 in the antrum and duodenum of duodenal ulcer patients, asymptomatic carriers, and uninfected individuals. We also determined gene expression levels of FOXP3 as well as anti- and proinflammatory cytokines before and after H. pylori eradication. METHODS: Cellular FOXP3 expression was studied by immunofluorescence and flow cytometry, and transcription levels of FOXP3, interleukin (IL)-10, transforming growth factor-beta, CD4, and interferon-gamma were analyzed by real-time reverse transcription-polymerase chain reaction. RESULTS: We found an increased (6-fold) frequency of CD4(+)FOXP3(+) T cells in H. pylori-infected gastric mucosa; interestingly 26% of these cells did not co-express CD25. The increase of FOXP3-expressing T cells in the antrum of infected individuals was dependent on the presence of H. pylori, since eradication therapy resulted in 4-fold lower levels of FOXP3 and IL-10 mRNA in the antrum. Furthermore, higher numbers of CD4(+)FOXP3(+) T cells were found in areas of duodenal gastric metaplasia in the duodenum of duodenal ulcer patients compared to duodenal gastric metaplasia of asymptomatic individuals and healthy mucosa in both patient groups. In duodenal ulcer patients, the CD4(+)FOXP3(+) T cells were more highly associated to aggregates in the duodenal mucosa. CONCLUSION: The numbers of CD4(+)FOXP3(+) T cells are increased and localized in CD4(+) T-cell aggregates in areas of duodenal gastric metaplasia in duodenal ulcer patients.
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| 20. |
- Larsen, Anders Hostrup, et al.
(author)
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A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes
- 2020
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:9, s. 1628-1637
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Journal article (peer-reviewed)abstract
- AimsThe present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes. Methods and resultsThirty-six HFrEF patients (ejection fraction 378%; median age 66years) were randomised to metformin (n = 19) or placebo (n = 17) for 3months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by C-11-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 +/- 550 mg/day) increased WMI [absolute mean difference, 1.0mmHg.mL.m(-2).10(6); 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6mL O-2.100 g(-1).min(-1); P = 0.014). Cardiac stroke work was preserved (-2J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups. ConclusionMetformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.
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| 21. |
- Loodin, Henrik, et al.
(author)
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Beteendeförändring, tag plats!
- 2021
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In: Efter antibiotika : Om smitta i en ny tid - Om smitta i en ny tid. - 9789189139954 ; , s. 62-72
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Book chapter (pop. science, debate, etc.)
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| 22. |
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| 23. |
- Malmgren, Linnea, et al.
(author)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Journal article (peer-reviewed)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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| 24. |
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| 25. |
- Nielsen, Roni, et al.
(author)
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Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients
- 2019
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 139:18, s. 2129-2141
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Journal article (peer-reviewed)abstract
- BACKGROUND: Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential doseresponse relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO 2); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers.METHODS: Study 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37 +/- 3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a doseresponse study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO 2 were evaluated using 11C-acetate positron emission tomography.RESULTS: 3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4 +/- 0.3 to 3.3 +/- 0.4 mM (P< 0.001). CO rose by 2.0 +/- 0.2 L/min (P< 0.001) because of an increase in stroke volume of 20 +/- 2 mL (P< 0.001) and heart rate of 7 +/- 2 beats per minute (bpm) (P< 0.001). Left ventricular ejection fraction increased 8 +/- 1% (P< 0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM (P< 0.001). 3-OHB increased MVO 2 without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers.CONCLUSIONS: 3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients.
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| 26. |
- Schmitz, Alexander, et al.
(author)
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Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission : results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial
- 2022
-
In: BMC Cancer. - : BMC. - 1471-2407. ; 22:1
-
Journal article (peer-reviewed)abstract
- Background: Multiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. We investigated, if longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments. Methods: Patients from the Nordic countries with newly diagnosed multiple myeloma enrolled in the European-Myeloma-Network-02/Hovon-95 (EMN02/HO95) trial and undergoing bone marrow aspiration confirmation of complete response, were eligible for this Nordic Myeloma Study Group (NMSG) substudy. Longitdudinal flow-MRD assessment of bone marrow samples was performed to identify and enumerate residual malignant plasma cells until observed clinical progression. Results: Minimal residual disease dynamics were compared to biochemically assessed changes in serum free light chain and M-component. Among 20 patients, reaching complete response or stringent complete response during the observation period, and with >= 3 sequential flow-MRD assessments analysed over time, increasing levels of minimal residual disease in the bone marrow were observed in six cases, preceding biochemically assessed disease and clinical progression by 5.5 months and 12.6 months (mean values), respectively. Mean malignant plasma cells doubling time for the six patients was 1.8 months (95% CI, 1.4-2.3 months). Minimal malignant plasma cells detection limit was 4 x 10-5. Conclusions: Flow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response. Increasing minimal residual disease levels precedes biochemically assessed changes and is an early indicator of subsequent clinical progression.
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| 27. |
- Skillbäck, Tobias, et al.
(author)
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A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer's disease
- 2017
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling. Spectral clustering was used to match MS/MS spectra. The top biomarker candidate cluster (215% higher in AD compared to controls, area under ROC curve = 0.96) was identified as a fragment of pleiotrophin located near the protein's C-terminus. Analysis of another cohort (n = 60 over four clinical groups) verified that the biomarker was increased in AD patients while no change in controls, Parkinson's disease or progressive supranuclear palsy was observed. The identification of the novel biomarker pleiotrophin 151-166 demonstrates that our quantification-driven proteomic approach is a promising method for biomarker discovery, which may be universally applicable in clinical proteomics.
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| 28. |
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| 29. |
- Öberg, Henrik, et al.
(author)
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Adsorption and Cyclotrimerization Kinetics of C2H2 at a Cu(110) Surface
- 2012
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In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 116:17, s. 9550-9560
-
Journal article (peer-reviewed)abstract
- The kinetics of acetylene adsorption and cyclotrimerization was studied by vibrational sum-frequency generation spectroscopy (SFG) and density functional theory (DFT) calculations. At low temperature, SFG shows two resonances corresponding to acetylene adsorbed in two different sites. Upon heating, two new vibrational resonances appear. We interpret these resonances as being due to C2H2 island formation and adsorbed C4H4, which is the intermediate in the subsequent cyclotrimerization reaction to form benzene. A kinetic model is applied, which allows determination of the relevant activation barriers. The barrier for C2H2 diffusion is determined to be 43 +/- 1 kJ/mol. The activation barrier for formation of the C4H4 intermediate is found to be 84 +/- 6 kJ/mol and the barrier for benzene formation 5 +/- 3 kJ/mol lower. Barriers to diffusion and formation of C4H4 and C6H6 obtained from DFT calculations are in quantitative agreement with the experiments once the locally high coverage in C2H2 islands is included.
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| 30. |
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| 31. |
- Adamsson, Jenni, 1977, et al.
(author)
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Immune Responses Against Helicobacter pylori in Gastric Cancer Patients and in Risk Groups for Gastric Cancer.
- 2013
-
In: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 18:1, s. 73-82
-
Journal article (peer-reviewed)abstract
- BACKGROUND: It has previously been reported that weak serum IgG but elevated IgA antibody responses against H.pylori may be associated with risk of gastric cancer (GC) development. To search for potential immunologic markers for GC, we analyzed antibody responses against H.pylori in risk groups of cancer development. MATERIAL AND METHODS: Sera and stomach biopsies collected from H.pylori-infected GC patients as well as from patients with gastric ulcer (GU), atrophic gastritis, intestinal metaplasia (IM) and duodenal ulcer and from H.pylori-infected control subjects without atrophy or IM, and in addition from H.pylori-negative subjects were analyzed for IgG and IgA antibodies against three different H.pylori antigen preparations, that is, membrane protein (MP), urease, and CagA. RESULTS: We observed an increased serum IgA/IgG titer ratio against H.pylori anti-MP in GC and GU patients, and against CagA in Hp-infected GC patients and risk groups. Female patients with GC had a higher serum anti-MP IgA/IgG titer ratio and a higher proportion of poorly differentiated cancer compared with male patients. As earlier observed, the non-tumorous mucosa of H.pylori-infected GC patients contained considerably lower levels of total IgA and H.pylori-specific IgA compared with H.pylori-infected controls. Similarly, we observed decreased specific mucosal anti-MP IgA response in patients with IM. CONCLUSION: We observed several differences in local and systemic immunologic responses against H.pylori in H.pylori-infected GC patients and putative GC risk group patients compared with H.pylori-infected controls. These findings may be of importance in efforts to identify risk groups of GC or early stages of GC.
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| 32. |
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| 33. |
- Aghaee, Naghmeh, et al.
(author)
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Interaction Gaps in PhD Education and ICT as a Way Forward: Results from a Study in Sweden
- 2016
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In: International Review of Research in Open and Distance Learning. - : Athabasca University Press. - 1492-3831. ; 17:3, s. 360-383
-
Journal article (peer-reviewed)abstract
- Many research studies have highlighted the low completion rate and slow progress in PhD education. Universities strive to improve throughput and quality in their PhD education programs. In this study, the perceived problems of PhD education are investigated from PhD students' points of view, and how an Information and Communication Technology Support System (ICTSS) may alleviate these problems. Data were collected through an online open questionnaire sent to the PhD students at the Department of (the institution's name has been removed during the double-blind review) with a 59% response rate. The results revealed a number of problems in the PhD education and highlighted how online technology can support PhD education and facilitate interaction and communication, affect the PhD students' satisfaction, and have positive impacts on PhD students' stress. A system was prototyped, in order to facilitate different types of online interaction through accessing a set of online and structured resources and specific communication channels. Although the number of informants was not large, the result of the study provided some rudimentary ideas that refer to interaction problems and how an online ICTSS may facilitate PhD education by providing distance and collaborative learning, and PhD students' self-managed communication.
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| 34. |
- Aghaee, Naghmeh, et al.
(author)
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Learners’ Perceptions on the Structure and Usefulness of e-Resources for the Thesis Courses
- 2014
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In: European Journal of Open, Distance and E-Learning. - : Walter de Gruyter GmbH. - 1027-5207. ; 17:1, s. 154-171
-
Journal article (peer-reviewed)abstract
- Nowadays, utility of information and communication technology (ICT) in education is a way to facilitate interaction and accessing information for learning in higher education. However, finding a set of structured e-resources to facilitate learning within specific courses is still a big challenge in most of the institutions and universities. This includes the problems and challenges for the thesis courses in both undergraduate (Bachelor) and graduate (Master) level in Sweden. To overcome or reduce the problems and enhance quality of outcomes in the thesis courses, the department of Computer and Systems Sciences (DSV) at Stockholm University has developed a Learning Support System, SciPro (Scientific Process), to support thesis process. This study aims at investigating learners’ perspectives on usefulness of structured e-resources in order to reduce challenges for finding information related to the thesis steps in SciPro. This is done based on an open online survey, carried out in 2012-2013 of students’ perspectives at DSV. The study found the actual problems and hence suggested a model as a way forward to sort the useful e-resources to support reducing the problems in the thesis process.
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| 35. |
- Aghaee, Naghmeh, et al.
(author)
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Peer Portal : Quality Enhancement in Thesis Writing Using Self-Managed Peer Review on a Mass Scale
- 2013
-
In: International Review of Research in Open and Distance Learning. - : Athabasca University Press. - 1492-3831. ; 14:1, s. 186-203
-
Research review (peer-reviewed)abstract
- This paper describes a specially developed online peer-review system, the Peer Portal, and the first results of its use for quality enhancement of bachelor's and master's thesis manuscripts. The peer-review system is completely student driven and therefore saves time for supervisors and creates a direct interaction between students without interference from supervisors. The purpose is to improve thesis manuscript quality, and thereby use supervisor time more efficiently, since peers review basic aspects of the manuscripts and give constructive suggestions for improvements. The process was initiated in 2012, and, in total, 260 peer reviews were completed between 1st January and 15th May, 2012. All peer reviews for this period have been analyzed with the help of content analysis. The purpose of analysis is to assess the quality of the students work. The results are categorized in four groups: 1) excellent (18.1%), 2) good (22.7%), 3) fragmented (18.5%), and 4) poor (40.7%). The overall result shows that almost 40% of the students produced excellent or good peer reviews and almost as many produced poor peer reviews. The result shows that the quality varies considerably. Explanations of these quality variations need further study. However, alternative hypotheses followed by some strategic suggestions are discussed in this study. Finally, a way forward in terms of improving peer reviews is outlined: 1) development of a peer wizard system and 2) rating of received peer reviews based on the quality categories created in this study. A Peer Portal version 2.0 is suggested, which will eliminate the fragmented and poor quality peer reviews, but still keep this review system student driven and ensure autonomous learning.
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| 36. |
- Aghaee, Naghmeh, 1986-
(author)
-
The Usefulness of ICT Support Systems for Thesis Courses : Learners' Perspectives at Bachelor and Master Level
- 2015
-
Doctoral thesis (other academic/artistic)abstract
- Doing a bachelor’s or master’s degree is a journey that leads to success or attrition (dropout). Previous research show to the significance of considering learners’ perspectives and their need for information and different types of interaction. This can be done through online ICTSS (information and communication technology support systems). The overall aim of this dissertation was to create knowledge about how the use of ICTSS can facilitate different types of interaction and support learners in order to reduce thesis problems and attrition and to enhance the quality of the thesis outcomes. The aim was operationalized by two research questions scrutinizing the interaction problems in the thesis process and investigating how the use of ICTSS can facilitate different types of interaction to reduce such problems and attrition, and to enhance the learning opportunities and quality of the thesis outcomes. To answer the research questions, five main studies were performed by applying different research methods on a case study. The empirical studies were performed at the Department of Computer and Systems Sciences (DSV) at Stockholm University, Sweden. The respondents were different learners (students) with active thesis projects at the bachelor or master level in different programs at DSV between 2012 and 2015. For the first two studies, conceptual and content analysis of the data collected from the case study was performed. For the three other studies, open-ended online questionnaires (survey) and interviews were conducted. On the basis of the findings, three main types of interaction issues were developed which related to the need for more learner-content, peer-to-peer, and learner-supervisor interaction in the thesis process. The hypothesis was that the interaction issues could be reduced by implementing a set of strategic suggestions through the use of an ICTSS including a set of functionalities and resources. The usefulness of these functionalities and resources was evaluated with regard to the learners’ perception and experiences. The findings were categorized to facilitate learner-content, peer-to-peer, and learner-supervisor interaction, as well as management of the contents, supervision, and communication of the supervisory team. From these categories, a conceptual framework was developed in this dissertation to illustrate how the use of the ICTSS supports the thesis process. In conclusion, providing access to a set of structured e-resources and supporting educational communication through different types of interaction with peers and the supervisory team, enables learners’ self-managed learning and facilitates similar learning opportunities for learners in thesis courses.
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| 37. |
- Aguillon, David, et al.
(author)
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Plasma p-tau217 predicts in vivo brain pathology and cognition in autosomal dominant Alzheimer's disease
- 2023
-
In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:6, s. 2585-2594
-
Journal article (peer-reviewed)abstract
- Introduction: Plasma-measured tau phosphorylated at threonine 217 (p-tau217) is a potential non-invasive biomarker of Alzheimer's disease (AD). We investigated whether plasma p-tau217 predicts subsequent cognition and positron emission tomography (PET) markers of pathology in autosomal dominant AD. Methods: We analyzed baseline levels of plasma p-tau217 and its associations with amyloid PET, tau PET, and word list delayed recall measured 7.61 years later in non-demented age- and education-matched presenilin-1 E280A carriers (n = 24) and non-carrier (n = 20) family members. Results: Carriers had higher plasma p-tau217 levels than non-carriers. Baseline plasma p-tau217 was associated with subsequent amyloid and tau PET pathology levels and cognitive function. Discussion: Our findings suggest that plasma p-tau217 predicts subsequent brain pathological burden and memory performance in presenilin-1 E280A carriers. These results provide support for plasma p-tau217 as a minimally invasive diagnostic and prognostic biomarker for AD, with potential utility in clinical practice and trials. Highlights: Non-demented presenilin-1 E280A carriers have higher plasma tau phosphorylated at threonine 217 (p-tau217) than do age-matched non-carriers. Higher baseline p-tau217 is associated with greater future amyloid positron emission tomography (PET) pathology burden. Higher baseline p-tau217 is associated with greater future tau PET pathology burden. Higher baseline p-tau217 is associated with worse future memory performance.
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| 38. |
- Ahlberg, Erik, et al.
(author)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
-
In: Dagens nyheter (DN debatt). - 1101-2447.
-
Journal article (pop. science, debate, etc.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 39. |
- Ahlgren, Kerstin. M, et al.
(author)
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Diabetes mellitus in dog - : No evidence for a type-1-like phenotype
-
Other publication (other academic/artistic)abstract
- Aims/hypothesis Diabetes mellitus (DM) is one of the most common endocrine disorders in dogs, and is commonly proposed to be of autoimmune origin. Although the clinical symptoms of human type 1 diabetes (T1D) and canine DM are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported. Methods Sera from 121 diabetic dogs representing 38 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs from 40 breeds. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immunoprecipitation. Results None of the canine sera analyzed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Conclusions/interpretations Based on sera from 121 diabetic dogs from 38 different breeds were tested for humoral autoreactivity using four different assays, contrary to previous observations, we find no support for an autoimmune aetiology in canine diabetes.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Almeland, Stian, et al.
(author)
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The effect of microsurgical training on novice medical students’ basic surgical skills—a randomized controlled trial
- 2020
-
In: European journal of plastic surgery. - : Springer Science and Business Media LLC. - 0930-343X .- 1435-0130. ; 43, s. 459-466
-
Journal article (peer-reviewed)abstract
- Background It has been demonstrated that medical students are capable of learning microsurgical techniques. We hypothesize that microsurgical training might give insight into the importance of delicate tissue handling and correct knot tying that could have a positive influence on macrosurgical skills. The primary aim of this study was to evaluate the effect of microsurgical training on macrosurgical suturing skills in novice medical students. Subjects and methods In 2018, 46 novice medical students were enrolled and randomized into two groups. The intervention group received both macro- and microsurgical training and the control group received only microsurgical training. Both groups underwent an assessment test that consisted of macrosurgical tasks of three simple interrupted sutures with a square knot and continuous three-stitch long over-and-over sutures. These tests were individually filmed and assessed using the University of Bergen suturing skills assessment tool (UBAT) and the Objective Structured Assessment of Technical Skill global rating scale (OSATS). Questionnaires regarding future career ambitions and attitudes towards plastic surgery were also completed both prior to and following the tests. Results The intervention group needed a longer time to complete the tasks than the control group (12.2 min vs. 9.6 min, p>0.001), and scored lower on both the UBAT (5.6 vs. 9.0, p>0.001) and the OSATS (11.1 vs. 13.1, p>0.001) assessments. The microsurgery course tended to positively influence the students’ attitudes towards a career in plastic surgery (p=0.002). This study demonstrates poorer macrosurgical skills in the medical students group exposed to microsurgical training. The true effect of microsurgical training warrants further investigation.
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| 44. |
- Amer-Wåhlin, Isis, et al.
(author)
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Fetal cerebral energy metabolism and electrocardiogram during experimental umbilical cord occlusion and resuscitation.
- 2010
-
In: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 23:2, s. 158-166
-
Journal article (peer-reviewed)abstract
- Objective. The purpose of this experimental study was to elucidate alterations in fetal energy metabolism in relation to ECG changes during extreme fetal asphyxia, postnatal resuscitation and the immediate post-resuscitatory phase. Study design. Five near-term fetal sheep were subjected to umbilical cord occlusion until cardiac arrest followed by delivery, resuscitation and postnatal pressure-controlled ventilation. Four sheep served as sham controls and were delivered immediately after ligation of the umbilical cord. Fetal ECG was analysed online for changes of the ST segment. Fetal metabolism was monitored by intracerebral and subcutaneous microdialysis catheters. Results. Fetal ECG reacted on cord occlusion with an increase in the T-wave height followed by changes in intracerebral levels of oxidative parameters. Cerebral lactate/pyruvate ratio and glutamate increased to median (range) of 240 (200-744) and 34.0 (22.6-60.5) mmol/l, respectively; both parameters returned to baseline after resuscitation. Cerebral glucose decreased to 0.1 (0.08-0.12) mmol/l after occlusion and increased above baseline upon resuscitation. In subcutaneous tissue as well as blood the increase in lactate occurred with a delay compared to cerebral levels. Conclusion. The fetal ECG changes related to asphyxia preceded the increase in excitotoxicity as determined by increase in cerebral glutamate during asphyxia. Cerebral lactate increase was superior to subcutaneous lactate increase.
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| 45. |
- Anckarsäter, Henrik, 1966, et al.
(author)
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Child neurodevelopmental and behavioural problems are intercorrelated and dimensionally distributed in the general population
- 2008
-
In: The Open Psychiatry Journal. - : Bentham Science Publishers Ltd.. - 1874-3544. ; 2, s. 5-11
-
Journal article (peer-reviewed)abstract
- The Autism – Tics, AD/HD, and other Comorbidities inventory (A-TAC) is a comprehensive interview for evaluating problems related to autism spectrum disorders (ASD), tic disorders, attention-deficit/hyperactivity disorder (AD/HD), and common comorbid conditions in children and adolescents. A-TAC telephone interviews were administered to parents of 2,957 children aged nine- or twelve-years, representing one in each twin pair included in the population- based Child and Adolescent Twin Study in Sweden (CATSS). A total of 16.4% were screen-positive for one or several of the targeted disorder, 1.3% for ASD and 5.6% for AD/HD. All types of problems were more common among boys, with the exception of those related to “eating habits”. They were all dimensionally/continuously distributed, highly inter-correlated, and overlapped across types. They aggregated in three ba- sic factors corresponding to externalizing/disruptiveness, socio-communicative problems, and compulsiveness. Population-based data on problems in children thus challenge current categorical diagnostic definitions, calling for dimen- sional and complementary models of problem descriptions.
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| 46. |
- Andersson, Emelie, et al.
(author)
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Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer's disease
- 2020
-
In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 95, s. 143-153
-
Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) neurofilament light (NfL) concentration has reproducibly been shown to reflect neurodegeneration in brain disorders, including Alzheimer's disease (AD). NfL concentration in blood correlates with the corresponding CSF levels, but few studies have directly compared the reliability of these 2 markers in sporadic AD. Herein, we measured plasma and CSF concentrations of NfL in 478 cognitively unimpaired (CU) subjects, 227 patients with mild cognitive impairment, and 113 patients with AD dementia. We found that the concentration of NfL in CSF, but not in plasma, was increased in response to Aβ pathology in CU subjects. Both CSF and plasma NfL concentrations were increased in patients with mild cognitive impairment and AD dementia. Furthermore, only NfL in CSF was associated with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF NfL increased before serum NfL in response to the development of Aβ pathology. In conclusion, NfL in CSF may be a more reliable biomarker of neurodegeneration than NfL in blood in preclinical sporadic AD.
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| 47. |
- Andersson, E., et al.
(author)
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Cerebral A beta deposition precedes reduced cerebrospinal fluid and serum A beta 42/A beta 40 ratios in the App(NL-F/NL-F) knock-in mouse model of Alzheimer's disease
- 2023
-
In: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 15:1
-
Journal article (peer-reviewed)abstract
- BackgroundA beta 42/A beta 40 ratios in cerebrospinal fluid (CSF) and blood are reduced in preclinical Alzheimer's disease (AD), but their temporal and correlative relationship with cerebral A beta pathology at this early disease stage is not well understood. In the present study, we aim to investigate such relationships using App knock-in mouse models of preclinical AD.MethodsCSF, serum, and brain tissue were collected from 3- to 18-month-old App(NL-F/NL-F) knock-in mice (n = 48) and 2-18-month-old App(NL/NL) knock-in mice (n = 35). The concentrations of A beta 42 and A beta 40 in CSF and serum were measured using Single molecule array (Simoa) immunoassays. Cerebral A beta plaque burden was assessed in brain tissue sections by immunohistochemistry and thioflavin S staining. Furthermore, the concentrations of A beta 42 in soluble and insoluble fractions prepared from cortical tissue homogenates were measured using an electrochemiluminescence immunoassay.ResultsIn App(NL-F/NL-F) knock-in mice, A beta 42/A beta 40 ratios in CSF and serum were significantly reduced from 12 and 16 months of age, respectively. The initial reduction of these biomarkers coincided with cerebral A beta pathology, in which a more widespread A beta plaque burden and increased levels of A beta 42 in the brain were observed from approximately 12 months of age. Accordingly, in the whole study population, A beta 42/A beta 40 ratios in CSF and serum showed a negative hyperbolic association with cerebral A beta plaque burden as well as the levels of both soluble and insoluble A beta 42 in the brain. These associations tended to be stronger for the measures in CSF compared with serum. In contrast, no alterations in the investigated fluid biomarkers or apparent cerebral A beta plaque pathology were found in App(NL/NL) knock-in mice during the observation time.ConclusionsOur findings suggest a temporal sequence of events in App(NL-F/NL-F) knock-in mice, in which initial deposition of A beta aggregates in the brain is followed by a decline of the A beta 42/A beta 40 ratio in CSF and serum once the cerebral A beta pathology becomes significant. Our results also indicate that the investigated biomarkers were somewhat more strongly associated with measures of cerebral A beta pathology when assessed in CSF compared with serum.
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| 48. |
- Andersson, Emelie, et al.
(author)
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Cerebral Aβ deposition precedes reduced cerebrospinal fluid and serum Aβ42/Aβ40 ratios in the App NL−F/NL−F knock-in mouse model of Alzheimer’s disease
- 2023
-
In: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 15:1
-
Journal article (peer-reviewed)abstract
- Background: Aβ42/Aβ40 ratios in cerebrospinal fluid (CSF) and blood are reduced in preclinical Alzheimer’s disease (AD), but their temporal and correlative relationship with cerebral Aβ pathology at this early disease stage is not well understood. In the present study, we aim to investigate such relationships using App knock-in mouse models of preclinical AD. Methods: CSF, serum, and brain tissue were collected from 3- to 18-month-old AppNL−F/NL−F knock-in mice (n = 48) and 2–18-month-old AppNL/NL knock-in mice (n = 35). The concentrations of Aβ42 and Aβ40 in CSF and serum were measured using Single molecule array (Simoa) immunoassays. Cerebral Aβ plaque burden was assessed in brain tissue sections by immunohistochemistry and thioflavin S staining. Furthermore, the concentrations of Aβ42 in soluble and insoluble fractions prepared from cortical tissue homogenates were measured using an electrochemiluminescence immunoassay. Results: In AppNL−F/NL−F knock-in mice, Aβ42/Aβ40 ratios in CSF and serum were significantly reduced from 12 and 16 months of age, respectively. The initial reduction of these biomarkers coincided with cerebral Aβ pathology, in which a more widespread Aβ plaque burden and increased levels of Aβ42 in the brain were observed from approximately 12 months of age. Accordingly, in the whole study population, Aβ42/Aβ40 ratios in CSF and serum showed a negative hyperbolic association with cerebral Aβ plaque burden as well as the levels of both soluble and insoluble Aβ42 in the brain. These associations tended to be stronger for the measures in CSF compared with serum. In contrast, no alterations in the investigated fluid biomarkers or apparent cerebral Aβ plaque pathology were found in AppNL/NL knock-in mice during the observation time. Conclusions: Our findings suggest a temporal sequence of events in AppNL−F/NL−F knock-in mice, in which initial deposition of Aβ aggregates in the brain is followed by a decline of the Aβ42/Aβ40 ratio in CSF and serum once the cerebral Aβ pathology becomes significant. Our results also indicate that the investigated biomarkers were somewhat more strongly associated with measures of cerebral Aβ pathology when assessed in CSF compared with serum.
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| 49. |
- Andersson, Emelie, et al.
(author)
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CSF Aβ42 and Aβ40 and their relation to brain soluble and insoluble Aβ in the 5xFAD mouse model of Alzheimer's disease
- 2021
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 17
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Journal article (peer-reviewed)abstract
- BACKGROUND: In patients with AD, CSF Aβ42 is reduced while Aβ40 remains unchanged. It has been suggested that altered CSF Aβ42 is due to aggregation of this peptide into insoluble plaques, resulting in less soluble Aβ42 available for secretion to the CSF. However, the relations between soluble and insoluble Aβ42 and Aβ40 in the brain and the concentrations of these Aβ peptides in CSF are not well studied. METHODS: CSF and cortical brain tissue was collected from 2, 4, 6, and 12 months old male and female 5xFAD mice (n=45). CSF Aβ42 and Aβ40 concentrations were measured using Single molecule array (Simoa) technology. Brain sections were prepared and immunohistochemically (IHC) stained using antibodies specific for Aβ42 and Aβ40. The concentrations of Aβ42 and Aβ40 in soluble (extracted with TBS) and insoluble (extracted with formic acid) cortical brain fractions were determined by the Meso Scale Discovery technique. RESULTS: CSF Aβ42 was decreased over time whereas CSF Aβ40 remained unaltered (Fig 1). In the same mice, IHC revealed an age-related increased deposition of both Aβ42 and Aβ40 in insoluble plaques from 2 months of age (Fig 2). Moreover, measurements of Aβ42 and Aβ40 in soluble and insoluble cortical brain fractions showed increased concentrations of both peptides over time (Fig 3). CSF Aβ42 correlated inversely with cortical deposition of Aβ42 determined with IHC and the concentrations of Aβ42 in soluble and insoluble brain fractions. In contrast, no such correlations were found for Aβ40 (Fig 4). Although cortical levels of the two Aβ peptides were higher in females than in males, these sex differences were not reflected in CSF (Fig 5). CONCLUSIONS: Although significant depositions of both Aβ42 and Aβ40 were found in the brain, only Aβ42 was altered in CSF. Together with the finding that Aβ42 was increased, and not reduced, in soluble cortical brain fractions, this may suggest that mechanisms other than aggregation of Aβ42 into insoluble plaques contribute to decreased CSF concentrations of this Aβ peptide in 5xFAD mice. However, additional characterization of Aβ in the soluble brain fraction is needed to further understand its relation to the concentrations in CSF.
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- Andersson, Henrik, et al.
(author)
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Constitutive dependence in finite-element modelling of crack closure during fatigue
- 2004
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In: Fatigue & Fracture of Engineering Materials & Structures. - : Wiley. - 1460-2695 .- 8756-758X. ; 27:2, s. 75-87
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Journal article (peer-reviewed)abstract
- The influence of choice of constitutive relation on the prediction of crack-opening stress for fatigue cracks using the finite-element method is investigated and compared with experimental results. Two different experimentally obtained stress–strain relations for IN718 at 550 °C were used for fitting material parameters to the linear kinematic and the Bodner–Partom viscoplastic constitutive models. In addition, one reference material description and one Bodner–Partom with parameters fitted to both types of experiment was used, i.e., in total six constitutive descriptions. Experimental values for crack-opening stress were found by the potential drop method for the two load cases analyzed. Two different load cases, load control and displacement control, have been examined. It turns out that the correlation between experimental and analytical crack-opening stress vary significantly with material description, opening criteria in the simulation and load case. The investigation shows that care must be taken when choosing material description and opening criteria for crack propagation simulations.
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