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Publications (10 of 193) Show all publications
Vyakaranam, A. R., Crona, J., Norlén, O., Hellman, P. & Sundin, A. (2019). C-11-hydroxy-ephedrine-PET/CT in the Diagnosis of Pheochromocytoma and Paraganglioma. Cancers, 11(6), Article ID 847.
Open this publication in new window or tab >>C-11-hydroxy-ephedrine-PET/CT in the Diagnosis of Pheochromocytoma and Paraganglioma
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2019 (English)In: Cancers, ISSN 2072-6694, Vol. 11, no 6, article id 847Article in journal (Refereed) Published
Abstract [en]

Pheochromocytomas (PCC) and paragangliomas (PGL) may be difficult to diagnose because of vague and uncharacteristic symptoms and equivocal biochemical and radiological findings. This was a retrospective cohort study in 102 patients undergoing C-11-hydroxy-ephedrine (C-11-HED)-PET/CT because of symptoms and/or biochemistry suspicious for PCC/PGL and/or with radiologically equivocal adrenal incidentalomas. Correlations utilized CT/MRI, clinical, biochemical, surgical, histopathological and follow-up data. C-11-HED-PET/CT correctly identified 19 patients with PCC and six with PGL, missed one PCC, attained one false positive result (nodular hyperplasia) and correctly excluded PCC/PGL in 75 patients. Sensitivity, specificity, positive and negative predictive values of C-11-HED-PET/CT for PCC/PGL diagnosis was 96%, 99%, 96% and 99%, respectively. In 41 patients who underwent surgical resection and for whom correlation to histopathology was available, the corresponding figures were 96%, 93%, 96% and 93%, respectively. Tumor C-11-HED-uptake measurements (standardized uptake value, tumor-to-normal-adrenal ratio) were unrelated to symptoms of catecholamine excess (p > 0.05) and to systolic blood pressure (p > 0.05). In PCC/PGL patients, norepinephrine and systolic blood pressure increased in parallel (R-2 = 0.22, p = 0.016). C-11-HED-PET/CT was found to be an accurate tool to diagnose and rule out PCC/PGL in complex clinical scenarios and for the characterization of equivocal adrenal incidentalomas. PET measurements of tumor C-11-HED uptake were not helpful for tumor characterization.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
pheochromocytoma, paraganglioma, PET-CT, C-11-hydroxy-ephedrine, adrenal incidentaloma
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-390633 (URN)10.3390/cancers11060847 (DOI)000475351200111 ()31248124 (PubMedID)
Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-09-10Bibliographically approved
Ramage, J. K., Valle, J., Nieveen van Dijkum, E. J., Sundin, A., Pascher, A., Couvelard, A. & Kloeppel, G. (2019). Colorectal Neuroendocrine Neoplasms - areas of unmet need. Neuroendocrinology, 108(1), 45-53
Open this publication in new window or tab >>Colorectal Neuroendocrine Neoplasms - areas of unmet need
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 45-53Article in journal (Refereed) Published
Abstract [en]

The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges. Because of bowel cancer screening programmes, colorectal NENs, like conventional adenocarcinomas, may be diagnosed at a stage that is associated with improved survival. In this article we intend to describe and define areas of unmet needs relating to the epidemiology, classification, pathology, diagnosis and therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally, mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the relevant literature.

Keywords
Carcinoid tumours, Gastroenteropancreatic neuroendocrine tumours, Neuroendocrine tumour, Somatostatin receptor
National Category
Cancer and Oncology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-362622 (URN)10.1159/000493767 (DOI)000456048400006 ()30219817 (PubMedID)
Note

ENETS 2016 Munich Advisory Board, Uppsala University: Falkerby, Jenny; Sundin, Anders; Tiensuu Janson, Eva & Welin, Staffan.

Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2019-02-11Bibliographically approved
Schiza, A., Irenaeus, S., Ortiz-Nieto, F., Loskog, A. S., Tötterman, T., Sundin, A., . . . Ahlström, H. (2019). Evaluation of Diffusion-Weighted MRI and FDG-PET/CT to Assess Response to AdCD40L treatment in Metastatic Melanoma Patients. Scientific Reports, 9, Article ID 18069.
Open this publication in new window or tab >>Evaluation of Diffusion-Weighted MRI and FDG-PET/CT to Assess Response to AdCD40L treatment in Metastatic Melanoma Patients
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 18069Article in journal (Refereed) Published
Abstract [en]

The purpose was to evaluate the potential of diffusion-weighted-magnetic resonance imaging (DW-MRI) and F-18-fludeoxy-glucose-positron emission tomography integrated with CT (FDG-PET/CT) for prediction of overall survival (OS) following AdCD40L-immunotherapy in patients with metastatic malignant melanoma (MMM). Twenty-four patients with refractory MMM were treated with immunostimulatory AdCD40L gene therapy in a phase I/IIa study. Pre-therapeutic DW-MRI and FDG-PET/CT were performed and then repeated at 5 and 9 weeks post-treatment. Evaluation was conducted according to RECIST 1.1 and EORTC criteria. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), maximum standardized uptake value (SUVmax) were measured in the injected lesions. Fold changes (F) in ADC (F ADC), D (FD), SUVmax (FSUVmax) were statistically assessed. F D >= 1 and F ADC >= 1 were associated with better OS in scans at week 5 and 9 respectively. F SUVmax was not correlated to OS. F ADC >= 1 in both post-treatment scans and F D >= 1 at week 5 were related to a significant decrease of size of the injected lesions. These results suggest that in patients with MMM treated with AdCD401, functional parameters of DW-MRI are better early predictors of OS than the established metabolic and morphologic criteria for FDG-PET/CT and MRI, respectively.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-400411 (URN)10.1038/s41598-019-54438-x (DOI)000500557500001 ()31792256 (PubMedID)
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved
Vyakaranam, A. R., Crona, J., Norlén, O., Granberg, D., Garske-Román, U., Sandström, M., . . . Sundin, A. (2019). Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE.. Cancers, 11(7), Article ID 909.
Open this publication in new window or tab >>Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE.
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2019 (English)In: Cancers, ISSN 2072-6694, Vol. 11, no 7, article id 909Article in journal (Refereed) Published
Abstract [en]

Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. Radiological response utilized response evaluation criteria in solid tumors 1.1 and toxicity was graded according to common terminology criteria for adverse events version 4. Median 4 (range 3-11) 7.4 GBq cycles of 177Lu-DOTATATE were administered as first-line therapy (n = 13) or because of progressive disease (n = 9). Partial response (PR) was achieved in two and stable disease (SD) in 20 patients. The median overall survival (OS) was 49.6 (range 8.2-139) months and median progression-free survival (PFS) was 21.6 (range 6.7-138) months. Scintigraphic response >50% was achieved in 9/19 (47%) patients. Biochemical response (>50% decrease) of chromogranin A was found in 6/15 (40%) patients and of catecholamines in 3/12 (25%) patients. Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). No hematological or kidney toxicity grade 3-4 was registered. 177Lu-DOTATATE therapy was associated with favorable outcome and low toxicity. High Ki-67 (≥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.

Keywords
pheochromocytoma, paraganglioma, Lu-177-DOTATATE, peptide receptor radiotherapy, PRRT, neuroendocrine tumor, NET, PCC, PGL
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-392835 (URN)10.3390/cancers11070909 (DOI)000479322800020 ()31261748 (PubMedID)
Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2019-10-30Bibliographically approved
Sandqvist, P., Nilsson, I.-L., Grybäck, P., Sanchez-Crespo, A. & Sundin, A. (2019). Multiphase Iodine Contrast-Enhanced SPECT/CT Outperforms Nonenhanced SPECT/CT for Preoperative Localization of Small Parathyroid Adenomas. Clinical Nuclear Medicine, 44(12), 929-935
Open this publication in new window or tab >>Multiphase Iodine Contrast-Enhanced SPECT/CT Outperforms Nonenhanced SPECT/CT for Preoperative Localization of Small Parathyroid Adenomas
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2019 (English)In: Clinical Nuclear Medicine, ISSN 0363-9762, E-ISSN 1536-0229, Vol. 44, no 12, p. 929-935Article in journal (Refereed) Published
Abstract [en]

Purpose

The aim of this study was to assess the value of intravenously contrast-enhanced CT in conjunction with 99mTc-MIBI SPECT for preoperative localization of parathyroid adenoma.

Methods

One hundred ninety-two patients with primary hyperparathyroidism were enrolled in the study between May 2015 and May 2017. The patients underwent a preoperative “one-stop shop” examination with 99mTc-MIBI SPECT/CT by using dual time-point (10 and 90 minutes) protocol and both nonenhanced CT and contrast-enhanced CT acquisition in the arterial and venous phase, 35 and 75 seconds, respectively, after contrast medium injection start. For 149 patients, the imaging results could be correlated to those at surgery and histopathology.

Results

The median adenoma weight was 330 mg. The addition of contrast-enhanced CT increased the sensitivity from 81.1% to 89.9% (P = 0.003). The specificity of nonenhanced SPECT/CT was similar to contrast-enhanced CT (96.1% vs 97.9%; P = 0.077). For patients with uniglandular disease (n = 140, 94.0%), the sensitivity increased from 86.4% to 93.6% (P = 0.021) and the specificity from 96.2% to 97.9% (P = 0.118) by adding contrast-enhanced CT. In patients with multiglandular disease (n = 9, 6.0%), adding contrast-enhanced CT improved detection sensitivity from 42.1% to 63.2%. However, these patients were few and significance was not reached (P = 0.125).

Conclusions

In this cohort, with generally small parathyroid adenomas, the sensitivity in preoperative localization was greatly improved by adding contrast-enhanced CT to 99mTc-MIBI SPECT/CT.

Keywords
SPECT, CT, 4-dimensional CT, contrast media, hyperparathyroidism, parathyroid adenoma, MIBI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-397542 (URN)10.1097/RLU.0000000000002778 (DOI)000498583200002 ()31689274 (PubMedID)
Available from: 2019-11-21 Created: 2019-11-21 Last updated: 2019-12-17Bibliographically 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
Sundin, A., Fanti, S., Giammarile, F. & de Herder, W. W. (2019). Response to Prof. Ingo Brink and Prof. Aubalewska-Dydejczyk regarding Their "Letter to the Editor".. Neuroendocrinology, 108(4), 366-366
Open this publication in new window or tab >>Response to Prof. Ingo Brink and Prof. Aubalewska-Dydejczyk regarding Their "Letter to the Editor".
2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 4, p. 366-366Article in journal (Refereed) Published
Place, publisher, year, edition, pages
S. Karger, 2019
National Category
Neurology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-382949 (URN)10.1159/000497419 (DOI)000471962300010 ()30917382 (PubMedID)
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-08-05Bibliographically approved
Lamarca, A., Ronot, M., Moalla, S., Crona, J., Opalinska, M., Lopez Lopez, C., . . . Dromain, C. (2019). Tumour Growth Rate as a validated early radiological biomarker able to reflect treatment-induced changes in Neuroendocrine Tumours: the GREPONET-2 study. Clinical Cancer Research, 15(25), 6692-6699
Open this publication in new window or tab >>Tumour Growth Rate as a validated early radiological biomarker able to reflect treatment-induced changes in Neuroendocrine Tumours: the GREPONET-2 study
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2019 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 15, no 25, p. 6692-6699Article in journal (Refereed) Published
Abstract [en]

PURPOSE: TGR represents the percentage change in tumour volume per month (%/m). Previous results from the GREPONET study showed that TGR measured after 3 months (TGR3m) of starting systemic treatment (ST) or watch and wait (WW) was an early biomarker predicting progression-free survival (PFS) in NETs.

EXPERIMENTAL DESIGN: Pts from7 centres with advanced grade(G) 1/2 NETs from the pancreas(P)/small bowel(SB) initiating ST/WW were eligible. Computed tomography (CT) / magnetic resonance imaging (MRI) performed at pre-baseline, baseline and 3(+/-1) months of study entry were retrospectively reviewed. Aim-1: explore treatment-induced changes in TGR (ΔTGR3m-BL) (paired T-test) and Aim-2: validate TGR3m (<0.8%/m vs ≥0.8%/m) as an early biomarker in an independent cohort (Kaplan-Meier/Cox Regression).

RESULTS: Out of 785 pts screened, 127 were eligible. Mean (SD) TGR0 and TGR3m were 5.4%/m (14.9) and -1.4%/m (11.8), respectively. Mean(SD) ΔTGR3m-BL paired-difference was -6.8%/m(19.3) (p<0.001). Most marked ΔTGR3m-BL (mean (SD);p) were identified with targeted therapies (-11.3%/m(4.7);0.0237) and chemotherapy (-7.9%/m(3.4);0.0261). Multivariable analysis confirmed the absence of previous treatment (Odds Ratio (OR) 4.65 (95%CI 1.31-16.52); p-value0.018) and low TGR3m (continuous variable; OR 1.09 (95%CI 1.01-1.19); p-value0.042) to be independent predictors of radiological objective response. When the multivariable Cox Regression was adjusted to grade (p-value 0.004) and stage (p-value0.017), TGR3m≥0.8 (vs.<0.8) maintained its significance (p<0.001), while TGR0 and ΔTGR3m-BL did not. TGR3m was confirmed as an independent prognosis factor for PFS (external validation; Aim-2) (multivariable HR 2.21 (95%CI 1.21-3.70); p-value0.003).

CONCLUSIONS: TGR has a role as biomarker for monitoring response to therapy for early prediction of PFS and radiological objective response.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-392838 (URN)10.1158/1078-0432.CCR-19-0963 (DOI)000497334300017 ()31375514 (PubMedID)
Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2019-12-11Bibliographically approved
Capdevila, J., Bodei, L., Davies, P., Gorbounova, V., Jensen, R. T., Knigge, U. P., . . . Pavel, M. E. (2019). Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms. Neuroendocrinology, 108(1), 18-25
Open this publication in new window or tab >>Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 18-25Article in journal (Refereed) Published
Abstract [en]

Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.

Keywords
Biomarkers, Imaging, Metastasis, Neuroendocrine neoplasms, Therapy, Unmet medical needs
National Category
Endocrinology and Diabetes Psychiatry
Identifiers
urn:nbn:se:uu:diva-375573 (URN)10.1159/000493319 (DOI)000456048400003 ()30153686 (PubMedID)
Note

ENETS 2016 Munich Advisory Board Participants, Uppsala University: Falkerby, Jenny; Sundin, Anders; Tiensuu Janson, Eva & Welin, Staffan.

Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-02-11Bibliographically approved
Baudin, E., Hayes, A. R., Scoazec, J.-Y., Filosso, P. L., Lim, E., Kaltsas, G., . . . Caplin, M. E. (2019). Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms. Neuroendocrinology, 108(1), 7-17
Open this publication in new window or tab >>Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 7-17Article in journal (Refereed) Published
Abstract [en]

Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e., typical and atypical carcinoid, respectively). There is a paucity of randomised studies dedicated to advanced PCs and management principles are drawn from the larger gastroenteropancreatic NEN experience. There is growing evidence that NEN anatomic subgroups have different biology and different responses to treatment and, therefore, should be investigated as separate entities in clinical trials. In this review, we discuss the existing evidence and limitations of tumour classification, diagnostics and staging, prognostication, and treatment in the setting of PC, with focus on unmet medical needs and directions for the future.

Keywords
Bronchial carcinoid tumours, NET, Neuroendocrine neoplasms, Pulmonary carcinoids
National Category
Endocrinology and Diabetes Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-375567 (URN)10.1159/000493980 (DOI)000456048400002 ()30248673 (PubMedID)
Note

ENETS 2016 Munich Advisory Board Participants (UU authors): Jenny Falkerby; Anders Sundin; Eva Tiensuu Janson & Staffan Welin

Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-02-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2214-6217

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