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Lubberink, Mark
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Publications (10 of 187) Show all publications
Nørgaard, M., Ganz, M., Svarer, C., Feng, L., Ichise, M., Lanzenberger, R., . . . Knudsen, G. M. (2019). Cerebral serotonin transporter measurements with [11C]DASB: A review on acquisition and preprocessing across 21 PET centres. Journal of Cerebral Blood Flow and Metabolism, 39(2), 210-222
Open this publication in new window or tab >>Cerebral serotonin transporter measurements with [11C]DASB: A review on acquisition and preprocessing across 21 PET centres
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2019 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 39, no 2, p. 210-222Article in journal (Refereed) Published
Abstract [en]

Positron Emission Tomography (PET) imaging has become a prominent tool to capture the spatiotemporal distribution of neurotransmitters and receptors in the brain. The outcome of a PET study can, however, potentially be obscured by suboptimal and/or inconsistent choices made in complex processing pipelines required to reach a quantitative estimate of radioligand binding. Variations in subject selection, experimental design, data acquisition, preprocessing, and statistical analysis may lead to different outcomes and neurobiological interpretations. We here review the approaches used in 105 original research articles published by 21 different PET centres, using the tracer [11C]DASB for quantification of cerebral serotonin transporter binding, as an exemplary case. We highlight and quantify the impact of the remarkable variety of ways in which researchers are currently conducting their studies, while implicitly expecting generalizable results across research groups. Our review provides evidence that the foundation for a given choice of a preprocessing pipeline seems to be an overlooked aspect in modern PET neuroscience. Furthermore, we believe that a thorough testing of pipeline performance is necessary to produce reproducible research outcomes, avoiding biased results and allowing for better understanding of human brain function.

Keywords
Positron Emission Tomography, [11C]DASB, data sharing, kinetic modeling, preprocessing
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-349497 (URN)10.1177/0271678X18770107 (DOI)000457647200002 ()29651896 (PubMedID)
Available from: 2018-04-27 Created: 2018-04-27 Last updated: 2019-03-05Bibliographically approved
Andersson, J., Lundström, E., Engström, M., Lubberink, M., Ahlström, H. & Kullberg, J. (2019). Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI. Scientific Reports, 9, Article ID 12358.
Open this publication in new window or tab >>Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12358Article in journal (Refereed) Published
Abstract [en]

Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.

Keywords
brown adipose tissue, 18F-FDG positron emission tomography, infrared thermography, magnetic resonance imagingm PET/MRI, water–fat signal separation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-390410 (URN)10.1038/s41598-019-48879-7 (DOI)000482564800014 ()31451711 (PubMedID)
Funder
Swedish Research Council, 2016-01040Swedish Heart Lung Foundation, 2170492EXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-10-18Bibliographically approved
Finnsson, J., Lubberink, M., Savitcheva, I., Fällmar, D., Melberg, A., Kumlien, E. & Raininko, R. (2019). Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy.. Acta Neurologica Scandinavica, 139(2), 135-142
Open this publication in new window or tab >>Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy.
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2019 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 2, p. 135-142Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: LMNB1-related autosomal dominant leukodystrophy is caused by an overexpression of the protein lamin B1, usually due to a duplication of the LMNB1 gene. Symptoms start in 5th to 6th decade. This slowly progressive disease terminates with death. We studied brain glucose metabolism in this disease using 18 F-fluorodeoxyglucose positron emission tomography (PET).

METHODS: We examined 8 patients, aged 48-64 years, in varying stages of clinical symptomatology. Two patients were investigated with quantitative PET on clinical indications after which six more patients were recruited. Absolute glucose metabolism was analyzed with the PVElab software in 6 patients and 18 healthy controls. A semiquantitative analysis using the CortexID software was performed in seven investigations, relating local metabolism levels to global glucose metabolism.

RESULTS: The clinical quantitative PET revealed low global glucose metabolism, with the most marked reduction in the cerebellum. In the PVElab analysis, patients presented low mean glucose metabolism in the cerebellum, brainstem and global grey matter. In the semiquantitative analysis, 2 patients showed a decreased metabolism in the cerebellum and 4 patients a relatively higher metabolism in parts of the temporal lobes. Since none of the patients showed an increased metabolism in the quantitative analysis, we interpret these increases as "pseudo-increases" related to a globally reduced metabolism.

CONCLUSIONS: Global reduction of grey matter glucose metabolism in this white matter disease most likely depends on a combination of cortical afferent dysfunction and, in later stages, neuronal loss. The lowest metabolism in the cerebellum is consistent with histopathological findings and prominent cerebellar symptoms.

Keywords
18F-fluorodeoxyglucose, adult-onset leukodystrophy, autosomal dominant leukodystrophy, glucose metabolism, positron emission tomography
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-362200 (URN)10.1111/ane.13024 (DOI)000454813600005 ()30192380 (PubMedID)
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2019-01-30Bibliographically approved
Jonasson, M., Wall, A., Chiotis, K., Leuzy, A., Eriksson, J., Antoni, G., . . . Lubberink, M. (2019). Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET.. NeuroImage: Clinical, 22, Article ID 101681.
Open this publication in new window or tab >>Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET.
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2019 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 22, article id 101681Article in journal (Refereed) Published
Abstract [en]

[18F]THK5317 is a PET tracer for in-vivo imaging of tau associated with Alzheimer's disease (AD). This work aimed to evaluate optimal timing for standardized uptake value ratio (SUVR) measures with [18F]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R1) parametric images. Nine AD patients and nine controls underwent 90 min [18F]THK5317 scans. SUVR-1 was calculated at transient equilibrium (TE) and for seven different 20 min intervals and compared with distribution volume ratio (DVR; reference Logan). Cerebellar grey matter (MRI) was used as reference region. A supervised cluster analysis (SVCA) method was implemented to automatically generate a reference region, directly from the dynamic PET volume without the need of a structural MRI scan, for computation of SUVR-1 and R1 images for a scan duration matching the optimal timing. TE was reached first in putamen, frontal- and parietal cortex at 22 ± 4 min for AD patients and in putamen at 20 ± 0 min in controls. Over all regions and subjects, SUVR20-40-1 correlated best with DVR-1, R2 = 0.97. High correlation was found between values generated using MRI- and SVCA-based reference (R2 = 0.93 for SUVR20-40-1; R2 = 0.94 for R1). SUVR20-40 allows for accurate semi-quantitative assessment of tau pathology and SVCA may be used to obtain a reference region for calculation of both SUVR-1 and R1 with 40 min scan duration.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Alzheimer's disease, PET, Parametric images, Supervised clustering, Tau imaging
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-382941 (URN)10.1016/j.nicl.2019.101681 (DOI)000470123000005 ()30710871 (PubMedID)
Funder
Swedish Research Council, 05817Stockholm County CouncilGun och Bertil Stohnes StiftelseThe Karolinska Institutet's Research FoundationThe Swedish Brain FoundationSwedish Foundation for Strategic Research EU, FP7, Seventh Framework Programme
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-26Bibliographically approved
Rosqvist, F., Kullberg, J., Ståhlman, M., Cedernaes, J., Heurling, K., Johansson, H.-E., . . . Risérus, U. (2019). Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat: a randomized trial. Journal of Clinical Endocrinology and Metabolism, 104(12), 6207-6219
Open this publication in new window or tab >>Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat: a randomized trial
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2019 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 12, p. 6207-6219Article in journal (Refereed) Published
Abstract [en]

CONTEXT: Saturated fat (SFA) versus polyunsaturated fat (PUFA) may promote non-alcoholic fatty liver disease (NAFLD) by yet unclear mechanisms.

OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.

DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.

SETTING: General community.Participants: n=61 overweight or obese men and women.

INTERVENTION: Muffins high in either palm (SFA)- or sunflower oil (PUFA) were added to the habitual diet.

MAIN OUTCOME MEASURE: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.

RESULTS: By design, body weight gain was similar in SFA (2.31±1.38 kg) and PUFA (2.01±1.90 kg) groups, P=0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat or total body fat compared with PUFA. SFA consistently increased, while PUFA reduced circulating ceramides; changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.

CONCLUSIONS: Saturated fat markedly induces liver fat and serum ceramides whereas dietary polyunsaturated fat prevent liver fat accumulation, reduce ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Nutrition and Dietetics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-391140 (URN)10.1210/jc.2019-00160 (DOI)31369090 (PubMedID)
Funder
Swedish Research Council, K2015-54X-22081-04-3Swedish Research Council, 2016-01040Swedish Research Council, 2015-02781Swedish Heart Lung Foundation, 20160491Stockholm County Council, ALF 20150447Ernfors FoundationSwedish Nutrition Foundation (SNF)EXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2020-03-20Bibliographically approved
Lindström, E., Velikyan, I., Regula, N. K., Alhuseinalkhudhur, A., Sundin, A., Sörensen, J. & Lubberink, M. (2019). Regularized reconstruction of digital time-of-flight Ga-68-PSMA-11 PET/CT for the detection of recurrent disease in prostate cancer patients. Theranostics, 9(12), 3476-3484
Open this publication in new window or tab >>Regularized reconstruction of digital time-of-flight Ga-68-PSMA-11 PET/CT for the detection of recurrent disease in prostate cancer patients
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2019 (English)In: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, Vol. 9, no 12, p. 3476-3484Article in journal (Refereed) Published
Abstract [en]

Accurate localization of recurrent prostate cancer (PCa) is critical, especially if curative therapy is intended. With the aim to optimize target-to-background uptake ratio in Ga-68-PSMA-11 PET, we investigated the image quality and quantitative measures of regularized reconstruction by block-sequential regularized expectation maximization (BSREM).

Methods:

The study encompassed retrospective reconstruction and analysis of 20 digital time-of-flight (TOF) PET/CT examinations acquired 60 min post injection of 2 MBq/kg of Ga-68-PSMA-11 in PCa patients with biochemical relapse after primary treatment. Reconstruction by ordered-subsets expectation maximization (OSEM; 3 iterations, 16 subsets, 5 mm gaussian postprocessing filter) and BSREM (beta-values of 100-1600) were used, both including TOF and point spread function (PSF) recovery. Background variability (BV) was measured by placing a spherical volume of interest in the right liver lobe and defined as the standard deviation divided by the mean standardized uptake value (SUV). The image quality was evaluated in terms of signal-to-noise ratio (SNR) and signal-to-background ratio (SBR), using SUVmax of the lesions. A visual assessment was performed by four observers.

Results:

OSEM reconstruction produced images with a BV of 15%, whereas BSREM with a beta-value above 300 resulted in lower BVs than OSEM (36% with beta 100, 8% with beta 1300). Decreasing the acquisition duration from 2 to 1 and 0.5 min per bed position increased BV for both reconstruction methods, although BSREM with beta-values equal to or higher than 800 and 1200, respectively, kept the BV below 15%. In comparison of BSREM with OSEM, the mean SNR improved by 25 to 66% with an increasing beta-value in the range of 200-1300, whereas the mean SBR decreased with an increasing beta-value, ranging from 0 to 125% with a beta-value of 100 and 900, respectively. Decreased acquisition duration resulted in beta-values of 800 to 1000 and 1200 to 1400 for 1 and 0.5 min per bed position, respectively, producing improved image quality measures compared with OSEM at a full acquisition duration of 2 min per bed position. The observer study showed a slight overall preference for BSREM beta 900 although the interobserver variability was high.

Conclusion:

BSREM image reconstruction with beta-values in the range of 400-900 resulted in lower BV and similar or improved SNR and SBR in comparison with OSEM.

Keywords
Ga-68-PSMA-11, prostate cancer, PET/CT, image reconstruction, BSREM, interobserver variability
National Category
Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-388045 (URN)10.7150/thno.31970 (DOI)000469953000006 ()
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved
Heurling, K., Ashton, N. J., Leuzy, A., Zimmer, E. R., Blennow, K., Zetterberg, H., . . . Schöll, M. (2019). Synaptic vesicle protein 2A as a potential biomarker in synaptopathies. Molecular and Cellular Probes, 97, 34-42
Open this publication in new window or tab >>Synaptic vesicle protein 2A as a potential biomarker in synaptopathies
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2019 (English)In: Molecular and Cellular Probes, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 97, p. 34-42Article in journal (Refereed) Published
Abstract [en]

Measuring synaptic density in vivo using positron emission tomography (PET) imaging-based biomarkers targeting the synaptic vesicle protein 2A (SV2A) has received much attention recently due to its potential research and clinical applications in synaptopathies, including neurodegenerative and psychiatric diseases. Fluid-based biomarkers in proteinopathies have previously been suggested to provide information on pathology and disease status that is complementary to PET-based measures, and the same can be hypothesized with respect to SV2A. This review provides an overview of the current state of SV2A PET imaging as a biomarker of synaptic density, the potential role of fluid-based biomarkers for SV2A, and related future perspectives.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Biomarkers, Position emission tomography, SV2A, Synaptopathies
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-382939 (URN)10.1016/j.mcn.2019.02.001 (DOI)000472239000004 ()30796959 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationMagnus Bergvall FoundationSwedish Research CouncilEU, European Research Council
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-08-07Bibliographically approved
Jahn, U., Ilan, E., Sandström, M., Garske-Román, U., Velikyan, I., Fröss-Baron, K., . . . Sundin, A. (2018). 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy; Gender Differences in Small Intestinal and Pancreatic Neuroendocrine Tumors. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S61-S62
Open this publication in new window or tab >>177Lu-DOTATATE Peptide Receptor Radionuclide Therapy; Gender Differences in Small Intestinal and Pancreatic Neuroendocrine Tumors
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S61-S62Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-372962 (URN)000449266200098 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Sandström, M., Fröss-Baron, K., Khan, T. S., Granberg, D., Sundin, A. & Lubberink, M. (2018). Absorbed doses based on a single measurement point versus three measurement points in 600 patients with neuroendocrine tumours receiving 177Lu-DOTATATE therapy. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45(Supplement 1), S31-S31
Open this publication in new window or tab >>Absorbed doses based on a single measurement point versus three measurement points in 600 patients with neuroendocrine tumours receiving 177Lu-DOTATATE therapy
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no Supplement 1, p. S31-S31Article in journal, Meeting abstract (Other academic) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-373335 (URN)10.1007/s00259-018-4148-3 (DOI)000449266200039 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Note

Meeting Abstract: OP-076

Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Boersma, G. J., Johansson, E., Pereira, M. J., Heurling, K., Skrtic, S., Lau, J., . . . Eriksson, J. (2018). Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study. Hormone and Metabolic Research, 50(8), 627-639
Open this publication in new window or tab >>Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study
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2018 (English)In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 50, no 8, p. 627-639Article in journal (Refereed) Published
Abstract [en]

We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=-0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

Place, publisher, year, edition, pages
Georg Thieme Verlag KG, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-356788 (URN)10.1055/a-0643-4739 (DOI)000440872200007 ()30001566 (PubMedID)
Funder
AstraZenecaEXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes AssociationSwedish Research CouncilErnfors Foundation
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-11-08Bibliographically approved
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