| 1. |
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| 2. |
- Brorström, Björn, et al.
(författare)
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Doktorsutbildning för framtidens förvaltningsdoktorander : ett strategidokument från Högskolan i Borås
- 2008
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Ett mera kunskapsintensivt arbetsliv och tilltagande utmaningar för välfärdssamhället samverkar till att öka behovet av forskarkompetenser inom den offentliga sektorn. Allt fler personer med kvalificerade befattningar kommer i en nära framtid att behöva utföra forskningsliknande arbetsuppgifter, och delta i olika former av utvecklingsarbete och problemlösning som förutsätter ett tillgodogörande av vetenskapliga och analytiska arbetssätt. Förvaltningsdoktorer skulle kunna fungera som brobyggare mellan den svenska högskolan och den offentliga sektorns professioner, och därmed bidra till ett ökat in- och utflöde mellan å ena sidan den högre utbildningen och forskningen och å den andra en central del av välfärdsektorn. I denna rapport presenterar forskarna Björn Brorström, Olov Forsgren, Mikael Lind och Mikael Löfström ett förslag till en nydanande och professionsinriktad doktorsutbildning som riktar sig till framtidens förvaltningsexpertis.
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| 3. |
- Linge, Jennifer, et al.
(författare)
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Adverse muscle composition predicts all-cause mortality in the UK Biobank imaging study
- 2021
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Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 12:6, s. 1513-1526
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Tidskriftsartikel (refereegranskat)abstract
- Background Adverse muscle composition (MC) as measured by magnetic resonance imaging has previously been linked to poor function, comorbidity, and increased hospitalization. The aim of this study was to investigate if adverse MC predicts all-cause mortality using data from UK Biobank. Methods There were 40 178 participants scanned using a 6 min magnetic resonance imaging protocol. Images were analysed for thigh fat-tissue free muscle volume and muscle fat infiltration (MFI) using AMRA (R) Researcher (AMRA Medical, Linkoping, Sweden). For each participant, a sex, weight, and height invariant muscle volume z-score was calculated. Participants were partitioned into four MC groups: (i) normal MC, (ii) only low muscle volume [<25th percentile for muscle volume z-score (population wide)], (iii) only high MFI [>75th percentile (population wide, sex-specific)], and (iv) adverse MC (low muscle volume z-score and high MFI). Association of MC groups with mortality was investigated using Cox proportional-hazard modelling with normal MC as referent (unadjusted and adjusted for low hand grip strength, sex, age, body mass index, previous diagnosis of disease (cancer, type 2 diabetes and coronary heart disease), lifestyle, and socioeconomic factors (smoking, alcohol consumption, physical activity, and Townsend deprivation index). Results Muscle composition measurements were complete for 39 804 participants [52% female, mean (SD) age 64.2 (7.6) years and body mass index 26.4 (4.4) kg/m(2)]. Three hundred twenty-eight deaths were recorded during a follow-up period of 2.9 (1.4) years after imaging. At imaging, adverse MC was detected in 10.5% of participants. The risk of death from any cause in adverse MC compared with normal MC was 3.71 (95% confidence interval 2.81-4.91, P < 0.001). Only low muscle volume and only high MFI were independently associated with all-cause mortality [1.58 (1.13-2.21), P = 0.007, and 2.02 (1.51-2.71), P < 0.001, respectively]. Adjustment of low hand grip strength [1.77 (1.28-2.44), P < 0.001] did not attenuate the associations with any of the MC groups. In the fully adjusted model, adverse MC and only high MFI remained significant (P P = 0.020) while the association with only low muscle volume was attenuated to non-significance (P = 0.560). The predictive performance of adverse MC [1.96 (1.42-2.71), P < 0.001] was comparable with that of previous cancer diagnosis [1.93 (1.47-2.53), P < 0.001] and smoking [1.71 (1.02-2.84), P = 0.040]. Low hand grip strength was borderline non-significant [1.34 (0.96-1.88), P = 0.090]. Conclusions Adverse MC was a strong and independent predictor of all-cause mortality. Sarcopenia guidelines can be strengthened by including cut-offs for myosteatosis enabling detection of adverse MC.
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| 4. |
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| 5. |
- Albinsson, Lars, et al.
(författare)
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Towards a Co-Design Approach for Open Innovation
- 2008
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Ingår i: <em>Designed for Co-designers workshop</em>, Participatory Design Conference 2008 (PDC 2008). - School of Informatics, Indiana University, Bloomington, U.S.A : School of Informatics, Indiana University, Bloomington, U.S.A.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Albinsson, Lars, et al.
(författare)
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Turning the Internet Around : e-Me: The Students Ideal e-Service
- 2006
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Konferensbidrag (refereegranskat)abstract
- Today students, as many other groups of citizens, are offered, indeed required to use, a rapidly increasing number of e-Services. They range from school and course sites to interactions with authorities as well as companies offering student discounts. This paper reports on a pioneering project in Sweden with a radical approach to this, namely to issue the student with a electronic assistant, an e-Me, that schools, authorities and companies are required to address when interacting with the student. A larger number of students and partners, universities, companies and authorities, have been engaged in the design of such an e-Me. It might be thought of as turning the internet around – rather than having students keep track of sites, they will have to come to the students and interact with them in the way specified by them.
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| 7. |
- Andersson, Thord, et al.
(författare)
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Consistent intensity inhomogeneity correction in water-fat MRI
- 2015
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley-Blackwell. - 1053-1807 .- 1522-2586. ; 42:2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To quantitatively and qualitatively evaluate the water-signal performance of the consistent intensity inhomogeneity correction (CIIC) method to correct for intensity inhomogeneitiesMETHODS: Water-fat volumes were acquired using 1.5 Tesla (T) and 3.0T symmetrically sampled 2-point Dixon three-dimensional MRI. Two datasets: (i) 10 muscle tissue regions of interest (ROIs) from 10 subjects acquired with both 1.5T and 3.0T whole-body MRI. (ii) Seven liver tissue ROIs from 36 patients imaged using 1.5T MRI at six time points after Gd-EOB-DTPA injection. The performance of CIIC was evaluated quantitatively by analyzing its impact on the dispersion and bias of the water image ROI intensities, and qualitatively using side-by-side image comparisons.RESULTS: CIIC significantly ( P1.5T≤2.3×10-4,P3.0T≤1.0×10-6) decreased the nonphysiological intensity variance while preserving the average intensity levels. The side-by-side comparisons showed improved intensity consistency ( Pint≤10-6) while not introducing artifacts ( Part=0.024) nor changed appearances ( Papp≤10-6).CONCLUSION: CIIC improves the spatiotemporal intensity consistency in regions of a homogenous tissue type.
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| 8. |
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| 9. |
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| 10. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 11. |
- Brännström, Kristoffer, et al.
(författare)
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A Generic Method for Design of Oligomer-Specific Antibodies
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e90857-
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies that preferentially and specifically target pathological oligomeric protein and peptide assemblies, as opposed to their monomeric and amyloid counterparts, provide therapeutic and diagnostic opportunities for protein misfolding diseases. Unfortunately, the molecular properties associated with oligomer-specific antibodies are not well understood, and this limits targeted design and development. We present here a generic method that enables the design and optimisation of oligomer-specific antibodies. The method takes a two-step approach where discrimination between oligomers and fibrils is first accomplished through identification of cryptic epitopes exclusively buried within the structure of the fibrillar form. The second step discriminates between monomers and oligomers based on differences in avidity. We show here that a simple divalent mode of interaction, as within e. g. the IgG isotype, can increase the binding strength of the antibody up to 1500 times compared to its monovalent counterpart. We expose how the ability to bind oligomers is affected by the monovalent affinity and the turnover rate of the binding and, importantly, also how oligomer specificity is only valid within a specific concentration range. We provide an example of the method by creating and characterising a spectrum of different monoclonal antibodies against both the A beta peptide and alpha-synuclein that are associated with Alzheimer's and Parkinson's diseases, respectively. The approach is however generic, does not require identification of oligomer-specific architectures, and is, in essence, applicable to all polypeptides that form oligomeric and fibrillar assemblies.
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| 12. |
- Bui, Anh T., et al.
(författare)
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Reduced metabolic flexibility is a predictor of weight gain among liver transplant recipients
- 2023
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Ingår i: Liver transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1527-6465 .- 1527-6473.
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole-room calorimetry and is expressed as a respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state. The clinical, metabolic, and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (& beta;-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (& beta;-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (& beta;-coefficient 0.447, p = 0.02) directly correlated with the severity of weight gain. No statistically significant relationship between peak RQ, trough RQ, and weight change was demonstrated. Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity after LT with the potential to develop new diagnostics and therapeutics.
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| 13. |
- Chakravarthy, Manu V., et al.
(författare)
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Harnessing Muscle-Liver Crosstalk to Treat Nonalcoholic Steatohepatitis
- 2020
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions, affecting an estimated one-quarter of the worlds adult population. Multiple organ systems have been implicated in the pathophysiology of NAFLD; however, the role of skeletal muscle has until recently been largely overlooked. A growing body of evidence places skeletal muscle-via its impact on insulin resistance and systemic inflammation-and the muscle-liver axis at the center of the NAFLD pathogenic cascade. Population-based studies suggest that sarcopenia is an effect-modifier across the NAFLD spectrum in that it is tightly linked to an increased risk of non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), and advanced liver fibrosis, all independent of obesity and insulin resistance. Longitudinal studies suggest that increases in skeletal muscle mass over time may both reduce the incidence of NAFLD and improve preexisting NAFLD. Adverse muscle composition, comprising both low muscle volume and high muscle fat infiltration (myosteatosis), is highly prevalent in patients with NAFLD. The risk of functional disability conferred by low muscle volume in NAFLD is further exacerbated by the presence of myosteatosis, which is twice as common in NAFLD as in other chronic liver diseases. Crosstalk between muscle and liver is influenced by several factors, including obesity, physical inactivity, ectopic fat deposition, oxidative stress, and proinflammatory mediators. In this perspective review, we discuss key pathophysiological processes driving sarcopenia in NAFLD: anabolic resistance, insulin resistance, metabolic inflexibility and systemic inflammation. Interventions that modify muscle quantity (mass), muscle quality (fat), and physical function by simultaneously engaging multiple targets and pathways implicated in muscle-liver crosstalk may be required to address the multifactorial pathogenesis of NAFLD/NASH and provide effective and durable therapies.
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| 14. |
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| 15. |
- Ekstrand, Jimmy, et al.
(författare)
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Breast Density and Estradiol Are Major Determinants for Soluble TNF-TNF-R Proteins in vivo in Human Breast Tissue
- 2022
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Ingår i: Frontiers in Immunology. - Lausanne, Switzerland : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- High mammographic density and exposure to sex steroids are independent risk factors for breast cancer by yet unknown mechanisms. Inflammation is one hallmark of cancer and the tumor necrosis factor family of proteins (TNFSFs) and receptors (TNFRSFs) are key determinants of tissue inflammation. The relationship between TNFSFs/TNFRSFs and breast tissue density or local breast estradiol levels is unknown. We investigated whether TNFSFs and soluble TNFRSFs (sTNFRSFs) are dysregulated in vivo in human breast cancer and dense breast tissue of postmenopausal women. We explored TNFSF/TNFRSF correlations with breast density and estradiol, both locally in the breast and in abdominal subcutaneous (s.c.) fat as a measure of systemic effects. Microdialysis was used for local sampling of in vivo proteins and estradiol in a total of 73 women; 12 with breast cancer, 42 healthy postmenopausal women with different breast densities, and 19 healthy premenopausal women. Breast density was determined as lean tissue fraction (LTF) using magnetic resonance imaging. Microdialysis was also performed in estrogen receptor (ER) positive breast cancer in mice treated with the pure anti-estrogen fulvestrant and tumor tissue was subjected to immunohistochemistry. 23 members of the TNFSF/sTNFRSF families were quantified using proximity extension assay.Our data revealed upregulation of TNFSF10, 13 and 13B, TNFRSF6, 6B, 9, 11A, 11B, 13B, 14, and 19, and TNFR-1 and -2 in ER+ breast cancer in women. In dense breast tissue TNFSF10, 13, and 14, TNFRSF3, 6, 9, 10B, 13B, 14, 19, and TNFR-1 and -2 were upregulated. Certain TNFSFs/TNFRSFs were increased in premenopausal breasts relative to postmenopausal breasts. Furthermore, estradiol correlated with most of the TNFSF/sTNFRSF members, though LTF only correlated with some of the proteins. Several of these associations were breast tissue-specific, as very few correlated with estradiol in abdominal s.c. fat. Estrogen dependent regulations of TNFSF2 (TNF-alpha) and TNF-R2 were corroborated in ER+ breast cancer in mice. Taken together, our data indicate TNFSFs/sTNFRSFs may represent potential targetable pathways for treatment of breast cancer patients and in prevention of breast cancer development in women with dense breasts.
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| 16. |
- Eriksson, Mikael, 1977-
(författare)
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The complex internationalization process unfolded : The case of Atlas Copco’s entry into the Chinese mid-market
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite its contemporary relevance, we still have limited empirical knowledge about the forces underlying complex internationalization processes as when multinational corporations (MNCs) seek to enter new growing markets. Based on a real-time process study comprising ninety interviews and two hundred hours of observation made between 2009 and 2012, Atlas Copco’s entry into the Chinese mid-market was investigated. The intra-organizational analysis showed that three inter-related processes were underlying Atlas’ market entry and the results suggest that multiple interrelated motors may drive many contemporary internationalization processes. The processes identified are a sequential strategy process, an evolutionary process which shows that routines changed, and a political process. A somewhat surprising finding is that the main driver of internationalization according to received theory, the firm’s accumulated experiences, not only can drive internationalization, but may also hamper MNC managers’ possibilities to enter many of today’s new and growing markets. The findings add to our knowledge of the internationalization process in an increasingly complex international business setting, and especially highlight the need to distinguish between the sequential strategy process – more in line with received theory – and the other processes, in order to get a more full-fledged picture of what internationalization in large MNCs is all about.
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| 17. |
- Fallgren, Mikael, et al.
(författare)
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An Optimization Approach to Joint Cell, Channel and Power Allocation in Wireless Communication Networks
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In multicell wireless networks the resource allocation task includes the selection of the serving cell and the allocation of channels and transmission powers. While all of these tasks have been studied in the past, all three jointly are seldom addressed. In this paper we formulate the joint cell, channel and power allocation problem as an optimization task, whose purpose is to maximize either the minimum user throughput or the multicell total throughput. The max-min problem and a simplified max-sum problem are both known to be NP-hard, and we therefore propose heuristic solution approaches. In particular, we decompose the joint problem to the separate subproblems of cell selection, channel assignment and power allocation. We propose heuristic and optimization based algorithms to solve each of these tasks. An iterative channel and power update approach then address both the max-min and max-sum problems. Further, we also perform an exhaustive search over feasible cell and channel allocations. We present numerical results that give new and valuable insights into the trade off between fair and sum throughput optimal joint resource allocation strategies. Our proposed heuristics perform surprisingly close to the optimization based approaches,while the run time performance is significantly improved.
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| 18. |
- Fallgren, Mikael, 1982-
(författare)
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Optimization of Joint Cell, Channel and Power Allocation in Wireless Communication Networks
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis we formulate joint cell, channel and power allocation problems within wireless communication networks. The objectives are to maximize the user with mini- mum data throughput (Shannon capacity) or to maximize the total system throughput, referred to as the max-min and max-sum problem respectively. The complexity is stud- ied together with proposed optimization- and heuristic-based approaches. In the first paper an overall joint cell, channel and power allocation max-min prob- lem is formulated. We show that the decision problem is NP-hard and that the op- timization problem is not approximable unless P is equal to NP, for instances with a sufficiently large number of channels. Further, it follows that for a feasible binary cell and channel allocation, the remaining continuous power allocation optimization problem is still not approximable unless P is equal to NP. In addition, it is shown that first-order optimality conditions give global optimum of the single channel power al- location optimization problem, although the problem is in general not convex. In the following two papers heuristics for solving the overall problem are proposed. In the second paper we consider the single channel problem with convex combinations of the max-min and the max-sum objective functions. This variable utility provides the ability of tuning the amount of fairness and total throughput. The third paper investi- gates the multiple channel setting. On a system with three cells, eight mobile users and three channels, we perform an exhaustive search over feasible cell and channel alloca- tions. The exhaustive search is then compared to the less computationally expensive heuristic approaches, presenting potential earnings to strive for. A conclusion is that several of the proposed heuristics perform very well. The final paper incorporates fixed relay stations into the overall joint cell, channel and power allocation max-min problem. The complexity is inherited from the formula- tion without relay stations. Further, we propose a heuristic channel allocation approach that shows good performance, compared to an optimization based approach, in numer- ical simulations on the relay setting.
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| 19. |
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| 20. |
- Forsgren, Lilian, 1990, et al.
(författare)
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Composites with surface-grafted cellulose nanocrystals (CNC)
- 2019
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Ingår i: Journal of Materials Science. - : Springer Science and Business Media LLC. - 0022-2461 .- 1573-4803. ; 54:4, s. 3009-3022
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxyazetidinium salts were used to surface-modify cellulose nanocrystals (CNC) by grafting the salts onto the sulphate ester groups on the CNC surfaces. The grafting was confirmed by ζ-potential measurements and by the thermal degradation behaviour of the modified CNC. The thermal stability (onset of degradation) of the CNC was improved by the surface modification (almost 100 °C). Composites containing surface-modified or unmodified CNC (0.1, 1.0 and 10 wt%) with an ethylene-based copolymer as matrix were produced by compression moulding. The thermal stability of the composites was not, however, markedly improved by the surface grafting onto the CNC. It is suggested that this is due to a degrafting mechanism, associated with the alkaline character of the system, taking place at high temperatures. Model experiments indicated, however, that this did not occur at the conditions under which the composites were produced. Furthermore, in the case of a reference based on pH-neutralised polymeric system and modified CNC, an upward shift in the onset of thermal degradation of the composite was observed. The addition of the CNC to the polymer matrix had a strong influence of the mechanical performance. For example, the tensile modulus increased approximately three times for some systems when adding 10 wt% CNC. The surface grafting of the hydroxyazetidinium salts appeared mainly to affect, in a positive sense, the yield behaviour and ductility of the composites. The results of the mechanical testing are discussed in terms of interactions between the grafted units and the matrix material and between the grafted groups.
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| 21. |
- Forsgren, Lilian, 1990, et al.
(författare)
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Injection Molding and Appearance of Cellulose-Reinforced Composites
- 2019
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Ingår i: Polymer Engineering and Science. - : John Wiley and Sons Inc.. - 0032-3888 .- 1548-2634. ; 60:1, s. 5-12
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Tidskriftsartikel (refereegranskat)abstract
- Composite materials based on an ethylene-acrylic acid (EAA) copolymer and 20 wt% cellulose fibers were compounded by two runs in a twin-screw extruder. The composite material with cellulose fibers (CF) and a reference of unfilled EAA were injection molded into plaques using three different temperature profiles with end zone temperatures of 170°C, 200°C, and 230°C. The injection molded samples were then characterized in terms of their mechanical properties, thermal properties, appearance (color and gloss), and surface topography. The higher processing temperatures resulted in a clear discoloration of the composites, but there was no deterioration in the mechanical performance. The addition of cellulose typically gave a tensile modulus three times higher than that of the unfilled EAA, but the strength and strain at rupture were reduced when fibers were added. The processing temperature had no significant influence on the mechanical properties of the composites. Gloss measurements revealed negligible differences between the samples molded at the different melt temperatures but the surface smoothness was somewhat higher when the melt temperature was increased. In general, addition of the cellulose to the EAA reduced the gloss level and the surface smoothness.
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| 22. |
- Forsgren, Lilian, 1990, et al.
(författare)
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Water-assisted extrusion and injection moulding of composites with surface-grafted cellulose nanocrystals – An upscaling study
- 2021
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Ingår i: Composites Part B: Engineering. - : Elsevier BV. - 1359-8368. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- The large-scale surface modification of cellulose nanocrystals (CNC) was carried out to produce CNC-containing composites, in a scale of 3 kg, using industrial-scale melt processing techniques such as twin-screw extrusion and injection moulding. Two different polymer matrices, ethylene-acrylic acid copolymer (EAA) and low-density polyethylene (LDPE), were reinforced with 10 wt% unmodified cellulose nanocrystals (CNC) or surface-treated CNC, where a 2-hydroxyproyl-N-diallyl group had been grafted onto the sulphate half-ester groups on the CNC surfaces. This was achieved by mixing an aqueous CNC dispersion and the polymer pellets directly in the twin-screw extruder followed by a second dry compounding step prior to shaping by injection moulding. The injection-moulded materials were characterized with respect to their mechanical properties and thermal stability. The addition of 10 wt % CNC resulted in all cases in an increase in the yield strength and stiffness by 50–100%, most significantly for the EAA based composites. There were indications of the presence of a stable interphase and a percolating network in the EAA-based materials, according to dynamic-mechanical measurements. A reduction in thermal stability was observed for the melt-processed samples containing diallyl-modified CNC and discoloration in the EAA based samples.
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| 23. |
- Forsgren, Mikael, et al.
(författare)
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31P MRS as a Potential Biomarker for Fibromyalgia
- 2012
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Ingår i: Proceedings of the 20th Annaal Meeting & Exhibition, 5-11 May, Melbourne, Australia. ; , s. 1493-1493
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Konferensbidrag (refereegranskat)abstract
- Major clinical symptoms in fibromyalgia (FM) are muscle pain, stiffness and fatigue. Studies have shown reduced voluntary strength and exercise capacity, lower endurance and more muscular pain even at low workload. An impaired muscle energy metabolism has therefore been proposed as a result of the disease. An earlier study using magnetic resonance spectroscopy (MRS) showed that at maximal dynamic and static contractions the concentration of inorganic phosphate was lower in FM [1]. A decrease in ATP, ADP and PCr and an increase in AMP and creatine was found in FM biopsies [2]. The purpose of this study was to non-invasively analyze the quantitative content of phosphagens in the resting muscle in FM in comparison to healthy controls using 31P MRS of the quadriceps muscle.
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| 24. |
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| 25. |
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| 26. |
- Forsgren, Mikael, et al.
(författare)
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Comparing 2D and 3D Magnetic Resonance Elastography Techniques in a Clinical Setting: Initial Experiences
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: It has been shown that liver fibrosis, and even cirrhosis, may be reversible in humans. For this reason there is a great need for the imminent introduction of non-invasive and clinically useful methods in order to monitor fibrosis in patients [1, 2]. A body of evidence points to the fact that MRE is a highly useful candidate towards this end [3]. However, before using such techniques more widely, it is important to verify that comparable physical measures are provided by alternative and clinically relevant MRE approaches. The aim of this pilot study was to compare 2D and 3D MRE, also known as MR Rheology, using a commercially available 2D system, with an acoustic transducer, and 3D MRE research system, with an electromagnetic transducer, with respect to liver stiffness and elasticity in patients with diffuse or suspected diffuse liver disease. Materials and Methods: Seven patients, referred to our hospital for evaluation of elevated serum alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) levels but without signs of cirrhosis on physical examination, were recruited from a previous study [4], and examined in the course of one day. Fibrosis staging from prior biopsy were gained from [4], see Table 1. The 3D MRE method included an active electromagnetic transducer generating waves at 56 Hz, and a 1.5 T Philips Achieva MR-scanner, with a phased array body coil (Sense TorsoXL, all 16 coil elements), GRE sequence parameters include; FOV = 320x256 mm2, matrix = 80x38, slice thickness = 4 mm, # slices = 9, FA = 15°, TR = 112 ms, TE = 9.21 ms, SENSE = 2. The 2D MRE method included a passive acoustic transducer generating waves at 60 Hz, and a 1.5 T GE 450W MR-scanner, with a phased array body coil (HD8 Torso, all 8 coil elements), GRE sequence parameters include; FOV = 440x440 mm2, matrix = 256x64, slice thickness = 10 mm, # slices = 4, FA = 30°, TR = 50 ms, TE = 21.7 ms, ASSET = 2. The transducers were on both systems placed on the anterior chest wall to the right of xiphoid process (patient in a supine position), the time between each MRE acquisition was dependent on how long it took to transfer the patient between the two MR systems in the hospital (<10 min) A region of interest (ROI) was placed in an appropriate single 10 mm slice acquired using the GE MR-scanner. A corresponding ROI for the Philips system, covering the same anatomical region, was placed over three slices (4 mm thickness each). This yielded a total cranio-caudal coverage of the ROIs equal to 10 mm (on the GE data) and 12 mm (on the Philips data). The mean and standard deviations of the stiffness (GE), elasticity (Philips) and Gabs,Elastic (Philips) were calculated. Gabs,Elastic is the absolute value of the shear modulus, which in principle is equivalent to the viscoelastic property, shear stiffness. In the 3D method the shear waves were obtained by applying the curl operator and using the Voigt rheological model to obtain shear elasticity maps [5, 6]. In the 2D method the GE system provided the stiffness maps. Statistics was performed using Mathematica 9. ROI drawing and quantification of the data from the GE system was performed using Sectra PACS IDS7, and ROI drawing and quantification of the data from the Philips system was performed using a custom software package implemented in ROOT, generously provided by R. Sinkus (Kings College, London, UK). Results: The measured values are presented in Table 1. Both elasticity and Gabs,Elastic correlates well with the stiffness measurement carried out in the GE system (Fig. 1), as was shown by the elasticity and stiffness correlation R2 = 0.96 (P < 0.001) slope = 1.08 (P < 0.001), intercept = 0.61 kPa (P = 0.08), Gabs,Elastic and stiffness correlation R2 = 0.96 (P < 0.001), slope = 0.95 (P< 0.001) intercept = 0.28 kPa (P = 0.43)
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| 27. |
- Forsgren, Mikael, et al.
(författare)
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Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences
- 2015
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Ingår i: European Journal of Radiology Open. - : Elsevier. - 2352-0477. ; 2, s. 66-70
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Tidskriftsartikel (refereegranskat)abstract
- PurposeContinuous monitoring of liver fibrosis progression in patients is not feasible with the current diagnostic golden standard (needle biopsy). Recently, magnetic resonance elastography (MRE) has emerged as a promising method for such continuous monitoring. Since there are different MRE methods that could be used in a clinical setting there is a need to investigate whether measurements produced by these MRE methods are comparable. Hence, the purpose of this pilot study was to evaluate whether the measurements of the viscoelastic properties produced by 2D (stiffness) and 3D (elasticity and ‘Gabs,Elastic’) MRE are comparable.Materials and methodsSeven patients with diffuse or suspect diffuse liver disease were examined in the same day with the two MRE methods. 2D MRE was performed using an acoustic passive transducer, with a 1.5 T GE 450 W MR system. 3D MRE was performed using an electromagnetic active transducer, with a 1.5 T Philips Achieva MR system. Finally, mean viscoelastic values were extracted from the same anatomical region for both methods by an experienced radiologist.ResultsStiffness correlated well with the elasticity, R2 = 0.96 (P < 0.001; slope = 1.08, intercept = 0.61 kPa), as well as with ‘Gabs,Elastic’ R2 = 0.96 (P < 0.001; slope = 0.95, intercept = 0.28 kPa).ConclusionThis pilot study shows that different MRE methods can produce comparable measurements of the viscoelastic properties of the liver. The existence of such comparable measurements is important, both from a clinical as well as a research perspective, since it allows for equipment-independent monitoring of disease progression.
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| 28. |
- Forsgren, Mikael F, 1983-, et al.
(författare)
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Biomarkers of liver fibrosis : prospective comparison of multimodal magnetic resonance, serum algorithms and transient elastography.
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:7, s. 848-859
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and 31P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available.METHODS: Patients were recruited prospectively if they were scheduled to undergo liver biopsy on a clinical indication due to elevated liver enzyme levels without decompensated cirrhosis. Within a month of the clinical work-up, an MR-examination and liver needle biopsy were performed on the same day. Based on late-phase gadoxetate-enhanced MRI, a mathematical model calculated hepatobiliary function (relating to OATP1 and MRP2). The hepatocyte gadoxetate uptake rate (KHep) and the normalised liver-to-spleen contrast ratio (LSC_N10) were also calculated. Nine serum fibrosis algorithms were investigated (GUCI, King's Score, APRI, FIB-4, Lok-Index, NIKEI, NASH-CRN regression score, Forns' score, and NAFLD-fibrosis score).RESULTS: The diagnostic performance (AUROC) for identification of significant fibrosis (F2-4) was 0.78, 0.80, 0.69, and 0.78 for MRE, TE, LSC_N10, and GUCI, respectively. For the identification of advanced fibrosis (F3-4), the AUROCs were 0.93, 0.84, 0.81, and 0.82 respectively.CONCLUSION: MRE and TE were superior for non-invasive identification of significant fibrosis. Serum fibrosis algorithms developed for specific liver diseases are applicable in this cohort of diverse liver diseases aetiologies. Gadoxetate-MRI was sufficiently sensitive to detect the low function losses associated with fibrosis. None was able to efficiently distinguish between stages within the low fibrosis stages.Lay summaryExcessive accumulation of scar tissue, fibrosis, in the liver is an important aspect in chronic liver disease. To replace the invasive needle biopsy, we have explored non-invasive methods to assess liver fibrosis. In our study we found that elastographic methods, which assess the mechanical properties of the liver, are superior in assessing fibrosis in a clinical setting. Of interest from a clinical trial point-of-view, none of the tested methods was sufficiently accurate to distinguish between adjacent moderate fibrosis stages.
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| 29. |
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| 30. |
- Forsgren, Mikael, et al.
(författare)
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Model-inferred mechanisms of liver function from magnetic resonance imaging data : Validation and variation across a clinically relevant cohort
- 2019
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Ingår i: PloS Computational Biology. - San Francisco, CA, United States : Public Library of Science. - 1553-734X .- 1553-7358. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Estimation of liver function is important to monitor progression of chronic liver disease (CLD). A promising method is magnetic resonance imaging (MRI) combined with gadoxetate, a liver-specific contrast agent. For this method, we have previously developed a model for an average healthy human. Herein, we extended this model, by combining it with a patient-specific non-linear mixed-effects modeling framework. We validated the model by recruiting 100 patients with CLD of varying severity and etiologies. The model explained all MRI data and adequately predicted both timepoints saved for validation and gadoxetate concentrations in both plasma and biopsies. The validated model provides a new and deeper look into how the mechanisms of liver function vary across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate. These mechanisms are shared across many liver functions and can now be estimated from standard clinical images.Author summaryBeing able to accurately and reliably estimate liver function is important when monitoring the progression of patients with liver disease, as well as when identifying drug-induced liver injury during drug development. A promising method for quantifying liver function is to use magnetic resonance imaging combined with gadoxetate. Gadoxetate is a liver-specific contrast agent, which is taken up by the hepatocytes and excreted into the bile. We have previously developed a mechanistic model for gadoxetate dynamics using averaged data from healthy volunteers. In this work, we extended our model with a non-linear mixed-effects modeling framework to give patient-specific estimates of the gadoxetate transport-rates. We validated the model by recruiting 100 patients with liver disease, covering a range of severity and etiologies. All patients underwent an MRI-examination and provided both blood and liver biopsies. Our validated model provides a new and deeper look into how the mechanisms of liver function varies across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate.
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| 31. |
- Forsgren, Mikael, et al.
(författare)
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Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:4, s. 0095700-
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Diffuse liver disease (DLD), such as non-alcoholic fatty liver disease (NASH) and cirrhosis, is a rapidly growing problem throughout the Westernized world. Magnetic resonance imaging (MRI), based on uptake of the hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive approach for diagnosing DLD. However, to fully utilize the potential of such dynamic measurements for clinical or research purposes, more advanced methods for data analysis are required. Methods: A mathematical model that can be used for such data-analysis was developed. Data was obtained from healthy human subjects using a clinical protocol with high spatial resolution. The model is based on ordinary differential equations and goes beyond local diffusion modeling, taking into account the complete system accessible to the CA. Results: The presented model can describe the data accurately, which was confirmed using chi-square statistics. Furthermore, the model is minimal and identifiable, meaning that all parameters were determined with small degree of uncertainty. The model was also validated using independent data. Conclusions: We have developed a novel approach for determining previously undescribed physiological hepatic parameters in humans, associated with CA transport across the liver. The method has a potential for assessing regional liver function in clinical examinations of patients that are suffering of DLD and compromised hepatic function.
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| 32. |
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| 33. |
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| 34. |
- Forsgren, Mikael
(författare)
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The Non-Invasive Liver Biopsy : Determining Hepatic Function in Diffuse and Focal LiverDisease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development.Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level.Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies.The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI).The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis.Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function).In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.
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| 35. |
- Forsgren, Mikael, et al.
(författare)
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Whole Body Mechanistic Minimal Model for Gd-EOB-DTPA Contrast Agent Pharmacokinetics in Evaluation of Diffuse Liver Disease
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Aiming for non-invasive diagnostic tools to decrease the need for biopsy in diffuse liver disease and to quantitatively describe liver function, we applied a mechanistic pharmacokinetic modelling analysis of liver MRI with Gd-EOB-DTPA. This modelling method yields physiologically relevant parameters and was compared to previously developed methods in a patient group with diffuse liver disease. Materials and Methods: Using data from healthy volunteers undergoing liver MRI, an identifiable mechanistic model was developed, based on compartments described by ordinary differential equations and kinetic expressions, and validated with independent data including Gd-EOB-DTPA concentration measurements in blood samples. Patients (n=37) with diffuse liver disease underwent liver biopsy and MRI with Gd-EOB-DTPA. The model was used to derive pharmacokinetic parameters which were then compared with other quantitative estimates in their ability to separate mild from severe liver fibrosis. Results: The estimations produced by the mechanistic model allowed better separation between mild and severe fibrosis than previously described methods for quantifying hepatic Gd-EOB-DTPA uptake. Conclusions: With a mechanistic pharmacokinetic modelling approach, the estimation of liver uptake function and its diagnostic information can be improved compared to current methods.
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| 36. |
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| 37. |
- Forsgren, Olov, et al.
(författare)
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Experiences from setting up an Internet Shopping Collaboratory
- 2007
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Ingår i: Expanding the Knowledge Economy: Issues, Applications, Case Studies. Volume 4, Part 1.. - Amsterdam : IOS Press. - 9781586038014 ; , s. 850-857
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Bokkapitel (refereegranskat)abstract
- In today’s business there is a clear need to find innovative procedures regarding product- or service development where several stakeholders meet in the same arena. An unresolved quest, however, is how such an arena could be set up and which activities to perform. This paper describes experiences from establishing such an arena, called an Internet Shopping Collaboratory (ISC). The ISC assembled researchers, practitioners, consumers, and solution providers in refining ideas to new products aimed to a future e-market. The basic idea has been to apply a co-design approach. The paper outlines why the ISC project did not work and lessons that were learnt. In the paper we make equivalent comparisons from the characteristics of the evolving ISC to the Living Lab concept. A focus on content was found vital for getting the different stakeholders engaged in the collaboratory. The case described uses an ideal scenario technique and applies a co-design approach.
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| 38. |
- Gerdle, Björn, et al.
(författare)
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Decreased muscle concentrations of ATP and PCR in the quadriceps muscle of fibromyalgia patients – A 31P-MRS study
- 2013
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Ingår i: European Journal of Pain. - : John Wiley & Sons. - 1090-3801 .- 1532-2149. ; 17:8, s. 1205-1215
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND METHODS:Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P magnetic resonance spectroscopy (31P-MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (Controls; n = 14) using (31) P-MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity.RESULTS:Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28-29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in Controls [FMS: 9.0 ± 0.5% vs. Controls: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities.CONCLUSIONS:Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.
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| 39. |
- Gerdle, Björn, et al.
(författare)
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Evidence of Mitochondrial Dysfunction in Fibromyalgia : Deviating Muscle Energy Metabolism Detected Using Microdialysis and Magnetic Resonance
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- In fibromyalgia (FM) muscle metabolism, studies are sparse and conflicting associations have been found between muscle metabolism and pain aspects. This study compared alterations in metabolic substances and blood flow in erector spinae and trapezius of FM patients and healthy controls. FM patients (n = 33) and healthy controls (n = 31) underwent a clinical examination that included pressure pain thresholds and physical tests, completion of a health questionnaire, participation in microdialysis investigations of the etrapezius and erector spinae muscles, and also underwent phosphorus-31 magnetic resonance spectroscopy of the erector spinae muscle. At the baseline, FM had significantly higher levels of pyruvate in both muscles. Significantly lower concentrations of phosphocreatine (PCr) and nucleotide triphosphate (mainly adenosine triphosphate) in erector spinae were found in FM. Blood flow in erector spinae was significantly lower in FM. Significant associations between metabolic variables and pain aspects (pain intensity and pressure pain threshold PPT) were found in FM. Our results suggest that FM has mitochondrial dysfunction, although it is unclear whether inactivity, obesity, aging, and pain are causes of, the results of, or coincidental to the mitochondrial dysfunction. The significant regressions of pain intensity and PPT in FM agree with other studies reporting associations between peripheral biological factors and pain aspects.
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| 40. |
- Gerdle, Björn, et al.
(författare)
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Fibromyalgia : Associations Between Fat Infiltration, Physical Capacity, and Clinical Variables
- 2022
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Ingår i: Journal of Pain Research. - : Dove Medical Press LTD. - 1178-7090. ; 15, s. 2517-2535
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a risk factor for the development of fibromyalgia (FM) and generally most studies report increased Body Mass Index (BMI) in FM. Obesity in FM is associated with a worse clinical presentation. FM patients have low physical conditioning and obesity further exacerbates these aspects. Hitherto studies of FM have focused upon a surrogate for overall measure of fat content, ie, BMI. This study is motivated by that ectopic fat and adipose tissues are rarely investigated in FM including their relationships to physical capacity variables. Moreover, their relationships to clinical variables including are not known. Aims were to 1) compare body composition between FM and healthy controls and 2) investigate if significant associations exist between body composition and physical capacity aspects and important clinical variables.Methods: FM patients (n = 32) and healthy controls (CON; n = 30) underwent a clinical examination that included pressure pain thresholds and physical tests. They completed a health questionnaire and participated in whole-body magnetic resonance imaging (MRI) to determine body composition aspects.Results: Abdominal adipose tissues, muscle fat, and BMI were significantly higher in FM, whereas muscle volumes of quadriceps were smaller. Physical capacity variables correlated negatively with body composition variables in FM. Both body composition and physical capacity variables were significant regressors of group belonging; the physical capacity variables alone showed stronger relationships with group membership. A mix of body composition variables and physical capacity variables were significant regressors of pain intensity and impact in FM. Body composition variables were the strongest regressors of blood pressures, which were increased in FM.Conclusion: Obesity has a negative influence on FM symptomatology and increases the risk for other serious conditions. Hence, obesity, dietary habits, and physical activity should be considered when developing clinical management plans for patients with FM.
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| 41. |
- Gerdle, Björn, et al.
(författare)
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Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content
- 2024
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Ingår i: FRONTIERS IN PAIN RESEARCH. - : FRONTIERS MEDIA SA. - 2673-561X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables in healthy subjects and in fibromyalgia patients (FM). There is a need to better understand the extent cytokines and chemokines are associated with body composition and which cytokines and chemokines differentiate FM from healthy controls.Methods Here, 32 female FM patients and 30 age-matched female healthy controls underwent a clinical examination that included blood sample, saliva samples, and pain threshold tests. In addition, the subjects completed a health questionnaire. From these blood and saliva samples, a panel of 68 mainly cytokines and chemokines were determined. Microdialysis of trapezius and erector spinae muscles, phosphorus-31 magnetic resonance spectroscopy of erector spinae muscle, and whole-body magnetic resonance imaging for determination of body composition (BC)-i.e., muscle volume, fat content and infiltration-were also performed.Results After standardizing BC measurements to remove the confounding effect of Body Mass Index, fat infiltration and content are generally increased, and fat-free muscle volume is decreased in FM. Mainly saliva proteins differentiated FM from controls. When including all investigated compounds and BC variables, fat infiltration and content variables were most important, followed by muscle compounds and cytokines and chemokines from saliva and plasma. Various plasma proteins correlated positively with pain intensity in FM and negatively with pain thresholds in all subjects taken together. A mix of increased plasma cytokines and chemokines correlated with an index covering fat infiltration and content in different tissues. When muscle compounds were included in the analysis, several of these were identified as the most important regressors, although many plasma and saliva proteins remained significant.Discussion Peripheral factors were important for group differentiation between FM and controls. In saliva (but not plasma), cytokines and chemokines were significantly associated with group membership as saliva compounds were increased in FM. The importance of peripheral factors for group differentiation increased when muscle compounds and body composition variables were also included. Plasma proteins were important for pain intensity and sensitivity. Cytokines and chemokines mainly from plasma were also significantly and positively associated with a fat infiltration and content index.Conclusion Our findings of associations between cytokines and chemokines and fat infiltration and content in different tissues confirm that inflammation and immune factors are secreted from adipose tissue. FM is clearly characterized by complex interactions between peripheral tissues and the peripheral and central nervous systems, including nociceptive, immune, and neuroendocrine processes.
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| 42. |
- Ghafouri, Bijar, et al.
(författare)
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Fibromyalgia in women : association of inflammatory plasma proteins, muscle blood flow, and metabolism with body mass index and pain characteristics
- 2022
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Ingår i: Pain Reports. - : Lippincott, Williams & Wilkins. - 2471-2531. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Obesity is a common comorbidity in fibromyalgia (FM). Both FM and obesity have been connected to low-grade inflammation, although it is possible that previously reported inflammatory alterations in FM primarily may be linked to increased body mass index (BMI). Objective: This study aimed to investigate whether the inflammatory plasma protein profile, muscle blood flow, and metabolism and pain characteristics (clinical parameters and patient-reported outcome measurements) differed between female patients with FM with and without obesity. Methods: Patients with FM underwent clinical examinations, physical tests, and answered questionnaires. They were dichotomized according to BMI (<30 kg/m(2) [n = 14]; >= 30 kg/m(2) [n = 13]). Blood samples were collected and analyzed using a panel of 71 inflammatory plasma proteins. Results: There were significant (P < 0.05) differences in blood pressure, pulse, max VO2, pain intensity, physical capacity, and Fibromyalgia Impact Questionnaire between the groups; the obese group had higher blood pressure, pulse, pain intensity, and Fibromyalgia Impact Questionnaire. There were 14 proteins that contributed to the group belonging. The 4 most important proteins for the group discrimination were MIP1 beta, MCP4, IL1RA, and IL6, which showed higher concentrations in obese patients with FM. Significantly decreased blood flow and increased concentration of pyruvate were detected in obese patients compared with nonobese patients. There was significant correlation between inflammatory proteins and sedentary behavior and health status in obese patients with FM. Conclusions: These findings suggest that metabolism and inflammation interact in female patients with FM with obesity and might cause chronic low-grade inflammation. Screening for obesity and monitoring of BMI changes should be considered in the treatment of patients with FM.
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| 43. |
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| 44. |
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| 45. |
- Karageorgis, Anastassia, et al.
(författare)
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A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Drug-induced liver injury (Dili) is a leading cause of acute liver failure and transplantation. Dili can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers. The mean gadoxetate uptake rate constant for the vehicle groups at all centers was 39.3 +/- 3.4 s -1 (n = 23) and 11.7 +/- 1.3 s -1 (n = 20) for the rifampicin groups. The mean gadoxetate efflux rate constant for the vehicle groups was 1.53 +/- 0.08 s -1 (n = 23) and for the rifampicin treated groups was 0.94 +/- 0.08 s -1 (n = 20). Both the uptake and excretion transporters of gadoxetate were statistically significantly inhibited by the clinical dose of rifampicin at all centers and the size of this treatment group effect was consistent across the centers. Gadoxetate is a clinically approved MRI contrast agent, so this method is readily transferable to the clinic. Conclusion: Rate constants of
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| 46. |
- Karlsson, Markus, et al.
(författare)
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Diffuse Liver Disease: Measurements of Liver Trace Metal Concentrations and R2* Relaxation Rates
- 2016
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer. - 0968-5243 .- 1352-8661. ; 29:1, s. S395-S395
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionOver the past decade, several methods for measuring of liver iron content (LIC) non-invasively with MRI have been developed and verified. The most promising methods uses relaxometry, measuring either R2- or R2* relaxation rate in the liver1,2. For instance, several studies have shown that there seems to be a linear relationship between R2* and LIC1. However, few of these studies have measured the liver content of other metals, which could also affect the relaxation rates. The goal of this study was to investigate if any trace metals, other than iron could affect the R2* relaxation rate in liver tissue in a patients with diffuse liver disease.Subjects and methods75 patients with suspected diffuse liver disease underwent an MRI examination followed by a liver biopsy the same day. The R2* relaxation rate of the water protons in the liver was measured using an axial 3D multi-slice fat-saturated multi-echo turbo field echo sequence (TE=4.60/9.20/13.80/18.40/23.00ms). Regions of interest (ROI) were drawn and R2* was estimated by fitting the mean signal intensity from the ROIs to a mono-exponential decay model. The biopsies were freeze dried and the concentrations of iron, manganese, copper, cobalt and gadolinium were measured using Inductively Coupled Plasma Sector Field Mass Spectrometry (ICP-SFMS). A multiple linear regression analysis was applied to determine which of the measured metals significantly affected the relaxation rate.ResultsA linear regression with the LIC and R2* showed a reasonable fit (Figure 1). The multiple linear regression analysis (Table 1) showed that iron as well as manganese had a significant affect on R2*. Unlike iron however, the regression coefficient of manganese was negative, meaning that an increasing manganese concentration gave a shorter R2* relaxation rate. The same trend can be seen when plotting the manganese concentration against R2* (Figure 2).
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| 47. |
- Karlsson, Markus, et al.
(författare)
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Increased bile excretion of Gd-EOB-DTPA in diffuse liver disease : mechanistic modeling of qDCE-MRI in patients with severe fibro-sis
- 2016
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer. - 0968-5243 .- 1352-8661. ; 29:1, s. S272-S273
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionOver the past decades, several different non-invasive methods for staging hepatic fibrosis have been proposed. One such method is dynamic contrast enhanced MRI (DCE-MRI) using the contrast agent (CA) Gd-EOB-DTPA. Gd-EOB-DTPA is liver specific, which means that it is taken up specifically by the hepatocytes via the OATP3B1/B3 transporters and excreted into the bile via the MRP2 transporter. Several studies have shown that DCE-MRI and Gd-EOBDTPA can separate patients with advanced (F3-F4) from mild (F0-F2) hepatic fibrosis by measuring the signal intensity, where patients with advanced fibrosis have a lower signal intensity than the mild fibrosis cases.1 However, none of the studies up to date have been able to differentiate if the reduced signal intensity in the liver is because of an decreased uptake of CA or an increased excretion. Analyzing the DCE-MRI data with mechanistic mathematical modelling has the possibility of investigating such a differentiation.Subjects and methods88 patients with diffuse liver disease were examined using DCE-MRI (1.5 T Philips Achieva, two-point Dixon, TR=6.5 ms, TE=2.3/4.6 ms, FA=13) after a bolus injection of Gd-EOB-DTPA, followed by a liver biopsy. Regions of interest were placed within the liver, spleen and veins and a whole-body mechanistic pharmacokinetic model2 was fitted to the data. The fitted parameters in the model correspond to the rate of CA transport between different compartments, e.g. hepatocytes, blood plasma, and bile (Fig. 1).ResultsAs can be seen in Fig. 2, the parameter corresponding to the transport of CA from the blood plasma to the hepatocytes, kph, is lower for patients with advanced fibrosis (p=0.01). Fig. 3 shows that the parameter corresponding to the CA excretion into the bile, khb, is higher for patients with advanced fibrosis (p<0.01).Discussion/ConclusionThis work shows that the decreased signal intensity in DCE-MRI images in patients with advanced fibrosis depends on both a decreased uptake of CA in the hepatocytes and an increased excretion into the bile. Similar results have also been observed in a rat study3. In that study, rats with induced cirrhosis had a higher MRP2-activity than the healthy control rats.References1Norén et al: Eur. Radiol, 23(1), 174-181, 2013.2Forsgren et al: PloS One, 9(4): e95700, 2014.3Tsuda & Matsui: Radiol, 256(3): 767-773, 2010.
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- Karlsson, Markus, et al.
(författare)
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Liver R2*is affected by both iron and fat: A dual biopsy-validated study of chronic liver disease
- 2019
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Ingår i: Journal of Magnetic Resonance Imaging. - : WILEY. - 1053-1807 .- 1522-2586. ; 50:1, s. 325-333
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Tidskriftsartikel (refereegranskat)abstract
- Background Liver iron content (LIC) in chronic liver disease (CLD) is currently determined by performing an invasive liver biopsy. MRI using R2* relaxometry is a noninvasive alternative for estimating LIC. Fat accumulation in the liver, or proton density fat fraction (PDFF), may be a possible confounder of R2* measurements. Previous studies of the effect of PDFF on R2* have not used quantitative LIC measurement. Purpose To assess the associations between R2*, LIC, PDFF, and liver histology in patients with suspected CLD. Study Type Prospective. Population Eighty-one patients with suspected CLD. Field Strength/Sequence 1.5 T. Multiecho turbo field echo to quantify R2*. PRESS MRS to quantify PDFF. Assessment Each patient underwent an MR examination, followed by two needle biopsies immediately following the MR examination. The first biopsy was used for conventional histological assessment of LIC, whereas the second biopsy was used to quantitatively measure LIC using mass spectrometry. R2* was correlated with both LIC and PDFF. A correction for the influence of fat on R2* was calculated. Statistical Tests Pearson correlation, linear regression, and area under the receiver operating curve. Results There was a positive linear correlation between R2* and PDFF (R = 0.69), after removing data from patients with elevated iron levels, as defined by LIC. R2*, corrected for PDFF, was the best method for identifying patients with elevated iron levels, with a correlation of R = 0.87 and a sensitivity and specificity of 87.5% and 98.6%, respectively. Data Conclusion PDFF increases R2*. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:325-333.
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- Karlsson, Mikael, 1978, et al.
(författare)
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Recovery of titanium dioxide and other pigments from waste paint by pyrolysis
- 2015
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Ingår i: Journal of Coatings Technology Research. - : Springer Science and Business Media LLC. - 1547-0091 .- 1935-3804. ; 12:6, s. 1111-1122
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Tidskriftsartikel (refereegranskat)abstract
- In this work, a model paint containing several types of inorganic pigments was pyrolyzed in a microwave-heated unit. The goal of the pyrolysis process was to recover and recycle the inorganic components in the paint, most importantly titanium dioxide (TiO2). The solid residue remaining after pyrolysis was further heat treated in air to remove most of the char in the TiO2-containing product. The recovered TiO2-containing product was used in two types of paint formulation as a replacement for virgin pigments. The properties of the paints containing recycled TiO2 pigment and extenders were evaluated and compared with a standard paint formulation containing only virgin TiO2 pigment and virgin extenders. A reduction in paint whiteness was observed but the opacity, gloss, and durability were nearly equivalent to that of the standard paint. Another consequence of using recycled pigments was that the recycled mix of TiO2 pigments and extenders was harder to disperse in the paint than the mix based on virgin materials, thus giving the painted surface a somewhat rough texture. The recycled material has shown promising results as a pigment/extender but further work is needed to optimize the recycled product to meet whiteness and dispersion requirements for incorporation in paint formulations on an industrial scale.
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