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Naredi, Peter
Publications (10 of 57) Show all publications
Franklin, O., Öhlund, D., Lundin, C., Öman, M., Naredi, P., Wang, W. & Sund, M. (2015). Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma. Cancer Biomarkers, 15(1), 1-10
Open this publication in new window or tab >>Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma
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2015 (English)In: Cancer Biomarkers, ISSN 1574-0153, Vol. 15, no 1, p. 1-10Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A lack of disease-specific symptoms and good tumour markers makes early detection and diagnosis of pancreatic ductal adenocarcinoma (PDAC) challenging. OBJECTIVE: To analyse the tissue expression and circulating levels of four stroma-derived substances (type IV collagen, endostatin/type XVIII collagen, osteopontin and tenascin C) and four conventional tumour markers (CA 19-9, TPS, CEA and Ca 125) in a PDAC cohort.

METHODS: Tissue expression of markers in normal pancreas and PDAC tissue was analysed with immunofluorescence. Plasma concentrations of markers were measured before and after surgery. Patients with non-malignant disorders served as controls.

RESULTS: The conventional and stromal substances were expressed in the cancer cell compartment and the stroma, respectively. Although most patients had increased levels of many markers before surgery, 2/12 (17%) of patients had normal levels of Ca 19-9 at this stage. High preoperative endostatin/type XVIII collagen, and postoperative type IV collagen was associated with short survival. Neither the pre-nor postoperative levels of TPS, Ca 125 or CA 19-9 were associated to survival.

CONCLUSIONS: PDAC is characterized by an abundant stroma. These initial observations indicate that the stroma can be a source of PDAC tumour markers that are found in different compartments of the cancer, thus reflecting different aspects of tumour biology.

Place, publisher, year, edition, pages
IOS Press, 2015
Keywords
Pancreatic ductal adenocarcinoma (PDAC), tumour markers, stroma, type IV collagen, type XVIII llagen, endostatin, osteopontin, tenascin C, TPS, Ca 125, Ca 19-9, CEA
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-97877 (URN)10.3233/CBM-140430 (DOI)000346079800001 ()
Available from: 2015-01-16 Created: 2015-01-08 Last updated: 2018-06-07Bibliographically approved
Henriksson, O., Lundgren, P. J., Kuklane, K., Holmér, I., Giesbrecht, G. G., Naredi, P. & Björnstig, U. (2015). Protection against cold in prehospital care: wet clothing removal or addition of a vapor barrier. Wilderness & environmental medicine (Print), 26(1), 11-20
Open this publication in new window or tab >>Protection against cold in prehospital care: wet clothing removal or addition of a vapor barrier
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2015 (English)In: Wilderness & environmental medicine (Print), ISSN 1080-6032, E-ISSN 1545-1534, Vol. 26, no 1, p. 11-20Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The purpose of this study was to evaluate the effect of wet clothing removal or the addition of a vapor barrier in shivering subjects exposed to a cold environment with only limited insulation available.

METHODS: Volunteer subjects (n = 8) wearing wet clothing were positioned on a spineboard in a climatic chamber (-18.5°C) and subjected to an initial 20 minutes of cooling followed by 30 minutes of 4 different insulation interventions in a crossover design: 1) 1 woolen blanket; 2) vapor barrier plus 1 woolen blanket; 3) wet clothing removal plus 1 woolen blanket; or 4) 2 woolen blankets. Metabolic rate, core body temperature, skin temperature, and heart rate were continuously monitored, and cold discomfort was evaluated at 5-minute intervals.

RESULTS: Wet clothing removal or the addition of a vapor barrier significantly reduced metabolic rate (mean difference ± SE; 14 ± 4.7 W/m(2)) and increased skin temperature rewarming (1.0° ± 0.2°C). Increasing the insulation rendered a similar effect. There were, however, no significant differences in core body temperature or heart rate among any of the conditions. Cold discomfort (median; interquartile range) was significantly lower with the addition of a vapor barrier (4; 2-4.75) and with 2 woolen blankets (3.5; 1.5-4) compared with 1 woolen blanket alone (5; 3.25-6).

CONCLUSIONS: In protracted rescue scenarios in cold environments with only limited insulation available, wet clothing removal or the use of a vapor barrier is advocated to limit the need for shivering thermogenesis and improve the patient's condition on admission to the emergency department.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
hypothermia, heat loss, thermal insulation, emergency medical services
National Category
Public Health, Global Health, Social Medicine and Epidemiology Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-100365 (URN)10.1016/j.wem.2014.07.001 (DOI)000350268800003 ()25712295 (PubMedID)
Available from: 2015-03-02 Created: 2015-03-02 Last updated: 2018-06-07Bibliographically approved
Palm-Espling, M., Lundin, C., Björn, E., Naredi, P. & Wittung-Stafshede, P. (2014). Interaction between anticancer drug Cisplatin and copper chaperone Atox1 in human melanoma cells. Protein peptide letters, 21(1), 63-68
Open this publication in new window or tab >>Interaction between anticancer drug Cisplatin and copper chaperone Atox1 in human melanoma cells
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2014 (English)In: Protein peptide letters, ISSN 0929-8665, E-ISSN 1875-5305, Vol. 21, no 1, p. 63-68Article in journal (Refereed) Published
Abstract [en]

Cisplatin (CisPt) is one of the most common anticancer drugs used against many severe forms of cancers. However, treatment with this drug causes many side effects and often, it results in the development of cell resistance. A majority of side effects as well as cell resistance are thought to develop due to CisPt interactions with proteins prior to reaching the nucleus and the DNA target. The copper (Cu) transport proteins Ctr1 and ATP7A/B have been implicated in cellular resistance of CisPt, possibly exporting the drug out of the cell. Recent in vitro work demonstrated that CisPt also interacts with the cytoplasmic Cu-chaperone Atox1, binding in or near the Cu-binding site, without expulsion of bound Cu. Whereas Ctr1 and ATP7B interactions with CisPt have been shown in vivo or ex vivo, there is no such information for Atox1-CisPt interactions. To address this, we developed a method to probe if CisPt interacts with Atox1 in human melanoma cells. Atox1-specific antibodies were linked to magnetic beads and used to immune-precipitate Atox1 from melanoma cells that had been pre-exposed to CisPt. Analysis of extracted Atox1 with inductively coupled plasma mass spectrometry demonstrated the presence of Pt in the protein fraction. Thus, CisPt-exposed human melanoma cells contain Atox1 molecules that bind some derivative of CisPt. This study gives the first indication for the intracellular presence of Atox1-CisPt complexes ex vivo.

Keywords
Copper-chaperone, Cisplatin, Atox1, anticancer, resistance
National Category
Biochemistry and Molecular Biology
Research subject
biological chemistry
Identifiers
urn:nbn:se:umu:diva-80714 (URN)10.2174/09298665113209990036 (DOI)000329022400011 ()
Available from: 2013-09-24 Created: 2013-09-24 Last updated: 2018-06-08Bibliographically approved
Lundgren, P., Henriksson, O., Kuklane, K., Holmér, I., Naredi, P. & Björnstig, U. (2014). Validity and reliability of the Cold Discomfort Scale: a subjective judgement scale for the assessment of patient thermal state in a cold environment.. Journal of clinical monitoring and computing, 28(3), 287-291
Open this publication in new window or tab >>Validity and reliability of the Cold Discomfort Scale: a subjective judgement scale for the assessment of patient thermal state in a cold environment.
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2014 (English)In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 28, no 3, p. 287-291Article in journal (Refereed) Published
Abstract [en]

Complementary measures for the assessment of patient thermoregulatory state, such as subjective judgement scales, might be of considerable importance in field rescue scenarios where objective measures such as body core temperature, skin temperature, and oxygen consumption are difficult to obtain. The objective of this study was to evaluate, in healthy subjects, the reliability of the Cold Discomfort Scale (CDS), a subjective judgement scale for the assessment of patient thermal state in cold environments, defined as test-retest stability, and criterion validity, defined as the ability to detect a difference in cumulative cold stress over time. Twenty-two healthy subjects performed two consecutive trials (test-retest). Dressed in light clothing, the subjects remained in a climatic chamber set to -20 °C for 60 min. CDS ratings were obtained every 5 min. Reliability was analysed by test-retest stability using weighted kappa coefficient that was 0.84 including all the 5-min interval measurements. When analysed separately at each 5-min interval the weighted kappa coefficients were was 0.48-0.86. Criterion validity was analysed by comparing median CDS ratings of a moving time interval. The comparison revealed that CDS ratings were significantly increased for every interval of 10, 15, and 30 min (p < 0.001) but not for every interval of 5 min. In conclusion, in a prehospital scenario, subjective judgement scales might be a valuable measure for the assessment of patient thermal state. The results of this study indicated that, in concious patients, the CDS may be both reliable and valid for such purpose.

Keywords
Hypothermia, Prehospital trauma care, Emergency medical services, Reliability, Validity, Subjective judgement scale, Thermal comfort
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-88038 (URN)10.1007/s10877-013-9533-7 (DOI)000336275800011 ()24311022 (PubMedID)
Available from: 2014-04-22 Created: 2014-04-22 Last updated: 2018-06-08Bibliographically approved
Natarajan, B., Gaur, R., Hemmingsson, O., Kao, G. & Naredi, P. (2013). Depletion of the ER chaperone ENPL-1 sensitizes C. elegans to the anticancer drug cisplatin. Worm, 2(1), Article ID e24059.
Open this publication in new window or tab >>Depletion of the ER chaperone ENPL-1 sensitizes C. elegans to the anticancer drug cisplatin
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2013 (English)In: Worm, ISSN 2162-4046, Vol. 2, no 1, article id e24059Article in journal (Refereed) Published
Abstract [en]

Cisplatin is an essential chemotherapeutic drug in the treatment of many cancers. Its use, however, is limited by the development of resistance in many tumors. The ability to re-sensitize resistant tumors could significantly strengthen cisplatin therapy in patients. Caenorhabditis elegans is a suitable model for studying the cytoplasmic role of cisplatin in tumor cells. We have previously shown that the ATPase ASNA-1 has similar roles as a factor governing cisplatin sensitivity in mammalian tumor cells and C. elegans. Here we study the endoplasmic reticulum (ER) resident chaperone ENPL-1/GRP94 and find that its depletion makes worms sensitive to cisplatin. Elevated ER stress levels in enpl-1 mutants is the likely cause of this sensitivity because a correlation can be made between cisplatin sensitivity and the high ER stress levels. We also find that asna-1 mutants have elevated unfolded protein response (UPR) activity and that the intrinsically cisplatin resistant wild-type worms become sensitive when ER stress is high. We conclude that enpl-1 is a cisplatin sensitizing factor and suggest that manipulation of its levels or of UPR activity will enhance the effects of cisplatin based cancer therapy.

Place, publisher, year, edition, pages
Landes Bioscience, 2013
Keywords
cisplatin, unfolded protein response, GRP94, asna-1, endoplasmic reticulum stress
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-90974 (URN)10.4161/worm.24059 (DOI)24058864 (PubMedID)
Available from: 2014-07-04 Created: 2014-07-04 Last updated: 2018-06-07Bibliographically approved
van de Velde, C. J., Aristei, C., Boelens, P. G., Beets-Tan, R. G., Blomqvist, L., Borras, J. M., . . . Valentini, V. (2013). EURECCA colorectal: Multidisciplinary Mission statement on better care for patients with colon and rectal cancer in Europe.. European Journal of Cancer, 49(13), 2784-2790
Open this publication in new window or tab >>EURECCA colorectal: Multidisciplinary Mission statement on better care for patients with colon and rectal cancer in Europe.
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2013 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 13, p. 2784-2790Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. METHODS: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. RESULTS: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. CONCLUSIONS: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-76653 (URN)10.1016/j.ejca.2013.04.032 (DOI)23769991 (PubMedID)
Available from: 2013-07-09 Created: 2013-07-09 Last updated: 2018-06-08Bibliographically approved
Eriksson, H., Lyth, J., Månsson-Brahme, E., Frohm-Nilsson, M., Ingvar, C., Lindholm, C., . . . Hansson, J. (2013). Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: a nationwide population-based study in Sweden. European Journal of Cancer, 49(12), 2705-2716
Open this publication in new window or tab >>Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: a nationwide population-based study in Sweden
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2013 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 12, p. 2705-2716Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.

METHODS: We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.

RESULTS: The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55years, patients with truncal tumours and during the first 5years after diagnosis.

CONCLUSION: Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.

Place, publisher, year, edition, pages
Oxford: Elsevier, 2013
Keywords
Melanoma, Survival, Socioeconomic status, Level of education, Stage at diagnosis, Population-based
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-76655 (URN)10.1016/j.ejca.2013.03.013 (DOI)000321336800010 ()23583439 (PubMedID)
Available from: 2013-07-09 Created: 2013-07-09 Last updated: 2018-06-08Bibliographically approved
Bodén, I., Nyström, J., Lundskog, B., Zazo, V., Geladi, P., Lindholm-Sethson, B. & Naredi, P. (2013). Non-invasive identification of melanoma with near-infrared and skin impedance spectroscopy. Skin research and technology, 19(1), e473-e478
Open this publication in new window or tab >>Non-invasive identification of melanoma with near-infrared and skin impedance spectroscopy
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2013 (English)In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 19, no 1, p. e473-e478Article in journal (Refereed) Published
Abstract [en]

Background/purpose: An early diagnosis of cutaneous malignant melanoma is of high importance for good prognosis. An objective, non-invasive instrument could improve the diagnostic accuracy of melanoma and decrease unnecessary biopsies. The aim of this study was to investigate the use of Near infrared and skin impedance spectroscopy in combination as a tool to distinguish between malignant and benign skin tumours.

Methods: Near infrared and skin impedance spectra were collected in vivo on 50 naevi or suspect melanomas prior to excision. Received data was analysed with multivariate techniques and the results were compared to histopathology analyses of the tumours. A total of 12 cutaneous malignant melanomas, 19 dysplastic naevi and 19 benign naevi were included in the study.

Results: The observed sensitivity and specificity of the proposed method were 83% and 95%, respectively, for malignant melanoma.

Conclusions: The results indicate that the combination of near infrared and skin impedance spectroscopy is a promising tool for non-invasive diagnosis of suspect cutaneous malignant melanomas. 

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
Keywords
NIR, PLS-DA classification, combination probe, skin cancer, in vivo
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:umu:diva-50452 (URN)10.1111/j.1600-0846.2012.00668.x (DOI)000313258100061 ()22958059 (PubMedID)
Available from: 2011-12-09 Created: 2011-12-09 Last updated: 2018-06-08Bibliographically approved
Lyth, J., Hansson, J., Ingvar, C., Mansson-Brahme, E., Naredi, P., Stierner, U., . . . Lindholm, C. (2013). Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark's level of invasion: results of a population-based study from the Swedish Melanoma Register. British Journal of Dermatology, 168(4), 779-786
Open this publication in new window or tab >>Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark's level of invasion: results of a population-based study from the Swedish Melanoma Register
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2013 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 168, no 4, p. 779-786Article in journal (Refereed) Published
Abstract [en]

Background Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed. Objectives The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark's level of invasion for risk stratification of T1 cutaneous melanoma. Methods From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13 026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11 165 patients with complete data. Results Ulceration, tumour thickness and Clark's level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67.9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1.5% (1.2-1.9%); an intermediate-risk group (28.6% of T1 cases) with a 10-year mortality rate of 6.1% (5.0-7.3%); and a high-risk group (3.5% of T1 cases) with a 10-year mortality rate of 15.6% (11.2-21.4%). The high-and intermediate-risk groups accounted for 66% of melanoma deaths within T1. Conclusions Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark's level of invasion, three distinct prognostic subgroups were identified.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
National Category
Cancer and Oncology Surgery
Identifiers
urn:nbn:se:umu:diva-70343 (URN)10.1111/bjd.12095 (DOI)000317016100030 ()
Available from: 2013-06-27 Created: 2013-05-14 Last updated: 2018-06-08Bibliographically approved
Billing, O., Natarajan, B., Mohammed, A., Naredi, P. & Kao, G. (2012). A directed RNAi screen based on larval growth arrest reveals new modifiers of C. elegans insulin signaling. PLoS ONE, 7(4), e34507
Open this publication in new window or tab >>A directed RNAi screen based on larval growth arrest reveals new modifiers of C. elegans insulin signaling
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e34507-Article in journal (Refereed) Published
Abstract [en]

Genes regulating Caenorhabditis elegans insulin/IGF signaling (IIS) have largely been identified on the basis of their involvement in dauer development or longevity. A third IIS phenotype is the first larval stage (L1) diapause, which is also influenced by asna-1, a regulator of DAF-28/insulin secretion. We reasoned that new regulators of IIS strength might be identified in screens based on the L1 diapause and the asna-1 phenotype. Eighty-six genes were selected for analysis by virtue of their predicted interaction with ASNA-1 and screened for asna-1-like larval arrest. ykt-6, mrps-2, mrps-10 and mrpl-43 were identified as genes which, when inactivated, caused larval arrest without any associated feeding defects. Several tests indicated that IIS strength was weaker and that insulin secretion was defective in these animals. This study highlights the role of the Golgi network and the mitochondria in insulin secretion and provides a new list of genes that modulate IIS in C. elegans.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-57394 (URN)10.1371/journal.pone.0034507 (DOI)000305338600033 ()
Available from: 2012-07-17 Created: 2012-07-16 Last updated: 2018-06-08Bibliographically approved
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