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Eriksson, Måns
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Publications (10 of 24) Show all publications
Åberg Lindell, M., Andersson, P., Grape, S., Hellesen, C., Håkansson, A. & Eriksson, M. (2018). Discrimination of irradiated MOX fuel from UOX fuel by multivariate statistical analysis of simulated activities of gamma-emitting isotopes. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 885, 67-78
Open this publication in new window or tab >>Discrimination of irradiated MOX fuel from UOX fuel by multivariate statistical analysis of simulated activities of gamma-emitting isotopes
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2018 (English)In: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, ISSN 0168-9002, E-ISSN 1872-9576, Vol. 885, p. 67-78Article in journal (Refereed) Published
Abstract [en]

This paper investigates how concentrations of certain fission products and their related gamma-ray emissions can be used to discriminate between uranium oxide (UOX) and mixed oxide (MOX) type fuel. Discrimination of irradiated MOX fuel from irradiated UOX fuel is important in nuclear facilities and for transport of nuclear fuel, for purposes of both criticality safety and nuclear safeguards. Although facility operators keep records on the identity and properties of each fuel, tools for nuclear safeguards inspectors that enable independent verification of the fuel are critical in the recovery of continuity of knowledge, should it be lost. A discrimination methodology for classification of UOX and MOX fuel, based on passive gamma-ray spectroscopy data and multivariate analysis methods, is presented. Nuclear fuels and their gamma-ray emissions were simulated in the Monte Carlo code Serpent, and the resulting data was used as input to train seven different multivariate classification techniques. The trained classifiers were subsequently implemented and evaluated with respect to their capabilities to correctly predict the classes of unknown fuel items. The best results concerning successful discrimination of UOX and MOX-fuel were acquired when using non-linear classification techniques, such as the k nearest neighbors method and the Gaussian kernel support vector machine. For fuel with cooling times up to 20 years, when it is considered that gamma-rays from the isotope  134Cs can still be efficiently measured, success rates of 100% were obtained. A sensitivity analysis indicated that these methods were also robust.

Keywords
Spent nuclear fuel, MOX, Gamma spectroscopy, Multivariate analysis, Classification
National Category
Physical Sciences
Identifiers
urn:nbn:se:uu:diva-337676 (URN)10.1016/j.nima.2017.12.020 (DOI)000424740800009 ()
Funder
Swedish Research Council, VR 621-2009-3991Swedish Radiation Safety Authority, SSM2016-661
Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-04-19Bibliographically approved
Åberg Lindell, M., Andersson, P., Grape, S., Håkansson, A. & Eriksson, M. (2018). Estimating irradiated nuclear fuel characteristics by nonlinear multivariate regression of simulated gamma-ray emissions. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 897, 85-91
Open this publication in new window or tab >>Estimating irradiated nuclear fuel characteristics by nonlinear multivariate regression of simulated gamma-ray emissions
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2018 (English)In: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, ISSN 0168-9002, E-ISSN 1872-9576, Vol. 897, p. 85-91Article in journal (Refereed) Published
Abstract [en]

In addition to verifying operator declared parameters of spent nuclear fuel, the ability to experimentally infer such parameters with a minimum of intrusiveness is of great interest and has been long-sought after in the nuclear safeguards community. It can also be anticipated that such ability would be of interest for quality assurance in e.g. recycling facilities in future Generation IV nuclear fuel cycles. One way to obtain information regarding spent nuclear fuel is to measure various gamma-ray intensities using high-resolution gamma-ray spectroscopy. While intensities from a few isotopes obtained from such measurements have traditionally been used pairwise, the approach in this work is to simultaneously analyze correlations between all available isotopes, using multivariate analysis techniques. Based on this approach, a methodology for inferring burnup, cooling time, and initial fissile content of PWR fuels using passive gamma-ray spectroscopy data has been investigated. PWR nuclear fuels, of UOX and MOX type, and their gamma-ray emissions, were simulated using the Monte Carlo code Serpent. Data comprising relative isotope activities was analyzed with decision trees and support vector machines, for predicting fuel parameters and their associated uncertainties. From this work it may be concluded that up to a cooling time of twenty years, the 95% prediction intervals of burnup, cooling time and initial fissile content could be inferred to within approximately 7 MWd/kgHM, 8 months, and 1.4 percentage points, respectively. An attempt aiming to estimate the plutonium content in spent UOX fuel, using the developed multivariate analysis model, is also presented. The results for Pu mass estimation are promising and call for further studies.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Nuclear safeguards, Spent nuclear fuel, Gamma-ray, Multivariate analysis, Nonlinear regression
National Category
Subatomic Physics
Identifiers
urn:nbn:se:uu:diva-357374 (URN)10.1016/j.nima.2018.04.034 (DOI)000433206800014 ()
Available from: 2018-08-24 Created: 2018-08-24 Last updated: 2018-08-24Bibliographically approved
Thulin, M. & Zwanzig, S. (2017). Exact confidence intervals and hypothesis tests for parameters of discrete distributions. Bernoulli, 23(1), 479-502
Open this publication in new window or tab >>Exact confidence intervals and hypothesis tests for parameters of discrete distributions
2017 (English)In: Bernoulli, ISSN 1350-7265, E-ISSN 1573-9759, Vol. 23, no 1, p. 479-502Article in journal (Refereed) Published
Abstract [en]

We study exact confidence intervals and two-sided hypothesis tests for univariate parameters of stochastically increasing discrete distributions, such as the binomial and Poisson distributions. It is shown that several popular methods for constructing short intervals lack strict nestedness, meaning that accepting a lower confidence level not always will lead to a shorter confidence interval. These intervals correspond to a class of tests that are shown to assign differing p-values to indistinguishable models. Finally, we show that among strictly nested intervals, fiducial intervals, including the Clopper-Pearson interval for a binomial proportion and the Garwood interval for a Poisson mean, are optimal.

Keywords
binomial distribution, confidence interval, expected length, fiducial interval, hypothesis test, Poisson distribution
National Category
Probability Theory and Statistics
Identifiers
urn:nbn:se:uu:diva-229398 (URN)10.3150/15-BEJ750 (DOI)000389565500017 ()
Available from: 2014-08-06 Created: 2014-08-06 Last updated: 2017-12-05Bibliographically approved
Bäckryd, E., Lind, A.-L., Thulin, M., Larsson, A., Gerdle, B. & Gordh, T. (2017). High levels of cerebrospinal fluid chemokines point to the presence of neuroinflammation in peripheral neuropathic pain: a cross-sectional study of 2 cohorts of patients compared with healthy controls. Pain, 158(12), 2487-2495
Open this publication in new window or tab >>High levels of cerebrospinal fluid chemokines point to the presence of neuroinflammation in peripheral neuropathic pain: a cross-sectional study of 2 cohorts of patients compared with healthy controls
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2017 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, no 12, p. 2487-2495Article in journal (Refereed) Published
Abstract [en]

Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called "gliotransmitters," a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile of patients with neuropathic pain. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation. Samples of CSF were collected from 2 cohorts of patients with neuropathic pain (n = 11 and n = 16, respectively) and healthy control subjects (n = 11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek Multiplex Inflammation I; Olink Bioscience, Uppsala, Sweden). Univariate testing with control of false discovery rate, as well as orthogonal partial least squares discriminant analysis, were used for statistical analyses. Levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23 in CSF, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared with healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in patients with fibromyalgia. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Because it has been suggested that prevalent comorbidities to chronic pain (eg, depression, anxiety, poor sleep, and tiredness) also are associated with neuroinflammation, it will be important to determine whether neuroinflammation is a common mediator.

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-335278 (URN)10.1097/j.pain.0000000000001061 (DOI)000419133700022 ()28930774 (PubMedID)
Available from: 2017-12-02 Created: 2017-12-02 Last updated: 2018-02-09Bibliographically approved
Hysing, E.-B., Smith, L., Eriksson, M., Karlsten, R., Butler, S. & Gordh, T. (2017). Identifying characteristics of the most severely impaired chronic pain patients treated at a specialized inpatient pain clinic. Scandinavian Journal of Pain, 17(1), 178-185
Open this publication in new window or tab >>Identifying characteristics of the most severely impaired chronic pain patients treated at a specialized inpatient pain clinic
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2017 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, no 1, p. 178-185Article in journal (Refereed) Published
Abstract [en]

Background and aims: Patients suffering from chronic nonmalignant pain constitute a heterogeneous population in terms of clinical presentation and treatment results. Few data are available about what distinguishes different groups in this huge population of patients with chronic persistent pain (CPP). A subgroup that is poorly studied, consists of the most severely impaired chronic pain patients. At the Uppsala University Hospital Pain Clinic, there is a specialized department accepting the most complex patients for rehabilitation. In the endeavour to improve and evaluate treatment for this subgroup, a better understanding of the complex nature of the illness is essential. This prospective study aimed to describe the characteristics of this subgroup of patients with CPP.

Methods: Seventy-two consecutive patients enrolled in the Uppsala programme were evaluated. We collected data on demographics, type of pain and experienced symptoms other than pain using a checklist of 41 possible symptoms. Psychiatric comorbidity was assessed by a psychiatrist using a structured clinical interview. Quality of life (QoL), pain rating and medication/drug/alcohol usage were measured by validated questionnaires: SF-36, NRS, DUDIT and AUDIT. Concerning physical functioning and sick leave, a comparison was made with data from the Swedish Quality Register Registry for pain rehabilitation (SQRP).

Results: The cohort consisted of 61% women and the average age was 45 (range 20-70) years. For this cohort, 74% reported being on sick leave or disability-pension. In the SQRP 59% were on sick leave at the time they entered the rehabilitation programmes [1]. On average, the study-population reported 22 symptoms other than pain, to be at a high rate of severity. Patients treated in conventional pain rehabilitation programmes reported a mean of 10 symptoms in average. Symptoms reported with the highest frequency (>80%), were lethargy, tiredness, headache and difficulties concentrating. Seventysix percent were diagnosed with a psychiatric disorder. Sixty-nine fulfilled the criteria for depression or depression/anxiety disorder despite that most (65%) were treated with psychotropic medication. Alcohol/drug abuse was minimal. Seventy-one percent were on opioids but the doses were moderate (<100 mg) MEq. The pain rating was >= 7 (out of a maximum of 10) for 60% of the patients.

Conclusion: This study describes what makes the subgroup of pain patients most affected by their pain special according to associated factors and comorbidity We found that they were distinguished by a high degree of psychiatric comorbidity, low physical functioning and extreme levels of symptom preoccupation/hypervigilance. Many severe symptoms additional to pain (e.g. depression/anxiety, tiredness, disturbed sleep, lack of concentration, constipation) were reported. The group seems hypervigilant, overwhelmed with a multitude of different symptoms on a high severity level.

Implications: When treating this complex group, the expressions of the illness can act as obstacles to achieve successful treatment outcomes. The study provides evidence based information, for a better understanding of the needs concerning these pain patients. Our result indicates that parallel assessment and treatment of psychiatric comorbidities and sleep disorders combined with traditional rehabilitation, i.e. physical activation and cognitive reorganization are imperative for improved outcomes.

Place, publisher, year, edition, pages
WALTER DE GRUYTER GMBH, 2017
Keywords
Characterization of patients with severe, chronic persistent pain, Subgrouping patients with chronic, persistent pain, Severely impaired patients with chronic, pain, Psychiatric comorbidity, Physical dysfunction, Systemic symptoms other than pain
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-341827 (URN)10.1016/j.sjpain.2017.09.008 (DOI)000419851500030 ()29032350 (PubMedID)
Available from: 2018-02-15 Created: 2018-02-15 Last updated: 2018-02-15Bibliographically approved
Thulin, E., Eriksson, M. & Andersson, D. I. (2017). Reversion of High-level Mecillinam Resistance to Susceptibility in Escherichia coli During Growth in Urine.. EBioMedicine, 23, 111-118
Open this publication in new window or tab >>Reversion of High-level Mecillinam Resistance to Susceptibility in Escherichia coli During Growth in Urine.
2017 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 23, p. 111-118Article in journal (Refereed) Published
Abstract [en]

Mecillinam (amdinocillin) is a β-lactam antibiotic used to treat uncomplicated urinary tract infections (UTIs). We have previously shown that inactivation of the Escherichia coli cysB gene is the major cause of mecillinam resistance (Mec(R)) in clinical isolates. In this study, we used different E. coli strains (laboratory and clinical isolates) that were Mec(R) due to cysB mutations to determine how mecillinam susceptibility was affected during growth in urine compared to growth in the commonly used growth medium Mueller Hinton (MHB). We also examined mecillinam susceptibility when bacteria were grown in urine obtained from 48 different healthy volunteers. Metabolome analysis was done on the urine samples and the association between the mecillinam susceptibility patterns of the bacteria and urine metabolite levels was studied. Two major findings with clinical significance are reported. First, Mec(R)E. coli cysB mutant strains (both laboratory and clinical isolates) were always more susceptible to mecillinam when grown in urine as compared to laboratory medium, with many strains showing complete phenotypic susceptibility in urine. Second, the degree of reversion to susceptibility varied between urine samples obtained from different individuals. This difference was correlated with osmolality such that in urine with low osmolality the Mec(R) mutants were more susceptible to mecillinam than in urine with high osmolality. This is the first example describing conditional resistance where a genetically stable antibiotic resistance can be phenotypically reverted to susceptibility by metabolites present in urine. These findings have several important clinical implications regarding the use of mecillinam to treat UTIs. First, they suggest that mecillinam can be used to treat also those clinical strains that are identified as Mec(R) in standard laboratory tests. Second, the results suggest that testing of mecillinam susceptibility in the laboratory ought to be performed in media that mimics urine to obtain clinically relevant susceptibility testing results. Third, these findings imply that changes in patient behavior, such as increased water intake or use of diuretics to reduce urine osmolality and increased intake of cysteine, might induce antibiotic susceptibility in an infecting Mec(R)E. coli strain and thereby increase treatment efficiency.

Keywords
Conditional resistance, Escherichia coli, Mecillinam, Metabolomics, Urinary tract infection, Urine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-330802 (URN)10.1016/j.ebiom.2017.08.021 (DOI)000410740900018 ()28855073 (PubMedID)
Funder
Swedish Research Council, 2012-03482
Available from: 2017-10-04 Created: 2017-10-04 Last updated: 2017-12-07Bibliographically approved
Aarnio, M., Appel, L., Fredriksson, M., Gordh, T., Wolf, O., Sörensen, J., . . . Linnman, C. (2017). Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.. Scandinavian Journal of Pain, 17, 418-424
Open this publication in new window or tab >>Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
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2017 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, p. 418-424Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

Keywords
Ankle injuries, Carbon-11, Deprenyl, Inflammation, PET, Pain
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-333782 (URN)10.1016/j.sjpain.2017.10.008 (DOI)000419851500070 ()29126847 (PubMedID)
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-04-09Bibliographically approved
Moen, A., Lind, A.-L., Thulin, M., Kamali-Moghaddam, M., Roe, C., Gjerstad, J. & Gordh, T. (2016). Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation. INTERNATIONAL JOURNAL OF INFLAMMATION, Article ID UNSP 3874964.
Open this publication in new window or tab >>Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation
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2016 (English)In: INTERNATIONAL JOURNAL OF INFLAMMATION, ISSN 2090-8040, article id UNSP 3874964Article in journal (Refereed) Published
Abstract [en]

Earlier studies suggest that lumbar radicular pain following disc herniation may be associated with a local or systemic inflammatory process. In the present study, we investigated the serum inflammatory protein profile of such patients. All 45 patients were recruited from Oslo University Hospital, Ulleval, Norway, during the period 2007-2009. The new multiplex proximity extension assay (PEA) technology was used to analyze the levels of 92 proteins. Interestingly, the present data showed that patients with radicular pain 12 months after disc herniation may be different from other patients with regard to many measurable serum cytokines. Given a false discovery rate (FDR) of 0.10 and 0.05, we identified 41 and 13 proteins, respectively, which were significantly upregulated in the patients with severe pain one year after disc herniation. On the top of the list ranked by estimated increase we found C-X-C motif chemokine 5 (CXCM5; 217% increase), epidermal growth factor (EGF; 142% increase), and monocyte chemotactic protein 4 (MCP-4; 70% increase). Moreover, a clear overall difference in the serum cytokine profile between the chronic and the recovered patients was demonstrated. Thus, the present results may be important for future protein serum profiling of lumbar radicular pain patients with regard to prognosis and choice of treatment. We conclude that serum proteins may be measurable molecular markers of persistent pain after disc herniation.

National Category
General Practice
Identifiers
urn:nbn:se:uu:diva-317717 (URN)10.1155/2016/3874964 (DOI)000394106300001 ()27293953 (PubMedID)
Funder
VINNOVASwedish Research Council, P29797-1
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2018-01-13Bibliographically approved
Thulin, M. (2016). Two-sample tests and one-way MANOVA for multivariate biomarker data with nondetects. Statistics in Medicine, 35(20), 3623-3644
Open this publication in new window or tab >>Two-sample tests and one-way MANOVA for multivariate biomarker data with nondetects
2016 (English)In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 35, no 20, p. 3623-3644Article in journal (Refereed) Published
Abstract [en]

Testing whether the mean vector of a multivariate set of biomarkers differs between several populations is an increasingly common problem in medical research. Biomarker data is often left censored because some measurements fall below the laboratory's detection limit. We investigate how such censoring affects multivariate two-sample and one-way multivariate analysis of variance tests. Type I error rates, power and robustness to increasing censoring are studied, under both normality and non-normality. Parametric tests are found to perform better than non-parametric alternatives, indicating that the current recommendations for analysis of censored multivariate data may have to be revised.

National Category
Probability Theory and Statistics
Identifiers
urn:nbn:se:uu:diva-283203 (URN)10.1002/sim.6945 (DOI)000380728800013 ()26999657 (PubMedID)
External cooperation:
Funder
Swedish National Infrastructure for Computing (SNIC), SNIC 2014-1-340
Available from: 2016-04-11 Created: 2016-04-11 Last updated: 2017-11-30Bibliographically approved
Larsson, A., Carlsson, L., Lind, A.-L., Gordh, T., Bodolea, C., Kamali-Moghaddam, M. & Thulin, M. (2015). The body mass index (BMI) is significantly correlated with levels of cytokines and chemokines in cerebrospinal fluid. Cytokine, 76(2), 514-518
Open this publication in new window or tab >>The body mass index (BMI) is significantly correlated with levels of cytokines and chemokines in cerebrospinal fluid
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2015 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 76, no 2, p. 514-518Article in journal (Refereed) Published
Abstract [en]

Cytokines and chemokines regulate many functions in the body including the brain. The interactions between adipose tissue and the central nervous system (CNS) are important for the regulation of energy balance. CNS function is also influenced by age. The aim of the present study was to investigate the effects of body mass index (BMI) and age on cytokine and chemokine levels in cerebrospinal fluid. Cerebrospinal fluid samples (n=89) were collected from patients undergoing routine surgical procedures. The samples were analyzed using the multiplex proximity extension assay (PEA) in which 92 different cytokines are measured simultaneously using minute sample volume. We found no significant correlations between age and cytokine levels for any of the studied markers. In contrast, at a false discovery rate of 10%, 19 markers were significantly associated with BMI (in decreasing significance: FGF-5, ADA, Beta-NGF, CD40, IL-10RB, CCL19, TGF-alpha, SIRT2, TWEAK, SCF, CSF-1, 4E-BP1, DNER, LIF-R, STAMPB, CXCL10, CXCL6, VEGF-A and CX3CL1). This study reveals a clear effect of BMI on cytokine and chemokine levels in cerebrospinal fluid.

Keywords
Age; Body mass index; Cytokine; Human; Proximity extension assay (PEA); Cerebrospinal fluid
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-259347 (URN)10.1016/j.cyto.2015.07.010 (DOI)000364244400051 ()26188367 (PubMedID)
Funder
VINNOVASwedish Research Council
Available from: 2015-07-31 Created: 2015-07-31 Last updated: 2017-12-04Bibliographically approved
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