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Pourazar, Jamshid
Publications (10 of 64) Show all publications
Gouveia-Figueira, S. C., Karimpour, M., Bosson, J. A., Blomberg, A., Unosson, J., Sehlstedt, M., . . . Nording, M. L. (2018). Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust. Analytica Chimica Acta, 1018, 62-69
Open this publication in new window or tab >>Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust
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2018 (English)In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1018, p. 62-69Article in journal (Refereed) Published
Abstract [en]

Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF(2 alpha), 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Oxylipin, Endocannabinoid, Eicosanoid, Mass spectrometry, Rapeseed methyl ester, Inflammation
National Category
Occupational Health and Environmental Health Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-148622 (URN)10.1016/j.aca.2018.02.032 (DOI)000428798200008 ()29605135 (PubMedID)
Funder
Swedish Research Council, 2010-303AFA Insurance, 130320
Available from: 2018-06-26 Created: 2018-06-26 Last updated: 2018-06-26Bibliographically approved
Linder, R., Rönmark, E., Pourazar, J., Behndig, A. F., Blomberg, A. & Lindberg, A. (2018). Proteolytic biomarkers are related to prognosis in COPD: report from a population-based cohort. Respiratory Research, 19, Article ID 64.
Open this publication in new window or tab >>Proteolytic biomarkers are related to prognosis in COPD: report from a population-based cohort
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2018 (English)In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 19, article id 64Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The imbalance between proteases and anti-proteases is considered to contribute to the development of COPD. Our aim was to evaluate the protease MMP-9, the antiprotease TIMP-1 and the MMP-9/TIMP-1-ratio as biomarkers in relation to prognosis. Prognosis was assessed as lung function decline and mortality. This was done among subjects with COPD in a population-based cohort.

METHODS: In 2005, clinical examinations including spirometry and peripheral blood sampling, were made in a longitudinal population-based cohort. In total, 1542 individuals participated, whereof 594 with COPD. In 2010, 1031 subjects participated in clinical examinations, and 952 subjects underwent spirometry in both 2005 and 2010. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbent assay (ELISA). Mortality data were collected from the Swedish national mortality register from the date of examination in 2005 until 31st December 2010.

RESULTS: The correlation between biomarkers and lung function decline was similar in non-COPD and COPD, but only significant for MMP-9 and MMP-9/TIMP-1-ratio in non-COPD. Mortality was higher in COPD than non-COPD (16% vs. 10%, p = 0.008). MMP-9 concentrations and MMP-9/TIMP-1 ratios in 2005 were higher among those who died during follow up, as well as among those alive but not participating in 2010, when compared to those participating in the 2010-examination. In non-COPD, male sex, age, burden of smoking, heart disease and MMP-9/TIMP-1 ratio were associated with increased risk for death, while increased TIMP-1 was protective. Among those with COPD, age, current smoking, increased MMP-9 and MMP-9/TIMP-1 ratio were associated with an increased risk for death.

CONCLUSIONS: The expected association between these biomarkers and lung function decline in COPD was not confirmed in this population-based study, probably due to a healthy survivor effect. Still, it is suggested that increased proteolytic imbalance may be of greater prognostic importance in COPD than in non-COPD.

Place, publisher, year, edition, pages
London: BioMed Central, 2018
Keywords
Chronic obstructive pulmonary disease (COPD), Matrix metalloproteinases, Mortality, Spirometry, Tissue inhibitor of metalloproteinases
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-146657 (URN)10.1186/s12931-018-0772-5 (DOI)000429829100001 ()29650051 (PubMedID)
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-06-09Bibliographically approved
Pfeffer, P. E., Ho, T. R., Mann, E. H., Kelly, F. J., Sehlstedt, M., Pourazar, J., . . . Hawrylowicz, C. M. (2018). Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes. Immunology, 153(4), 502-512
Open this publication in new window or tab >>Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes
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2018 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 153, no 4, p. 502-512Article in journal (Refereed) Published
Abstract [en]

Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) -stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T-lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naive CD8 T-cell responses. Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow cytometry after stimulation with UPM in vitro in the presence/absence of granulocyte-macrophage colony-stimulating factor (GM-CSF). The capacity of these mDCs to stimulate naive CD8 T-lymphocyte responses in allogeneic co-culture was then assessed by measuring T-cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon-γ (IFN-γ)-producing T lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of mDCs enhanced CD8 T-cell proliferation and the frequency of IFN-γ+ cells. The secretion of tumour necrosis factor-α, interleukin-13, Granzyme A and Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced many of these T-cell functions. The PM-induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and increases production of pro-inflammatory cytokines. Such UPM-induced stimulation of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
CD8(+) T lymphocyte, dendritic cells, granulocyte-macrophage colony-stimulating factor, granzyme, lung, particulate matter
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-146142 (URN)10.1111/imm.12852 (DOI)000426728600010 ()29044495 (PubMedID)
Available from: 2018-05-15 Created: 2018-05-15 Last updated: 2018-06-09Bibliographically approved
Scholz, S., Baharom, F., Rankin, G., Maleki, K. T., Gupta, S., Vangeti, S., . . . Smed-Sörensen, A. (2017). Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways. PLoS Pathogens, 13(6), Article ID e1006462.
Open this publication in new window or tab >>Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways
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2017 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 13, no 6, article id e1006462Article in journal (Refereed) Published
Abstract [en]

Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS). Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.

Place, publisher, year, edition, pages
Public library science, 2017
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-137809 (URN)10.1371/journal.ppat.1006462 (DOI)000404511700047 ()28640917 (PubMedID)
Available from: 2017-07-26 Created: 2017-07-26 Last updated: 2018-06-09Bibliographically approved
Baharom, F., Rankin, G., Scholz, S., Pourazar, J., Ahlm, C., Blomberg, A. & Smed-Sörensen, A. (2017). Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry. Jove-journal pf visualized experiments (119), Article ID e55222.
Open this publication in new window or tab >>Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry
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2017 (English)In: Jove-journal pf visualized experiments, ISSN 1940-087X, no 119, article id e55222Article in journal (Refereed) Published
Abstract [en]

The lungs are constantly exposed to the external environment, which in addition to harmless particles, also contains pathogens, allergens, and toxins. In order to maintain tolerance or to induce an immune response, the immune system must appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in maintaining a delicate balance to initiate immunity when required without causing collateral damage to the lungs due to an exaggerated inflammatory response. While there is a detailed understanding of the phenotype and function of immune cells such as DCs in human blood, the knowledge of these cells in less accessible tissues, such as the lungs, is much more limited, since studies of human lung tissue samples, especially from healthy individuals, are scarce. This work presents a strategy to generate detailed spatial and phenotypic characterization of lung tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling of endobronchial biopsies. Several small biopsies can be collected from each individual and can be subsequently embedded for ultrafine sectioning or enzymatically digested for advanced flow cytometric analysis. The outlined protocols have been optimized to yield maximum information from small tissue samples that, under steady-state conditions, contain only a low frequency of DCs. While the present work focuses on DCs, the methods described can directly be expanded to include other (immune) cells of interest found in mucosal lung tissue. Furthermore, the protocols are also directly applicable to samples obtained from patients suffering from pulmonary diseases where bronchoscopy is part of establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD), sarcoidosis, or lung cancer.

Place, publisher, year, edition, pages
Cambridge: MyJoVE Corp., 2017
Keywords
Immunology, Issue 119, bronchoscopy, monocyte, dendritic cell, tissue digestion, munohistochemistry, flow cytometry
National Category
Respiratory Medicine and Allergy Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-133678 (URN)10.3791/55222 (DOI)000397847200073 ()
Available from: 2017-04-20 Created: 2017-04-20 Last updated: 2018-06-09Bibliographically approved
Gouveia-Figueira, S., Karimpour, M., Bosson, J. A., Blomberg, A., Unosson, J., Pourazar, J., . . . Nording, M. L. (2017). Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure. Analytical and Bioanalytical Chemistry, 409(11), 2967-2980
Open this publication in new window or tab >>Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure
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2017 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, no 11, p. 2967-2980Article in journal (Refereed) Published
Abstract [en]

The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 mu g/m(3)) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, Nacylethanolamines, and related lipid metabolites in the collected BWand BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE2, 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG, 2017
Keywords
BAL, BW, Lipidome, Air pollution, Bronchoscopy, Eicosanoid
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-134210 (URN)10.1007/s00216-017-0243-8 (DOI)000398515900019 ()28235994 (PubMedID)
Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2018-06-09Bibliographically approved
Pourazar, J., Rankin, G. D., Muala, A., Unosson, J., Sehlstedt, M., Behndig, A. F., . . . Sandstrom, T. (2016). Bronchoalveolar Eosinophilia In Human Subjects After Exposure To Biomass Smoke From Wood Pellet Combustion. In: : . Paper presented at International Conference of the American-Thoracic-Society (ATS), MAY 13-18, 2016, San Francisco, CA. , 193
Open this publication in new window or tab >>Bronchoalveolar Eosinophilia In Human Subjects After Exposure To Biomass Smoke From Wood Pellet Combustion
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2016 (English)Conference paper, Oral presentation with published abstract (Refereed)
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-131011 (URN)000390749607595 ()
Conference
International Conference of the American-Thoracic-Society (ATS), MAY 13-18, 2016, San Francisco, CA
Available from: 2017-02-09 Created: 2017-02-09 Last updated: 2018-06-09Bibliographically approved
Rasmuson, J., Pourazar, J., Mohamed, N., Lejon, K., Evander, M., Blomberg, A. & Ahlm, C. (2016). Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection. European Journal of Clinical Microbiology and Infectious Diseases, 35(4), 713-721
Open this publication in new window or tab >>Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection
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2016 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 4, p. 713-721Article in journal (Refereed) Published
Abstract [en]

Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments.

National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-120634 (URN)10.1007/s10096-016-2592-1 (DOI)000373300000023 ()26873376 (PubMedID)
Available from: 2016-08-17 Created: 2016-05-18 Last updated: 2018-06-07Bibliographically approved
Baharom, F., Thomas, S., Rankin, G., Lepzien, R., Pourazar, J., Behndig, A. F., . . . Smed-Sorensen, A. (2016). Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans. Journal of Immunology, 196(11), 4498-4509
Open this publication in new window or tab >>Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans
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2016 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, no 11, p. 4498-4509Article in journal (Refereed) Published
Abstract [en]

Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-123437 (URN)10.4049/jimmunol.1600071 (DOI)000377676000010 ()27183618 (PubMedID)
Available from: 2016-07-20 Created: 2016-07-04 Last updated: 2018-06-07Bibliographically approved
Behndig, A. F., Linder, R., Pourazar, J., Lindberg, A. & Blomberg, A. (2016). Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies. Paper presented at International Conference of the American-Thoracic-Society (ATS), MAY 13-18, 2016, San Francisco, CA. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 193
Open this publication in new window or tab >>Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies
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2016 (English)In: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, ISSN 1073-449X, Vol. 193Article in journal, Meeting abstract (Refereed) Published
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-131014 (URN)000390749602732 ()
Conference
International Conference of the American-Thoracic-Society (ATS), MAY 13-18, 2016, San Francisco, CA
Available from: 2017-02-23 Created: 2017-02-23 Last updated: 2018-06-09Bibliographically approved
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